Standard treatment for patient with peritoneal metastases from colorectal cancer is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In recent years, the efficacy of ...oxaliplatin-based HIPEC has been challenged. An intensified HIPEC (oxaliplatin+irinotecan) in combination with early postoperative intraperitoneal chemotherapy (EPIC) has shown increased recurrence-free survival in retrospective studies. The aim of this trial is to develop a new HIPEC/EPIC regimen and evaluate its effect on morbidity, oncological outcome, and quality-of-life (QoL). This study is designed as a combined phase I/III multicenter randomized trial (RCT) of patients with peritoneal metastases from colorectal cancer eligible for CRS-HIPEC. An initial phase I dose escalation study, designed as a 3+3 stepwise escalation, will determine the maximum tolerable dose of 5-Fluorouracil (5-FU) as 1-day EPIC, enrolling a total of 15-30 patients in 5 dose levels. In the phase III efficacy study, patients are randomly assigned intraoperatively to either the standard treatment with oxaliplatin HIPEC (control arm) or oxaliplatin/irinotecan-HIPEC in combination with single dose of 1-day 5-FU EPIC (experimental arm). 5-FU is administered intraoperatively after CRS-HIPEC and closure of the abdomen. The primary endpoint is 12-month recurrence-free survival. Secondary endpoints include 5-year overall survival, 5-year recurrence-free survival (registry based), postoperative complications, and QoL up to 3 years after study treatment. This phase I/III trial aims to identify a more effective treatment of colorectal peritoneal metastases by combination of HIPEC and EPIC.
The study aim was to report survival and morbidity of all patients in Sweden with peritoneal mesothelioma treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy ...(HIPEC) as well as investigate whether the survival has increased on a population level since this treatment was nationalized 2011. Study data were collected from the Swedish HIPEC registry and the Swedish National Cancer Registry. All patients with peritoneal mesothelioma scheduled for CRS/HIPEC treatment in Sweden January 2011 to March 2018 were retrieved from the Swedish HIPEC registry. Clinicopathological and survival data were collected. For population‐level analysis, all patients with diffuse malignant peritoneal mesothelioma (DMPM) were identified from the Swedish National Cancer Registry and data were retrieved from two separate 5‐year time periods: 1999‐2003 and 2011‐2015. Thirty‐two patients were accepted for CRS/HIPEC. Four were open/close cases. Two‐year survival rate was 84% or 59% when excluding borderline peritoneal mesotheliomas (n = 17). Median overall survival was not reached. Grade III‐IV Clavien‐Dindo events occurred in 22% with no mortality. From the national cancer registry, 102 DMPM cases were retrieved: 40 cases between 1999 and 2003, and 62 cases between 2011 and 2015 (corresponding to an increase from 0.9 to 1.24/million/year, P = .04). Six patients (10%) received CRS/HIPEC in the second period. Median OS increased between periods from 7 to 15 months and 5‐year survival from 14% to 29% (P = .03). Peritoneal mesothelioma of both borderline and DMPM subtypes undergoing CRS/HIPEC have good long‐term survival. The incidence of DMPM in Sweden has increased. Overall survival has increased alongside the introduction of CRS/HIPEC, which may be a contributing factor.
Peritoneal mesothelioma of both borderline and malignant subtypes can be successfully managed with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. The incidence of diffuse malignant peritoneal mesothelioma has statistically increased over time in Sweden; fortunately likewise, the overall survival has also increased statistically in part due to the implementation of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
The optimal treatment for patients with locally recurrent rectal cancer (LRRC) is controversial. The aim of this study was to investigate different treatment strategies in two leading tertiary ...referral hospitals in Europe.
All patients who underwent curative surgery for LRRC between January 2003 and December 2017 in Catharina Hospital, Eindhoven, the Netherlands (CHE), or Karolinska University Hospital, Stockholm, Sweden (KAR), were studied retrospectively. Available MRIs were reviewed to obtain a uniform staging for optimal comparison of both cohorts. The main outcomes studied were overall survival (OS), local re-recurrence-free survival (LRFS), and metastasis-free survival (MFS).
In total, 377 patients were included, of whom 126 and 251 patients came from KAR and CHE respectively. At 5 years, the LRFS rate was 62.3 per cent in KAR versus 42.3 per cent in CHE (P = 0.017), whereas OS and MFS were similar. A clear surgical resection margin (R0) was the strongest prognostic factor for survival, with a hazard ratio of 2.23 (95 per cent c.i. 1.74 to 2.86; P < 0.001), 3.96 (2.87 to 5.47; P < 0.001), and 2.00 (1.48 to 2.69; P < 0.001) for OS, LRFS, and MFS respectively. KAR performed more extensive operations, resulting in more R0 resections than in CHE (76.2 versus 61.4 per cent; P = 0.004), whereas CHE relied more on neoadjuvant treatment and intraoperative radiotherapy, to reduce the morbidity of multivisceral resections (P < 0.001).
