Metastatic colorectal cancer (mCRC): French intergroup clinical practice guidelines for diagnosis,treatments and follow-up (SNFGE,FFCD, GERCOR,UNICANCER, SFCD,SFED, SFRO,SFR)

IntroductionThis document is a summary of the French intergroup guidelines regarding the management of metastatic colorectal cancer (mCRC) published in January 2019, and available on the French Society of Gastroenterology website (SNFGE) (www.tncd.org).MethodsThis collaborative work was realized by all French medical and surgical societies involved in the management of mCRC. Recommendations are graded in three categories (A, B and C), according to the level of evidence found in the literature, up until December 2018.ResultsThe management of metastatic colorectal cancer has become complex because of increasing available medical, radiological and surgical treatments alone or in combination. The therapeutic strategy should be defined before the first-line treatment, mostly depending on the presentation of the disease (resectability of the metastases, symptomatic and/or threatening disease), of the patient’s condition (ECOG PS, comorbidities), and tumor biology (RAS, BRAF, MSI). The sequence of targeted therapies also seems to have an impact on the outcome (angiogenesis inhibition beyond progression). Surgical resection of metastases was the only curative intent treatment to date, joined recently by percutaneous tumor ablation tools (radiofrequency, microwave). Localized therapies such as hepatic intra-arterial infusion, radioembolization and hyperthermic intraperitoneal chemotherapy, also have seen their indications specified (liver-dominant disease and resectable peritoneal carcinomatosis). New treatments have been developed in heavily pretreated patients, increasing overall survival and preserving quality of life (regorafenib and trifluridine/tipiracil). Finally, immune checkpoint inhibitors have demonstrated high efficacy in MSI mCRC.ConclusionFrench guidelines for mCRC management are put together to help offer the best personalized therapeutic strategy in daily clinical practice, as the mCRC therapeutic landscape is complexifying. These recommendations are permanently being reviewed and updated. Each individual case must be discussed within a multidisciplinary team (MDT).     

Rectal cancer: French Intergroup clinical practice guidelines for diagnosis,treatments and follow-up (SNFGE,FFCD, GERCOR,UNICANCER, SFCD,SFED, SFRO)

IntroductionThis document is a summary of the French Intergroup guidelines regarding the management of rectal adenocarcinoma published in February 2016.MethodThis collaborative work, under the auspices of most of the French medical societies involved in the management of rectal cancer, is based on the previous guidelines published in 2013. Recommendations are graded into 3 categories according to the level of evidence of data found in the literature.ResultsIn agreement with the ESMO guidelines (2013), non-metastatic rectal cancers have been stratified in 4 risk groups according to endoscopy, MRI or endorectal-ultrasonography. Locally-advanced tumors are limited to groups 3 and 4 (T3 ≥4 cm or T3c–d or N1-2 or T4). These tumors are usually treated using neoadjuvant treatment and total proctectomy (TME). Adjuvant treatment depends on the pathological findings. Very early (group 1) or early (group 2) tumors are managed mainly by surgery, and organ preservation may be an option in selected cases. For metastatic tumors, the recommendations are based on less robust evidence and chemotherapy plays a major role.ConclusionSuch recommendations are constantly being optimized and each individual case must be discussed within a Multi-Disciplinary Team.     

Gastrointestinal lymphomas: French Intergroup clinical practice recommendations for diagnosis,treatment and follow-up (SNFGE,FFCD, GERCOR,UNICANCER, SFCD,SFED, SFRO,SFH)

IntroductionThis document is a summary of the French Intergroup guidelines on the management of gastro-intestinal lymphomas, available on the web-site of the French Society of Gastroenterology, SNFGE (www.tncd.org), updated in September 2017.MethodsThis collaborative work was realised under the auspices of several French medical societies and involved clinicians with specific expertise in the field of gastrointestinal lymphomas, including gastroenterologists, haematologists, pathologists, and radiation oncologist, representing the major French or European clinical trial groups. It summarises their consensus on the management of gastrointestinal lymphomas, based on the recent literature data, previous published guidelines and the expert opinions.ResultsThe clinical management, and especially the therapeutic strategies of the gastro-intestinal lymphomas are specific to their histological subtypes and to their locations in the digestive tract, with the particularity of gastric MALT lymphomas which are the most frequent and usually related to gastritis induced by Helicobacter pylori.ConclusionLymphomas are much less common than epithelial tumours of gastro-intestinal digestive tract. Their different histological subtypes determine their management and prognosis. Each individual case should be discussed within the expert multidisciplinary team.     

