American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity.

This joint ASGE-ESGE guideline provides an evidence-based summary and recommendations regarding the role of endoscopic bariatric and metabolic therapies (EBMTs) in the management of obesity. The document was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. It evaluates the efficacy and safety of EBMT devices and procedures that currently have CE mark or FDA-clearance/approval, or that had been approved within five years of document development. The guideline suggests the use of EBMTs plus lifestyle modification in patients with a BMI of ≥30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity. Furthermore, it suggests the utilization of intragastric balloons and devices for endoscopic gastric remodeling (EGR) in conjunction with lifestyle modification for this patient population.

American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity.

This joint ASGE-ESGE guideline provides an evidence-based summary and recommendations regarding the role of endoscopic bariatric and metabolic therapies (EBMTs) in the management of obesity. The document was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. It evaluates the efficacy and safety of EBMT devices and procedures that currently have CE mark or FDA-clearance/approval, or that had been approved within five years of document development. The guideline suggests the use of EBMTs plus lifestyle modification in patients with a BMI of ≥ 30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity. Furthermore, it suggests the utilization of intragastric balloons and devices for endoscopic gastric remodeling (EGR) in conjunction with lifestyle modification for this patient population.

Immunotherapy and Targeted Therapies Efficacy in Thymic Epithelial Tumors: A Systematic Review.

BACKGROUND: Thymic epithelial tumors (TET) are rare neoplasms of the anterior mediastinum. Surgery is the mainstay treatment for resectable TET, whereas systemic treatments are reserved for unresectable and metastatic tumors. The development of new treatments, such as immune checkpoint inhibitors (ICI) and targeted therapies, with promising results in other types of solid tumors, has led to the investigation of their potential efficacy in TET. The study of tumor microenvironments (TME) is another field of investigation that has gained the interest of researchers. Taking into account the complex structure of the thymus and its function in the development of immunity, researchers have focused on TME elements that could predict ICI efficacy. MATERIALS AND METHODS: The primary objective of this systematic review was to investigate the efficacy of ICI in TET. Secondary objectives included the toxicity of ICI, the efficacy of targeted therapies in TET, and the evaluation of the elements of TME that may be predictive factors of ICI efficacy. A literature search was conducted in February 2023 using the Ovid Medline and SciVerse Scopus databases. RESULTS: 2944 abstracts were retrieved, of which 31 were retained for the systematic review. Five phase II and one retrospective study assessed ICI efficacy. The overall response rate (ORR) varied from 0% to 34%. Median progression-free survival (PFS) ranged from 3.8 to 8.6 months, being lower in thymic carcinoma (TC) (3.8-4.2 months). Median overall survival (OS) ranged from 14.1 to 35.4 months. Treatment-related adverse events occurred in 6.6% to 27.3% of patients. Sixteen studies assessed targeted therapies. The most active molecule was lenvatinib, with 38% ORR in patients with TC while no activity was detected for imatinib, erlotinib plus bevacizumab, and saracatinib. Ten studies assessed TME elements that could predict ICI efficacy. Four studies focused on the tumor-infiltrating immune cells suggesting improved outcomes in patients with TC and high tumor-infiltrating lymphocyte densities. Another study showed that CD8+, CD20+, and CD204+ tumor-infiltrating immune cells in cancer stroma might be prognostic biomarkers in TC. Another study identified the immune-related long non-coding RNAs as a predictor of response to ICI. Tumor mutational burden was identified as a predictive factor of ICI efficacy in one study. CONCLUSIONS: Despite study heterogeneity, this review shows that ICI could be a therapeutic option for selected patients with TET that are not amenable to curative radical treatment after first-line chemotherapy.

Systemic treatment for neuroendocrine non-small cell lung carcinoma: A cases series and a systematic review of the literature.