In radiotherapy-naive patients, neoadjuvant full-course chemoradiation confers the best oncological outcome. However, neoadjuvant therapy does not diminish the need for extended radical surgery to increase R0 resection rates.
ObjectiveLow anterior resection syndrome (LARS) is one of the most common functional impairments after rectal cancer surgery with a high impact on quality of life. The Pre-Operative LARS score ...(POLARS) nomogram and its online tool has been developed to predict the degree of postoperative LARS. The aim of this study was to analyse how accurately the POLARS score could predict LARS scores when compared with actual patient-reported LARS (PR-LARS) scores in a population-based Swedish cohort.DesignThis retrospective cohort study included patients who underwent curative rectal cancer surgery between 2007 and 2013 in Stockholm County and were identified using the Swedish Colorectal Cancer Registry (SCRCR). Information regarding preoperative risk factors, patient and treatment characteristics, and presence of LARS postoperatively were collected from patient charts, SCRCR and patient questionnaires. The POLARS model formula was used to predict LARS scores, which then were compared with the actual PR-LARS scores. Individual LARS score differences between the two estimates were shown with a modified Bland-Altman plot of difference.ResultsThe cohort included 477 patients, of whom 359 (75%) of patients were categorised as having no/minor LARS based on the POLARS score. The correctly identified patients by the POLARS score were 80/255 (31%) in the major LARS group and 184/222 (83%) no/minor LARS group. The sensitivity was 31% for major LARS and the positive predictive value was 68%.ConclusionThe POLARS score has a low sensitivity for major LARS in this Swedish cohort. Other methods to predict the risk of LARS need to be developed.
The aim of the study was to evaluate transanal irrigation (TAI) as a treatment for low anterior resection syndrome (LARS).
LARS is a bowel disorder that is common after sphincter preserving rectal ...cancer surgery. Despite symptomatic medical treatment of LARS many patients still experience bowel symptoms that may have a negative impact on quality of life (QoL). TAI is a treatment strategy, of which the clinical experience is promising but scientific evidence is limited.
A multicenter randomized trial comparing TAI (intervention) with conservative treatment (control) was performed. Inclusion criteria were major LARS, age above 18 years, low anterior resection with anastomosis and a defunctioning stoma as primary surgery, >6 months since stoma reversal, anastomosis without signs of leakage or stricture, and no signs of recurrence at 1-year follow-up. The primary endpoint was differences in bowel function at 12-month follow-up measured by LARS score, Cleveland Clinic Florida Fecal Incontinence Score, and 4 study-specific questions. The secondary outcome was QoL.
A total of 45 patients were included, 22 in the TAI group and 23 in the control group. Follow-up was available for 16 and 22 patients, respectively. At 12 months, patients in the TAI group reported significantly lower LARS scores (22.9 vs 32.4; P =0.002) and Cleveland Clinic Florida Fecal Incontinence Score (6.4 vs 9.2; P =0.050). In addition, patients in the TAI group also scored significantly higher QoL 8 of 16 European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) QoL aspects compared with the control group.
The results confirm our clinical experience that TAI reduces symptoms included in LARS and improves QoL.
Secondary treatment of recurrent colorectal peritoneal metastases after previous cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is poorly investigated.
To evaluate ...the overall survival outcome of secondary (repeat) CRS + HIPEC compared to palliative treatment in recurrent peritoneal disease.
Patients with colorectal peritoneal metastases treated with an index CRS + HIPEC and subsequently having recurrent peritoneal disease were identified from the prospective Swedish national HIPEC registry. Patients were divided into interventional group (secondary CRS + HIPEC) or palliative group. Multivariable logistic regression, propensity-score matching, and survival outcomes were calculated.
Among 575 patients who underwent complete CRS between 2010 and 2021, 208 (36 %) were diagnosed with a subsequent recurrent peritoneal disease. Forty-two patients (20 %) were offered secondary CRS + HIPEC. Propensity-score matching of secondary interventional cases with palliative cases succeeded in 88 % (n = 37) in which female sex, lower peritoneal cancer index at index surgery, longer disease-free interval, and absence of extra-peritoneal metastases were identified as the most relevant matching covariates. Median OS from date of recurrence was 38 months (95%CI 30–58) in the interventional group and 19 months (95%CI: 15–24) in the palliative group (HR 0.35 95%CI: 0.20–0.63, p = 0.0004). Sensitivity analyses confirmed the results. As reference, the median OS from index CRS + HIPEC in the whole colorectal registry (n = 575) was 41 months (95%CI: 38–45).
After matching for relevant factors, the hazard ratio for death was significantly reduced in patients who were offered a secondary CRS + HIPEC procedure for recurrent peritoneal disease. Selection bias is inherent, but survival outcomes were comparable to those achieved after the initial procedure.
An increasing number of patients are surviving a diagnosis of rectal cancer. The majority of the patients are treated with the sphincter-sparing surgical procedure low anterior resection, and 50% to ...90% of these patients experience bowel dysfunction, known as the low anterior resection syndrome. No previous studies have investigated the association between the low anterior resection syndrome and quality of life in an international setting with the use of a validated instrument for the classification of the low anterior resection syndrome.