Digestive Neuroendocrine Neoplasms (NEN): French Intergroup clinical practice guidelines for diagnosis,treatment and follow-up (SNFGE,GTE, RENATEN,TENPATH, FFCD,GERCOR, UNICANCER,SFCD, SFED,SFRO, SFR)

IntroductionThis document is a summary of the French Intergroup guidelines regarding the management of digestive neuroendocrine neoplasms (NEN) published in February 2020 (www.tncd.org).MethodsAll French medical societies involved in the management of NEN took part in this work. Recommendations were graded into four categories (A, B, C or D), according to the level of evidence found in the literature until May 2019.ResultsThe management of NEN is challenging because of their heterogeneity and the increasing complexity of diagnostic and therapeutic procedures. Pathological analysis is required for their diagnostic and prognostic characterization, which mainly relies on differentiation, grade and stage. The two main emergency situations are functioning syndromes and poorly-differentiated carcinoma. Chromogranin A is the main biochemical marker of NET, although of limited clinical interest. Initial characterization relies on morphological and isotopic imaging. The treatment of localized NET relies on watchful follow-up and local or surgical resection depending on its supposed aggressiveness. Treatment options for metastatic disease include surgery, somatostatin analogues, chemotherapy, targeted therapies, organ-driven locoregional therapies and peptide-receptor radionuclide therapy. As specific predictive factors of treatment efficacy are yet to be identified and head-to-head comparisons have not or only rarely been performed, the therapeutic strategy currently depends on prognostic factors. Cumulative toxicity and the impact of treatment on quality of life must be considered since survival is relatively long in most patients with NET.ConclusionThese guidelines are proposed to achieve the most beneficial therapeutic strategy in clinical practice as the therapeutic landscape of NEN is becoming ever more complex. These recommendations are permanently being reviewed.     

Small bowel adenocarcinoma: French intergroup clinical practice guidelines for diagnosis,treatments and follow-up (SNFGE,FFCD, GERCOR,UNICANCER, SFCD,SFED, SFRO)

BackgroundThis document is a summary of the French intergroup guidelines regarding the management of small bowel adenocarcinoma published in October 2016.MethodThis collaborative work, co-directed by most French Medical Societies, summarizes clinical practice recommendations (guidelines) on the management of small bowel adenocarcinoma. Given the lack of specific data in the literature, all references are given by analogy with colon cancer. The classification used is the AJCC (American Joint Committee on Cancer) pTNM classification (7th edition 2009).ResultsSmall bowel adenocarcinoma has a poor prognosis; less than 30% of patients survive for 5 years after the (first) diagnosis (5-year survival of less than 30%). Due to the rarity of the disease and the retrospective data, most recommendations are based on expert agreement. The initial evaluation is based on chest-abdomen-pelvis CT scan, CEA assay, GI endoscopy and colonoscopy in order detect lesions associated with a predisposing disease. Surgical treatment is currently the only curative option for stage I and II. Adjuvant chemotherapy can be discussed for Stage III and Stage II with T4 (expert agreement). With regard to metastatic tumors, treatment with fluoropyrimidine combined with platinum salts should be considered (expert agreement).ConclusionFew specific data exist in the literature on this type of tumor; most of the recommendations come from expert agreements or by analogy with colon cancer. Thus, each case must be discussed within a multidisciplinary team.     

