Radiofrequency ablation versus surgical resection for the treatment of oligometastatic lung disease.

PURPOSE: The purpose of this study was to compare efficacy and tolerance between radiofrequency ablation (RFA) and surgery for the treatment of oligometastatic lung disease. MATERIALS AND METHODS: This retrospective study reviewed patients treated in two institutions for up to 5 pulmonary metastases with a maximal diameter of 4cm and without associated pleural involvement or thoracic lymphadenopathy. Patient demographics, tumor characteristics, treatment outcome, and length of hospital stay were compared between the two groups. Efficacy endpoints were overall survival (OS), progression-free survival (PFS) and pulmonary or local tumor progression rates. RESULTS: Among 204 patients identified, 78 patients (42 men, 36 women; mean age, 53.3±14.9 [SD]; age range: 15-81 years) were treated surgically, while 126 patients (59 men, 67 women; mean age, 62.2±10.8 [SD]; age range: 33-80 years) were treated by RFA. In the RFA cohort, patients were significantly older (P<0.0001), with more extra-thoracic localisation (P=0.015) and bilateral tumour burden (P=0.0014). In comparison between surgery and RFA cohorts, respectively, the 1- and 3-year OS were 94.8 and 67.2% vs. 94 and 72.1% (P=0.46), the 1- and 3-year PFS were 49.4% and 26.1% vs. 38.9% and 14.8% (P=0.12), the pulmonary progression rates were 39.1% and 56% vs. 41.2% and 65.3% (P>0.99), and the local tumour progression rates were 5.4% and 10.6% vs. 4.8% and 18.6% (P=0.07). Tumour size>2cm was associated with a significantly higher local tumor progression in the RFA group (P=0.010). Hospitalisation stay was significantly shorter in the RFA group (median of 3 days; IQR=2 days; range: 2-12 days) than in the surgery group (median of 9 days; IQR=2 days; range: 6-21 days) (P<0.01). CONCLUSION: RFA should be considered a minimally-invasive alternative with similar OS and PFS to surgery in the treatment of solitary or multiple lung metastases measuring less than 4cm in diameter without associated pleural involvement or thoracic lymphadenopathy.

Artificial intelligence solution to classify pulmonary nodules on CT.

PURPOSE: The purpose of this study was to create an algorithm to detect and classify pulmonary nodules in two categories based on their volume greater than 100 mm3 or not, using machine learning and deep learning techniques. MATERIALS AND METHOD: The dataset used to train the model was provided by the organization team of the SFR (French Radiological Society) Data Challenge 2019. An asynchronous and parallel 3-stages pipeline was developed to process all the data (a data "pre-processing" stage; a "nodule detection" stage; a "classifier" stage). Lung segmentation was achieved using 3D U-NET algorithm; nodule detection was done using 3D Retina-UNET and classifier stage with a support vector machine algorithm on selected features. Performances were assessed using area under receiver operating characteristics curve (AUROC). RESULTS: The pipeline showed good performance for pathological nodule detection and patient diagnosis. With the preparation dataset, an AUROC of 0.9058 (95% confidence interval [CI]: 0.8746-0.9362) was obtained, 87% yielding accuracy (95% CI: 84.83%-91.03%) for the "nodule detection" stage, corresponding to 86% specificity (95% CI: 82%-92%) and 89% sensitivity (95% CI: 84.83%-91.03%). CONCLUSION: A fully functional pipeline using 3D U-NET, 3D Retina-UNET and classifier stage with a support vector machine algorithm was developed, resulting in high capabilities for pulmonary nodule classification.

[Role of immunotherapy in locally advanced non-small cell lung cancer]. / Place de l'immunothérapie dans le cancer bronchique non à petites cellules localement avancé.

