Guidelines for treatment of umbilical and epigastric hernias from the European Hernia Society and Americas Hernia Society.

BACKGROUND: Umbilical and epigastric hernia repairs are frequently performed surgical procedures with an expected low complication rate. Nevertheless, the optimal method of repair with best short- and long-term outcomes remains debatable. The aim was to develop guidelines for the treatment of umbilical and epigastric hernias. METHODS: The guideline group consisted of surgeons from Europe and North America including members from the European Hernia Society and the Americas Hernia Society. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, the Scottish Intercollegiate Guidelines Network (SIGN) critical appraisal checklists, and the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument were used. A systematic literature search was done on 1 May 2018, and updated on 1 February 2019. RESULTS: Literature reporting specifically on umbilical and epigastric hernias was limited in quantity and quality, resulting in a majority of the recommendations being graded as weak, based on low-quality evidence. The main recommendation was to use mesh for repair of umbilical and epigastric hernias to reduce the recurrence rate. Most umbilical and epigastric hernias may be repaired by an open approach with a preperitoneal flat mesh. A laparoscopic approach may be considered if the hernia defect is large, or if the patient has an increased risk of wound morbidity. CONCLUSION: This is the first European and American guideline on the treatment of umbilical and epigastric hernias. It is recommended that symptomatic umbilical and epigastric hernias are repaired by an open approach with a preperitoneal flat mesh.

ANTECEDENTES: La reparación de las hernias umbilicales y epigástricas es un procedimiento quirúrgico frecuente con una tasa esperada de complicaciones baja. Sin embargo, sigue en discusión cuál es el mejor método de reparación óptimo para obtener los mejores resultados a corto y a largo plazo. El objetivo del estudio fue desarrollar una guía para el tratamiento de las hernias umbilicales y epigástricas. MÉTODOS: El grupo para la elaboración de la guía estuvo formado por cirujanos europeos y norteamericanos junto con miembros de la European Hernia Society (EHS) y de la America's Hernia Society (AHS). Para elaborar la guía, se siguieron las recomendaciones GRADE (Grading of Recommendations Assessment, Development and Evaluation), SIGN (Scottish Intercollegiate Guidelines Network) y AGREE (Appraisal of Guidelines for Research & Evaluation). Se realizó una búsqueda sistemática de la literatura el 1 de mayo de 2018, que luego se actualizó el 1 de febrero de 2019. RESULTADOS: Los trabajos dedicados de forma específica a las hernias umbilicales y epigástricas eran muy limitados en cantidad y calidad, por lo que la mayoría de las recomendaciones que se extrajeron fueron calificadas como débiles y basadas en una baja calidad de la evidencia. La recomendación principal era utilizar una malla en la reparación de las hernias umbilicales y epigástricas para reducir la tasa de recidiva. La mayoría de las hernias umbilicales y epigástricas pueden repararse mediante un abordaje abierto con una malla plana preperitoneal. Se puede considerar el abordaje laparoscópico si el defecto de la hernia es grande o si el paciente tiene un riesgo aumentado de morbilidad de la herida. CONCLUSIÓN: Esta es la primera guía europea y americana del tratamiento de las hernias umbilicales y epigástricas. Se sugiere reparar las hernias sintomáticas umbilicales y epigástricas mediante un abordaje abierto con una malla plana preperitoneal.

Delphi consensus statement for understanding and managing the subcostal hernia: subcostal hernias collaborative report (scholar study).