Anal cancer: French Intergroup Clinical Practice Guidelines for diagnosis,treatment and follow-up (SNFGE,FFCD, GERCOR,UNICANCER, SFCD,SFED, SFRO,SNFCP)

IntroductionThis document is a summary of the French Intergroup guidelines regarding the management of anal carcinomas, published in November 2016.MethodsIt is a collaborative work produced under the auspices of the majority of the French medical societies involved in the management of anal cancer. It is based on the previous guidelines published in 2010. Recommendations are graded in three categories, according to the amount of evidence found in the literature.ResultsNon-metastatic anal carcinomas can be divided into two risk groups, according to magnetic resonance imaging (MRI) or endorectal-ultrasonograpy. Localized small cancers (T1N0) are mainly treated by exclusive radiation therapy in the case of cancers of the anal canal, or by surgery in the case of cancers of the anal margin. The recommended treatment of locally advanced tumours (T2-T4, N0-N2) is definitive concomitant radio-chemotherapy. Salvage surgery should be reserved for patients with poor response, tumour progression or local relapse after radio-chemotherapy, or in cases of persistent vaginal fistula or total anal incontinence after the cessation of radio-chemotherapy. In the case of metastatic tumours, current therapeutic recommendations are based on less robust evidence; with chemotherapy playing a major role.ConclusionThese recommendations are permanently being reviewed, and each individual case must be discussed inside a multidisciplinary team.     

Gastrointestinal stromal tumours (GISTs): French Intergroup Clinical Practice Guidelines for diagnosis,treatments and follow-up (SNFGE,FFCD, GERCOR,UNICANCER, SFCD,SFED, SFRO)

BackgroundThis document is a summary of the French Intergroup guidelines regarding the management of gastrointestinal stromal tumours (GISTs) updated in December 2018.DesignThis collaborative work summarizes clinical practice recommendations (guidelines) on the management of GISTs. It is based on recent literature review, ESMO recommendations and expert opinions.ResultsThe diagnosis of GIST is based on histological examination and immunohistochemistry with markers KIT and DOG-1. Each case must be discussed within a multidisciplinary team. Complete surgical resection tumour, avoiding peroperative perforation, is the potentially curative treatment of localized GISTs. The estimation of the recurrence risk is essential, or adjuvant treatment,and follow-up adaptation. Genotyping (KIT and PDGFRA) of all but very low-risk GISTs is recommended. The nature of mutation has a prognostic value and predictive influence on drug efficacy. Imatinib, a tyrosine-kinase inhibitor, is the standard adjuvant treatment after R0 resection of a GIST with a high risk of recurrence, and the first line therapy for advanced GISTs. Suninitib and regorafenib are respectively the second- and third-line standard treatments for advanced GISTs.ConclusionGuidelines for management of GISTs are continuously evolving and need to be regularly updated. This constant progress is made possible through clinical and translational research.     

Desmoid tumors located in the abdomen or associated with adenomatous polyposis: French intergroup clinical practice guidelines for diagnosis,treatment, and follow-up (SNFGE,FFCD, GERCOR,UNICANCER, SFCD,SFED, SFRO,ACHBT, SFR)

IntroductionDesmoid tumor (DT) of the abdomen is a challenging and rare disease. The level of evidence available to document their treatment is relatively low, however, recent publications of prospective studies have allowed to precise their management.MethodsThis document is a summary of the French intergroup guidelines realized by all French medical and surgical societies involved in the management of DT located in the abdomen or associated with adenomatous polyposis. Recommendations are graded in four categories (A, B, C and D), according to the level of evidence found in the literature until January 2021.ResultsWhen the diagnosis of DT is suspected a percutaneous biopsy should be performed when possible. A molecular analysis looking for pathogenic mutations of the CTNNB1 and APC genes should be systematically performed. When a somatic pathogenic variant of the APC gene is present, an intestinal polyposis should be searched. Due to a high rate of spontaneous regression, non-complicated DT should first benefit from an active surveillance with MRI within 2 months after diagnosis to assess the dynamic of tumor growth. The treatment decision must be discussed in an expert center, favoring the less toxic treatments which can include broad spectrum tyrosine kinase inhibitor or conventional chemotherapy (methotrexate-vinblastine). Surgery, outside the context of emergency, should only be considered for favorable location in an expert center.ConclusionFrench guidelines for DT management were elaborated to help offering the best personalized therapeutic strategy in daily clinical practice as the DT therapeutic landscape is complexifying. Each individual case must be discussed within a multidisciplinary expert team.     

