PEC-PRO: A new prognostic score from a series of 87 patients with localized perivascular epithelioid cell neoplasms (PEComas) treated with curative intent.

BACKGROUND: Perivascular epithelioid cell neoplasms (PEComas) encompass a heterogeneous family of mesenchymal tumors. Previously described clinicopathologic features aimed at distinguishing benign from malignant variants but lacked prognostic value. METHODS: This retrospective analysis examined clinicopathologic data from patients who had localized PEComa across French Sarcoma Network centers. The authors analyzed 12 clinicopathologic features in a Cox proportional hazard framework to derive a multivariate prognostic risk model for event-free survival (EFS). They built the PEComa prognostic score (PEC-PRO), in which scores ranged from 0 to 5, based on the coefficients of the multivariate model. Three groups were identified: low risk (score = 0), intermediate risk (score = 1), and high risk (score ≥ 2). RESULTS: Analyzing 87 patients who had a median 46-month follow-up (interquartile range, 20-74 months), the median EFS was 96.5 months (95% confidence interval [CI], 47.1 months to not applicable), with 2-year and 5-year EFS rates of 64.7% and 58%, respectively. The median overall survival was unreached, with 2-year and 5-year overall survival rates of 82.3% and 69.3%, respectively. The simplified Folpe classification did not correlate with EFS. Multivariate analysis identified three factors affecting EFS: positive surgical margins (hazard ratio [HR], 5.17; 95% CI, 1.65-16.24; p = .008), necrosis (HR, 3.94; 95% CI, 1.16-13.43; p = .030), and male sex (HR, 3.13; 95% CI, 1.19-8.27; p = 0.023). Four variables were retained in the prognostic model. Patients with low-risk PEC-PRO scores had a 2-year EFS rate of 93.7% (95% CI, 83.8%-100.0%), those with intermediate-risk PEC-PRO scores had a 2-year EFS rate of 67.4% (95% CI, 53.9%-80.9%), and those with high-risk PEC-PRO scores had a 2-year EFS rate of 2.3% (95% CI, 0.0%-18.3%). CONCLUSIONS: The PEC-PRO score reliably predicts the risk of postoperative recurrence in patients with localized PEComa. It has the potential to improve follow-up strategies but requires validation in a prospective trial.

Hypoxia as a potential inducer of immune tolerance, tumor plasticity and a driver of tumor mutational burden: Impact on cancer immunotherapy.

In cancer patients, immune cells are often functionally compromised due to the immunosuppressive features of the tumor microenvironment (TME) which contribute to the failures in cancer therapies. Clinical and experimental evidence indicates that developing tumors adapt to the immunological environment and create a local microenvironment that impairs immune function by inducing immune tolerance and invasion. In this context, microenvironmental hypoxia, which is an established hallmark of solid tumors, significantly contributes to tumor aggressiveness and therapy resistance through the induction of tumor plasticity/heterogeneity and, more importantly, through the differentiation and expansion of immune-suppressive stromal cells. We and others have provided evidence indicating that hypoxia also drives genomic instability in cancer cells and interferes with DNA damage response and repair suggesting that hypoxia could be a potential driver of tumor mutational burden. Here, we reviewed the current knowledge on how hypoxic stress in the TME impacts tumor angiogenesis, heterogeneity, plasticity, and immune resistance, with a special interest in tumor immunogenicity and hypoxia targeting. An integrated understanding of the complexity of the effect of hypoxia on the immune and microenvironmental components could lead to the identification of better adapted and more effective combinational strategies in cancer immunotherapy. Clearly, the discovery and validation of therapeutic targets derived from the hypoxic tumor microenvironment is of major importance and the identification of critical hypoxia-associated pathways could generate targets that are undeniably attractive for combined cancer immunotherapy approaches.

Frequency and mutational spectrum of PIK3CA gene mutations in breast cancer patients: Largest and first report from Lebanon.

