Evolution of clinical nature, treatment and survival of locally recurrent rectal cancer: Comparative analysis of two national cross-sectional cohorts.

BACKGROUND: In the Netherlands, use of neoadjuvant radiotherapy for rectal cancer declined after guideline revision in 2014. This decline is thought to affect the clinical nature and treatability of locally recurrent rectal cancer (LRRC). Therefore, this study compared two national cross-sectional cohorts before and after the guideline revision with the aim to determine the changes in treatment and survival of LRRC patients over time. METHODS: Patients who underwent resection of primary rectal cancer in 2011 (n = 2094) and 2016 (n = 2855) from two nationwide cohorts with a 4-year follow up were included. Main outcomes included time to LRRC, synchronous metastases at time of LRRC diagnosis, intention of treatment and 2-year overall survival after LRRC. RESULTS: Use of neoadjuvant (chemo)radiotherapy for the primary tumour decreased from 88.5% to 60.0% from 2011 to 2016. The 3-year LRRC rate was not significantly different with 5.1% in 2011 (n = 114, median time to LRRC 16 months) and 6.3% in 2016 (n = 202, median time to LRRC 16 months). Synchronous metastasis rate did not significantly differ (27.2% vs 33.7%, p = 0.257). Treatment intent of the LRRC shifted towards more curative treatment (30.4% vs. 47.0%, p = 0.009). In the curatively treated group, two-year overall survival after LRRC diagnoses increased from 47.5% to 78.7% (p = 0.013). CONCLUSION: Primary rectal cancer patients in 2016 were treated less often with neoadjuvant (chemo)radiotherapy, while LRRC rates remained similar. Those who developed LRRC were more often candidate for curative intent treatment compared to the 2011 cohort, and survival after curative intent treatment also improved substantially.

Health-related quality of life (HRQoL) after different axillary treatments in women with breast cancer: a 1-year longitudinal cohort study.

PURPOSE: As life expectancy continues to rise, post-treatment health-related quality of life (HRQoL) of breast cancer patients becomes increasingly important. This study examined the one-year longitudinal relation between axillary treatments and physical, psychosocial, and sexual wellbeing and arm symptoms. METHODS: Women diagnosed with breast cancer who received different axillary treatments being axilla preserving surgery (APS) with or without axillary radiotherapy or full axillary lymph node dissection (ALND) with or without axillary radiotherapy were included. HRQoL was assessed at baseline, 6- and 12-months postoperatively using the BREAST-Q and the European Organization for Research and Treatment of Cancer QoL Questionnaire Breast Cancer Module (EORTC QLQ-BR23). Mixed regression models were constructed to assess the impact of axillary treatment on HRQoL. HRQoL at baseline was compared to HRQoL at 6- and at 12-months postoperatively. RESULTS: In total, 552 patients were included in the mixed regressions models. Except for ALND with axillary radiotherapy, no significant differences in physical and psychosocial wellbeing were found. Physical wellbeing decreased significantly between baseline and 6- and 12-months postoperatively (p < 0.001, p = 0.035) and psychosocial wellbeing decreased significantly between baseline and 12 months postoperatively (p = 0.028) for ALND with axillary radiotherapy compared to APS alone. Arm symptoms increased significantly between baseline and 6 months and between baseline and 12 months postoperatively for APS with radiotherapy (12.71, 13.73) and for ALND with radiotherapy (13.93, 16.14), with the lowest increase in arm symptoms for ALND without radiotherapy (6.85, 7.66), compared to APS alone (p < 0.05). CONCLUSION: Physical and psychosocial wellbeing decreased significantly for ALND with radiotherapy compared to APS alone. Shared decision making and expectation management pre-treatment could be strengthened by discussing arm symptoms per axillary treatment with the patient.

The Effect of Intraoperative Margin Assessment During Breast Conserving Surgery for Breast Cancer in a Dutch Cohort.