Concomitant radiochemotherapy has been the standard of care for unresectable stage III non-small cell lung cancer (NSCLC), irrespective of histological sub-type or molecular characteristics. Currently, only 15-30 % of patients are alive five years after radiochemotherapy, and this figure remains largely unchanged despite multiple phase III randomised trials. In recent years, immune-checkpoint blockades with anti-PD-(L)1 have revolutionised the care of metastatic NSCLC, becoming the standard front- and second-line strategy. Several preclinical studies reported an increased tumour antigen release, improved antigen presentation, and T-cell infiltration in irradiated tumours. Immunotherapy has therefore recently been evaluated for patients with locally advanced stage III NSCLC. Following the PACIFIC trial, the anti-PD-L1 durvalumab antibody has emerged as a new standard consolidative treatment for patients with unresectable stage III NSCLC whose disease has not progressed following concomitant platinum-based chemoradiotherapy. Immunoradiotherapy therefore appears to be a promising association in patients with localised NSCLC. Many trials are currently evaluating the value of concomitant immunotherapy and chemoradiotherapy and/or consolidative chemotherapy with immunotherapy in patients with locally advanced unresectable NSCLC.

Five simultaneous artificial intelligence data challenges on ultrasound, CT, and MRI.

PURPOSE: The goal of this data challenge was to create a structured dynamic with the following objectives: (1) teach radiologists the new rules of General Data Protection Regulation (GDPR), while building a large multicentric prospective database of ultrasound, computed tomography (CT) and MRI patient images; (2) build a network including radiologists, researchers, start-ups, large companies, and students from engineering schools, and; (3) provide all French stakeholders working together during 5 data challenges with a secured framework, offering a realistic picture of the benefits and concerns in October 2018. MATERIALS AND METHODS: Relevant clinical questions were chosen by the Société Francaise de Radiologie. The challenge was designed to respect all French ethical and data protection constraints. Multidisciplinary teams with at least one radiologist, one engineering student, and a company and/or research lab were gathered using different networks, and clinical databases were created accordingly. RESULTS: Five challenges were launched: detection of meniscal tears on MRI, segmentation of renal cortex on CT, detection and characterization of liver lesions on ultrasound, detection of breast lesions on MRI, and characterization of thyroid cartilage lesions on CT. A total of 5,170 images within 4 months were provided for the challenge by 46 radiology services. Twenty-six multidisciplinary teams with 181 contestants worked for one month on the challenges. Three challenges, meniscal tears, renal cortex, and liver lesions, resulted in an accuracy>90%. The fourth challenge (breast) reached 82% and the lastone (thyroid) 70%. CONCLUSION: Theses five challenges were able to gather a large community of radiologists, engineers, researchers, and companies in a very short period of time. The accurate results of three of the five modalities suggest that artificial intelligence is a promising tool in these radiology modalities.

Circulating innate immune markers and outcomes in treatment-naïve advanced non-small cell lung cancer patients.

INTRODUCTION: Innate immunity represents the first step of activation of the immune system and dictates the quality of adaptive immune responses. Studies have reported links between systemic inflammatory or innate immune markers and prognosis in patients with lung cancer. To our knowledge, the prospective and concomitant study of these systemic markers has never been performed. METHODS: Advanced treatment-naive non-small cell lung cancer (NSCLC) patients eligible for first-line platinum-based chemotherapy were prospectively included from December 2012 to July 2015 (N = 148). Blood samples of patients were collected before the first cycle for fresh NK cell phenotyping. Peripheral blood mononuclear cells were cryopreserved for natural cytotoxicity receptor (NCR) genotyping as well as sera for NCR's ligand quantification. Data on leukocytes, neutrophils and monocyte counts and lactate dehydrogenase (LDH) levels were extracted from electronic medical records. RESULTS: Among all studied markers, monocytosis, neutrophilia, leucocytosis, high LDH and sBAG6 levels and reduced levels of NCR3 transcripts were associated with poor overall survival (OS) in univariate analysis. The levels of NCR3 transcripts was linked to age, number of metastatic sites, monocyte counts, LDH and sBAG6 levels. Neutrophilia was associated to high sBAG6 levels. NCR3 was the unique innate immune parameter that remained as an independent factor associated with both OS (P = 0.003) and progression-free survival (P = 0.009) in the multivariate analysis. CONCLUSION: This study brought evidence that these biomarkers are entangled; parameters associated with an inflammatory process were related to reduced levels of NCR3 transcripts. Finally, the level of NCR3 transcripts was independently associated with outcomes in treatment-naive patients with advanced NSCLC.

Patterns of responses in metastatic NSCLC during PD-1 or PDL-1 inhibitor therapy: Comparison of RECIST 1.1, irRECIST and iRECIST criteria.

