Cancer outpatients during the COVID-19 pandemic: what Oncoral has to teach us about medical drug use and the perception of telemedicine.

PURPOSE: The COVID-19 pandemic has disrupted healthcare access and telemedicine has been widely deployed. The aim of this study is to assess the impact of this health crisis on treatment consumption and telemedicine development in outpatients treated by oral anti-cancer agents and followed by the Oncoral hospital/community multidisciplinary program where continuity care is maintained by a pharmacist/nurse pair. METHODS: A prospective monocentric study was conducted among cancer patients who received Oncoral telephone follow-up during the 1st lockdown in France using a 56-item questionnaire which covered sociodemographic data, patient medication management, and telehealth. RESULTS: 178 patients received Oncoral follow-up during the 1st lockdown and 67.4% responded to the questionnaire. During lockdown, 9.2% of patients took medication or CAM for fatigue, 6.7% for mood alteration, 10.8% for sleep disorder, 11.7% for stress and anxiety, and 12.5% to get more energy. Homeopathy consumption was triggered by the pandemic. Habits about getting drugs from the pharmacy changed significantly (p < 0.001), while other treatment habits did not. 83% of patients were satisfied by the telephone follow-up established, 69% would be in favor of repeating this in case of a new epidemic wave. Those most in favor of using telemedicine seemed to be the youngest (p < 0.001), with several dependent children (p < 0.007), high school degree or higher education (p = 0.023), and in work (p < 0.001). CONCLUSION: Health system reorganization enables to limit the impact of the crisis on patients' drug use in oncology care. Telemedicine is a promising public health tool.

No significant clinical and radiological differences between fixed versus mobile bearing total knee replacement using the same semi-constrained implant type: a randomized controlled trial with mean 10 years follow-up.

PURPOSE: The aim of this study was to compare the long-term clinical and radiological results between fixed (FB) and mobile bearing (MB) implants with identical design from the same manufacturer. METHODS: From March 2007 to May 2009, we recruited 160 patients in a prospective, single centered, randomized controlled trial. The authors compared 81 FB total knee arthroplasty (TKA) versus 79 MB with medial compartment osteoarthritis. The same posterior stabilized HLS Noetos knee prosthesis (CORIN) was used in all patients. The two groups only differed by the tibial insert (fixed or mobile). The authors compared the postoperative Knee Society Score (KSS), the passive clinical and active radiological knee flexion, the implant survivorship, the complications, and the presence of radiolucent lines. RESULTS: At mean 10.5 years' follow-up (range 8-12.1 years) no significant differences were found in clinical scores (KSS (p = 0.54), pain score (p = 0.77), stair climbing (p = 0.44), passive maximum flexion (p = 0.5)) or for radiological analyses (maximum active radiological flexion (p = 0.06), presence of progressive radiolucent lines (5 (MB group) versus 6 (FB group); p = 0.75)) between groups. No significant difference was found in overall implant survivorship (82% (MB group) versus 78% (FB group) p = 0.58) or complication rate (p = 0.32) at the last follow-up. CONCLUSION: No significant clinical and radiological differences were found between fixed and mobile bearing TKA using the same semi-constrained implant type with comparable overall survivorship. The choice between a fixed or mobile bearing implant should be based on surgeon preference and experience with the selected implant. LEVEL OF EVIDENCE: Prospective randomized controlled trial, Level II.

The TeloDIAG: how telomeric parameters can help in glioma rapid diagnosis and liquid biopsy approaches.