Management of digestive cancers during the COVID-19 second wave: A French intergroup point of view (SNFGE,FFCD, GERCOR,UNICANCER, SFCD,SFED, SFRO,ACHBT, SFR)

IntroductionThe COVID-19 pandemic has major impact of healthcare systems, including cancer care pathways. The aim of this work is to discuss in a multidisciplinary approach the therapeutic and/or strategies adaptations for patients treated for a digestive cancer during the European second wave of COVID-19 pandemic.MethodsA collaborative work was performed by several French societies to answer how to preserve digestive cancer care with no loss of chance during the second wave of COVID-19. In this context, all recommendations are graded as expert’s agreement according to level evidence found in literature until October 2020 and the experience of the first wave of the COVID-19 pandemic.ResultsAs far as possible, no therapeutic modification should be carried out. If necessary, therapeutic adjustments may be considered if they do not constitute a loss of chance for patients. Considering the level of evidence all therapeutic modifications need to be discussed in multidisciplinary tumor board meeting and with patient consent. By contrast to first wave cancer prevention, cancer screening, supportive care and clinical trials should be continued.ConclusionRecommendations proposed could limit cancer excess mortality due to the COVID-19 pandemic but should be adapted according to the situation in each hospital.     

COVID-19 epidemic: Proposed alternatives in the management of digestive cancers: A French intergroup clinical point of view (SNFGE,FFCD, GERCOR,UNICANCER, SFCD,SFED, SFRO,SFR)

IntroductionPatients treated for malignancy are considered at risk of severe COVID-19. This exceptional pandemic has affected countries on every level, particularly health systems which are experiencing saturation. Like many countries, France is currently greatly exposed, and a complete reorganization of hospitals is ongoing. We propose here adaptations of diagnostic procedures, therapies and care strategies for patients treated for digestive cancer during the COVID-19 epidemic.MethodsFrench societies of gastroenterology and gastrointestinal (GI) oncology carried out this study to answer two main questions that have arisen (i) how can we limit high-risk situations for GI-cancer patients and (ii) how can we limit contact between patients and care centers to decrease patients’ risk of contamination while continuing to treat their cancer. All recommendations are graded as experts’ agreement according to the level of evidence found in the literature until March 2020.ResultsA proposal to adapt treatment strategies was made for the main GI oncology situations. Considering the level of evidence and the heterogeneous progression of the COVID-19 epidemic, all proposals need to be considered by a multidisciplinary team and implemented with patient consent.ConclusionCOVID-19 epidemic may significantly affect patients treated for digestive malignancies. Healthcare teams need to consider adapting treatment sequences when feasible and according to the epidemic situation.     

Appendiceal tumors and pseudomyxoma peritonei: French Intergroup Clinical Practice Guidelines for diagnosis,treatments and follow-up (RENAPE,RENAPATH, SNFGE,FFCD, GERCOR,UNICANCER, SFCD,SFED, SFRO,ACHBT, SFR)

IntroductionThis document is a summary of the French Intergroup guidelines regarding the management of appendicular epithelial tumors (AT) and pseudomyxoma peritonei (PMP) published in March 2020, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org).MethodsAll French medical societies specialized in the management of AT and PMP collaboratively established these recommendations based on literature until December 2019 and the results of a Delphi vote carried out by the Peritoneal Surface Oncology Group International experts, and graded into 4 categories (A, B, C, Expert Agreement) according to their level of evidence.ResultsAT and PMP are rare but represent a wide range of clinico-pathological entities with several pathological classification systems and different biological behaviors. Their treatment modalities may vary accordingly and range from simple surveillance or laparoscopic appendectomy to complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) and / or systemic chemotherapy. The prognosis of these neoplasms may also largely vary according to their pathological grade and spreading at diagnosis or during the follow-up. Given the rarity of certain situations, the therapeutic strategy adapted to each patient, must be discussed in a specialized multidisciplinary meeting after a specialized pathological and radiological pre-therapeutic assessment and a clinical examination by a surgeon specializing in the management of rare peritoneal malignancies.ConclusionThese recommendations are proposed to achieve the most beneficial strategy in a daily practice as the wide range and the rareness of these entities renders their management challenging. These guidelines are permanently being reviewed.     

