Local recurrence in malignant peripheral nerve sheath tumours: multicentre cohort study.

BACKGROUND: Malignant peripheral nerve sheath tumours (MPNSTs) have high local recurrence (LR) rates. Literature varies on LR risk factors and treatment. This study aimed to elucidate treatment options and risk factors for first and second LRs (LR1 and LR2) in a large multicentre cohort. METHOD: Surgically treated primary MPNSTs between 1988 and 2019 in the MONACO multicentre cohort were included. Cox regression analysed LR1 and LR2 risk factors and overall survival (OS) after LR1. Treatment of LR1 and LR2 was evaluated. RESULTS: Among 507 patients, 28% developed LR1. Median follow-up was 66.9 months, and for survivors 111.1 months. Independent LR1 risk factors included high-grade tumours (HR 2.63; 95% c.i. 1.15 to 5.99), microscopically positive margins (HR 2.19; 95% c.i. 1.51 to 3.16) and large tumour size (HR 2.14; 95% c.i. 1.21 to 3.78). Perioperative radiotherapy (HR 0.62; 95% c.i. 0.43 to 0.89) reduced the risk. LR1 patients had poorer OS. Synchronous metastasis worsened OS (HR 1.79; 95% c.i. 1.02 to 3.14) post-LR1, while surgically treated LR was associated with better OS (HR 0.38; 95% c.i. 0.22 to 0.64) compared to non-surgical cases. Two-year survival after surgical treatment was 71% (95% c.i. 63 to 82%) versus 28% (95% c.i. 18 to 44%) for non-surgical LR1 patients. Most LR1 (75.4%) and LR2 (73.7%) patients received curative-intent treatment, often surgery alone (64.9% versus 47.4%). Radiotherapy combined with surgery was given to 11.3% of LR1 and 7.9% of LR2 patients. CONCLUSION: Large, high-grade MPNSTs with R1 resections are at higher LR1 risk, potentially reduced by radiotherapy. Surgically treated recurrences may provide improved survival in highly selected cases.

Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for borderline resectable and unresectable colorectal liver metastases: phase II feasibility study.

BACKGROUND: Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy (HAIP-SYS) for liver-only colorectal liver metastases (CRLMs) has shown promising results but has not been adopted worldwide. This study evaluated the feasibility of HAIP-SYS in the Netherlands. METHODS: This was a single-arm phase II study of patients with CRLMs who received HAIP-SYS consisting of floxuridine with concomitant systemic FOLFOX or FOLFIRI. Main inclusion and exclusion criteria were borderline resectable or unresectable liver-only metastases, suitable arterial anatomy and no previous local treatment. Patients underwent laparotomy for pump implantation and primary tumour resection if in situ. Primary end point was feasibility, defined as ≥70% of patients completing two cycles of HAIP-SYS. Sample size calculations led to 31 patients. Secondary outcomes included safety and tumour response. RESULTS: Thirty-one patients with median 13 CRLMs (i.q.r. 6-23) were included. Twenty-eight patients (90%) received two HAIP-SYS cycles. Three patients did not get two cycles due to extrahepatic disease at pump placement, definitive pathology of a recto-sigmoidal squamous cell carcinoma, and progressive disease. Five patients experienced grade 3 surgical or pump device-related complications (16%) and 11 patients experienced grade ≥3 chemotherapy toxicity (38%). At first radiological evaluation, disease control rate was 83% (24/29 patients) and hepatic disease control rate 93% (27/29 patients). At 6 months, 19 patients (66%) had experienced grade ≥3 chemotherapy toxicity and the disease control rate was 79%. CONCLUSION: HAIP-SYS for borderline resectable and unresectable CRLMs was feasible and safe in the Netherlands. This has led to a successive multicentre phase III randomized trial investigating oncological benefit (EUDRA-CT 2023-506194-35-00). Current trial registration number: clinicaltrials.gov (NCT04552093).

Clinical Safety and Performance of GATT-Patch for Hemostasis in Minimal to Moderate Bleeding During Open Liver Surgery.