INTRODUCTION: Subcostal hernias are categorized as L1 based on the European Hernia Society (EHS) classification and frequently involve M1, M2, and L2 sites. These are common after hepatopancreatic and biliary surgeries. The literature on subcostal hernias mostly comprises of retrospective reviews of small heterogenous cohorts, unsurprisingly leading to no consensus or guidelines. Given the limited literature and lack of consensus or guidelines for dealing with these hernias, we planned for a Delphi consensus to aid in decision making to repair subcostal hernias. METHODS: We adopted a modified Delphi technique to establish consensus regarding the definition, characteristics, and surgical aspects of managing subcostal hernias (SCH). It was a four-phase Delphi study reflecting the widely accepted model, consisting of: 1. Creating a query. 2. Building an expert panel. 3. Executing the Delphi rounds. 4. Analysing, presenting, and reporting the Delphi results. More than 70% of agreement was defined as a consensus statement. RESULTS: The 22 experts who agreed to participate in this Delphi process for Subcostal Hernias (SCH) comprised 7 UK surgeons, 6 mainland European surgeons, 4 Indians, 3 from the USA, and 2 from Southeast Asia. This Delphi study on subcostal hernias achieved consensus on the following areas-use of mesh in elective cases; the retromuscular position with strong discouragement for onlay mesh; use of macroporous medium-weight polypropylene mesh; use of the subcostal incision over midline incision if there is no previous midline incision; TAR over ACST; defect closure where MAS is used; transverse suturing over vertical suturing for closure of circular defects; and use of peritoneal flap when necessary. CONCLUSION: This Delphi consensus defines subcostal hernias and gives insight into the consensus for incision, dissection plane, mesh placement, mesh type, and mesh fixation for these hernias.

Water resources management in southern Europe: clues for a research and innovation based regional hypercluster.

European countries are facing increasing pressures on their water resources despite stringent regulations and systematic efforts on environmental protection. In this context, research and innovation play a strategic role reinforcing the efficiency of water policies. The present study provides a multilevel assessment of research and innovation practices in the field of water resource management in southern European countries and regions (more specifically; Cyprus, Albania, Poitou-Charentes in France, Andalusia in Spain and the North of Portugal). The analysis was based on a strategic framework aimed at gaining an insight of the current constraints, as well as of the existing and future technological solutions for a better water resource management. The triple helix model proved to be a useful analytical framework for assessing the efforts of different groups towards a common goal. The analysis proved the existence of a significant evolution in the use of technological tools to assist decision-making processes in integrated river basin management in all regions. Nevertheless, the absence of formal channels for knowledge and data exchange between researchers and water resource managers complicates the formers involvement in the decision-making process regarding water allocation. Both researchers and consultants emphasize the low availability of data, together with the need to advance on water resource economics as relevant constraints in the field. The SWOT analysis showed similar concerns among the participating regions and provided a battery of effective projects that resulted in the preparation of a Joint Action Plan.

ICU without walls project. Effect of the early detection of patients at risk.

OBJECTIVES: To describe and evaluate the impact of a system for early detection and intervention in patients at risk outside the ICU upon the outcome of patients admitted to the ICU and the number of cases of hospital cardiopulmonary arrest. SETTING: A second-level hospital in the Community of Madrid (Spain) with electronic clinical histories. METHODS: An intensivist reviewed each of the patients meeting the inclusion criteria, and decided the need or not for intervention. Posteriorly, in collaboration with the physician supervising the patient, the needed level of care was decided, along with the subsequent management protocol. DESIGN: A descriptive and quasi-experimental "before-after" study was made. RESULTS: A total of 202 patients were intervened during the study period, With the inclusion of 147 after detecting altered laboratory test results through our software application. During the control period, the mortality rate in the ICU was 9%, versus 4.4% during the intervention period (P=.03). In the multivariate analysis, the two factors significantly related to mortality were admission during the intervention period (OR=0.42; 95%CI: 0.18-0.98; P=.04) and SAPS 3 (OR=1.11; 95%CI: 1.07-1.14; P<0.05). There were 10 cardiopulmonary arrest alerts during the control period, versus three in the intervention period (P=.07). CONCLUSIONS: Early detection activities in patients at risk outside the ICU can have beneficial effects upon the patients admitted to the ICU, and can contribute to reduce the number of hospital cardiopulmonary arrests.

Pathways of the preperitoneal plane: from the "fatty triangle" in Rives to the "fatty trident" in extended retromuscular abdominal wall reconstruction. A tribute to Prof. Schumpelick.