BACKGROUND: In glioma, TERT promoter mutation and loss of ATRX (ATRX loss) are associated with reactivation of telomerase or alternative lengthening of telomeres (ALT), respectively, i.e. the two telomere maintenance mechanisms (TMM). Strangely, 25% of gliomas have been reported to display neither or both of these alterations. MATERIALS AND METHODS: The C-circle (CC) assay was adapted to tumor (formalin-fixed paraffin-embedded and frozen) and blood samples to investigate the TMM. RESULTS: We constructed a CC-based algorithm able to identify the TMM and reported a sensitivity of 100% and a specificity of 97.3% (n = 284 gliomas). By combining the TMM, the mutational status of the isocitrate dehydrogenase 1/2 (IDH) gene (IDHmt), and the histological grading, we propose a new classification tool: TeloDIAG. This classification defined five subtypes: tOD, tLGA, tGBM_IDHmt, tGBM, and tAIV, corresponding to oligodendroglioma, IDHmt low-grade astrocytoma, IDHmt glioblastoma, and IDHwt glioblastoma (GBM), respectively; the last class gathers ALT+ IDHwt gliomas that tend to be related to longer survival (21.2 months) than tGBM (16.5 months). The TeloDIAG was 99% concordant with the World Health Organization classification (n = 312), and further modified the classification of 55 of 144 (38%) gliomas with atypical molecular characteristics. As an example, 14 of 69 (20%) of TERTwt, ATRXwt, and IDHwt GBM were actually tAIV. Outstandingly, CC in blood sampled from IDHmt astrocytoma patients was detected with a sensitivity of 56% and a specificity of 97% (n = 206 gliomas and 30 healthy donors). CONCLUSION: The TeloDIAG is a new, simple, and effective tool helping in glioma diagnosis and a promising option for liquid biopsy.

Low expression of ANT1 confers oncogenic properties to rhabdomyosarcoma tumor cells by modulating metabolism and death pathways.

Rhabdomyosarcoma (RMS) is the most frequent form of pediatric soft-tissue sarcoma. It is divided into two main subtypes: ERMS (embryonal) and ARMS (alveolar). Current treatments are based on chemotherapy, surgery, and radiotherapy. The 5-year survival rate has plateaued at 70% since 2000, despite several clinical trials. RMS cells are thought to derive from the muscle lineage. During development, myogenesis includes the expansion of muscle precursors, the elimination of those in excess by cell death and the differentiation of the remaining ones into myofibers. The notion that these processes may be hijacked by tumor cells to sustain their oncogenic transformation has emerged, with RMS being considered as the dark side of myogenesis. Thus, dissecting myogenic developmental programs could improve our understanding of RMS molecular etiology. We focused herein on ANT1, which is involved in myogenesis and is responsible for genetic disorders associated with muscle degeneration. ANT1 is a mitochondrial protein, which has a dual functionality, as it is involved both in metabolism via the regulation of ATP/ADP release from mitochondria and in regulated cell death as part of the mitochondrial permeability transition pore. Bioinformatics analyses of transcriptomic datasets revealed that ANT1 is expressed at low levels in RMS. Using the CRISPR-Cas9 technology, we showed that reduced ANT1 expression confers selective advantages to RMS cells in terms of proliferation and resistance to stress-induced death. These effects arise notably from an abnormal metabolic switch induced by ANT1 downregulation. Restoration of ANT1 expression using a Tet-On system is sufficient to prime tumor cells to death and to increase their sensitivity to chemotherapy. Based on our results, modulation of ANT1 expression and/or activity appears as an appealing therapeutic approach in RMS management.

Cutaneous adverse events: a predictor of tumour response under anti-PD-1 therapy for metastatic melanoma, a cohort analysis of 189 patients.