The aim of this study was to investigate the association between quality of life and the low anterior resection syndrome in European patients who have had rectal cancer.
The study was designed as an international cross-sectional study involving 5 centers in 4 European countries.
All patients had undergone low anterior resection for rectal cancer, had no stoma, had no dissemination or recurrence at the time of the study, and were at least 16 months past surgery.
The patients received by mail the Low Anterior Resection Syndrome Score and the quality-of-life questionnaire EORTC QLQ-C30.
Eight subscales were selected to be the focus of this study: global quality of life; physical, role, emotional, and social functioning; fatigue; constipation; and diarrhea.
A total of 796 patients were included, which corresponds to a response rate of 75.0%. In comparison with patients without low anterior resection syndrome, patients with major low anterior resection syndrome fared substantially worse in all selected subscales (difference ≥ 10 points, p < 0.01), with the exception of constipation.
The cross-sectional design prevents an evaluation of causality.
The quality of life of patients who have had rectal cancer is closely associated with the severity of the low anterior resection syndrome. Therefore, it is important that clinicians and researchers focus on this syndrome to improve the prevention and the treatment of bowel dysfunction and the information given to patients.
Abstract
Background
Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of ...patients with synchronous colorectal cancer and liver metastases, with a focus on terminology, diagnosis, and management.
Methods
This project was a multiorganizational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis, and management. Statements were refined during an online Delphi process, and those with 70 per cent agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising 12 key statements.
Results
Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term ‘early metachronous metastases' applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour, the term ‘late metachronous metastases’ applies to those detected after 12 months. ‘Disappearing metastases’ applies to lesions that are no longer detectable on MRI after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards, and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways, including systemic chemotherapy, synchronous surgery, and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed.
Conclusion
The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases.
This consensus provides a practical framework for the clinician treating patients with synchronous colorectal cancer and liver metastases.
Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with ...synchronous colorectal cancer and liver metastases with a focus on terminology, diagnosis and management.
This project was a multi-organisational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis and management. Statements were refined during an online Delphi process and those with 70% agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising twelve key statements.
Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term “early metachronous metastases” applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour with “late metachronous metastases” applied to those detected after 12 months. Disappearing metastases applies to lesions which are no longer detectable on MR scan after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways including systemic chemotherapy, synchronous surgery and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed.
The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases.
Rectal cancer is common in Sweden, with about 1650 patients diagnosed annually. In 10–15% of the patients the tumour is locally advanced at diagnosis, i.e. the cancer is growing outside the ...mesorectal fascia, into adjacent organs in the pelvis. The incidence of local recurrences, after surgery for primary rectal cancer has decreased as a result of preoperative radiotherapy (RT) and improved surgical techniques, but still the local failure rate is 5–15%.Treatment of patients with locally advanced primary rectal cancer and recurrent rectal cancer remains a challenge but, with radical surgical resection 5-year survival rates up to 50–60% is reached at dedicated centres.The aim of this thesis was to analyse management, outcome and the quality of life in patients with both locally advanced primary rectal cancer and locally recurrent rectal cancer, focusing on the preoperative assessment and on multimodality treatment with a multidisciplinary approach.Two of the studies were population-based and included all patients in the Stockholm-Gotland region with respectively locally advanced primary rectal cancer and local recurrences during 1995–2005. The patients were identified by means of the colorectal cancer registry at the Regional Oncological Centre and their medical records were scrutinised. The other two studies involved patients with locally advanced rectal cancer at a single centre, the Karolinska University Hospital, and treated during 1991–2003.During 1995–2004 in the Stockholm region, 10% of all rectal cancer patients were found to have a locally advanced primary rectal cancer. In all patients with a potentially curative resection of primary rectal cancer treated during 1995–2003, a local recurrence of rectal cancer was detected in 6% by 2005.It was concluded that appropriate preoperative radiological tumour staging in patients with locally advanced rectal cancer increased both the proportion of patients who received neo-adjuvant treatment and the rate of potentially curative resections. Local control and survival were improved. Multidisciplinary team (MDT) discussions further enhanced the proportion of curative resections and local control, but no influence on survival was seen.The overall outcome for patients with locally recurrent rectal cancer was dismal, with a 5-year survival of 9%, but, in patients with a potentially curative resection, an improved estimated 5-year survival of 57% was obtained. A radical resection was necessary for cure and the proportion of curative resections had increased after improved preoperative management and refined surgery compared to an earlier study of local recurrences in Stockholm.After the introduction of a multimodality treatment programme for patients with rectal cancer, one third of the patients with locally advanced rectal cancer could be cured if a radical resection was performed. Patients with locally advanced primary rectal cancer had a higher rate of curative resections than patients with locally recurrent rectal cancer. The extensive surgery and RT led to a high morbidity.In measurements of the quality of life in disease-free patients treated for locally advanced rectal cancer several functions, such as role, social and physical function, were low compared with patients treated for primary resectable rectal cancer.
PDF