INTRODUCTION: Intraoperative specimen radiography is a routinely used procedure to ensure adequate resection of non-palpable breast tumors. Intraoperative digital specimen mammography (IDSM) is an alternative to conventional specimen radiography (CSR) which provides immediate specimen evaluation and can potentially decrease operation time. IDSM may also result in lower positive margin and re-excision rates. IDSM was implemented in our hospital in 2018. The objective of this study was to evaluate the effect of using IDSM versus CSR on operation time, margin status and re-excision rates in breast conserving surgery. METHODS: The present study is a single-center retrospective cohort study with 2 patient cohorts: one which underwent CSR (n = 532) and one which underwent IDSM (n = 475). The primary outcome was the operation time. Secondary outcomes were the margin status of the primary surgery, the cavity shaving rate, and the re-excision rate. Differences between cohorts were compared using univariate statistics and multiple regression analyses to adjust for variables that were significantly different between the groups. RESULTS: IDSM use was associated with an 8-minute reduction in surgery time (B = -8.034, 95% CI [-11.6, -4.5]; P < .001). Treatment variables independently associated with the operation time included use of IDSM, type of surgery, and performance of cavity shaving. Cavity shaves were more often performed when IDSM was used (24% for IDSM vs. 14% for CSR, P < .001), while the proportion of negative margin rates (93% for IDSM vs. 96% for CSR, P = .070) was comparable. CONCLUSION: IDSM was associated with a modest reduction in operation time. Surgeons performed more cavity shaves since the introduction of IDSM, but this increase was not reflected by difference in negative margin rates.

Can we use a simple blood test to reduce unnecessary adverse effects from radiotherapy by timely identification of radiotherapy-resistant rectal cancers? MeD-Seq rectal study protocol.

BACKGROUND: Chemoradiation therapy (CRT) followed by surgery is currently the standard of care to treat patients with locally advanced rectal cancer (LARC). CRT reduces local recurrences, but is associated with significant damage to the surrounding healthy tissue that can severely impact patients quality of life. Additionally, a proportion of patients (hardly) benefit from CRT. We aim to develop a diagnostic innovation, using DNA-methylation, which can enable a more selective and thereby more effective use of the available therapies for rectal cancer patients. METHODS: MeD-Seq Rectal is a prospective single centre, observational study. 75 patients diagnosed with rectal cancer and will receive CRT as neoadjuvant treatment are will be included. DNA-methylation profiling will be performed on liquid biopsies to predict pathological response to CRT. DISCUSSION: To data no clinical or image-based features were found that predict response to CRT. we hypothesize that DNA methylation patterns in liquid biopsies may provide a promising and patient-friendly strategy to predict CRT resistance upfront. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT06035471).

The Effect of Histopathological Growth Patterns of Colorectal Liver Metastases on the Survival Benefit of Adjuvant Hepatic Arterial Infusion Pump Chemotherapy.

BACKGROUND: Histopathological growth patterns (HGPs) are a prognostic biomarker in colorectal liver metastases (CRLM). Desmoplastic HGP (dHGP) is associated with liver-only recurrence and superior overall survival (OS), while non-dHGP is associated with multi-organ recurrence and inferior OS. This study investigated the predictive value of HGPs for adjuvant hepatic arterial infusion pump (HAIP) chemotherapy in CRLM. METHODS: Patients undergoing resection of CRLM and perioperative systemic chemotherapy in two centers were included. Survival outcomes and the predictive value of HAIP versus no HAIP per HGP group were evaluated through Kaplan-Meier and Cox regression methods, respectively. RESULTS: We included 1233 patients. In the dHGP group (n = 291, 24%), HAIP chemotherapy was administered in 75 patients (26%). In the non-dHGP group (n = 942, 76%), HAIP chemotherapy was administered in 247 patients (26%). dHGP was associated with improved overall survival (OS, HR 0.49, 95% CI 0.32-0.73, p < 0.001). HAIP chemotherapy was associated with improved OS (HR 0.61, 95% CI 0.45-0.82, p < 0.001). No interaction could be demonstrated between HGP and HAIP on OS (HR 1.29, 95% CI 0.72-2.32, p = 0.40). CONCLUSIONS: There is no evidence that HGPs of CRLM modify the survival benefit of adjuvant HAIP chemotherapy in patients with resected CRLM.