INTRODUCTION: Cutaneous adverse events (AEs) are the most prevalent toxicity under checkpoint inhibitors in clinical trials. In 'real-life' conditions of use, skin toxicities under anti-PD-1 have not been described to date in a large cohort. The objective of this study was to determine the clinical features of skin toxicities in patients with advanced melanoma receiving anti-PD-1 therapy under 'real-life' conditions of use. Secondary objectives were to evaluate the characteristics of patients with skin toxicities and to analyse associated extra-cutaneous toxicities, progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS: Advanced melanoma patients treated with nivolumab or pembrolizumab between August 2014 and October 2017 were included. Patients lost to follow-up or receiving anti-PD-1 as part of a clinical trial were excluded. RESULTS: One hundred and eighty-nine patients with metastatic melanoma (with 109 men (57.7%) were included. Cutaneous AE occurred in 39 patients (20.6%). The three most prevalent cutaneous AEs were skin eruption (macular-papular or eczematous) (n = 18, 9.5%), vitiligo (n = 16; 8.5%) and isolated pruritus (n = 5, 2.6%). Grade 3-4 skin toxicity was diagnosed in five patients (2.6%). Atopy (28.2% vs. 12.0%; P = 0.024), hypereosinophilia (20.5% vs. 8.7%; P = 0.046), thyroiditis (17.9% vs. 4.7%; P = 0.011) and renal toxicity (15.4% vs. 4%; P = 0.019) were significantly associated with cutaneous AE. Patients with skin eruption (log-rank = 0.001), vitiligo (log-rank = 0.001) and any type of cutaneous AE (log-rank < 0.001) had a better overall survival. CONCLUSIONS: Cutaneous AEs are frequent and often manageable toxicity and were a predictor of tumour response in melanoma patients under anti-PD-1 therapy in this cohort.

[Anticoagulation impact on bleeding risk during HoLEP: Monocentric study of 156 patients]. / Impact des anticoagulants sur le risque hémorragique au cours de l'HoLEP : étude monocentrique de 156 patients.

OBJECTIVE: Compare the length of hospital stay and the complications after HoLEP between three groups of patients: a control group, a group with antiplatelet therapy, a group with anticoagulation therapy. MATERIALS: Retrospective cohort study that included all consecutive patients who underwent HoLEP for prostatic hyperplasia in our center from may 2013 to may 2016. Anticoagulated patients and patients under clopidogrel had respectively a relay with heparine and aspirine. Patients were seen after surgery at 1 and 3 months. RESULTS: A hundred and fifty six patients were analysed, mean age was 70.7 years (DS 6.8), mean prostate volume 88.8g (DS 34.1). 106 patients were in the control group, 34 had antiplatelet therapy and 16 had anticoagulation therapy. There were no difference between the 3 groups for mean age, mean prostatic volume, PSA. There was also no difference for length of intervention, irrigated volume and length of morcellation between the three groups. There were no difference between patients in the control group and patients with antiplatelet therapy for length of hospital stay (2.1 days vs 2.0 days), lenght of urethral catheterization (1.6 days vs 1.5 days). There was a statistical difference between patients in the control group and patients with anticoagulation therapy for lenght of hospital stay (2.0 days vs 4.4 days; P=0.01), length of bladder irrigation (0.9 day vs 1.8 days; P=0.01), lenght of urethral catheterization (1.6 days vs 3.5 days; P=0.01). Transfusion rate was 18.75% (n=3) for patients with anticoagulation, 2.9% (n=1) for patients under antiplatelet therapy and 0.9% (n=1) for patients in the control group. CONCLUSION: Anticoagulation during HoLEP is a valid option but need to be proceed with carefully management. LEVEL OF PROOF: 4.

No impact on long-term survival of prolonged ICU stay and re-admission for patients undergoing cytoreductive surgery with HIPEC.

BACKGROUND: Cytoreductive surgery (CRS) and Hyperthermic intraperitoneal chemotherapy (HIPEC) are promising new approaches of peritoneal metastases. However these surgical procedures are associated with a high morbidity rate thus intensive care (IC) management following serious complications may be warranted for these patients. The impact of the prolonged IC stay or re-admission on long-term survival remains unknown. METHODS: We retrospectively analysed 122 consecutive HIPEC procedures over a one year period (2010-2011) in a single academic hospital. We analysed complications that would lead to prolonged stay or re-admission into ICU and analysed long term follow-up in patients whether they required intensive care (ICU group) or not (Control group). RESULTS: ICU group represented 26.2% of the cohort mainly due to septic or haemorrhagic shock. Among them acute kidney injury and respiratory failure were present in 50% and 47% respectively. Cohort overall mortality rate was of 5.7%. Patients were followed for 4 years and survival analysis was performed adjusting for main confounding factors in a Cox survival model. Survival was not different between groups, with a median survival of 38 months [32; 44] vs. 33 months [26; 39] in the ICU group and Control group respectively. CONCLUSION: Prolonged stay or re-admission into ICU does not seem to statistically impact long term prognosis of patients undergoing CRS with HIPEC.