PURPOSE: Extended retromuscular dissection performed for abdominal wall reconstruction in complex abdominal wall repair has progressively exposed the anatomy between the peritoneal layer and abdominal wall muscles. This study aimed to assess the morphology and distribution of preperitoneal fat in a cadaveric model and its influence in retromuscular preperitoneal dissections. METHODS: Thirty frozen cadaver torsos were dissected by posterior component separation. The shape of the preperitoneal fat was identified, and the dimensions and more significant distances were calculated. RESULTS: The results showed that the preperitoneal fat resembles a trident, exists along the midline under the linea alba, and expands in the epigastric area into a rhomboid shape. The fatty triangle was found to be a part of this rhomboid. Caudally, the midline preperitoneal fat widened under the arcuate line to reach the Retzius space. Laterally, the Bogros space communicated the root of the trident with the paracolic gutters, Toldt's fascia, and pararenal fats, forming the lateral prong of the trident. The peritoneum not covered by the preperitoneal fatty trident was easy to break. Three pathways could be tracked following the distribution of this fat that facilitated the dissection of the preperitoneal space to prepare the landing zone of the meshes in hernia repair. CONCLUSION: The concept of preperitoneal fatty trident may be of practical assistance to perform various hernia procedures, from the simple ventral hernia repair to the more complex preperitoneal ventral repair or posterior component separation techniques. The consistency of this layer allows us to follow three specific pathways to find our plane between the peritoneum and muscle layers to extend the preperitoneal dissection.

An evidence map and synthesis review with meta-analysis on the risk of incisional hernia in colorectal surgery with standard closure.

PURPOSE: To assess the incidence of incisional hernia (IH) across various type of incisions in colorectal surgery (CS) creating a map of evidence to define research trends, gaps and areas of future interest. METHODS: Systematic review of PubMed and Scopus from 2010 onwards. Studies included both open (OS) and laparoscopic (LS). The primary outcome was incidence of IH 12 months after index procedure, secondary outcomes were the study features and their influence on reported proportion of IH. Random effects models were used to calculate pooled proportions. Meta-regression models were performed to explore heterogeneity. RESULTS: Ninetyone studies were included reporting 6473 IH. The pooled proportions of IH for OS were 0.35 (95% CI 0.27-0.44) I2 0% in midline laparotomies and 0.02 (95% CI 0.00-0.07), I2 52% for off-midline. In case of LS the pooled proportion of IH for midline extraction sites were 0.10 (95% CI 0.07-0.16), I2 58% and 0.04 (95% CI 0.03-0.06), I2 86% in case of off-midline. In Port-site IH was 0.02 (95% CI 0.01-0.04), I2 82%, and for single incision surgery (SILS) of 0.06-95% CI 0.02-0.15, I2 81%. In case of stoma reversal sites was 0.20 (95% CI 0.16-0.24). CONCLUSION: Midline laparotomies and stoma reversal sites are at high risk for IH and should be considered in research of preventive strategies of closure. After laparoscopic approach IH happens mainly by extraction sites incisions specially midline and also represent an important area of analysis.

Preventing incisional ventral hernias: important for patients but ignored by surgical specialities? A critical review.

PURPOSE: Incisional ventral hernias (IHs) are a common complication across all surgical specialities requiring access to the abdomen, pelvis, and retroperitoneum. This public health issue continues to be widely ignored, resulting in appreciable morbidity and expenses. In this critical review, the issue is explored by an interdisciplinary group. METHODS: A group of European surgeons encompassing representatives from abdominal wall, vascular, urological, gynecological, colorectal and hepato-pancreatico-biliary surgery have reviewed the occurrence of His in these disciplines. RESULTS: Incisional hernias are a major public health issue with appreciable morbidity and cost implications. General surgeons are commonly called upon to repair IHs following an initial operation by others. Measures that may collectively reduce the frequency of IH across specialities include better planning and preparation (e.g. a fit patient, no time pressure, an experienced operator). A minimally invasive technique should be employed where appropriate. Our main recommendations in midline incisions include using the 'small bites' suture technique with a ≥ 4:1 suture-to-wound length, and adding prophylactic mesh augmentation in patients more likely to suffer herniation. For off-midline incisions, more research of this problem is essential. CONCLUSION: Meticulous closure of the incision is significant for every patient. Raising awareness of the His is necessary in all surgical disciplines that work withing the abdomen or retroperitoneum. Across all specialties, surgeons should aim for a < 10% IH rate.