Markers for Major Complications at Day-One Postoperative in Fast-Track Metabolic Surgery: Updated Metabolic Checklist.

INTRODUCTION: In fast-track metabolic surgery, the window to identify complications is narrow. Postoperative checklists can be useful tools in the decision-making of safe early discharge. The aim of this study was to evaluate the predictive value of a checklist used in metabolic surgery. METHODS: Retrospective data from June 2018 to January 2021 was collected on all patients that underwent metabolic surgery in a high-volume bariatric hospital in the Netherlands. Patients without an available checklist were excluded. The primary outcome was major complications and the secondary outcomes were minor complications, readmission, and unplanned hospital visits within 30 days postoperatively. RESULTS: Major complications within 30 days postoperatively occurred in 62/1589 (3.9%) of the total included patients. An advise against early discharge was significantly more seen in patients with major complications compared to those without major complications (90.3% versus 48.1%, P < 0.001, respectively), and a negative checklist (advice for discharge) had a negative predictive value of 99.2%. The area under the curve for the total checklist was 0.80 (P < 0.001). Using a cut-off value of ≥3 positive points, the sensitivity and specificity were 65% and 82%, respectively. Individual parameters from the checklist: oral intake, mobilization, calf pain, willingness for discharge, heart rate, drain (>30 ml/24 h), hemoglobin, and leukocytes count were also significantly different between groups. CONCLUSION: This checklist is a valuable tool to decide whether patients can be safely discharged early. Heart rate appeared to be the most predictive parameter for the development of major complications. Future studies should conduct prediction models to identify patients at risk for major complications.

Molecular alterations and potential actionable mutations in peritoneal mesothelioma: a scoping review of high-throughput sequencing studies.

BACKGROUND: Peritoneal mesothelioma (PeM) is a rare malignancy with a poor prognosis. Currently there is a lack of effective systemic therapies. Due to the rarity of PeM, it is challenging to study new treatment options. Off-label use of targeted drugs could be an effective approach. This scoping review aims to explore the genomic landscape of PeM to identify potential therapeutic targets. MATERIALS AND METHODS: A systematic literature search of Embase, Medline, Web of Science, the Cochrane Library, and Google Scholar was carried out up to 1 November 2022. Studies that reported on molecular alterations in PeM detected by high-throughput sequencing techniques were included. Genes that were altered in ≥1% of PeMs were selected for the identification of potential targeted therapies. RESULTS: Thirteen articles were included, comprising 824 PeM patients. In total, 142 genes were altered in ≥1% of patients, of which 7 genes were altered in ≥10%. BAP1 was the most commonly altered gene (50%). Other commonly altered genes were NF2 (25%), CDKN2A (23%), CDKN2B (17%), PBRM1 (15%), TP53 (14%), and SETD2 (13%). In total, 17% of PeM patients were carriers of a germline mutation, mainly in BAP1 (7%). CONCLUSIONS: This scoping review provides an overview of the mutational landscape of PeM. Germline mutations might be a larger contributor to the incidence of PeM than previously thought. Currently available targeted therapy options are limited, but several targeted agents [such as poly (ADP-ribose) polymerase (PARP), enhancer of zeste homolog 2 (EZH2), and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors] were identified that might provide new targeted therapy options in the future.

Implementation of vacuum-assisted excision as a management option for benign and high-risk breast lesions.