Posterior mandibular widening secondary to advancement sagittal split osteotomy: A retrospective study.

INTRODUCTION: Patients sometimes spontaneously report a modification of the width of their lower face after an advancement bilateral sagittal split osteotomy (ABSSO). The main goal of our study was to assess the variation of the bigonial distance (BGD) before and after ABSSO in a group of patients. The second goal was to look for a possible relation between the variation of BGD and the amount of mandibular advancement. MATERIALS AND METHODS: We conducted a retrospective radiological study on patients who underwent an isolated ABSSO (Obwegeser-Dal Pont II type osteotomy) for a class II malocclusion in our department over a 26 months period. The measures were made on standardized frontal and lateral teleradiographies taken before, one day and one year postoperatively. RESULTS: Fifty patients (36 females, 14 males; mean age: 24) could be included. BGD was significantly increased one day (+9.8mm, P<10(-3)) and one year after surgery (+4mm, P<10(-3)). There was no relation between the amount of mandibular advancement and the increase of BGD. DISCUSSION: Our results suggest that ABSSO is responsible for posterior mandibular enlargement which must be taken into account during the aesthetic preoperative assessment. Further studies are mandatory to identify the risk factors for this phenomenon.

Open side-to-side repair for non-repairable tendon-to-bone rotator cuff tear. Clinical and anatomic outcome at a mean 5 years' follow-up.

INTRODUCTION: Anatomical tendon-to-bone repair of retracted rotator cuff tear is a difficult challenge given the high rate of recurrence. HYPOTHESIS: The study hypothesis was that side-to-side repair of U-shaped retracted tear allows tendon healing with satisfactory medium-term clinical results. MATERIALS AND METHODS: Between 1999 and 2007, 35 patients (mean age 53.5 years) were operated on with this open technique. On the De Orio and Cofield classification, tendon lesions were medium in 5 cases, large in 25 and massive in 5. Subacromial space was in all cases greater than 7 mm. Fatty infiltration grade was less than or equal to 2 on Goutallier's classification in all cases except for 1 grade3 (supraspinatus only). At last follow-up, patients were assessed clinically (Constant score) and radiographically. Tendon healing was assessed by ultrasound (31 cases) or CT-arthrography (4 cases). RESULTS: Mean follow-up was 60 months. Constant score improved significantly, from 64.7 ± 10 preoperatively to 77.1 ± 14 postoperatively (P < 0.05). Recurrence rate was 17.1%. Subacromial space was < 6 mm postoperatively in 2 cases. DISCUSSION: Side-to-side repair, bringing the posterior cuff onto the anterior edge of the tear, allowed tension-free repair of retracted tear if the preoperative reparability criteria are met: subacromial space equal to or greater than 7 mm, and absence of fatty infiltration significantly greater than grade 2 on the Goutallier classification. Under these conditions, clinical and anatomical results were satisfactory at a mean 5 years' follow-up. LEVEL OF EVIDENCE: IV, retrospective.

Systemic lupus erythematosus-associated acute transverse myelitis: manifestations, treatments, outcomes, and prognostic factors in 20 patients.

BACKGROUND: Transverse myelitis is a rare complication of systemic lupus erythematosus (SLE). This retrospective multicentre study identifies the prognostic factors in a relatively large patient series. PATIENTS AND METHODS: Twenty patients fulfilled the SLE criteria of the ACR classification and the Transverse Myelitis Consortium Working Group. A severe neurological flare was defined as muscle strength grade <3/5 in more than half the muscle groups at the motor neurological level. Inability to run or another significant ambulation-unrelated disability was considered as 'unfavourable neurological outcome'. RESULTS: Myelitis was the first SLE symptom in 12 patients; in the eight others, it occurred 8.6 years (median delay) after SLE onset. Eleven patients presented severe neurological impairments. The treatment included corticosteroids in all patients associated with intravenous cyclophosphamide in 11 and/or hydroxychloroquine in 14. Unfavourable outcomes were observed in 53% of the patients at six months and in 28% at end of follow-up (median: 5.9 years). An initial severe neurological impairment and no cyclophosphamide use were associated with unfavourable neurological outcomes at six months and at end of follow-up, respectively. CONCLUSION: Transverse myelitis may reveal SLE or occur more than 10 years after SLE diagnosis. The initial severity of the neurological flare (with paraplegia) is the main prognostic marker. The study provides arguments for cyclophosphamide use.