INTRODUCTION: Intraoperative blood loss and postoperative hemorrhage affect outcomes after liver resection. GATT-Patch is a new flexible, pliable hemostatic sealant patch comprising fibrous gelatin carrier impregnated with N-hydroxy-succinimide polyoxazoline. We evaluated safety and performance of the GATT-Patch for hemostasis at the liver resection plane. METHODS: Adult patients undergoing elective open liver surgery were recruited in three centers. GATT-Patch was used for minimal to moderate bleeding at the liver resection plane. The primary endpoint was hemostasis of the first-treated bleeding site at 3 min versus a prespecified performance goal of 65.4%. RESULTS: Two trial stages were performed: I (n = 8) for initial safety and II (n = 39) as the primary outcome cohort. GATT-Patch was applied in 47 patients on 63 bleeding sites. Median age was 60.0 (range 25-80) years and 70% were male. Most (66%) surgeries were for colorectal cancer metastases. The primary endpoint was met in 38 out of 39 patients (97.4%; 95% confidence interval: 84.6%-99.9%) versus 65.4% (P < 0.001). Of all the 63 bleeding sites, hemostasis was 82.7% at 30, 93.7% at 60, and 96.8% at 180 s. No reoperations for rebleeding or device-related issues occurred. CONCLUSIONS: When compared to a performance goal derived from state-of-the-art hemostatic agents, GATT-Patch for the treatment of minimal to moderate bleeding during liver surgery successfully and quickly achieved hemostasis with acceptable safety outcomes. (ClinicalTrials.gov Identifier: NCT04819945).

Genomic characterization and detection of potential therapeutic targets for peritoneal mesothelioma in current practice.

Peritoneal mesothelioma (PeM) is an aggressive tumor with limited treatment options. The current study aimed to evaluate the value of next generation sequencing (NGS) of PeM samples in current practice. Foundation Medicine F1CDx NGS was performed on 20 tumor samples. This platform assesses 360 commonly somatically mutated genes in solid tumors and provides a genomic signature. Based on the detected mutations, potentially effective targeted therapies were identified. NGS was successful in 19 cases. Tumor mutational burden (TMB) was low in 10 cases, and 11 cases were microsatellite stable. In the other cases, TMB and microsatellite status could not be determined. BRCA1 associated protein 1 (BAP1) mutations were found in 32% of cases, cyclin dependent kinase inhibitor 2A/B (CDKN2A/B) and neurofibromin 2 (NF2) mutations in 16%, and ataxia-telangiectasia mutated serine/threonine kinase (ATM) in 11%. Based on mutations in the latter two genes, potential targeted therapies are available for approximately a quarter of cases (i.e., protein kinase inhibitors for three NF2 mutated tumors, and polyADP-ribose polymerase inhibitors for two ATM mutated tumors). Extensive NGS analysis of PeM samples resulted in the identification of potentially effective targeted therapies for about one in four patients. Although these therapies are currently not available for patients with PeM, ongoing developments might result in new treatment options in the future.

Extrahepatic perfusion and incomplete hepatic perfusion after hepatic arterial infusion pump implantation: incidence and clinical implications.

INTRODUCTION: This study investigates the incidence of extrahepatic perfusion and incomplete hepatic perfusion at intraoperative methylene blue testing and on postoperative nuclear imaging in patients undergoing hepatic arterial infusion pump (HAIP) chemotherapy. METHODS: The first 150 consecutive patients who underwent pump implantation in the Netherlands were included. All patients underwent surgical pump implantation with the catheter in the gastroduodenal artery. All patients underwent intraoperative methylene blue testing and postoperative nuclear imaging (99mTc-Macroaggregated albumin SPECT/CT) to determine perfusion via the pump. RESULTS: Patients were included between January-2018 and December-2021 across eight centers. During methylene blue testing, 29.3% had extrahepatic perfusion, all successfully managed intraoperatively. On nuclear imaging, no clinically relevant extrahepatic perfusion was detected (0%, 95%CI: 0.0-2.5%). During methylene blue testing, 2.0% had unresolved incomplete hepatic perfusion. On postoperative nuclear imaging, 8.1% had incomplete hepatic perfusion, leading to embolization in only 1.3%. CONCLUSION: Methylene blue testing during pump placement for intra-arterial chemotherapy identified extrahepatic perfusion in 29.3% of patients, but could be resolved intraoperatively in all patients. Postoperative nuclear imaging found no clinically relevant extrahepatic perfusion and led to embolization in only 1.3% of patients. The role of routine nuclear imaging after HAIP implantation should be studied in a larger cohort.