BACKGROUND: Immune checkpoint inhibitors are an important tool in the therapeutic strategy against metastatic non-small cell lung cancer (NSCLC); however, radiological evaluation is challenging due to the emergence of atypical patterns of responses. Several evaluation criteria have been proposed, such as the Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1, immune -related RECIST (irRECIST) and iRECIST, but have not been systematically compared in a homogeneous population. PATIENTS AND METHODS: We conducted a monocentric retrospective analysis of consecutive advanced NSCLC patients treated with an anti-programmed cell death-1 or anti-program death-ligand 1. Response patterns and the discordance between RECIST 1.1, irRECIST and iRECIST guidelines were described, and associations of response patterns and clinical outcome were explored. RESULTS: Overall, 160 patients treated between February 2013 and October 2016 were included. Atypical responses were observed in 20 patients (13%), including eight pseudoprogressions (PsPDs) (5%) and 12 dissociated responses (8%). Thirteen of the 20 patients demonstrated clinical benefit. Per the RECIST 1.1, 37 patients (23%) showed an objective response or stable disease, and 123 patients (77%) exhibited progression. Eighty progressive patients were assessable for irRECIST and iRECIST: 15 patients were assessed differently; however, only three (3.8%) mismatches with a theoretical impact on the therapeutic decision were identified. Patients with PsPD or dissociated response had higher overall survival than patients with true progression. CONCLUSION: Atypical responses (PsPD/dissociated response) occurred in 13% of NSCLC patients under immune checkpoint inhibitors. Based on survival analyses, the RECIST 1.1 evaluation underestimated the benefit of immune checkpoint inhibitors in 11% of the progressive patients. Immune-related RECIST and iRECIST identified these unconventional responses, with a 3.8% discrepancy rate.

Alpha tocopherol loaded chitosan oleate nanoemulsions for wound healing. Evaluation on cell lines and ex vivo human biopsies, and stabilization in spray dried Trojan microparticles.

An amphiphilic chitosan salt, chitosan oleate (CS-OA), was previously proposed for the physical stabilization of lemongrass antimicrobial nanoemulsions (NE) through a mild spontaneous emulsification process. As both chitosan and oleic acid are described in the literature for their positive effects in wound healing, in the present study CS-OA has been proposed to encapsulate alpha tocopherol (αTph) in NEs aimed to skin wounds. A NE formulation was developed showing about 220 nm dimensions, 36% drug loading, and αTph concentration up to 1 mg/ml. Both CS-OA and αTph NE stimulated cell proliferation on keratinocytes and fibroblast cell cultures, and in ex vivo skin biopsies, suggesting the suitability of CS-OA and of the antioxidant agent for topical application in wound healing. αTph stability was further improved with respect of encapsulation, by spray drying the NE into a powder (up to about 90% αTph residual after 3 months). The spray drying process was optimized, to improve powder yield and αTph recovery, by a design of experiments approach. The powder obtained was easily re-suspended to deliver the NE and resulted able to completely release αTph.

A prospective examination of circulating tumor cell profiles in non-small-cell lung cancer molecular subgroups.

BACKGROUND: We report the first study examining the clinical, numerical and biological properties of circulating tumor cells according to molecular subtypes of non-small-cell lung cancer. PATIENTS AND METHODS: 125 patients with treatment-naïve stage IIIb-IV NSCLC were prospectively recruited for CellSearch analysis. Anti-vimentin antibody was included for examination of CTCs to assess their mesenchymal character. Associations of total CTCs and vimentin-positive (vim +) CTCs with clinical characteristics, tumor genotype, and survival were assessed. RESULTS: 51/125 patients (40.8%) were total CTC+ and 26/125 (20.8%) were vim CTC+ at baseline. Multivariate analysis showed patients with ≥5 total CTCs had significantly reduced OS (HR 0.55, 95% CI 0.33-0.92, P = 0.022) but not PFS (HR 0.68, 95% CI 0.42-1.1, P = 0.118) compared to patients with <5 total CTCs. No OS difference was evident between vim+ CTC and vim-negative CTC patients overall (HR 1.24, 95% CI 0.67-2.28, P = 0.494), but after subdivision according to NSCLC driver mutation, we found an increase of vim+ CTCs in the EGFR-mutated subgroup (N = 21/94 patients; mean 1.24 vs 1.22 vim+ CTCs, P = 0.013), a reduction of total CTCs in the ALK-rearranged subgroup (N = 13/90 patients; mean 1.69 vs 5.82 total CTCs, P = 0.029), and a total absence of vim+ CTCs in KRAS-mutated adenocarcinomas (N = 19/78 patients; mean 0 vs 1.4 vim+ CTCs, P = 0.006). CONCLUSIONS: We validate that the baseline presence of ≥5 total CTCs in advanced NSCLC confers a poor prognosis. CTCs from EGFR-mutant NSCLC express epithelial-mesenchymal transition characteristics, not seen in CTCs from patients with KRAS-mutant adenocarcinoma.