The PIK3CA pathway is one of the most frequently altered pathways in human cancers, especially in breast cancer with approximately 40% of HR+/HER2- advanced breast cancer cases exhibiting mutations in the PIK3CA gene. While the mutations can occur across the entire gene, the most common are observed in exon 9 corresponding to the helical domain, and in exon 20 encompassing the kinase domain. This study constitutes the first attempt at determining the frequency and mutational spectrum in Lebanese breast cancer patients. For this purpose, DNA samples from 280 breast cancer patients from across Lebanon were screened for PIK3CA mutations using the Therascreen® PIK3CA RGQ Real-time PCR assay. In line with previous reports, 38.57% of cases were positive for at least one PIK3CA mutation, among which approximately 59% were in exon 9 and 37% in exon 20. However, PIK3CA mutations are breast cancer are heterogeneous whereby 20% of known PIK3CA mutants might not be detected by compact PCR based assays. Thus, the adoption of comprehensive Next Generation Sequencing based panels to decipher the complete clinical, molecular and immunohistochemical profile of breast cancer tumor requires further investigation.

Airborne transmission of SARS-Cov2: What consequences for digestive endoscopy?

The SARS-Cov-2 disease disrupted essential hospital procedures, such as gastrointestinal (GI) endoscopy, due to concerns about air transmission and the risk of exposing health care workers. With the spread of the pandemic, air transmission was considered as the main source of SARS-Cov2 transmission. This raised the problem of transmission by aerosolization of viral particles in operating rooms as well as endoscopy units. This is in line with the known airborne transmission of many other respiratory viruses. The risk of SARS-Cov-2 transmission during GI endoscopy was initially reduced by controlled measures, involving personal protections (mask…), restricted access to endoscopy rooms, and detection of infected patients. Gastrointestinal endoscopy generates aerosols, which may carry viruses. In addition, the endoscopy system may facilitate the diffusion of virus particles or fomites considering the forced-air cooling system used to maintain a stable temperature inside the box (25°C). The volume of air that goes through the light source box is high (240-300 m3 for a 1-h period). Moreover, the light system contains an air pump to inflate air inside the gut lumen. In order to isolate people from hazard, different levels of protection and solutions to avoid airborne transmission of microorganisms should be proposed, such as the reinforcement of personal protective equipment, the change in the way people work and engineering control of the risk.

Single-agent gemcitabine in patients with advanced, pre-treated angiosarcoma: A multicenter, retrospective study.

Gemcitabine has shown clinical activity against angiosarcoma in small series, alone, or combined with taxanes. We aimed to evaluate its activity as a single-agent in a larger series of patients with advanced angiosarcoma. We retrospectively reviewed the electronic medical records of consecutive adult patients with advanced angiosarcoma treated with single-agent gemcitabine at our institutions from January 2010 to January 2021. Response was evaluated according to RECIST 1.1, and toxicity was graded according to NCI-CTC v5.0. 42 patients were identified. 38 patients (90%) had received prior anthracyclines and weekly paclitaxel, and 9 (21%) had received pazopanib. The best tumor response was partial response (PR) in 16 patients (38%), or stable disease (10 patients, 24%). All 8 patients with cardiac angiosarcoma experienced a PR. Median PFS was 5.4 months (95%CI: 3.1-6.5), and median OS was 9.9 months (95%CI: 6.6-13.4). Single-agent gemcitabine has clinically meaningful activity in advanced, heavily pre-treated angiosarcoma.

Bridge plating with decortication, autologous bone graft, and tight closure: a "stepwise surgical diamond concept" for treatment of nonunion in a series of fifty five patients.