Development of a prediction model for recurrence in patients with colorectal peritoneal metastases undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

INTRODUCTION: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival outcomes for selected patients with colorectal peritoneal metastases (PM), but recurrence rates are high. The aim of this study was to develop a tool to predict recurrence in patients with colorectal PM that undergo CRS-HIPEC. MATERIALS AND METHODS: For this retrospective cohort study, data of patients that underwent CRS-HIPEC for colorectal PM from four Dutch HIPEC centers were used. Exclusion criteria were perioperative systemic therapy and peritoneal cancer index (PCI) ≥20. Nine previously identified factors were considered as predictors: gender, age, primary tumor characteristics (location, nodal stage, differentiation, and mutation status), synchronous liver metastases, preoperative Carcino-Embryonal Antigen (CEA), and peritoneal cancer index (PCI). The prediction model was developed using multivariable Cox regression and validated internally using bootstrapping. The performance of the model was evaluated by discrimination and calibration. RESULTS: In total, 408 patients were included. During the follow-up, recurrence of disease occurred in 318 patients (78%). Significant predictors of recurrence were PCI (HR 1.075, 95% CI 1.044-1.108) and primary tumor location (left sided HR 0.719, 95% CI 0.550-0.939). The prediction model for recurrence showed fair discrimination with a C-index of 0.64 (95% CI 0.62, 0.66) after internal validation. The model was well-calibrated with good agreement between the predicted and observed probabilities. CONCLUSION: We developed a prediction tool that could aid in the prediction of recurrence in patients with colorectal PM who undergo CRS-HIPEC.

Development and validation of a novel model to predict recurrence-free survival and melanoma-specific survival after sentinel lymph node biopsy in patients with melanoma: an international, retrospective, multicentre analysis.

BACKGROUND: The introduction of adjuvant systemic treatment for patients with high-risk melanomas necessitates accurate staging of disease. However, inconsistencies in outcomes exist between disease stages as defined by the American Joint Committee on Cancer (8th edition). We aimed to develop a tool to predict patient-specific outcomes in people with melanoma rather than grouping patients according to disease stage. METHODS: Patients older than 13 years with confirmed primary melanoma who underwent sentinel lymph node biopsy (SLNB) between Oct 29, 1997, and Nov 11, 2013, at four European melanoma centres (based in Berlin, Germany; Amsterdam and Rotterdam, the Netherlands; and Warsaw, Poland) were included in the development cohort. Potential predictors of recurrence-free and melanoma-specific survival assessed were sex, age, presence of ulceration, primary tumour location, histological subtype, Breslow thickness, sentinel node status, number of sentinel nodes removed, maximum diameter of the largest sentinel node metastasis, and Dewar classification. A prognostic model and nomogram were developed to predict 5-year recurrence-free survival on a continuous scale in patients with stage pT1b or higher melanomas. This model was also calibrated to predict melanoma-specific survival. Model performance was assessed by discrimination (area under the time-dependent receiver operating characteristics curve [AUC]) and calibration. External validation was done in a cohort of patients with primary melanomas who underwent SLNB between Jan 30, 1997, and Dec 12, 2013, at the Melanoma Institute Australia (Sydney, NSW, Australia). FINDINGS: The development cohort consisted of 4071 patients, of whom 2075 (51%) were female and 1996 (49%) were male. 889 (22%) had sentinel node-positive disease and 3182 (78%) had sentinel node-negative disease. The validation cohort comprised 4822 patients, of whom 1965 (41%) were female and 2857 (59%) were male. 891 (18%) had sentinel node-positive disease and 3931 (82%) had sentinel node-negative disease. Median follow-up was 4·8 years (IQR 2·3-7·8) in the development cohort and 5·0 years (2·2-8·9) in the validation cohort. In the development cohort, 5-year recurrence-free survival was 73·5% (95% CI 72·0-75·1) and 5-year melanoma-specific survival was 86·5% (85·3-87·8). In the validation cohort, the corresponding estimates were 66·1% (64·6-67·7) and 83·3% (82·0-84·6), respectively. The final model contained six prognostic factors: sentinel node status, Breslow thickness, presence of ulceration, age at SLNB, primary tumour location, and maximum diameter of the largest sentinel node metastasis. In the development cohort, for the model's prediction of recurrence-free survival, the AUC was 0·80 (95% CI 0·78-0·81); for prediction of melanoma-specific survival, the AUC was 0·81 (0·79-0·84). External validation showed good calibration for both outcomes, with AUCs of 0·73 (0·71-0·75) and 0·76 (0·74-0·78), respectively. INTERPRETATION: Our prediction model and nomogram accurately predicted patient-specific risk probabilities for 5-year recurrence-free and melanoma-specific survival. These tools could have important implications for clinical decision making when considering adjuvant treatments in patients with high-risk melanomas. FUNDING: Erasmus Medical Centre Cancer Institute.