OBJECTIVE: Previous studies have shown that vacuum-assisted excision (VAE) is a safe and effective alternative for surgical excision (SE) of benign breast lesions. However, the use of VAE in high-risk lesions is controversial and guidelines are ambiguous. This study describes the impact of the implementation of VAE in terms of management and outcomes compared to a cohort before implementation. METHODS: A single centre retrospective study with two cohorts: 'before' and 'after' implementation of VAE was performed. All patients with a benign or high-risk lesion treated by VAE or SE between 2016 and 2019 were included. Excision, complication, and upgrade rates were compared between both cohorts. Cox regression was used for the evaluation of recurrences and re-excisions. RESULTS: The overall excision rate of all benign and high-risk lesions was comparable in both cohorts (17% vs 16%, p = 0.700). After implementation, benign lesions were significantly more often managed by VAE (101/151, 67%, p < 0.001). Re-excision, recurrence, and complication rates were low and comparable between cohorts (4.3% vs 3.9%, p > 0.999; 3.0 vs 2.0%, p = 0.683; 3.4 vs 6.6%, p = 0.289, respectively). CONCLUSION: SE could safely be replaced by VAE in 58% of patients treated for a benign or high-risk lesion. With this shift in management, the use of operating rooms and general anaesthesia can safely be omitted in this patient group. Further research on high-risk lesions is warranted since our data are exploratory. ADVANCES IN KNOWLEDGE: This study provides supportive data for the use of VAE as a management option for both benign (up to 5 cm) and high-risk lesions. Outcomes on re-excision, recurrence should be confirmed in prospective studies especially in high-risk lesions.

Histopathological growth patterns of neuroendocrine tumor liver metastases.

Histopathological growth patterns (HGPs) of liver metastases represent a potential biomarker for prognosis after resection. They have never been studied in neuroendocrine tumor liver metastases (NETLM). This study evaluated if distinct HGPs can be observed in resected NETLM and if they have prognostic value. Sixty-three patients who underwent resection of NETLM between 01-01-2001 and 31-12-2021 were retrospectively included. HGPs were scored on Haematoxylin&Eosin slides using light microscopy, distinguishing desmoplastic- (dHGP), pushing- (pHGP) and replacement HGP (rHGP). Average HGP scores were calculated per patient. Each patient was classified according to predominant HGP. Overall and Disease-Free Survival (OS and DFS) were evaluated through Kaplan-Meier analysis and Cox regression. Eighteen patients had predominant dHGP (29%), 33 had predominant pHGP (52%) and 11 had predominant rHGP (17%). One patient had mixed HGP (2%). Five-year OS was 76% (95%CI: 66-87%) for the overall cohort. Five-year OS was 92% (95%CI: 77-100%) for dHGP, was 73% (95%CI: 59-91%) for pHGP, 50% (95%CI: 25-100%) for rHGP. Five-year DFS was 39% (95%CI: 19-83%) for dHGP, 44% (95%CI: 27-71%) for rHGP and 50% (95%CI: 23-100%) for pHGP. There was no significant association between HGP and OS or DFS in multivariable analysis. Distinct HGPs could be identified in NETLM. In patients who underwent resection of NETLM, no association was found between HGPs and postoperative survival. Half of the patients with NETLM have a predominant pushing growth pattern, which is a rare growth pattern in liver metastases from breast and colorectal cancer.

Locally recurrent rectal cancer and distant metastases: is there still a chance ofcure?

INTRODUCTION: Patients with locally recurrent rectal cancer (LRRC) generally have poor prognosis, especially those who have (a history of) distant metastases. The aim of this study was to investigate the impact of distant metastases on oncological outcomes in LRRC patients undergoing curative treatment. METHODS: Consecutive patients with surgically treated LRRC between 2005 and 2019 in two tertiary referral hospitals were retrospectively analysed. Oncological survival of patients without distant metastases were compared with outcomes of patients with synchronous distant metastases with the primary tumour, patients with distant metastases in the primary-recurrence interval, and patients with synchronous LRRC distant metastases. RESULTS: A total of 535 LRRC patients were analysed, of whom 398 (74%) had no (history of) metastases, 22 (4%) had synchronous metastases with the primary tumour, 44 (8%) had metachronous metastases, and 71 (13%) had synchronous LRRC metastases. Patients with synchronous LRRC metastases had worse survival compared to patients without metastases (adjusted hazard ratio: 1.56 [1.15-2.12]), whilst survival of patients with synchronous primary metastases and metachronous metastases of the primary tumour was similar as those patients who had no metastases. In LRRC patients who had metastases in primary-recurrence interval, patients with early metachronous metastases had better disease-free survival as patients with late metachronous metastases (3-year disease-free survival: 48% vs 22%, p = 0.039). CONCLUSION: LRRC patients with synchronous distant metastases undergoing curative surgery have relatively poor prognosis. However, LRRC patients with a history of distant metastases diagnosed nearby the primary tumour have comparable (oncological) survival as LRRC patients without distant metastases.