PURPOSE: This study was conducted to assess a stepwise surgical procedure applied to treat a continuous series of patients with aseptic atrophic nonunion of long bones. METHODS: A retrospective review was performed of the medical files of patients treated by the senior author between January 2014 and January 2021 for aseptic atrophic nonunion of long bones using a standard stepwise surgical procedure consisting of four successive surgical steps: bridge locked plating, aggressive osteoperiosteal decortication, copious autologous iliac bone grafting, and tight closure without drainage. Patients were clinically and radiographically evaluated until bone healing, then at final follow-up for the purpose of the study. The primary objective of the study was to assess completion of bone healing; secondary objectives were the time required reaching bone union, the occurrence of complications at the iliac bone graft donor site, and the achievement of bone consolidation after a second attempt of treatment when indicated following failure of the index procedure. RESULTS: There were a total of 55 patients. One patient died from myocardial infarction before reaching bone healing and another one lost from early follow-up. There were remaining 53 patients with 37 years of mean age. The affected bone was the clavicle in five patients, humerus in 14, ulna in four, radius in one, femur in 13, and tibia in 16. The mean follow-up period was 3.4 years. A total of 52 patients (98.1%) achieved bone healing at a mean of 14.8 weeks from the index procedure. The only patient who did not reach bone healing after the index procedure was successfully revised using decortication-bone graft and new fixation with intra-medullary femoral nailing. Four patients (7.5%) developed local complications at the site of iliac bone harvesting. CONCLUSION: Our stepwise surgical procedure was very effective treating aseptic atrophic nonunion of long bones. However, as this study is a retrospective review of a limited series of one surgeon's experience, prospective comparative studies with large number of patients are suitable to define the advantages and indications of the procedure herein described.

Modulating tumor-associated macrophages to enhance the efficacy of immune checkpoint inhibitors: A TAM-pting approach.

Tumor-associated macrophages (TAM) plasticity and diversity are both essential hallmarks of the monocyte-macrophage lineage and the tumor-derived inflammation. TAM exemplify the perfect adaptable cell with dynamic phenotypic modifications that reflect changes in their functional polarization status. Under several tumor microenvironment (TME)-related cues, TAM shift their polarization, hence promoting or halting cancer progression. Immune checkpoint inhibitors (ICI) displayed unprecedented clinical responses in various refractory cancers; but only approximately a third of patients experienced durable responses. It is, therefore, crucial to enhance the response rate of immunotherapy. Several mechanisms of resistance to ICI have been elucidated including TAM role with its essential immunosuppressive functions that reduce both anti-tumor immunity and the subsequent ICI efficacy. In the past few years, thorough research has led to a better understanding of TAM biology and innovative approaches can now be adapted through targeting macrophages' recruitment axis as well as TAM activation and polarization status within the TME. Some of these therapeutic strategies are currently being evaluated in several clinical trials in association with ICI agents. This combination between TAM modulation and ICI allows targeting TAM intrinsic immunosuppressive functions and tumor-promoting factors as well as overcoming ICI resistance. Hence, such strategies, with a better understanding of the mechanisms driving TAM modulation, may have the potential to optimize ICI efficacy.

The instep flap for anterior ankle coverage with bone and hardware exposure.

PURPOSE: The instep medial plantar flap is a well-known flap based on the medial plantar artery of the foot and usually used for coverage of soft tissue defects of the heel area. It has seldom been reported for coverage of anterior ankle area with exposure of the bone and metallic hardware after open reduction and internal fixation of distal tibial fractures. The primary purpose of this study is to evaluate the feasibility and viability of this flap as well as its reliability saving the internal fixation devices and efficiency protecting bone healing; the secondary purpose is to assess the condition of the flap and its cosmetic appearance, as well as occurrence of complications related to its harvesting. MATERIAL AND METHODS: This is a retrospective review of medical records of patients operated from December 2015 to December 2020 with application of an instep flap for coverage of the anterior ankle area with exposure of the bone and metallic hardware secondary to open reduction and internal fixation of distal tibial fractures. All patients were reviewed for the purpose of this study; they were assessed for the viability and functional and sensory condition of the flap, signs of local infection, as well as for residual pain and sensory impairment of the toes; subjective cosmetic appearance of the flap was also judged. RESULTS: There were four patients with 32 years mean age and 35 months mean follow-up. The mean flap size was 7.75 cm × 5.75 cm. At final follow-up, all fractures were completely consolidated, and all flaps were living, stable, and sensitive. No distal sensation disturbance was noticed, and none of the patients had pain or annoyance caused by the flap or presented signs of infection. Only one patient expressed mild aesthetic complain. CONCLUSION: The fascio-cutaneous instep medial plantar flap is a reliable solution to cover the anterior ankle area with exposure of the bone and metallic hardware after open reduction and internal fixation of distal tibial fractures, especially for defects measuring up to 9 cm × 6 cm. This flap is technically valid and reproducible; it offers good quality of soft tissue coverage with satisfactory cosmetic appearance and minimal morbidity.