The importance of integrating diagnostic modalities in patient selection for CRS-HIPEC in colorectal peritoneal metastases.

BACKGROUND: Despite thorough preoperative work-up for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), so called open-close (OC) procedures as a result of irresectable disease remain common. Currently, diagnostic laparoscopy (DLS) is considered the gold standard, and consequently overrules the results of computed tomography (CT) scans; however, certain regions of the abdomen are difficult to assess and postoperative adhesion formation may further compromise staging during DLS. PURPOSE: To determine whether better clinical assessment could be achieved by combining the results of DLS and preoperative CT scans during a multidisciplinary team (MDT) meeting. MATERIAL AND METHODS: All patients who were eligible for CRS-HIPEC after DLS, but eventually underwent an OC procedure between 2010 and 2018 were selected. Radiological reassessment of CT scans was performed and combined with assessment of the DLS during a MDT meeting. The MDT was blinded for the outcome of the procedure (OC vs. CRS-HIPEC). RESULTS: The majority of the OC procedures (69%) was correctly predicted by the MDT. In most patients (88%), this conclusion was based on the combination of the radiological and surgical peritoneal cancer index (PCI). CT was particularly accurate for detection of larger tumor deposits in the abdominal regions, as 84%-86% was detected. Assessment of lesions in the small bowel regions is troublesome; 72% of lesions are missed on the preoperative CT scan. CONCLUSIONS: A combination of radiological and surgical assessment of the PCI may lead to improved preoperative patient selection for CRS-HIPEC.

Changes in Health-Related Quality of Life following Surgery in Patients with High-Grade Extremity Soft-Tissue Sarcoma: A Prospective Longitudinal Study.

INTRODUCTION: Changes in health-related quality of life (HRQoL) during the diagnostic and treatment trajectory of high-grade extremity soft-tissue sarcoma (eSTS) has rarely been investigated for adults (18-65 y) and the elderly (aged ≥65 y), despite a potential variation in challenges from diverse levels of physical, social, or work-related activities. This study assesses HRQoL from time of diagnosis to one year thereafter among adults and the elderly with eSTS. METHODS: HRQoL of participants from the VALUE-PERSARC trial (n = 97) was assessed at diagnosis and 3, 6 and 12 months thereafter, utilizing the PROMIS Global Health (GH), PROMIS Physical Function (PF) and EQ-5D-5L. RESULTS: Over time, similar patterns were observed in all HRQoL measures, i.e., lower HRQoL scores than the Dutch population at baseline (PROMIS-PF:46.8, PROMIS GH-Mental:47.3, GH-Physical:46.2, EQ-5D-5L:0.76, EQ-VAS:72.6), a decrease at 3 months, followed by an upward trend to reach similar scores as the general population at 12 months (PROMIS-PF:49.9, PROMIS GH-Physical:50.1, EQ-5D-5L:0.84, EQ-VAS:81.5), except for the PROMIS GH-Mental (47.5), where scores remained lower than the general population mean (T = 50). Except for the PROMIS-PF, no age-related differences were observed. CONCLUSIONS: On average, eSTS patients recover well physically from surgery, yet the mental component demonstrates no progression, irrespective of age. These results underscore the importance of comprehensive care addressing both physical and mental health.

Assessing patients' needs in the follow-up after treatment for colorectal cancer-a mixed-method study.