INTRODUCTION: Neuroendocrine lung cancer constitutes a continuum from carcinoid tumours (CT) to large cell neuroendocrine (LCNEC) and small-cell carcinomas (SCLC). Except for SCLC, there is no consensual agreement on systemic therapy. The aim of this study is to review our clinical experience among patients with CT and LCNEC in the light of a systematic review of the literature. METHODS: A retrospective study of all patients with CT and LCNEC receiving a systemic therapy at Institut Jules Bordet and Erasme Hospital between 01/01/2000-31/12/2020. A systematic review of the literature was performed in Ovid Medline. RESULTS: 53 patients (21 CT and 32 LCNEC) were included. Despite limited response rates, patients with CT receiving a "carcinoid-like" 1st-line regimen (somatostatin analogues (SSA), everolimus, peptide receptor radionuclide therapy (PRRT)) had a numerically longer survival compared to those receiving other type of regimens (median 51.4 vs 18.6 months, respectively; p = 0.17). We observed a similar survival between 1st line "SCLC-like" vs "non-small cell lung cancer (NSCLC)-like" schemes in LCNEC (median 11.2 vs 12.6 months, respectively; p = 0.46). The systematic review identified 23 studies (12 prospective, 15 and 8 for CT and LCNEC respectively). For CT, everolimus and SSA led to prolonged disease control with an acceptable toxicity profile, while higher response rates but lower tolerance were associated with PRRT and chemotherapy regimens including oxaliplatine and dacarbazine. For LCNEC, no difference emerged when comparing "SCLC-like" and "NSCLC-like" regimens considering response rate, progression-free or overall survival. CONCLUSIONS: SSA, everolimus and PRRT present a good therapeutic index for CT, while the role of chemotherapy remains limited to aggressive and rapidly evolving CT. The best type of chemotherapy regimen remains an open question in LCNEC.

Systemic treatment and radiotherapy for patients with non-small cell lung cancer (NSCLC) and HIV infection - A systematic review.

Lung cancer is the most common non-AIDS defining cancer among people living with HIV (PLWH), but there is a paucity of data regarding the efficacy and toxicity of radiotherapy and systemic regimens, including immunotherapy, in the treatment of these patients. In order to answer this question, we have performed a systematic search of the literature in Ovid Medline until March 17, 2022. We included 21 publications, enrolling 513 PLWH with non-small cell lung cancer (NSCLC), mostly male (75-100%), (ex-)smokers (75-100%) and with stage III-IV at diagnosis (65-100%). The overall response rate (ORR) to chemotherapy (n = 186 patients, mostly receiving platinum-based regimens) was highly variable (17 %-83 %), with a substantial hematological toxicity. ORR varied between 13 % and 50 % with single-agent immunotherapy (n = 68), with median overall survival between 9 and 11 months and a very acceptable toxicity profile, in line with studies in the HIV non-infected population. All five patients receiving tyrosine kinase inhibitors (TKIs; gefitinib or erlotinib) showed a partial response and long overall survival. Yet, combination of TKIs with antiretroviral therapy using pharmacological boosters, such as ritonavir, should be avoided. Radiotherapy was evaluated among 42 patients, showing high ORR (55 %-100 %), but 18 % of patients had a pneumonitis. This systematic review shows that radiotherapy and systemic therapy are effective and safe among PLWH with controlled infection diagnosed with NSCLC. Nonetheless, most reports were small and heterogeneous and larger studies are needed to confirm these encouraging findings. Moreover, clinical trials should not restrict the inclusion of PLWH, as more data is needed regarding the long-term efficacy and safety of treatments among this underserved population, especially of immunotherapy.

European Respiratory Society guideline on various aspects of quality in lung cancer care.

This European Respiratory Society guideline is dedicated to the provision of good quality recommendations in lung cancer care. All the clinical recommendations contained were based on a comprehensive systematic review and evidence syntheses based on eight PICO (Patients, Intervention, Comparison, Outcomes) questions. The evidence was appraised in compliance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Evidence profiles and the GRADE Evidence to Decision frameworks were used to summarise results and to make the decision-making process transparent. A multidisciplinary Task Force panel of lung cancer experts formulated and consented the clinical recommendations following thorough discussions of the systematic review results. In particular, we have made recommendations relating to the following quality improvement measures deemed applicable to routine lung cancer care: 1) avoidance of delay in the diagnostic and therapeutic period, 2) integration of multidisciplinary teams and multidisciplinary consultations, 3) implementation of and adherence to lung cancer guidelines, 4) benefit of higher institutional/individual volume and advanced specialisation in lung cancer surgery and other procedures, 5) need for pathological confirmation of lesions in patients with pulmonary lesions and suspected lung cancer, and histological subtyping and molecular characterisation for actionable targets or response to treatment of confirmed lung cancers, 6) added value of early integration of palliative care teams or specialists, 7) advantage of integrating specific quality improvement measures, and 8) benefit of using patient decision tools. These recommendations should be reconsidered and updated, as appropriate, as new evidence becomes available.