Adjuvant treatments for gastric cancer: From practice guidelines to clinical practice

BackgroundFor gastric cancers, the benefits of adjuvant radiochemotherapy and of perioperative chemotherapy have been demonstrated since 2001 and 2006 respectively. The aim of this study was to evaluate the diffusion of adjuvant treatments in a French population.Methods334 incident gastric cancers UICC Stage IB, II, III or IVM0 resected for cure and recorded in the Burgundy digestive cancer registry were retrospectively included. Patients were classified as having received an effective adjuvant treatment if they had been treated by adjuvant radiochemotherapy since 2001 or perioperative chemotherapy since 2006.ResultsThe proportion of patients treated with an effective adjuvant treatment increased from 21.8% (2001–2005) to 40.1% (2006–2009). Patients treated in 2006–2009 were twice as likely to receive effective adjuvant treatment as those treated during the period 2001–2005. During the 2004–2009 period, 62.4% of cases were presented in a multidisciplinary team meeting. These patients were almost three times more likely to receive effective adjuvant treatment than patients excluded from multidisciplinary team consultation. Age was a significant factor, independent of comorbidities.ConclusionAdministration of adjuvant treatment is still far from being considered a reference regimen in routine practice for R0 resected gastric cancer. The increase in multidisciplinary team meetings should improve the situation.     

Australian clinical practice guidelines for the diagnosis and management of Barrett's esophagus and early esophageal adenocarcinoma

Barrett's esophagus (BE), a common condition, is the only known precursor to esophageal adenocarcinoma (EAC). There is uncertainty about the best way to manage BE as most people with BE never develop EAC and most patients diagnosed with EAC have no preceding diagnosis of BE. Moreover, there have been recent advances in knowledge and practice about the management of BE and early EAC. To aid clinical decision making in this rapidly moving field, Cancer Council Australia convened an expert working party to identify pertinent clinical questions. The questions covered a wide range of topics including endoscopic and histological definitions of BE and early EAC; prevalence, incidence, natural history, and risk factors for BE; and methods for managing BE and early EAC. The latter considered modification of lifestyle factors; screening and surveillance strategies; and medical, endoscopic, and surgical interventions. To answer each question, the working party systematically reviewed the literature and developed a set of recommendations through consensus. Evidence underpinning each recommendation was rated according to quality and applicability.     

Towards more effective use of decision support in clinical practice: what the guidelines for guidelines don't tell you

The Brisbane Cardiac Consortium Clinical Support Systems Program used multiple strategies in optimising quality of care of patients with either of two cardiac conditions. One of these strategies was the development and active implementation of decision support systems centred on evidence-based, locally agreed clinical practice guidelines. Our experience in undertaking this task highlighted numerous operational challenges for which solutions were difficult to extract from existing published literature. In the present article we provide a methodology grounded in both theory and real-world experience that may assist others in developing and implementing systems of guideline-based decision support.     

Development of evidence-based clinical guidelines for the diagnosis and treatment of hepatocellular carcinoma in Japan.

The Clinical Practice Guidelines for Hepatocellular Carcinoma (HCC), the first evidence-based guidelines for the treatment of HCC in Japan, were compiled by an expert panel supported by the Japanese Ministry of Health, Labour, and Welfare. This set of guidelines covers six research fields: prevention, diagnosis and surveillance, surgery, chemotherapy, transarterial chemoembolization, and percutaneous local ablation therapy. A systematic review of the English medical literature on HCC was performed, and a total of 7192 publications were extracted, mainly from MEDLINE (1966-2002). After the second selection, 334 articles were adopted for the guidelines to form 58 pairs of research questions and recommendations. For the users' convenience, practical algorithms for the surveillance and treatment of HCC were also created, which were based on evidence from the selected articles forthe guidelines and modified according to the current status of medical practice in Japan, where liver resection for HCC is regarded as safe with less than 1% mortality and cadaveric donors for liver transplantation are extremely difficult to obtain. The formation of the guidelines and the outline of their contents are described. The Japanese HCC guidelines may be useful in decision making at every clinical step, both for patients and physicians. Although the main users of these guidelines are assumed to be Japanese physicians, the accumulated evidence and interpretation in the guidelines may attract universal attention.     