Pregnancy-associated desmoid fibromatosis: A Dutch multi-centre retrospective study.

INTRODUCTION: The development of desmoid fibromatosis (DF) is associated with pregnancy. The current treatment consensus recommends active surveillance (AS). However, data in pregnancy-associated DF is scarce and it is uncertain whether AS is the best management strategy for this DF-subgroup. The aim of this study was to describe demographic, tumor, obstetric, treatment characteristics and treatment outcome in pregnancy-associated DF. METHODS: Female DF patients who were 18-50 years old at time of diagnosis (2000-2020) and had a history (≤5 years) of pregnancy at time of diagnosis were included. RESULTS: Overall, 62 patients were included. The most common locations were abdominal wall (74%), pelvis (10%) and extremities (10%). Mutational analysis was conducted in 31 patients of which 94% had CTNNB1-mutations. Ten patients (16%) were diagnosed during pregnancy, while the remainder were diagnosed after pregnancy with a median time from delivery to diagnosis of 19 months (1-60). The frontline management was AS in 38 patients (61%) of whom 12 (33%) developed progressive disease and surgery in 23 patients (37%). In total, 30 patients underwent surgery and five had local recurrence (17%). Positive resection margins were no prognostic factor. Nine patients received systemic treatment in second- or third-line. CONCLUSIONS: Pregnancy-associated DF generally has an indolent behavior, where our results underscore the difficulty of establishing a clear definition of this entity. This study shows that AS should be the frontline management strategy for pregnancy-associated DF. When active treatment is indicated, surgery is a good option with low recurrence rates, even with positive (R1) resection margins.

Circulating tumour cells are associated with histopathological growth patterns of colorectal cancer liver metastases.

Histopathological Growth Patterns (HGPs) have prognostic and predictive value in patients with Colorectal Liver Metastases (CRLM). This study examined whether preoperative measurement of Circulating Tumour Cells (CTCs) is associated with HGP. CTCs were prospectively enumerated in 7.5 ml of blood using the FDA-approved CellSearch system in patients who underwent local treatment of CRLM with curative intent between 2008 and 2021. All CTC samples were collected on the day of local treatment. Patients treated with neoadjuvant chemotherapy for CRLM or with extrahepatic disease at the time of CTC sampling were excluded. HGP was scored retrospectively following the current consensus guidelines. The association between CTCs and HGP was investigated through multivariable logistic regression. Data were available for 177 patients, desmoplastic HGP (dHGP) was observed in 34 patients (19%). There were no statistically significant differences in patient and tumour characteristics between dHGP and non-dHGP at baseline. Patients with dHGP had longer overall - and disease-free survival (logrank p = 0.003 and 0.003, respectively) compared to patients with non-dHGP. CTCs were not detected in 25(74%) of dHGP patients and in 68(48%) of non-dHGP patients (chi-squared p = 0.006). Preoperative absence of CTCs was the only significant predictor for dHGP in multivariable logistic regression (Odds Ratio 2.7, 95%CI 1.1-6.8, p = 0.028), Table 3. Preoperative absence of CTCs is associated with dHGP in chemo naive CRLM patients without extrahepatic disease. Based on our results, CTC count alone is not sufficient to preoperatively identify HGPs, but integration of CTC count in multivariable prediction models may aid the preoperative identification of HGPs of CRLM.

The oncological outcomes of isolated limb perfusion and neo-adjuvant radiotherapy in soft tissue sarcoma patients - A nationwide multicenter study.