Trabectedin-Related Heart Failure: Case Report and a Systematic Review of the Literature.

New drugs come not only with benefits but also with unexpected toxicities which need to be promptly recognized and managed. Starting from a scholar case of acute heart failure with preserved ejection fraction following the administration of trabectedin (ET-743, Yondelis®) in a patient with a metastatic solitary fibrous tumor, we performed a systematic review of the literature encompassing the results of previous cardiac safety analysis published ten years ago, a review of clinical trials published during the last 10 years as well as single-case descriptions related to trabectedin cardiotoxicity. The estimated incidence of cardiac toxicity was 3,4% among patients receiving trabectedin, with recent data suggesting a higher rate of heart failure than previously recognized. Previous or concomitant anthracyclines exposure may represent a risk factor. Assaying for NT-pro-BNP may be useful for the early detection of individuals with trabectedin-induced heart failure.

Current and future research efforts in oligometastatic non-small cell lung cancer-a systematic review.

BACKGROUND: Major progresses in the systemic treatment of non-small cell lung cancer (NSCLC) were obtained during the last decade, including the use of immunotherapy and tyrosine kinase inhibitors (TKIs), with impressive results in terms of response and survival rates. Moreover, novel imaging and radiotherapy techniques have allowed the development of stereotactic body radiotherapy (SBRT), with high rates of local disease control and minimal toxicity. These factors propelled the use of combined systemic and local treatment strategies in patients with a low burden of metastases-the oligometastatic disease (OMD). METHODS: We systematically review the evidence from prospective randomized and non-randomized trials on local ablative therapy for OMD NSCLC published until June 2020. In addition, we present a review of the ongoing and/or recruiting trials in the field. RESULTS: We included 16 articles, reporting on 14 prospective clinical trials, starting from the pilot trial conducted in the early 2000's to the recent randomized trials that have showed benefits in survival. We found 24 ongoing trials, which combine multiple local ablative regimens with new systemic therapies, such as new generation TKIs and immunotherapy. DISCUSSION: Despite these vast current and ongoing prospective research efforts, there are several issues that impair the generalizability of their findings. These include the heterogeneous definition of OMD, trial design, staging, patient selection, tumor mutational status and treatments used, which may limit their applicability in the clinical practice.

Antiphospholipid syndrome-induced ischemic stroke following pembrolizumab: Case report and systematic review.

Immune checkpoint inhibitors (ICI) improve the prognosis of patients with advanced non-small cell lung cancer. However, clinicians should be aware of potentially life-threatening immune-related adverse events (irAEs). We report a case of a 67-year-old man with lung adenocarcinoma who developed an acute ischemic stroke after the second administration of pembrolizumab. The patient benefited from thrombolysis and mechanical thrombectomy with improved neurological outcome. An anti-phospholipid syndrome (APS) was diagnosed. Simultaneously, he developed a grade IV autoimmune hepatitis. Bothmanifestations were considered irAEs and the ICI treatment was discontinued. Steroids were initiated resulting in irAEs resolution. Remarkably, the patient achieved a complete oncological response and persistent remission after one year follow-up despite early discontinuation of pembrolizumab. Of note, APS is rarely reported as irAE. To our knowledge, this is the first case reported in the context of lung cancer. A systematic review of the literature is provided.

Management of thymoma associated autoimmune pure red cell aplasia: Case report and systematic review of the literature.