PURPOSE: The accessibility of cancer care faces challenges due to the rising prevalence of colorectal cancer (CRC) coupled with a shrinkage of healthcare professionals-known as the double aging phenomenon. To ensure sustainable and patient-centred care, innovative solutions are needed. This study aims to assess the needs of CRC patients regarding their follow-up care. METHODS: This study uses a mixed-method approach divided in three phases. The initial phase involved focus group sessions, followed by semi-structured interviews to identify patients' needs during follow-up. Open analysis was done to define main themes and needs for patients. In the subsequent quantitative phase, a CRC follow-up needs questionnaire was distributed to patients in the follow-up. RESULTS: After two focus groups (n = 14) and interviews (n = 5), this study identified six main themes. Findings underscore the importance of providing assistance in managing both physical and mental challenges associated with cancer. Participants emphasised the need of a designated contact person and an increased focus on addressing psychological distress. Furthermore, patients desire individualised feedback on quality of life questionnaires, and obtaining tailored information. The subsequent questionnaire (n = 96) revealed the priority of different needs, with the highest priority being the need for simplified radiology results. A possible approach to address a part of the diverse needs could be the implementation of a platform; nearly 70% of patients expressed interest in the proposed platform. CONCLUSIONS: CRC patients perceive substantial room for improvement of their follow-up care. Findings can help to develop a platform fulfilling the distinct demands of CRC patients during follow-up.

Lymph node regression after neoadjuvant chemoradiotherapy in rectal cancer.

AIMS: Lymph node metastases (LNM) are one of the most important prognostic indicators in solid tumours and a major component of cancer staging. Neoadjuvant therapy might influence nodal status by induction of regression. Our aim is to determine the prevalence and role of regression of LNM on outcomes in patients with rectal cancer. METHODS AND RESULTS: Four independent study populations of rectal cancer patients treated with similar regimens of chemoradiotherapy were pooled together to obtain a total cohort of 469 patients. Post-treatment nodal status (ypN) and signs of tumour regression (Reg) were incorporated to form three-tiered (ypN- Reg+, ypN- Reg- and ypN+) and four-tiered (ypN- Reg+, ypN- Reg-, ypN+ Reg+ and ypN+ Reg-) classifications. In our cohort, 31% of patients presented with ypN+ rectal cancer. As expected, we found significantly worse overall survival (OS) in ypN+ patients compared to ypN- patients (P = 0.002). The percentage of ypN- patients with lymph nodes with complete regression was 20% in our cohort. While node-negative patients with and without regression had similar OS (P = 0.09), disease-free survival (DFS) was significantly better in node-negative patients with regression (P = 0.009). CONCLUSIONS: Regression in lymph nodes is frequent, and node-negative patients with evidence of lymph node regression have better DFS compared to node-negative patients without such evidence.

Intraperitoneal irinotecan with concomitant FOLFOX and bevacizumab for patients with unresectable colorectal peritoneal metastases: protocol of the multicentre, open-label, phase II, INTERACT-II trial.

INTRODUCTION: The peritoneum is the second most affected organ for the dissemination of colorectal cancer (CRC). Patients with colorectal peritoneal metastases (CPM) face a poor prognosis, despite the majority of patients being treated with palliative systemic therapy. The efficacy of palliative systemic therapy is limited due to the plasma-peritoneum barrier. The poor prognosis of unresectable CPM patients has resulted in the development of new treatment strategies where systemic therapy is combined with local, intraperitoneal chemotherapy. In the recently published phase I study, the maximum tolerated dose and thus the recommended phase II dose of intraperitoneal irinotecan was investigated and determined to be 75 mg. In the present study, the overall survival after treatment with 75 mg irinotecan with concomitant mFOLFOX4 and bevacizumab will be investigated. MATERIALS AND METHODS: In this single-arm phase II study in two Dutch tertiary referral centres, 85 patients are enrolled. Eligibility criteria are an adequate performance status and organ function, histologically confirmed microsatellite stable and unresectable CPM, no previous palliative therapy for CRC, no systemic therapy<6 months for CRC prior to enrolment and no previous cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC). Patients will undergo a diagnostic laparoscopy as standard work-up for CPM and if the peritoneal disease is considered unresectable (eg, Peritoneal Cancer Index (PCI)>20, too extensive small bowel involvement), a peritoneal access port and a port-a-cath are placed for administration of intraperitoneal and intravenous chemotherapy, respectively. Patients may undergo up to 12 cycles of study treatment. Each cycle consists of intravenous mFOLFOX4 with bevacizumab and concomitant intraperitoneal irinotecan (75 mg), which is repeated every 2 weeks, with a maximum of 12 cycles. Modified FOLFOX-4 regimen consists of 85 mg/m2 oxaliplatin plus 200 mg/m2 LV and 5-FU 400 mg/m2 bolus on day 1 followed by 1600 mg/m2 5-FU as a 46 hours infusion. Study treatment ends after the 12th cycle, or earlier in case of disease progression or unacceptable toxicity. The primary outcome is overall survival and key secondary outcomes are progression-free survival, safety (measured by the amount of grade ≥3 adverse events (Common Terminology Criteria for Adverse Events V.5.0)), patient-reported outcomes and pharmacokinetics of irinotecan. It is hypothesised that the trial treatment will lead to a 4 month increase in overall survival; from a median of 12.2 to 16.2 months. ETHICS AND DISSEMINATION: This study is approved by the Dutch Authority (CCMO, the Hague, the Netherlands), by a central medical ethics committee (MEC-U, Nieuwegein, the Netherlands) and by the institutional research boards of both research centres. Results will be submitted for publication in peer-reviewed medical journals and presented to patients and healthcare professionals. TRIAL REGISTRATION NUMBER: NCT06003998.