Breakage of sliding hip screw after fixation of pertrochanteric hip fracture: A rare complication.

INTRODUCTION: The authors report a rare case of lag screw breakage in a patient treated using locking DHS with home-made trochanteric stabilizing plate (TSP) for pertrochanteric hip fracture. CASE PRESENTATION: A 67 year-old female was operated for pertrochanteric hip fracture with incompetent lateral wall using locking DHS with home-made TSP. At seven months postoperative, there was radiographic nonunion with breakage of the sliding lag screw. Patient was consequently scheduled for total hip replacement. DISCUSSION: Breakage of DHS lag screw has been attributed to multiple-cycle, low-stress fatigue failure associated with nonunion. Predisposing factors are: situation of the medial edge of the barrel at the level of the fracture site prohibiting fracture compression, and mechanical obstacle to the lag screw back sliding into the barrel. In our case, the use of handmade TSP interdicted lag screw back sliding and prevented fracture impaction which was already impaired by the location of the medial edge of the barrel at the fracture level. Additionally our fixation construct was very rigid because of the use of locking screws in the DHS side plate. CONCLUSION: When DHS fixation is planned for unstable or potentially unstable trochanteric hip fracture the surgeon should be prepared by making available a TSP from the manufacturer in the operative room rather than improvising intra-operatively with handmade TSP; this augmentation device shouldn't interfere with lag screw back sliding. Furthermore the DHS barrel should ideally not impinge with the fracture site, and the use of locking screws in the DHS plate should be cautious.

Impact of follow-up on generalized pairwise comparisons for estimating the irinotecan benefit in advanced/metastatic gastric cancer.

BACKGROUND AND OBJECTIVES: The net treatment effect (∆) is a new method to assess the treatment benefit that combines multiple time-to-event, binary and continuous endpoints according to a pre-specified sequence. It represents the net probability for a random patient treated in the experimental arm to have a better overall outcome than a random patient from the control arm does. We aimed at characterizing the impact of follow-up on ∆ estimated from both time-to-event and binary toxicity endpoints, in randomized controlled trials (RCTs) of irinotecan-based regimen in advanced/metastatic gastric cancer (AGC). STUDY DESIGN: Three RCTs are reanalysed. The net treatment effect using from one to three outcomes (i.e. overall survival, time to progression and toxicity in this order) and the hazard ratio (HR) were estimated after various cut-off dates and compared to the values obtained after complete follow-up were reported. RESULTS: In all three RCTs (897 patients), the irinotecan-based regimen was superior to the non-irinotecan containing regimen in terms of HR and ∆. This superiority was lower when the net treatment effect also accounted for toxicity. The HR was slightly less influenced by an incomplete follow-up than ∆ was, but correction proposed by Péron to account for censored observations showed quite robust results. CONCLUSIONS: The net treatment effect using Péron's correction can be used in case of interim analyses or high censoring rates. In addition to relative measures such as the hazard ratio, it provides a simple mean to evaluate the net treatment effect with and without toxicity outcomes.

The adjunct use of lateral hinged external fixator in the treatment of traumatic destabilizing elbow injuries.