Implementing clinical guidelines for chronic obstructive pulmonary disease: barriers and solutions

Chronic obstructive pulmonary disease (COPD) is a complex chronic lung disease characterised by progressive fixed airflow limitation and acute exacerbations that frequently require hospitalisation. Evidence-based clinical guidelines for the diagnosis and management of COPD are now widely available. However, the uptake of these COPD guidelines in clinical practice is highly variable, as is the case for many other chronic disease guidelines. Studies have identified many barriers to implementation of COPD and other guidelines, including factors such as lack of familiarity with guidelines amongst clinicians and inadequate implementation programs. Several methods for enhancing adherence to clinical practice guidelines have been evaluated, including distribution methods, professional education sessions, electronic health records (EHR), point of care reminders and computer decision support systems (CDSS). Results of these studies are mixed to date, and the most effective ways to implement clinical practice guidelines remain unclear. Given the significant resources dedicated to evidence-based medicine, effective dissemination and implementation of best practice at the patient level is an important final step in the process of guideline development. Future efforts should focus on identifying optimal methods for translating the evidence into everyday clinical practice to ensure that patients receive the best care.     

Clinical practice guidelines for hepatocellular carcinoma: The Japan Society of Hepatology 2017 (4th JSH‐HCC guidelines) 2019 update

The fourth version of Clinical Practice Guidelines for Hepatocellular Carcinoma was revised by the Japan Society of Hepatology, according to the methodology of evidence‐based medicine and partly to the Grading of Recommendations Assessment, Development, and Evaluation system, which was published in October 2017 in Japanese. New or revised recommendations were described, herein, with a special reference to the surveillance, diagnostic, and treatment algorithms.     

Gastric cancer among peptic ulcer patients: Retrospective, long-term follow-up

BACKGROUND: Patients with duodenal ulcer are not at high risk although Helicobacter pylori infection is no doubt associated with gastric cancer development. However, little is known about the risk after long-term follow-up. AIMS: We investigated the incidence for gastric cancer development in peptic ulcer patients in a long term. PATIENTS AND METHODS: Between 1965 and 2004, endoscopic follow-up of more than 1 year was conducted on 1504 peptic ulcer patients in our hospital. They consisted of 978 gastric ulcer patients, 444 duodenal ulcer patients and 82 gastric and duodenal ulcer patients. Gastric and duodenal ulcer patients were excluded from the analysis because of their limited number. RESULTS: Gastric cancers developed in 32 (3.3%) of gastric ulcer patients and 3 (0.68%) of duodenal ulcer patients. Kaplan-Meier analysis showed that the incidence of gastric cancer in duodenal ulcer patients was significantly lower than that in gastric ulcer patients (log-rank test, p=0.0059). Cox's proportional hazard model denoted the relative risk for duodenal ulcer against gastric ulcer adjusted by sex and age as 0.23 (95% CI: 0.072-0.77, p=0.016). CONCLUSION: The risk for patients with duodenal ulcer to develop gastric cancer over the long term is significantly less than in those with gastric ulcer.     

Gastric cancer: Prevention,screening and early diagnosis

Gastric cancer continues to be an important healthcare problem from a global perspective. Most of the cases in the Western world are diagnosed at late stages when the treatment is largely ineffective. Helicobacter pylori (H. pylori) infection is a well-established carcinogen for gastric cancer. While lifestyle factors are important, the efficacy of interventions in their modification, as in the use of antioxidant supplements, is unconvincing. No organized screening programs can be found outside Asia (Japan and South Korea). Although several screening approaches have been proposed, including indirect atrophy detection by measuring pepsinogen in the circulation, none of them have so far been implemented, and more study data is required to justify any implementation. Mass eradication of H. pylori in high-risk areas tends to be cost-effective, but its adverse effects and resistance remain a concern. Searches for new screening biomarkers, including microRNA and cancer-autoantibody panels, as well as detection of volatile organic compounds in the breath, are in progress. Endoscopy with a proper biopsy follow-up remains the standard for early detection of cancer and related premalignant lesions. At the same time, new advanced high-resolution endoscopic technologies are showing promising results with respect to diagnosing mucosal lesions visually and targeting each biopsy. New histological risk stratifications (classifications), including OLGA and OLGIM, have recently been developed. This review addresses the current means for gastric cancer primary and secondary prevention, the available and emerging methods for screening, and new developments in endoscopic detection of early lesions of the stomach.