INTRODUCTION: Patients with locally extensive high-grade extremity soft tissue sarcomas (eSTS) are often presented in multidisciplinary teams to decide between ablative surgery (amputation) or limb-salvage surgery supplemented with either neo-adjuvant radiotherapy (RT) or induction isolated limb perfusion (ILP). In The Netherlands, ILP typically aims to reduce the size of tumors that would otherwise be considered irresectable, whereas neo-adjuvant RT aims mainly at improving local control and reducing morbidity of required marginal margins. This study presents a 15-year nationwide cohort to describe the oncological outcomes of both pre-operative treatment strategies. METHODS: All consecutive patients with locally extensive primary high-grade eSTS surgically treated between 2000 and 2015 at five tertiary sarcoma centers that received neo-adjuvant ILP or RT were included. 169 patients met the inclusion criteria (89 ILP, 80 RT). Median follow-up was 7.3 years. RESULTS: Limb salvage was achieved in 84% of cases in the ILP group (80% for patients with amputation indication) and 96% of cases in the RT group. 5-Year overall survival was 47% in the ILP group, 69% in the RT group. 5-Year local recurrence rate was 14% in the ILP group, 10% in the RT group. Distant metastasis rate was 55% in the ILP group, 36% in the RT group. CONCLUSION: We find oncological outcomes and limb salvage rates in line with existing literature for both treatment modalities. Whether the tumor was locally advanced with an indication for induction therapy to prevent amputation or morbid surgery appeared to be the main determinant in choosing between neo-adjuvant ILP or RT.

Implementation of robotic rectal cancer surgery: a cross-sectional nationwide study.

AIM: An increasing number of centers have implemented a robotic surgical program for rectal cancer. Several randomized controls trials have shown similar oncological and postoperative outcomes compared to standard laparoscopic resections. While introducing a robot rectal resection program seems safe, there are no data regarding implementation on a nationwide scale. Since 2018 robot resections are separately registered in the mandatory Dutch Colorectal Audit. The present study aims to evaluate the trend in the implementation of robotic resections (RR) for rectal cancer relative to laparoscopic rectal resections (LRR) in the Netherlands between 2018 and 2020 and to compare the differences in outcomes between the operative approaches. METHODS: Patients with rectal cancer who underwent surgical resection between 2018 and 2020 were selected from the Dutch Colorectal Audit. The data included patient characteristics, disease characteristics, surgical procedure details, postoperative outcomes. The outcomes included any complication within 90 days after surgery; data were categorized according to surgical approach. RESULTS: Between 2018 and 2020, 6330 patients were included in the analyses. 1146 patients underwent a RR (18%), 3312 patients a LRR (51%), 526 (8%) an open rectal resection, 641 a TaTME (10%), and 705 had a local resection (11%). The proportion of males and distal tumors was higher in the RR compared to the LRR. Over time, the proportion of robotic procedures increased from 15% (95% confidence intervals (CI) 13-16%) in 2018 to 22% (95% CI 20-24%) in 2020. Conversion rate was lower in the robotic group [4% (95% CI 3-5%) versus 7% (95% CI 6-8%)]. Anastomotic leakage rate was similar with 16%. Defunctioning ileostomies were more common in the RR group [42% (95% CI 38-46%) versus 29% (95% CI 26-31%)]. CONCLUSION: Rectal resections are increasingly being performed through a robot-assisted approach in the Netherlands. The proportion of males and low rectal cancers was higher in RR compared to LRR. Overall outcomes were comparable, while conversion rate was lower in RR, the proportion of defunctioning ileostomies was higher compared to LRR.

The meaning of screening: detection of brain metastasis in the adjuvant setting for stage III melanoma.