Pure red cell aplasia (PRCA) is a rare paraneoplastic syndrome observed in 2-5 % of thymomas. Literature reports great variability in its management. Based on an illustrative clinical case, we present a systematic literature review whose main objective is to evaluate the therapeutic management of PRCA. The literature search was performed based on the PICO method in the Medline and Scopus databases. The reference clinical case concerns a 51-year-old woman with stage IVa thymoma. After initial response to chemotherapy, a locoregional progression occurred with PRCA development that responded favorably under second line chemotherapy. The patient finally died in a context of bicytopenia with febrile neutropenia. The systematic review covers 135 articles published between 1950 and 2019. Thymectomy alone or in combination with other therapies showed a 31 % complete remission (CR) rate for PRCA of, whereas none was reported with anti-tumor treatments without thymectomy. Among immunomodulatory therapies, cyclosporin gave the highest percentage of CR (74 %). Finally, the combination of thymectomy and immunomodulatory treatments showed a CR rate of 45 %. Thymectomy appeared to be the most effective anti-tumor treatment for PRCA. Immunomodulatory therapies, particularly cyclosporine, are shown effective, but the risk of infectious complications must be considered. The optimal place of anti-tumor and immunomodulatory therapies against PRCA has yet to be determined.

Adverse events reporting in stage III NSCLC trials investigating surgery and radiotherapy.

BACKGROUND: Current treatment options for stage III non-small cell lung cancer (NSCLC) consist of different combinations of chemotherapy, surgery, radiotherapy and immunotherapy. Treatment choices are highly individual decisions, in which adverse events (AEs) are relevant for decision-making. This study aims to analyse reporting of AEs in prospective stage III NSCLC trials, focussing on trials including radiotherapy and/or surgery. METHODS: PubMed was searched for prospective studies dealing with stage III NSCLC from January 1987 to April 2019. Meta-analyses were screened as a positive control. Pearson's Chi-squared test and smooth kernel distribution were used to estimate distributions. Data was resampled using bootstrapping. RESULTS: Out of 1193 initially identified studies, 119 met the inclusion criteria. Of these, 31 had a surgical procedure in any study arm. Grade 3 and 4 AEs were reported in 94.12% and 92.44% of the included studies, respectively. Reporting of grade 5 AEs was provided in 87.39% of cases. Grade 1 and 2 AEs were less commonly reported at 53.78% and 63.03%, respectively. One study did not mention any AEs. Of the 31 treatment arms including any form of surgery, AEs were not reported in 10. Overall, 231 different AE items were reported, only 18 of them were included in at least 20% of the analysed studies. CONCLUSION: Overall, AE reporting in stage III NSCLC was inconsistent and inhomogeneous. Studies including surgical study arms often reported only treatment-related deaths in regards of surgical AEs. Underreporting of AEs prohibits the extraction of patient-relevant information for decision-making and represents a suboptimal use of invested resources.

ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma.

The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009-2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally via image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including BAP-1 and CDKN2A (p16) for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pre-therapeutic assessment. Monitoring: patient's performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres.

ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma.

The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009-2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally via image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including BAP-1 and CDKN2A (p16) for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pretherapeutic assessment. Monitoring: patient's performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasize that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres.

Immunotherapy: From Advanced NSCLC to Early Stages, an Evolving Concept.

Immunotherapy in lung cancer treatment is a long history paved with failures and some successes. During the last decade, the discovery of checkpoints inhibitors led to major advances in treating advanced and metastatic non-small cell lung cancer (NSCLC). Impressive data from early phase I-II studies were subsequently confirmed in large prospective randomized trials and meta-analyses (High-level of evidence). Three anti- programmed death-1 (PD1) (pembrolizumab, nivolumab) or antiPD-ligand(L)1 (atezolizumab) antibodies showed clinically significant improved survival compared to second-line docetaxel. Then, first-line pembrolizumab monotherapy demonstrated its superiority over platinum-doublet in high PD-L1 NSCLC. The addition of pembrolizumab or atezolizumab to chemotherapy derived the same results regardless of the PD-L1 status. On the opposite, antiCTLA4 (Cytotoxic T-Lymphocyte Associated 4) results are currently disappointing in unselected patients while recent development suggest that the combination of antiPD1 and antiCTLA4 (nivolumab-ipilimumab) positively impact on overall survival. Some secondary analyses also showed that immunotherapy has a positive impact on quality of life and that the clinical improvement can be done at an acceptable incremental cost per QALY. A lot of questions remain unresolved: which is the best treatment duration and is it the same for all patients, how to choose the patients that will have the highest benefit of immunotherapy, how to identify the patients who will have rapid progression, how to improve the current data (new targets, new combinations)….