Failure of talc seromadesis for the treatment of subcutaneous chronic seromas after incisional hernia surgery.

BACKGROUND AND AIM: Talc poudrage has been used since many years for sclerosing chronic pleural effusion. Several reports have shown good results managing chronic seromas after breast, vascular, and incisional hernia surgeries. The purpose of this study is to determine the utility of talc seromadesis for the management of chronic seromas after incisional hernia surgery. MATERIALS AND METHODS: Multicentric prospective observational study including patients diagnosed of chronic seromas after incisional hernia surgery. Under local anesthesia and ultrasonographic control, two percutaneous trocars were placed in the seroma, washing the seroma cavity with 0.9% saline solution and aspirating the remaining liquid. A sample of 4 g of talcum powder was introduced in the seroma cavity, and a 15-F drain was left in place. Patients were followed each week during at least 4 weeks after drainage removal. RESULTS: Between January 2013 and December 2016, a total of six patients were enrolled in the study. Talc poudrage was performed without any complications. Drains were pulled out in a mean time of 3 (range: 2-4) weeks. One case of the chronic seromas was efficiently sclerosed with talc without recurrence in time. In three cases, the seroma recurred, and the final solution was surgical decortication of the seroma. In the other two cases, seroma also recurred and were managed with instillation of ethanol and iodine povidone. CONCLUSION: In our experience, the management of chronic seromas after incisional hernia repair with talc seromadesis is ineffective and is associated with a high rate of seroma recurrence.

EHS and AHS guidelines for treatment of primary ventral hernias in rare locations or special circumstances.

BACKGROUND: Rare locations of hernias, as well as primary ventral hernias under certain circumstances (cirrhosis, dialysis, rectus diastasis, subsequent pregnancy), might be technically challenging. The aim was to identify situations where the treatment strategy might deviate from routine management. METHODS: The guideline group consisted of surgeons from the European and Americas Hernia Societies. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used in formulating the recommendations. The Scottish Intercollegiate Guidelines Network (SIGN) critical appraisal checklists were used to evaluate the quality of full-text papers. A systematic literature search was performed on 1 May 2018 and updated 1 February 2019. The Appraisal of Guidelines for Research and Evaluation (AGREE) instrument was followed. RESULTS: Literature was limited in quantity and quality. A majority of the recommendations were graded as weak, based on low quality of evidence. In patients with cirrhosis or on dialysis, a preperitoneal mesh repair is suggested. Subsequent pregnancy is a risk factor for recurrence. Repair should be postponed until after the last pregnancy. For patients with a concomitant rectus diastasis or those with a Spigelian or lumbar hernia, no recommendation could be made for treatment strategy owing to lack of evidence. CONCLUSION: This is the first European and American guideline on the treatment of umbilical and epigastric hernias in patients with special conditions, including Spigelian and lumbar hernias. All recommendations were weak owing to a lack of evidence. Further studies are needed on patients with rectus diastasis, Spigelian and lumbar hernias.