Role of obesity on the thickness of primary cutaneous melanoma.

BACKGROUND: Thick primary cutaneous melanoma (PCM) is associated with older age, male sex, being single, a low educational level, self-detection and general practice detection, nodular melanoma (NM) and acral lentiginous melanoma (ALM) types; and are found in the head-neck and lower limb locations. Obesity plays a direct role on melanoma tumour growth, as it has been shown in animal models, but its role in the thickness of PCM remains unknown. OBJECTIVES: We investigated the impact of obesity on the thickness of invasive PCM. METHODS: A cross-sectional study was performed in a prospective cohort for which we collected several clinical and histological data already known to be associated with thick PCM and the Body Mass Index from new cases of invasive PCM which were referred to the dermatology department in Valence. RESULTS: Four hundred and twenty-seven patients were studied. In an univariate analysis, thick PCM was associated with low educational level, obesity, identification by the patient or the general practitioner (GP), location on the cephalic extremity, in a non-visible area of the body, the NM and ALM type, and an ulceration. In a multivariate analysis, NM, ulceration, topography of the melanoma and identification of the melanoma by the patient or GP were significantly associated with thick melanoma. When including only clinical features in the model, low educational level, mode of melanoma identification and obesity were significantly associated with a risk of thick melanoma. CONCLUSIONS: Obesity is a clinical independent risk factor of thick PCM. For health policies, governments should pay greater attention to detect melanoma in obese patients. Our results encourage the basic research on tumoural growth mechanisms due to obesity in melanoma.

French adaptation of the new Knee Society Scoring System for total knee arthroplasty.

INTRODUCTION: In November 2011, the Knee Society published its new KSS score to evaluate objective clinical data and also patient expectations, satisfaction and knee function during various physical activities before and after total knee arthroplasty (TKA). We undertook the French cross-cultural adaptation of this scoring system according to current recommendations. HYPOTHESIS: The French version of the new KSS score is a consistent, feasible, reliable and discriminating score. PATIENTS AND METHODS: Eighty patients with knee osteoarthritis were recruited from two centers: one group of 40 patients had a TKA indication, while the other group of 40 patients had an indication for conservative treatment. After the new KSS score was translated and back-translated, it was compared to three other validated instruments (KOOS, AMIQUAL and SF-12) to determine construct validity, discriminating power, feasibility in terms of response rate and existence of floor or ceiling effect, internal consistency with Chronbach's alpha and reliability based on reproducibility and sensitivity to change (responsiveness). RESULTS: Due to missing data, two cases were eliminated. We found that the score could discriminate between groups; it had a nearly 100% response rate, a ceiling effect in the "expectations" domain, satisfactory Chronbach's alpha, excellent reproducibility and good responsiveness. DISCUSSION: These results confirm that the French version of the new KSS score is reliable, feasible, discriminating, consistent and responsive. The novelty of this scoring system resides in the "expectations" and "satisfaction" domains, its availability as a self-assessment questionnaire and the evaluation of function during various activities. LEVEL OF PROOF, TYPE OF STUDY: Level III.

High level of soluble programmed cell death ligand 1 in blood impacts overall survival in aggressive diffuse large B-Cell lymphoma: results from a French multicenter clinical trial.