Genioplasty with surgical guide using 3D-printing technology: A systematic review.

BACKGROUND: The purpose of this systematic review is to evaluate the current state of the art of making genioplasties using 3D printing technology. MATERIAL AND METHODS: A multi-database single-reviewer systematic review identified sixteen papers that fulfilled the selection criteria. There were mainly case series and case reports available (Level IV of the Oxford Evidence-based medicine scale); only two prospective study (Level III) evaluated this subject. These articles are analyzed in details and summarized in this review. RESULTS: The realization of genioplasties with surgical guide using 3D-printing technology could improve predictability and accuracy. It protects anatomical structures in the environment of the surgery, reducing by this way the morbidity and providing safer results. The type of printer and material used as well as the sterilization techniques should be further developed by the authors. The use of open-access software should also be further explored to allow the use of these new technologies by the largest number of surgeons. CONCLUSIONS: Finally, prospective multi-center studies with larger samples should be performed to definitively conclude the benefits of this new technology and allow for its routine use. This article is the first systematic review on this topic. Key words:Genioplasty, printing, three-dimensional, surgery, computer-assisted.

What Means A Quality Professional-Patient Relationship From The Asthmatic Patients' Perspective? A Narrative Review Of Their Needs And Expectations.

INTRODUCTION: Poor treatment adherence among asthmatic patients currently remains a public health challenge. One of the most quoted determinants is the quality of the professional-patient relationship although it has clearly not been fully described. PURPOSE: This study aims at deeply exploring asthmatic patients' needs and expectations about the accompaniment proposed by their healthcare professionals. METHODS: A rigorous narrative review was performed. RESULTS: According to patients, what they expect from professionals can be split into eight themes: getting exhaustive information, relying on an available healthcare professional, being more involved into life with one's asthma, being accompanied by a multidisciplinary team, being respected in one's uniqueness, being cared through a humanist approach, feeling the professional is skilled and Other needs. DISCUSSION AND CONCLUSION: Asthmatic patients' needs have little evolved in 20 years illustrating that if they are met, that would positively affect the way patients want to be followed by healthcare professionals and so, that would increase their treatment adherence. Several recommendations such as setting up a doctor - asthma nurse practitioner binomial or studying a concrete care pathway may help in fulfilling these needs. Finally, this research opens the way to other studies since similar results have been found in populations suffering from other chronic diseases than asthma.

Defining Synchronous Oligometastatic Non-Small Cell Lung Cancer: A Systematic Review.

INTRODUCTION: Synchronous oligometastatic (sOM) disease is an oncological concept characterized by a limited cancer burden. Patients with oligometastasis could potentially benefit from local radical treatments. Despite the fact that the sOM condition is well recognized, a universal definition, including a specific definition for NSCLC, is not yet available. The aim of this systematic review was to summarize the definitions of and staging requirements for use of the term synchronous oligometastatic in the context of NSCLC. METHODS: The key issue was formulated in one research question according to the population, intervention, comparator, and outcomes strategy. The question was introduced in MEDLINE (OvidSP). All articles dealing with sOM NSCLC and providing a definition of synchronous oligometastasis in NSCLC were selected and analyzed. RESULTS: A total of 21 eligible articles focusing on sOM NSCLC were retrieved and analyzed. In 17 studies (81%), patients had to be staged with magnetic resonance imaging or computed tomography of the brain, thoracic and abdominal computed tomography, and positron emission tomography. The total number of metastases allowed in the definitions ranged from one to eight, but in 38.1% of studies the maximum number was 5. Most of the publications did not define the number of involved organs or the maximum number of metastases per organ. For mediastinal lymph node involvement, only five articles (27.8%) counted this as a metastatic site. CONCLUSIONS: No uniform definition of sOM NSCLC could be retrieved by this systematic review. However, extended staging was mandated in most of the studies. An accepted oncological definition of synchronous oligometastasis is essential for patient selection to define prospective clinical trials.