ANTECEDENTES: Las hernias de localización rara, así como las hernias ventrales primarias en determinadas circunstancias (cirrosis, diálisis, diástasis de recto, tras un embarazo) pueden ser complejas desde el punto de vista técnico. El objetivo fue identificar situaciones en las que la estrategia de tratamiento pudiera ser diferente del tratamiento habitual. MÉTODOS: Esta guía fue elaborada por cirujanos de las sociedades europeas y americana de hernia (European Hernia Society, EHS y American Hernia Society, AHS). La búsqueda sistemática de la literatura se efectuó el 1 de mayo de 2018 y se actualizó el 1 de febrero de 2019. Para evaluar la calidad de los artículos completos seleccionados se utilizó la normativa SIGN (Scottish Intercollegiate Guidelines Network). Las recomendaciones formuladas siguieron la metodología GRADE (Grading of Recommendations Assessment, Development and Evaluation) y la redacción de la guía siguió las normas AGREE (Appraisal of Guidelines for Research & Evaluation). RESULTADOS: La literatura es limitada en cantidad y calidad. La mayoría de las recomendaciones se calificaron como débiles en función de la baja calidad de la evidencia. En pacientes con cirrosis o en diálisis, se sugiere una reparación con malla preperitoneal. Un embarazo tras la reparación de una hernia es un factor de riesgo de recidiva. La reparación debería posponerse hasta después del último embarazo. Debido a la falta de evidencia no se pudo hacer ninguna recomendación para la reparación de hernias en pacientes con diástasis de recto concomitante o con hernias de Spigel o lumbares. CONCLUSIÓN: Esta es la primera guía europea y americana del tratamiento de hernias umbilicales y epigástricas en pacientes con patologías especiales, incluyendo las hernias de Spigel y lumbares. Todas las recomendaciones fueron débiles debido a la falta de evidencia. Se necesitan más estudios en pacientes con diástasis de recto, hernias de Spigel y lumbares.

Evaluation of a workshop to teach a new surgical technique in abdominal wall reconstruction.

PURPOSE: Assess the utility of a hands-on workshop on abdominal wall reconstruction for teaching the posterior components separation (PCS) with transversus abdominis release. METHODS: Our department has been organizing a training course on abdominal wall reconstruction for the last 6 years. It is a 2-day-long course and 10-12 surgeons with experience in abdominal wall surgery attend to every course. The first day is dedicated to theoretical lectures and two simultaneous live surgeries, and the second day there is a cadaver dissection. Feedback from the trainees was collected at the end of the workshop. A survey was sent to all the surgeons who had completed the course at least a year ago, to inquire how the course had improved their surgical practice. RESULTS: From 2013 to April 2017, we have made 15 editions of the course. A total of 192 surgeons from Europe, South Africa and Middle East attended. All the surgeons answered the survey that was carried out at the end of the course. It showed a very high level of satisfaction in more than 98% of the cases. The second survey was answered by 79 surgeons (41.15%). 96% of the surgeons had modified, after attending the course, their way of dealing with complex abdominal wall problems. Only 29% of the surgeons had made a TAR before attending the course, while 86% are performing it after attending the course and 60% do it on a regular basis. In fact, 43% of surgeons have performed more than five posterior component separations in the last year. CONCLUSIONS: A workshop of abdominal wall surgery that combines live surgery, theoretical content and a cadaver lab can be a very useful tool to expand the use of new surgical techniques.

Combining anterior and posterior component separation for extreme cases of abdominal wall reconstruction.

PURPOSE: The closure of midline in abdominal wall incisional hernias is an essential principle. In some exceptional circumstances, despite adequate component separation techniques, this midline closure cannot be achieved. This study aims to review the results of using both anterior and component separation in these exceptional cases. METHODS: We reviewed our experience using the combination of both anterior and posterior component separation in the attempt to close the midline. Our first step was to perform a TAR and a complete extensive dissection of the retromuscular preperitoneal plane developed laterally as far as the posterior axillary line. When the closure of midline was not possible, an external oblique release was made. A retromuscular preperitoneal reinforcement was made with the combination of an absorbable mesh and a 50 × 50 polypropylene mesh. RESULTS: Twelve patients underwent anterior and posterior component separation. The mean hernia width was 23.5 ± 5. The majority were classified as severe complex incisional hernia and had previous attempts of repair. After a mean follow-up of 27 months (range 8-45), no case of recurrence was registered. Only one patient (8.33%) presented with an asymptomatic bulging in the follow-up. European Hernia Society's quality of life scores showed a significant improvement at 2 years postoperatively in the three domains: pain (p = 0.01), restrictions (p = 0.04) and cosmetic (p = 0.01). CONCLUSIONS: The combination of posterior and anterior component separation can effectively treat massive and challenging cases of abdominal wall reconstruction in which the primary midline closure is impossible to achieve despite appropriate optimization of surgery.