PURPOSE: The purpose of this study is to evaluate the results of using a lateral hinged external fixator as an adjunct stabilizer in the treatment of a variety of acute destabilizing elbow injuries. METHODS: A retrospective review was performed on the medical records of patients in whom a lateral monolateral elbow hinged external fixator was applied by the senior author. The indication to apply the fixator corresponded to a variety of acute injury patterns ranging from simple elbow trauma or dislocation to complex fracture-dislocation, and the decision was based on either the presence of recurrent or persistent instability in any direction and/or to secure a vulnerable or weak bony fixation or soft tissue repair as intra-operatively judged by the surgeon. The fixator was inserted in the same setting after the repair of the associated ligamentous and/or bony structures. Patients operated after one month of the trauma and those presented with open elbow injury or associated humeral or ulnar shaft fracture were excluded. Rehabilitation was immediately started and the fixator removed at six to eight weeks with elbow testing and gentle manipulation under general anaesthesia, and resuming of rehabilitation after removal. Clinical assessment was performed for all patients according to the Mayo Elbow Performance Score (MEPS) with evaluation of range of motion at regular intervals till the end of the post-operative first year, then at final follow-up for the purpose of the study with radiographic assessment for evaluation of elbow reduction and concentricity. RESULTS: There were 13 patients with a mean age of 42 years. Two patients had instability secondary to LCL rupture; one patient had redislocation because of associated coronoid process fracture; one patient had radial head fracture with rupture of both collateral ligaments; five patients had terrible triad injury with variable association of collateral ligaments lesions; and four patients had posterior Monteggia fracture-dislocation. The mean MEPS was 90 at a mean follow-up of seven years with six excellent, six good, and one fair result. All patients had a concentrically reduced and stable elbow as assessed clinically and radiologically with a mean functional arc of motion of 132° for extension-flexion and 178° for pronation-supination. CONCLUSION: The hinged elbow external fixator represents a valuable adjunct in the therapeutic arsenal for the treatment of unstable elbows after bony and soft tissue repair. It provides satisfactory results in terms of stability and function and should be available in the operating room when a surgeon treats a complex elbow dislocation or fracture-dislocation.

Efficacy and safety of oral metronomic etoposide in adult patients with metastatic osteosarcoma.

Therapeutic options in patients with metastatic osteosarcoma are limited and effective systemic treatments are needed in this setting. The aim of this case series was to assess the efficacy and toxicity of oral metronomic etoposide in adult patients with progressive metastatic osteosarcoma. We retrospectively reviewed the electronic records of patients treated with oral metronomic etoposide (25 mg thrice daily, 3 weeks out of 4) from December 2002 to December 2018 at Gustave Roussy (Villejuif, France). The primary endpoint was progression-free rate (PFR) at 4 months; secondary endpoints were: best response (according to RECIST v1.1), progression-free survival (PFS), overall survival (OS) and safety. With a median follow-up of 9.8 months, 37 patients were eligible for this analysis: 68% males, median age 42 (range: 21-75), 19% with synchronous metastases, 92% with lung metastases, median PS: 1 (range: 0-3). Median number of previous treatment lines in the metastatic setting was 1 (range: 0-4). Progression-free rate at 4 months was 40.3% (95% CI: 24.5-56.2). Best response was partial response in 11% and stable disease in 35% of patients (disease control rate: 46%). Median PFS was 3.1 months (95% CI: 2.5-4.7) and median OS was 9.8 months (95% CI: 5.1-12.3). Toxicity profile was acceptable, with 13% grade 3 haematological toxicities (anaemia and neutropenia), without any grade 3-4 non-haematological toxicity. In our experience, oral metronomic etoposide demonstrated effective palliation along with acceptable toxicity in patients with progressive metastatic osteosarcoma.

Minimally invasive percutaneous plate osteosynthesis for treatment of proximal humeral shaft fractures.