Bullous Lupus Under Nivolumab Treatment for Lung Cancer: A Case Report With Systematic Literature Review.

BACKGROUND: Various immune-related adverse events (irAEs) have been reported to be associated with the use of immune checkpoint inhibitors. We report a case of a patient with lung cancer treated with nivolumab who developed a bullous eruption and give a systematic review of the literature on irAEs in patients treated with immune checkpoint inhibitors for lung cancer. CASE REPORT: A patient with lung adenocarcinoma developed a non-specific skin lesion at the time of his cancer diagnosis followed by flare episodes until the eighth cycle of nivolumab, when he developed a bullous lupus. As the first eruption had started a few months after his cancer diagnosis and was exacerbated during immunotherapy, a paraneoplastic origin is discussed. Since the patient also presented with flares under nivolumab, we reviewed reported irAEs. No bullous lupus was found but to date, 33 cases of paraneoplastic lupus and two of lupus erythematosus have been reported. CONCLUSION: To our knowledge, this is the first description of a bullous lupus exacerbated by nivolumab.

Management of Acute Complications of Targeted Therapy in Patients With Cancer: A Review of Cases Managed in ICU.

INTRODUCTION: Targeted therapies, molecules in full expansion, are not free of side effects that can lead patients to intensive care. We performed an extensive review of the published evidence and propose a management strategy for acute complications of targeted therapy in critically ill patients with cancer. METHODS: The literature search was performed in August 2017 using the Ovid Medline system by a scientific librarian and physicians. We made a review of cases admitted in intensive care unit (ICU) and a review of toxicities of grades greater or equal to 3. RESULTS: Our search selected 59 articles. The main cardiovascular side effects requiring ICU are heart failure, which is generally reversible, severe hypertension, thrombotic and ischemic events, and rhythm disturbances. The main pulmonary side effects are interstitial lung disease essentially caused by crizotinib, respiratory infections, pneumothorax, and alveolar hemorrhage. The main gastrointestinal side effects are fulminant hepatitis that may be fatal, colitis that may be complicated by hemorrhage, and perforation. The main neurological side effect is posterior reversible encephalopathy syndrome essentially caused by bevacizumab. The main other side effects are Steven-Johnson syndrome, necrotizing fasciitis, and anaphylactic reactions. CONCLUSIONS: The side effects induced by targeted therapies may be fatal but are generally potentially reversible. The main treatment includes stopping current therapy and symptomatic management. Treatment rechallenge should be discussed on a case-by-case basis.

Systemic treatments for thymoma and thymic carcinoma: A systematic review.

Thymic tumours are rare diseases that for most of the cases are cured with surgery and eventually adjuvant radiotherapy. However, about 30% of patients present with advanced stage or relapsing tumours, which require administration of chemotherapy. While cisplatin-adriamycin-cyclophosphamide combination is regularly prescribed, other drugs have been assessed in the literature. Our aim is to evaluate the effectiveness (response rate) of systemic treatments, whatever the therapeutic line, including chemotherapy, targeted therapies and immunotherapies, in thymoma and thymic carcinoma, using the principles of evidence-based medicine. A systematic review was designed using the PICO system, by an experienced librarian and clinicians' experts in thoracic oncology, through the Ovid Medline system. Only phase II-IV trials and retrospective studies including at least 14 patients treated with the same regimen were considered. Articles were independently selected by at least two investigators. Fifty-five eligible articles were retrieved. Sixty% were dealing with platinum-based regimens, mainly cisplatin, and showed overall similar activity (mostly response rate above 50%) independently of the line of treatment or histological type (thymoma versus thymic carcinoma). Non-platinum based regimens included octreotide-prednisone and capecitabine-gemcitabine. Promising data of immunotherapy with antiPDL1 antibody (pembrolizumab) requires confirmation. Based on available data, the most popular and active regimens are cisplatin-anthracycline (CAP or ADOC) or cisplatin-etoposide combinations that should be recommended when considering first-line chemotherapy in thymoma or thymic carcinoma.