BACKGROUND: The incidence of melanoma is increasing and 37% of patients with metastatic melanoma eventually have brain metastasis (BM). Currently, there is no consensus on screening for BM in patients with resected stage III melanoma. However, given the high incidence of BM, routine screening magnetic resonance imaging (MRI) of the brain is considered in patients with completely resected stage III melanoma before the start of adjuvant treatment. The aim of this study was to assess the yield of screening for BM in these patients. MATERIALS AND METHODS: A single-center cohort study was carried out in the Erasmus MC, Rotterdam, The Netherlands, a large tertiary referral center for patients with melanoma. Eligible patients with complete resection of stage III melanoma and a screening MRI of the brain, made within 12 weeks after resection and before adjuvant treatment (programmed cell death protein 1 inhibitors, dabrafenib-trametinib), available between 1 August 2018 and 1 January 2021, were included. RESULTS: A total of 202 patients were included. Eighteen (8.9%) of 202 patients had extracranial metastasis at screening. Two (1.1%) of the remaining 184 patients had BM at screening, resulting in a switch from adjuvant treatment to ipilimumab-nivolumab. At a median follow-up of 21.2 months, BM was detected in another 4 (2.4%) of 166 patients who started with adjuvant treatment. CONCLUSIONS: The yield of screening MRI of the brain is low after complete resection of stage III melanoma, before the start of adjuvant treatment. Therefore, routine screening MRI is not recommended in this setting.

Neoadjuvant FOLFOXIRI prior to chemoradiotherapy for high-risk ("ugly") locally advanced rectal cancer: study protocol of a single-arm, multicentre, open-label, phase II trial (MEND-IT).

BACKGROUND: The presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes (LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients. METHODS: This multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life. DISCUSSION: This trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04838496 , registered on 02-04-2021 Netherlands Trial Register: NL9790. PROTOCOL VERSION: Version 3 dd 11-4-2022.

Peritoneal metastases in elderly patients with colorectal cancer.

BACKGROUND: With the introduction of cytoreductive surgery with intraperitoneal chemotherapy and the development of new systemic anti-cancer agents, the treatment of colorectal cancer (CRC) patients with peritoneal metastases has changed. Real-world data on the treatment of elderly patients and their clinical outcomes is lacking. METHODS: All CRC patients diagnosed with synchronous peritoneal metastases (SPM) during 2008-2019 (n = 7,748) were identified from the Netherlands Cancer Registry. Trends in treatment and postoperative mortality were described by age category (<70, 70-74, 75-79, ≥80 years) and period of diagnosis (2008-2013, 2014-2019). Kaplan-Meier curves were constructed, and log-rank tests were performed to evaluate differences in overall survival (OS). RESULTS: With increasing age, less patients received multimodality treatment and systemic treatment. Of the patients aged <70 years, 38% underwent multimodality treatment and 35% palliative systemic therapy, declining to 4% and 12% in patients ≥80 years. A large and increasing proportion of elderly patients did not receive cancer-directed treatment, this increased from 32% in 2008-2013 to 41% in 2014-2019 in 75-79 years old patients and from 52% to 65% in ≥80 years old. Postoperative mortality decreased in all age categories over time, OS remained stable. The median OS of elderly patients ranged from 8 months in 70-74 years old to 3 months in patients aged ≥80 years. DISCUSSION: Age strongly affects treatment of patients with SPM, with a large and increasing proportion of elderly patients not receiving cancer-directed treatment. Their prognosis remains very poor. There is a need for therapeutic options that are well tolerable for elderly patients.

Propensity score matching demonstrates similar results for radiofrequency ablation compared to surgical resection in colorectal liver metastases.

PURPOSE: Minimally invasive ablative treatments, such as radiofrequency ablation (RFA), are increasingly used in the curative treatment of patients with colorectal liver metastases (CRLM). Selection bias plays an important role in the evaluation of early and late results between RFA and surgery. The purpose of this study was to evaluate recurrences and oncological survival following these two treatment modalities using single pair propensity score matching. METHODS: Between 2000 and 2018, patients curatively treated for CRLM were included in a multicentre database. Patients were excluded when receiving two-staged treatment, synchronous treatment with primary tumor or combination of modalities. Propensity score matching was used to minimize influence of known covariates, i.e., age, ASA, FONG CRS, location and T-stage of the primary tumor. RESULTS: Before matching, the RFA group contained 39 patients and the surgery group 982 patients, after matching both groups contained 36 patients. After matching, mean age was 69 years (53-86) for RFA and 68 (50-86) for surgery, with a mean tumor size of respectively 2.5 cm (0.8-6.5) and 3.4 cm (1-7.5). Both groups showed similar complication rate according to Clavien-Dindo (17vs.33%; p = 0.18), recurrence rate (58vs.64%; p = 0.09) without significant differences in 5-year DFS and OS (RFA compared to surgery respectively 25vs.37%; p = 0.09 and 42vs.53%; p = 0.09). CONCLUSION: After propensity score matching, RFA showed lower complications and similar oncological survival compared to surgical resection. In patients who are suboptimal candidates for surgery, RFA seems to be a good and safe alternative.