Osimertinib benefit in EGFR-mutant NSCLC patients with T790M-mutation detected by circulating tumour DNA.

Background: Approximately 50% of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) will acquire resistance by the T790M mutation. Osimertinib is the standard of care in this situation. The present study assesses the efficacy of osimertinib when T790M status is determined in circulating cell-free tumour DNA (ctDNA) from blood samples in progressing advanced EGFR-mutant NSCLC patients. Material and methods: ctDNA T790M mutational status was assessed by Inivata InVision™ (eTAm-Seq™) assay in 48 EGFR-mutant advanced NSCLC patients with acquired resistance to EGFR TKIs without a tissue biopsy between April 2015 and April 2016. Progressing T790M-positive NSCLC patients received osimertinib (80 mg daily). The objectives were to assess the response rate to osimertinib according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, the progression-free survival (PFS) on osimertinib, and the percentage of T790M positive in ctDNA. Results: The ctDNA T790M mutation was detected in 50% of NSCLC patients. Among assessable patients, osimertinib gave a partial response rate of 62.5% and a stable disease rate of 37.5%. All responses were confirmed responses. After median follow up of 8 months, median PFS by RECIST criteria was not achieved (95% CI: 4-NA), with 6- and 12-months PFS of 66.7% and 52%, respectively. Conclusion(s): ctDNA from liquid biopsy can be used as a surrogate marker for T790M in tumour tissue.

Cardiophrenic angle lymph node is an indicator of metastatic spread but not specifically peritoneal carcinomatosis in colorectal cancer patients: Results of a prospective validation study in 91 patients.

BACKGROUND: The presence of cardiophrenic angle lymph node (CPALN) has been associated with the risk of peritoneal carcinomatosis (PC) in high risk colon cancer patients. Its accuracy to predict PC and its prognostic value in non-selected CRC patients has not been validated prospectively. METHODS: From 2011 to 2013, all patients undergoing colectomy for colon cancer were included prospectively. Presence of CPALN was assessed on preoperative computed tomography scan by two radiologists. Surgical exploration was used as reference for the diagnosis of PC. Factors associated with presence of CPALN and progression-free survival were analyzed. RESULTS: Ninety one patients fulfilled inclusion criteria. CPALN was detected in 36 patients (39.5%) on CT scan. At surgical exploration, PC was found in 6 patients (6.5%). Sensitivity, specificity, negative predictive value, positive predictive value and overall accuracy of CPALN on CT scan for predicting PC were 67%, 62%, 96%, 11% and 63% respectively. In multivariate analysis, the presence of distant metastases whatever the site was associated with the presence of CPALN (p = 0.03; hazard ratio HR = 3.8; confidence interval CI 95% = 1.1-13.3). In the multivariate analysis, only vascular involvement (p = 0.034, HR = 3.574, CI 95% = 1.10-11.60) was associated with progression-free survival whereas CPALN was not found to predict outcome (p = 0.893). CONCLUSION: CPALN is a common finding in non-selected colon cancer patients. Although in the absence of CPALN, PC can almost be excluded, its value for the diagnosis of PC is limited. Our findings support that CPALN is mainly an indicator of metastatic spread of the tumor.

Antitumor activity in advanced cancer patients with thymic malignancies enrolled in early clinical drug development programs (Phase I trials) at Gustave Roussy.