PURPOSE: The objective of this study was to evaluate the feasibility and safety of a minimally invasive percutaneous plate osteosynthesis (MIPPO) procedure for proximal humeral shaft fractures using lateral minimal proximal and distal approaches and lateral bridge plating with primary radial nerve control, and to assess its clinical and radiographic outcomes. METHODS: A retrospective review was done for the medical records of adult patients admitted for fracture of the proximal humeral shaft without associated injury to the ipsilateral upper limb and who consented to undergo a novel MIPPO technique herein reported. Patients were reviewed at regular follow-up periods and assessed at a final follow-up for evaluation of Constant, normalized Constant, and QuickDASH scores. RESULTS: There were 21 adult patients with mean age of 56 years. Three patients were lost from early follow-up; one of them had post-operative radial nerve paralysis. Eighteen patients were reviewed for the purpose of this study at a mean of 20 months of final follow-up; among them, one patient developed post-operative radial nerve paralysis with complete recovery after three months. Bone healing was achieved without any malalignment in 17 patients at a mean of 15 weeks, and one patient developed nonunion. At final assessment (mean, 20 months), the mean values of Constant, normalized Constant, and QuickDASH scores were 84 (range, 59 to 100), 95 (range, 73 to 100), and 5 (range, 0 to 18.2) respectively. CONCLUSION: Compared to pre-reported methods of MIPPO, this technique of lateral proximal and distal mini-approaches with lateral bridge plating after primary control of the radial nerve seems safe and feasible for proximal humeral shaft fractures. It gives good clinical and radiographic results with excellent restoration of upper limb function, very low incidence of post-operative radial nerve injury, and high rate of bone union in good alignment.

Patellar Clunk Syndrome Following Posterior Stabilized Total Knee Replacement: Report of Two Cases.

Patellar clunk syndrome (PCS) occasionally occurs after posterior stabilized total knee replacement (PS-TKR), and is characterized by a painful palpable audible clunk of the patella when the knee moves from flexion to extension. It has been classically attributed to the formation of fibrous nodule at the junction of the proximal pole of the patella and the undersurface of the distal quadriceps tendon. However, various intra-articular peripatellar proliferative fibrous formations have also been reported with a wide spectrum of symptoms, ranging from crepitation to frank patellar clunk. Treatment of the syndrome remains essentially surgical, and usually consists of resection of the fibrous nodules. This paper reports two cases of PCS and aims at bringing attention to this entity in terms of pathogenesis, clinical diagnosis, and treatment, through a review of the literature.

Missed Bilateral Anterior Shoulder Dislocation With Bilateral Coracoid Fracture and Unilateral Long Head of Biceps Rupture.

Missed or chronic bilateral anterior shoulder dislocation is a rare presentation, usually secondary to epileptic attack. We present herein an exceptional case of this injury pattern, associated with bilateral displaced fracture of the coracoid process, and unilateral rupture of the long head of biceps. Treatment consisted of open reduction through osteotomy of the lesser tuberosity, with additional stabilization of the glenohumeral joint, using the Latarjet procedure by transposition of the coracoid fragment with its attached conjoint tendon to the antero-inferior glenoid rim. Rupture of the long head of the biceps required tenodesis. Temporary glenohumeral pin transfixation was performed for residual instability at the end of the procedure. Patients with postictal shoulder pain, discomfort, or disability should be investigated with adequate radiographs, in addition to CT scan or MRI when needed. Early diagnosis allows for safe closed reduction, and helps avoid late and more complex surgical treatment required for missed or chronic dislocations.

Outcomes of patients with metastatic gastrointestinal stromal tumors (GIST) treated with multi-kinase inhibitors other than imatinib as first-line treatment.