Association of modified textbook outcome and overall survival after surgery for colorectal liver metastases: A nationwide analysis.

BACKGROUND: Textbook outcome (TO) represents a multidimensional quality measurement, encompassing the desirable short-term outcomes following surgery. This study aimed to investigate whether achieving TO after resection of colorectal liver metastases (CRLM) surgery is related to better overall survival (OS) in a national cohort. METHOD: Data was retrieved from the Dutch Hepato Biliary Audit. A modified definition of TO (mTO) was used because readmissions were only recorded from 2019. mTO was achieved when no severe postoperative complications, mortality, prolonged length of hospital stay, occurred and when adequate surgical resection margins were obtained. To compare outcomes of patients with and without mTO and reduce baseline differences between both groups propensity score matching (PSM) was used for patients operated on between 2014 and 2018. RESULTS: Out of 6525 eligible patients, 81 % achieved mTO. For the cohort between 2014 and 2018, those achieving mTO had a 5-year OS of 46.7 % (CI 44.8-48.6) while non-mTO patients had a 5-year OS of 33.7 % (CI 29.8-38.2), p < 0.001. Not achieving mTO was associated with a worse OS (aHR 1.34 (95 % CI 1.17-1.53), p < 0.001. Median follow-up was 76 months., PSM assigned 519 patients to each group. In the PSM cohort patients achieving mTO, 5-year OS was 43.6 % (95 % CI 39.2-48.5) compared to 36.4 % (95 % CI 31.9-41.2) in patients who did not achieve mTO, p = 0.006. CONCLUSION: Achieving mTO is associated with improved long-term survival. This emphasizes the importance of optimising perioperative care and reducing postoperative complications in surgical treatment of CRLM.

Management of Postthyroidectomy Hypoparathyroidism and Its Effect on Hypocalcemia-Related Complications: A Meta-Analysis.

OBJECTIVE: The aim of this Meta-analysis is to evaluate the impact of different treatment strategies for early postoperative hypoparathyroidism on hypocalcemia-related complications and long-term hypoparathyroidism. DATA SOURCES: Embase.com, MEDLINE, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and the top 100 references of Google Scholar were searched to September 20, 2022. REVIEW METHODS: Articles reporting on adult patients who underwent total thyroidectomy which specified a treatment strategy for postthyroidectomy hypoparathyroidism were included. Random effect models were applied to obtain pooled proportions and 95% confidence intervals. Primary outcome was the occurrence of major hypocalcemia-related complications. Secondary outcome was long-term hypoparathyroidism. RESULTS: Sixty-six studies comprising 67 treatment protocols and 51,096 patients were included in this Meta-analysis. In 8 protocols (3806 patients), routine calcium and/or active vitamin D medication was given to all patients directly after thyroidectomy. In 49 protocols (44,012 patients), calcium and/or active vitamin D medication was only given to patients with biochemically proven postthyroidectomy hypoparathyroidism. In 10 protocols (3278 patients), calcium and/or active vitamin D supplementation was only initiated in case of clinical symptoms of hypocalcemia. No patient had a major complication due to postoperative hypocalcemia. The pooled proportion of long-term hypoparathyroidism was 2.4% (95% confidence interval, 1.9-3.0). There was no significant difference in the incidence of long-term hypoparathyroidism between the 3 supplementation groups. CONCLUSIONS: All treatment strategies for postoperative hypocalcemia prevent major complications of hypocalcemia. The early postoperative treatment protocol for postthyroidectomy hypoparathyroidism does not seem to influence recovery of parathyroid function in the long term.

Regional Collaboration and Trends in Clinical Management of Thyroid Cancer.