OBJECTIVES: Thymic epithelial neoplasms (TENs) represent a rare entity with poor prognosis and limited systemic treatment options. The aim of this study was to assess the clinical benefit, the efficacy and toxicities of agents for patients with TEN enrolled in Phase I trials. MATERIALS AND METHODS: We reviewed retrospectively patients with advanced TEN enrolled in Phase I trials at Gustave Roussy (DITEP) between 1994 and 2012. Efficacy was assessed using RECIST version 1.1. RESULTS: Twenty-two treated patients were enrolled (15 with thymic carcinoma, 7 with thymoma). The median number of prior systemic therapies was 2 (0-8). The median age was 50 years (range 23-72), and 4 females were treated. Treatments received encompassed mTOR inhibitor (mTORi) in 4 of patients, antiangiogenic agents (AA) in 11 patients, and other targeted therapies in 7 patients. 18% had grade 3-4 toxicity, 85% all grade toxicity and no toxic death was reported. One patient experienced a complete response (CR) and 3 a partial response (PR); 16 patients had stable disease (median 6.6 months; range 1.0-30.7) and 2 had a progressive disease. The median overall survival was 54.5 months (95% CI 25-75.50). The median progression free survival (PFS) was 6.6 months (95% CI 1.35-11.59). Median PFS was 11.6 months for mTORi, 6.9 for AA, and 6.6 for other targeted therapies. CONCLUSION: Phase I trials appear as a sound therapeutic option in TENs pts progressing after standard treatments. Use of AA and mTORi seem to yield a good clinical response and warrant further investigation.

Therapeutic Strategies for Advanced Pancreatic Neuroendocrine Tumors with Segmental Portal Hypertension.

BACKGROUND: Pancreatic neuroendocrine tumors (PNET) locally advanced may lead to significant local symptoms especially segmental portal hypertension (SPH) with risk of bleeding. The aim of our study was to evaluate the role of SPH on the PNET management in an expert center. METHODS: Forty-two patients treated for locally advanced PNET with SPH between January 1984 and December 2012 were retrospectively analyzed. RESULTS: The median age was 55 years (25-75). The median tumor size was 7.5 cm (3-20). Thirty four (80.9%) patients were metastatic mainly in the liver (n=33, 79%) with a frequent (n=16, 38.1%) involvement>20%. The surgery was impossible because of SPH in 7 (16.6%) cases. Pancreatic resection was performed in 28 (66.7%) cases by distal pancreatectomy. Neoadjuvant chemotherapy (n=24, 57%) had no impact on SPH with no modification of collateral circulation. Among operated on patients, complete macroscopic resection was obtained in 19 (67.8%) patients. The mortality and severe morbidity rate was respectively 3.6 and 18%. Five year overall survival (OS) was similar in operated and no operated patients. (61%; p=0.64). The 5-year OS was 77.9 or 55.4% in patients who underwent a complete or incomplete macroscopic resection of primary and metastases, respectively. CONCLUSION: PNET resection associated with SPH is feasible with a low morbimortality. SPH was not improved by chemotherapy. Prolonged survival was observed after complete macroscopic resection.

Post-first-line FOLFOX chemotherapy for grade 3 neuroendocrine carcinoma.

There is no standard for second-line chemotherapy in poorly differentiated grade 3 neuroendocrine carcinoma (G3-NEC) patients. We analyzed the antitumor efficacy of 5-fluorouracil and oxaliplatin (FOLFOX) chemotherapy in this population. A single-center retrospective analysis of consecutive G3-NEC patients treated with FOLFOX chemotherapy after failure of a cisplatinum-based regimen between December 2003 and June 2012 was performed. Progression-free survival (PFS), overall survival (OS), response rate, and safety were assessed according to RECIST 1.1 and NCI.CTC v4 criteria. Twenty consecutive patients were included (seven males and 13 females; median age 55; range 23-87 years) with a performance status of 0-1 in 75% of them. Primary location was gastroenteropancreatic in 12, thoracic in four, other in two, and unknown in two patients. There were 12 (65%) large-cell and 7 (30%) small-cell G3-NEC tumors, and 1 (5%) unknown. All patients had distant metastases. Twelve (60%) patients received FOLFOX as second-line treatment and 8 (40%) as third-line treatment or later and the median number of administered cycles was 6 (range 3-14). The median follow-up was 19 months. Median PFS was 4.5 months. Among the 17 evaluable patients, five partial responses (29%), six stable diseases (35%), and six progressive diseases (35%) were observed. Median OS was 9.9 months. Main Grade 3-4 toxicities were neutropenia (35%), thrombopenia (20%), nausea/vomiting (10%), anemia (10%), and elevated liver transaminases (10%). Our results indicate that the FOLFOX regimen could be considered as a second-line option in poorly differentiated G3-NEC patients after cisplatinum-based first-line treatment but warrant further confirmation in future larger prospective studies.