BACKGROUND: Imatinib is the standard first-line therapy in metastatic gastrointestinal stromal tumours (GIST). Investigational multi-kinase inhibitors (MKIs) such as nilotinib, dasatinib or masitinib have been tested as first-line therapies in phase II/III studies. This might theoretically result either in increased survival or in early emergence of resistance to approved MKIs. METHODS: To assess whether using MKIs other than imatinib in first line decreases imatinib efficacy in second line for patients with GIST, a retrospective chart review was performed from 2005 to 2011 in two French tertiary centres of patients with GIST who received investigational MKIs (in phase II/III trials) as first-line treatment, followed by imatinib as second line. RESULTS: Of 46 patients, (55% women, median age 55 years (range 24-81)), 22 (47%) had a KIT exon 11 mutation, 1 a KIT exon 9 mutation (2%), 1 a PDGFRA D842V mutation (2%). Out of 46 patients, 21 (46%) received masitinib, 17 (37%) received dasatinib and 8 (17%) received nilotinib as first-line treatment with a median progression-free survival of 18.0 months (95% CI: 8.5 to 25.5). Median time to imatinib failure was 19.7 months (95% CI: 13.5 to 29.0). Median time to second relapse was 48.7 months (95% CI: 31.2 to 72.0). Median overall survival from time of initial metastasis diagnosis was 5.7 years (95% CI: 4.5 to 7.4). CONCLUSIONS: Patients with GIST who received investigational MKIs as first-line treatment and imatinib as second line had a time to second relapse longer than that observed historically with imatinib in first line, suggesting that using MKIs other than imatinib in first line does not decrease the efficacy of subsequent treatment lines.

Patellar Sleeve Fracture in an Eight-Year-Old Girl.

The patellar sleeve fracture is a rare entity in pediatric traumatology. Its diagnosis is challenging due to its rarity and subtle radiographic finding, and it is easily missed by emergency physicians. Early recognition and treatment of this fracture is of paramount importance in order to guarantee better outcomes. We present herein a case of severely displaced patellar sleeve fracture in an eight-year-old girl, which was treated successfully by open reduction and fixation of the osteochondral fragments using anchor sutures, yielding very positive clinical outcomes at the two-year follow-up.

Long-term Outcomes of Oral Vinorelbine in Advanced, Progressive Desmoid Fibromatosis and Influence of CTNNB1 Mutational Status.

PURPOSE: Desmoid-type fibromatosis (DF) are locally aggressive neoplasms, with a need for effective systemic treatment in case of progression to avoid the short- and long-term complications of local treatments. EXPERIMENTAL DESIGN: We retrospectively analyzed the outcomes of adult patients with DF treated with oral vinorelbine (90 mg once weekly) at Gustave Roussy Cancer Institute (Villejuif, Paris, France). Only patients with documented progressive disease according to RECIST v1.1 for more than 3 months (±2 weeks) before treatment initiation were included. RESULTS: From 2009 to 2019, 90 out of 438 patients with DF were eligible for this analysis. Vinorelbine was given alone in 56 patients (62%), or concomitantly with endocrine therapy in 34 patients, for a median duration of 6.7 months. A partial response was observed in 29% and stable disease in another 57%. With a median follow-up of 52.4 months, the median time to treatment failure (TTF) was not reached. Progression-free rates at 6 and 12 months were 88.7% and 77.5%, respectively. Concomitant endocrine therapy was associated with longer TTF in women [HR, 2.16; 95% confidence interval (CI), 1.06-4.37; P = 0.03). Among 64 patients with documented CTNNB1 mutational status, p.S45F or p.S45P mutations were associated with longer TTF compared with p.T41A or wild-type tumors (HR, 2.78; 95% CI, 1.23-6.27; P = 0.04). Toxicity profile was favorable, without grade 3-4 toxicity, except for one grade 3 neutropenia. CONCLUSIONS: Oral vinorelbine is an effective, affordable, and well-tolerated regimen in patients with advanced, progressive DF. Prolonged activity was observed in patients with tumors harboring CTNNB1 p.S45F or p.S45P mutations.