The dosage of soluble programmed cell death ligand 1 (sPD-L1) protein in the blood of adults with cancer has never been performed in a prospective patient cohort. We evaluated the clinical impact of sPD-L1 level measured at the time of diagnosis for newly diagnosed diffuse large B-cell lymphoma (DLBCL). Soluble PD-L1 was measured in the plasma of 288 patients enrolled in a multicenter, randomized phase III trial that compared R-high-dose chemotherapy with R-CHOP. The median follow-up was 41.4 months. A cutoff of 1.52 ng/ml of PD-L1 level was determined and related to overall survival (OS). Patients with elevated sPD-L1 experienced a poorer prognosis with a 3-year OS of 76% versus 89% (P<0.001). Considering clinical characteristics, the multivariate analysis retained this biomarker besides bone marrow involvement and abnormal lymphocyte-monocyte score as independently related to poor outcome. sPD-L1 was detectable in the plasma and not in the serum, found elevated in patients at diagnosis compared with healthy subjects and its level dropped back to normal value after CR. The intention-to-treat analysis showed that elevated sPD-L1 was associated with a poorer prognosis for patients randomized within the R-CHOP arm (P<0.001). Plasma PD-L1 protein is a potent predicting biomarker in DLBCL and may indicate usefulness of alternative therapeutic strategies using PD-1 axis inhibitors.

[Surgery of high-grade gliomas guided by fluorescence: a retrospective study of 22 patients]. / Exérèse neurochirurgicale optimale des gliomes de haut grade guidée par fluorescence : mise au point à partir d'une série rétrospective de 22 patients.

BACKGROUND AND PURPOSE: Optimal surgical resection improves the prognosis of glioblastomas. However, this goal is far from being achieved due to its invasive nature. Several studies have already shown the efficacy of fluorescence-guided surgery, in improving the quality of resection of glioblastoma. We report herein our experience through a retrospective serie and describe the principles, limitations and advantages of this technique. METHODS: Between 2006 and 2009, 22 patients underwent resection of a glioblastoma guided by fluorescence. Following operations, all patients underwent sequential clinical examination and radiological monitoring using multimodal MRI. The extent of resection was assessed by the surgeon during the procedure and by the radiologist on MRI. The curves of progression-free clinical survival (SSP) and overall survival (SG) were analyzed. The prognostic value of the extent of resection was studied. RESULTS: We obtained 68.2% of complete resection according to the absence of residual fluorescence as assessed by the surgeon, and 75% according to the absence of residual tumor on early MRI. The median SSP was 10.75 months and the median SG was 17 months. Complete tumoral resection confirmed by loss of fluorescence significatively increases the median SSP of 6.7 months to 12.9 months (p=0.001559) and the median SG of 12.3 months to 20.9 months (p=0.000559). After 1 year, 81.8% of patients were still alive. CONCLUSIONS: Our study confirms the use of fluorescence as an effective method to allow optimal resection of glioblastoma. In addition to neuronavigation, surgical experience, vision and proprioception, fluorescence contributes to achieve a complete tumor resection.

Rationale for carbon ion therapy in high-grade glioma based on a review and a meta-analysis of neutron beam trials.

PURPOSE: The standard treatment of high-grade glioma is still unsatisfactory: the 2-year survival after radiotherapy being only 10-25%. A high linear energy transfer (LET) ionising radiotherapy has been used to overcome tumour radioresistance. An overview of the field is needed to justify future prospective controlled studies on carbon ion therapy. MATERIALS AND METHODS: A meta-analysis of clinical trials on neutron beam therapy and a literature review of clinical investigations on light ion use in high-grade glioma were carried out. RESULTS: Four randomised controlled trials on neutron beam therapy were retained. The meta-analysis showed a non-significant 6% increase of two-year mortality (Relative risk [RR]=1.06 [0.97-1.15]) in comparison with photon therapy. Two phase I/II trials on carbon and neon ion therapy reported for glioblastoma 10% and 31% two-year overall survivals and 13.9 and 19.0 months median survivals, respectively. CONCLUSION: This meta-analysis suggests that neutron beam therapy does not improve the survival of high-grade glioma patients while there is no definitive conclusion yet regarding carbon therapy. The ballistic accuracy and the improved biological efficacy of carbon ions renew the interest in prospective clinical trials on particle beam radiotherapy of glioma and let us expect favourable effects of dose escalation on patients' survival.