Treatment of metachronous colorectal cancer metastases in the Netherlands: A population-based study.

BACKGROUND: This study aimed to describe the treatment of metachronous colorectal cancer metastases in a recent population-based cohort. METHOD: Patients with stage I-III colorectal cancer (CRC), diagnosed between January 1st and June 30th, 2015 who were surgically treated with curative intent were selected from the Netherlands Cancer Registry. Follow-up was at least 3 years after diagnosis of the primary tumour. Treatment of metachronous metastases was categorized into local treatment, systemic treatment, and best supportive care. Overall survival was estimated using Kaplan-Meier method. RESULTS: Out of 5412 patients, 782 (14%) developed metachronous metastases, of whom 393 (50%) underwent local treatment (LT) with or without systemic therapy, 30% of patients underwent only systemic therapy (ST) and 19% only best supportive care (BSC). The most common metastatic site was the liver (51%) followed by lungs (33%) and peritoneum (22%). LT rates were 69%, 66%, and 44% for liver-only, lung-only and, peritoneal-only metastases respectively. Patients receiving LT and ST were significantly younger than patients receiving LT alone, while patients receiving BSC were significantly older than the other groups (p < 0.001). Patients with liver-only or lung-only metastases had a 3-year OS of 50.2% (43.3-56.7 95% CI) and 61.5% (50.7-70.6 95% CI) respectively. Patients with peritoneal-only disease had a lower 3-year OS, 18.1% (10.1-28.0 95% CI). CONCLUSION: Patients with metastases confined to the liver and lung have the highest rates of local treatment for metachronous metastatic colorectal cancer. The number of patients who underwent local treatment is higher than reported in previous Dutch and international studies.

Treatment of clinical T1 rectal cancer in the Netherlands; a population-based overview of clinical practice.

INTRODUCTION: Local excision is increasingly used as an alternative treatment for radical surgery in patients with early stage clinical T1 (cT1) rectal cancer. This study provides an overview of incidence, staging accuracy and treatment strategies in patients with cT1 rectal cancer in the Netherlands. MATERIALS AND METHODS: Patients with cT1 rectal cancer diagnosed between 2005 and 2018 were included from the Netherlands Cancer Registry. An overview per time period (2005-2009, 2010-2014 and 2015-2018) of the incidence and various treatment strategies used, e.g. local excision (LE) or major resection, with/without neoadjuvant treatment (NAT), were given and trends over time were analysed using the Chi Square for Trend test. In addition, accuracy of tumour staging was described, compared and analysed over time. RESULTS: In total, 3033 patients with cT1 rectal cancer were diagnosed. The incidence of cT1 increased from 540 patients in 2005-2009 to 1643 patients in 2015-2018. There was a significant increased use of LE. In cT1N0/X patients, 9.2% received NAT, 25.5% were treated by total mesorectal excision (TME) and 11.4% received a completion TME (cTME) following prior LE. Overall accuracy in tumour staging (cT1 = pT1) was 77.3%, yet significantly worse in cN1/2 patients, as compared to cN0 patients (44.8% vs 77.9%, respectively, p < 0.001). CONCLUSION: Over time, there was an increase in the incidence of cT1 tumours. Both the use of neoadjuvant therapy and TME surgery in clinically node negative patients decreased significantly. Clinical accuracy in T1 tumour staging improved over time, but remained significantly worse in clinical node positive patients.