Capecitabine in combination with irinotecan (XELIRI), administered as a 2-weekly schedule, as first-line chemotherapy for patients with metastatic colorectal cancer: a phase II study of the Spanish GOTI group.

BACKGROUND: Combination chemotherapy is standard treatment for metastatic colorectal cancer (MCRC). The aim of this study was to determine the efficacy and safety of capecitabine+irinotecan (2-weekly schedule), as first-line therapy of MCRC. METHODS: Patients received irinotecan 175 mg m(-2) on day 1 and oral capecitabine 1000 mg m(-2) twice daily on days 2-8 every 2 weeks. For patients aged > or =65 years, the starting doses of irinotecan and capecitabine were reduced to 140 and 750 mg m(-2), respectively. RESULTS: A total of 53 patients were enrolled: 29 (55%) were > or =65 years old. In an intention-to-treat analysis, complete response was achieved in three patients for an overall response rate (ORR) of 32%. The disease control rate (ORR + stable disease) was 66% and the median duration of response was 7.3 months. Median time to progression and overall survival were 9.0 and 19.2 months, respectively. Grade 4 neutropenia was reported in one patient: no other grade 4 toxicities were recorded. Grade 3 diarrhoea occurred in 8 (15%) patients and grade 1-2 hand-foot syndrome in 7 (13%) patients. CONCLUSION: Capecitabine and irinotecan, given every 2 weeks, as first-line treatment of MCRC is an active regimen with a manageable toxicity profile, even in older patients.

[Persistent left superior vena cava. Implications in central venous catheterisation]. / Vena cava superior izquierda persistente. Implicaciones en la cateterización venosa central.

The placement of central catheters through the subclavian and jugular venous path can be complicated by the cannulation of an artery or an aberrant venous path. The most frequent anomaly of the embryological development of the caval vein is the persistence of the left superior vena cava (LSVC). The implantation of catheters in the LSVC can be suspected by its anomalous route in thorax radiography. Gasometry and the pressure curve of the vessel make it possible to rule out an arterial catheterisation. Diagnostic confirmation is obtained through angiography, echocardiography, computerised tomography or cardiac resonance. The doctor who regularly implants central venous catheters must be familiar with the anatomy of the venous system and its variants and anomalies, since their presence might influence the handling of the patient.

The intensive care unit in the postoperative period of major abdominal surgery. / La unidad de cuidados intensivos en el postoperatorio de cirugía mayor abdominal.

Despite low mortality in patients undergoing major abdominal surgery, the number of high-risk patients is increasing and has become a health problem. At present, surgery is understood as a continuous process, in which numerous guidelines added to less invasive techniques offering a lesser physiological impact upon patients with serious comorbidities are responsible for the final outcome. The prevention, identification and early treatment of complications prove as important as the preoperative or surgical technique.?The introduction of ERAS (enhanced recovery after surgery) protocols is the cornerstone for the management of these patients, and is advocated by most surgical societies for reducing mortality, length of hospital stay and hospital costs. The postoperative management of these patients in postsurgery Intensive Care Units guarantees effectiveness and efficiency in maintaining optimum patient care.

[Diagnosis and satisfactory surgical treatment of a jejunal stromal tumor]. / Diagnóstico y tratamiento quirúrgico satisfactorio de un tumor estromal del yeyuno.

GIST is the most common mesenchymal tumor of the gastrointestinal tract. The discovery of KIT proto-oncogene mutations in the pathogenesis of this tumor, and the development of imatinib mesylate, a specific inhibitor of KIT tyrosine kinase function have revolutionized the treatment of GIST. We present the clinical case of a patient with an upper digestive bleeding secondary to a jejunal GIST. Therapeutic options are highlighted.