OBJECTIVE: This study examines the trends in the management of thyroid cancer and clinical outcomes in the Southwestern region of The Netherlands from 2010 to 2021, where a regional collaborative network has been implemented in January 2016. STUDY DESIGN: Retrospective cohort study. SETTING: This study encompasses all patients diagnosed with thyroid cancer of any subtype between January 2010 and June 2021 in 10 collaborating hospitals in the Southwestern region of The Netherlands. METHODS: The primary outcome of this study was the occurrence of postoperative complications. Secondary outcomes were trends in surgical management, centralization, and waiting times of patients with thyroid cancer. RESULTS: This study included 1186 patients with thyroid cancer. Median follow-up was 58 [interquartile range: 24-95] months. Surgery was performed in 1027 (86.6%) patients. No differences in postoperative complications, such as long-term hypoparathyroidism, permanent recurrent nerve paresis, or reoperation due to bleeding were seen over time. The percentage of patients with low-risk papillary thyroid carcinoma referred to the academic hospital decreased from 85% (n = 120/142) in 2010 to 2013 to 70% (n = 120/171) in 2014 to 2017 and 62% (n = 100/162) in 2018 to 2021 (P < .01). The percentage of patients undergoing a hemithyroidectomy alone was 9% (n = 28/323) in 2010 to 2013 and increased to 20% (n = 63/317; P < .01) in 2018 to 2021. CONCLUSION: The establishment of a regional oncological network coincided with a de-escalation of thyroid cancer treatment and centralization of complex patients and interventions. However, no differences in postoperative complications over time were observed. Determining the impact of regional oncological networks on quality of care is challenging in the absence of uniform quality indicators.

MRI in addition to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): an international, multicentre, prospective, diagnostic accuracy trial.

BACKGROUND: Guidelines are inconclusive on whether contrast-enhanced MRI using gadoxetic acid and diffusion-weighted imaging should be added routinely to CT in the investigation of patients with colorectal liver metastases who are scheduled for curative liver resection or thermal ablation, or both. Although contrast-enhanced MRI is reportedly superior than contrast-enhanced CT in the detection and characterisation of colorectal liver metastases, its effect on clinical patient management is unknown. We aimed to assess the clinical effect of an additional liver contrast-enhanced MRI on local treatment plan in patients with colorectal liver metastases amenable to local treatment, based on contrast-enhanced CT. METHODS: We did an international, multicentre, prospective, incremental diagnostic accuracy trial in 14 liver surgery centres in the Netherlands, Belgium, Norway, and Italy. Participants were aged 18 years or older with histological proof of colorectal cancer, a WHO performance status score of 0-4, and primary or recurrent colorectal liver metastases, who were scheduled for local therapy based on contrast-enhanced CT. All patients had contrast-enhanced CT and liver contrast-enhanced MRI including diffusion-weighted imaging and gadoxetic acid as a contrast agent before undergoing local therapy. The primary outcome was change in the local clinical treatment plan (decided by the individual clinics) on the basis of liver contrast-enhanced MRI findings, analysed in the intention-to-image population. The minimal clinically important difference in the proportion of patients who would have change in their local treatment plan due to an additional liver contrast-enhanced MRI was 10%. This study is closed and registered in the Netherlands Trial Register, NL8039. FINDINGS: Between Dec 17, 2019, and July 31, 2021, 325 patients with colorectal liver metastases were assessed for eligibility. 298 patients were enrolled and included in the intention-to-treat population, including 177 males (59%) and 121 females (41%) with planned local therapy based on contrast-enhanced CT. A change in the local treatment plan based on liver contrast-enhanced MRI findings was observed in 92 (31%; 95% CI 26-36) of 298 patients. Changes were made for 40 patients (13%) requiring more extensive local therapy, 11 patients (4%) requiring less extensive local therapy, and 34 patients (11%) in whom the indication for curative-intent local therapy was revoked, including 26 patients (9%) with too extensive disease and eight patients (3%) with benign lesions on liver contrast-enhanced MRI (confirmed by a median follow-up of 21·0 months [IQR 17·5-24·0]). INTERPRETATION: Liver contrast-enhanced MRI should be considered in all patients scheduled for local treatment for colorectal liver metastases on the basis of contrast-enhanced CT imaging. FUNDING: The Dutch Cancer Society and Bayer AG - Pharmaceuticals.