Screening in asymptomatic SDHx mutation carriers: added value of ¹8F-FDG PET/CT at initial diagnosis and 1-year follow-up.

PURPOSE: Specific recommendations on screening modalities for paraganglioma (PGL) and phaeochromocytoma (PCC) in asymptomatic SDHx mutation carriers (relatives) are still lacking. We evaluated the added value of (18)F-FDG PET/CT in comparison with morphological imaging at initial diagnosis and 1 year of follow-up in this population. METHODS: The study included 30 consecutive relatives with a proven SDHx mutation who were investigated by (18)F-FDG PET/CT, gadolinium-enhanced magnetic resonance angiography of the head and neck, thoracic/abdominal/pelvic (TAP) contrast-enhanced CT and/or TAP MRI. (123)I-MIBG scintigraphy was performed in 20 subjects and somatostatin receptor scintigraphy (SRS) in 20 subjects. The gold standard was based on pathology or a composite endpoint as defined by any other positive imaging method and persistent tumour on follow-up. Images were considered as false-positive when the lesions were not detected by another imaging method or not confirmed at 1 year. RESULTS: At initial work-up, an imaging abnormality was found in eight subjects (27%). The final diagnosis was true-positive in five subjects (two with abdominal PGL, one with PCC and two with neck PGL) and false-positives in the other three subjects (detected with (18)F-FDG PET/CT in two and TAP MRI in one). At 1 year, an imaging abnormality was found in three subjects of which one was an 8-mm carotid body PGL in a patient with SDHD mutaion and two were considered false-positive. The tumour detection rate was 100% for (18)F-FDG PET/CT and conventional imaging, 80% for SRS and 60% for (123)I-MIBG scintigraphy. Overall, disease was detected in 4% of the subjects at the 1-year follow-up. CONCLUSION: (18)F-FDG PET/CT demonstrated excellent sensitivity but intermediate specificity justifying combined modality imaging in these patients. Given the slow progression of the disease, if (18)F-FDG PET/CT and MRI are normal at baseline, the second imaging work-up should be delayed and an examination that does not expose the patient to radiation should be used.

Liver, lung and peritoneal metastases in colorectal cancers: is the patient still curable? What should the radiologist know.

Regardless of the advances in chemotherapy, the only curative treatment for colorectal metastases is surgery, which must be complete and excise all of the metastatic sites of disease. Thanks to advances in neoadjuvant chemotherapy and also to alternative techniques, such as radiofrequency ablation, however, surgical treatments have become available to a larger number of patients and have improved patient survival. The aim of this article is to describe the different treatment strategies for colorectal metastases and to examine the role of imaging in defining the resect ability of these metastases. The key factors in the radiological report in the initial and post-chemotherapy assessments are described.

Whole body MRI in paediatric oncology.

Whole body MRI provides excellent contrast resolution imaging and is an interesting alternative to nuclear medicine examinations in paediatric oncology because it does not involve exposure to radiation. This technique, now feasible in clinical practice, helps to evaluate metastatic spread and response to treatment, which are of great prognostic interest. Numerous studies have demonstrated the non-inferiority of this technique when compared to nuclear medicine examinations. However, there is still a need to standardize indications in each type of cancer and at every stage of it. This article first discusses the technical principles of whole body MRI, then reviews current clinical applications for the modality in children, and finally, discusses future useful developments for paediatric oncology.

Does KRAS mutational status predict chemoresistance in advanced non-small cell lung cancer (NSCLC)?