Long-term outcomes after prophylactic use of onlay mesh in midline laparotomy.

BACKGROUND: The prevalence of incisional hernias (IHs) is still high after midline laparotomy (ML). There is an increasing body of evidence that prophylactic mesh placement (PMP) can be safe and efficient in the short-term outcomes, but there still are some concerns about the potential long-term complications of these meshes. This study describes our long-term PMP experience. METHODS: Observational and prospective study including all patients undergoing the use of prophylactic onlay large-pore polypropylene meshes for the closure of ML since 2008 to 2014. Outcome measures included demographics, perioperative details, wound complications, recurrences, reoperations and chronic complications. RESULTS: A cohort of 172 patients was analysed: 75% elective surgery, 25% emergency cases. Mean age was 68 years with mean body mass index (BMI) of 28.6 kg/m2. Wound classification: 6.4% clean; 85% clean-contaminated; 1.2% contaminated and 8.1% dirty. Follow-up of patients was up to 8 years (mean: 5 ± 1.6). Two meshes were removed due to chronic infection in first six postoperative months. Of the 13 patients (9.02%) who developed IH, 5 of them have been reoperated for IH repair without any difficulty related to previous mesh. During follow-up, 8 patients have been reoperated for other reasons and the integrity of abdominal wall was also checked. After the comparative study, higher BMI and emergency surgery were still risk factors for IH despite PMP. CONCLUSIONS: In our setting, the use of polypropylene prophylactic meshes in MLs is safe, efficient and durable.

First-line mFOLFOX plus cetuximab followed by mFOLFOX plus cetuximab or single-agent cetuximab as maintenance therapy in patients with metastatic colorectal cancer: Phase II randomised MACRO2 TTD study.

BACKGROUND: This multicentre, randomised, and phase II study evaluated mFOLFOX+cetuximab followed by maintenance mFOLFOX+cetuximab or single-agent cetuximab in metastatic colorectal cancer (mCRC) patients (NCT01161316). PATIENTS AND METHODS: Previously, untreated mCRC patients (wild-type KRAS) were randomised to receive cetuximab+mFOLFOX-6 (8 cycles for 2 weeks) followed by maintenance therapy: single-agent cetuximab (Arm-A) or mFOLFOX-6 + cetuximab (Arm-B) until progression. Primary endpoint was progression-free survival (PFS) at 9 months. RESULTS: One hundred ninety-three patients (median [range] age 60 [33-74] years) were randomised (2:1): 129 Arm-A versus 64 Arm-B. PFS at 9 months (95% confidence interval) showed non-inferiority between arms (Arm-A/Arm-B: 60 [52, 69]%/72 [61, 83]%, p [non-inferiority]<0.1). There were no statistically significant differences in the PFS (Arm-A/Arm-B: 9 [95% CI 7, 10] months/10 [7,13] months, hazard ratio [HR] = 1.19 [0.80, 1.79]) or overall survival (23 [19, 28] months/27 [18, 36] months, HR = 1.24 [0.85, 1.79]) between arms. The objective response rate was also similar (48 [39, 57]%/39 [27, 52]%). The safety profile was similar between arms, and all patients experienced at least one adverse event (AE) (Arm-A/Arm-B grade ≥III AEs: 70%/68%). The most common grade ≥III AEs were as follows: neutropenia (Arm-A/Arm-B: 28%/26%), rash acneiform (15%/24%) and sensory neuropathy (2%/15%) in any group. Arm-A was associated with less grade ≥III rash and sensory neuropathy and a lower rate of serious AEs (20%/27%). CONCLUSION(S): This phase II exploratory trial with a non-inferiority design suggests that maintenance therapy with single-agent cetuximab following mFOLFOX+cetuximab induction could be a valuable option compared with mFOLFOX+cetuximab treatment continuation. We await phase III trials to confirm single-agent cetuximab as maintenance therapy in mCRC patients.