Abandonment of Routine Radiotherapy for Nonlocally Advanced Rectal Cancer and Oncological Outcomes.

Importance: Neoadjuvant short-course radiotherapy was routinely applied for nonlocally advanced rectal cancer (cT1-3N0-1M0 with >1 mm distance to the mesorectal fascia) in the Netherlands following the Dutch total mesorectal excision trial. This policy has shifted toward selective application after guideline revision in 2014. Objective: To determine the association of decreased use of neoadjuvant radiotherapy with cancer-related outcomes and overall survival at a national level. Design, Setting, and Participants: This multicenter, population-based, nationwide cross-sectional cohort study analyzed Dutch patients with rectal cancer who were treated in 2011 with a 4-year follow-up. A similar study was performed in 2021, analyzing all patients that were surgically treated in 2016. From these cohorts, all patients with cT1-3N0-1M0 rectal cancer and radiologically unthreatened mesorectal fascia were included in the current study. The data of the 2011 cohort were collected between May and October 2015, and the data of the 2016 cohort were collected between October 2020 and November 2021. The data were analyzed between May and October 2022. Main Outcomes and Measures: The main outcomes were 4-year local recurrence and overall survival rates. Results: Among the 2011 and 2016 cohorts, 1199 (mean [SD] age, 68 [11] years; 430 women [36%]) of 2095 patients (57.2%) and 1576 (mean [SD] age, 68 [10] years; 547 women [35%]) of 3057 patients (51.6%) had cT1-3N0-1M0 rectal cancer and were included, with proportions of neoadjuvant radiotherapy of 87% (2011) and 37% (2016). Four-year local recurrence rates were 5.8% and 5.5%, respectively (P = .99). Compared with the 2011 cohort, 4-year overall survival was significantly higher in the 2016 cohort (79.6% vs 86.4%; P < .001), with lower non-cancer-related mortality (13.8% vs 6.3%; P < .001). Conclusions and Relevance: The results of this cross-sectional study suggest that an absolute 50% reduction in radiotherapy use for nonlocally advanced rectal cancer did not compromise cancer-related outcomes at a national level. Optimizing clinical staging and surgery following the Dutch total mesorectal excision trial has potentially enabled safe deintensification of treatment.

Deep learning models for automatic tumor segmentation and total tumor volume assessment in patients with colorectal liver metastases.

BACKGROUND: We developed models for tumor segmentation to automate the assessment of total tumor volume (TTV) in patients with colorectal liver metastases (CRLM). METHODS: In this prospective cohort study, pre- and post-systemic treatment computed tomography (CT) scans of 259 patients with initially unresectable CRLM of the CAIRO5 trial (NCT02162563) were included. In total, 595 CT scans comprising 8,959 CRLM were divided into training (73%), validation (6.5%), and test sets (21%). Deep learning models were trained with ground truth segmentations of the liver and CRLM. TTV was calculated based on the CRLM segmentations. An external validation cohort was included, comprising 72 preoperative CT scans of patients with 112 resectable CRLM. Image segmentation evaluation metrics and intraclass correlation coefficient (ICC) were calculated. RESULTS: In the test set (122 CT scans), the autosegmentation models showed a global Dice similarity coefficient (DSC) of 0.96 (liver) and 0.86 (CRLM). The corresponding median per-case DSC was 0.96 (interquartile range [IQR] 0.95-0.96) and 0.80 (IQR 0.67-0.87). For tumor segmentation, the intersection-over-union, precision, and recall were 0.75, 0.89, and 0.84, respectively. An excellent agreement was observed between the reference and automatically computed TTV for the test set (ICC 0.98) and external validation cohort (ICC 0.98). In the external validation, the global DSC was 0.82 and the median per-case DSC was 0.60 (IQR 0.29-0.76) for tumor segmentation. CONCLUSIONS: Deep learning autosegmentation models were able to segment the liver and CRLM automatically and accurately in patients with initially unresectable CRLM, enabling automatic TTV assessment in such patients. RELEVANCE STATEMENT: Automatic segmentation enables the assessment of total tumor volume in patients with colorectal liver metastases, with a high potential of decreasing radiologist's workload and increasing accuracy and consistency. KEY POINTS: • Tumor response evaluation is time-consuming, manually performed, and ignores total tumor volume. • Automatic models can accurately segment tumors in patients with colorectal liver metastases. • Total tumor volume can be accurately calculated based on automatic segmentations.