BACKGROUND: Clinical implications of KRAS mutational status in advanced non-small cell lung cancer (NSCLC) remain unclear. To clarify this point, we retrospectively explored whether KRAS mutations could impact tumor response, and disease control rate (DCR) to first-line platinum-based chemotherapy (CT) as well as progression-free survival (PFS) or overall survival (OS). METHODS: Between June 2009 and June 2012, 340 patients with advanced (stage IIIB/IV) NSCLC were reviewed in a single institution (Institut Gustave Roussy). Two hundred and one patients had a biomolecular profile and received a platinum-based first-line CT. Patients with an unknown mutational status or with actionable alterations were excluded. We retained two groups: patients with KRAS mutated tumor (MUT) and patients with wild-type KRAS/EGFR (WT). Multivariate analyses with Cox model were used. Survival curves were calculated with Kaplan-Meier method. RESULTS: One hundred and eight patients were included in the analysis: 39 in the MUT group and 69 in the WT group. Baseline radiological assessment demonstrated more brain (P=0.01) and liver (P=0.04) metastases in MUT patients. DCR was 76% for MUT vs. 91% for WT group (P=0.03), regardless of the type of platinum-based CT (use of pemetrexed or not). Although no statistically significant differences were found, shorter PFS (4.9 vs. 6.0 months; P=0.79) and OS (10.3 vs. 13.2 months; P=0.40) were observed for patients with KRAS mutated tumors in univariate analysis. CONCLUSIONS: KRAS mutant tumors had a lower DCR after the first-line platinum-based CT, but this difference did not translate in PFS or OS. The presence of KRAS mutations may confer a more aggressive disease, with greater baseline incidence of hepatic and cerebral metastases.

Prognostic significance of visible cardiophrenic angle lymph nodes in the presence of peritoneal metastases from colorectal cancers.

BACKGROUND: Visible cardiophrenic angle lymph nodes (CPALN) (enlarged or not), detected on CT scan are correlated with the presence of peritoneal metastases (PM), and contribute to the diagnosis of PM in colorectal cancer patients. OBJECTIVE: To study whether visible CPALN exert a prognostic impact on survival after complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CCRS + HIPEC) treating PM. PATIENTS AND METHODS: From 1999 to 2010, 114 patients with colorectal cancer and PM were treated with CCRS + HIPEC. CPALN were depicted in 64% of cases. The impact of visible CPALN on survival was investigated retrospectively. RESULTS: The mean peritoneal cancer index (PCI) score was 9.2, 21% of the patients had presented with associated liver metastases, and 71% of the women with ovarian metastases. Median follow-up was 3.9 years. Visible CPALN had no impact on OS nor on DFS, unlike the PCI score which was unequivocably the most potent prognostic factor in the multivariate analysis. CONCLUSION: Although some arguments might suggest that CPALN are malignant, paradoxically, we found that visible CPALN did not exert a positive nor a negative impact on survival after CCRS + HIPEC. SYNOPSIS: Visible cardiophrenic angle lymph nodes (CPALN) on CT-scan are strongly associated with the presence of peritoneal metastases. But this study demonstrates that the presence of CPALN has no prognostic impact after optimal cytoreductive surgery plus HIPEC.

Value of cardiophrenic angle lymph node for the diagnosis of colorectal peritoneal carcinomatosis.

BACKGROUND: Cardiophrenic angle lymph nodes (CPALN) have been reported in patients with abdominopelvic malignancies. We aimed to assess whether the presence of CPALN is associated with peritoneal carcinomatosis (PC) in colorectal cancer. PATIENTS AND METHODS: Between 2007 and 2011, 550 patients with colorectal cancer, including 165 (30%) with PC, had undergone surgery with complete peritoneal exploration. We retrospectively reviewed preoperative CT scans for the presence of CPALN and assessed its association with confirmed PC by univariate and multivariate analyses. RESULTS: CPALN were present in 123 (75%) patients with PC, but absent in 263 (68%) patients without PC (Se: 0.72; Sp: 0.68; PPV: 0.49; NPV: 0.85; [OR], 3.3; p<0.001). PC was the only factor independently associated with CPALN in the multivariate analysis. CPALN was not correlated with the presence of liver metastases. 99 of the 165 patients with PC (62%) had visible signs of PC on CT scan. Among the remaining 66 patients, CPALN were the only potential sign of PC in 41 (62%), (Se 0.62, Sp 0.68, PPV 0.24, and NPV 0.92). CONCLUSION: The detection of CPALN on CT may be of valuable help for the diagnosis of PC in patients with CRC.