[Translation into French and republication of: "Treatment of cancer-associated venous thromboembolism in patients under palliative care"]. / Traduction et republication de : « Traitement de la maladie thromboembolique veineuse associée au cancer chez les patients en soins palliatifs ¼.

Many patients with cancer require palliative care at some stage and the vast majority of people followed in palliative care are cancer patients. Patients with cancer are at high risk of venous thromboembolism (VTE), and this is particularly true during the advanced palliative phase when mobility is limited or absent. Patients with cancer in palliative care are at higher bleeding risk compared to non-cancer patients. Decisions to treat VTE or withhold anticoagulation for these patients have proven to be difficult and depend largely on an individual clinician's judgment. For this reason, we have developed a consensus proposal for appropriate management of cancer-associated thromboembolism (CAT) in patients in palliative care, which is presented in this article. The proposal was informed by the recent scientific literature retrieved through a systematic literature review. In cancer patients in advanced palliative care, the benefit/risk ratio of anticoagulation seems unfavourable with a higher haemorrhagic risk than the benefit associated with prevention of CAT recurrence and, above all, in the absence of any benefit on quality of life. For this reason, we recommend that patients should be prescribed anticoagulants on a case-by-case basis. The choice of whether to treat, and with which type of treatment, should take into account anticipated life expectancy and patient preferences, as well as clinical factors such as the estimated bleeding risk, the type of VTE experienced and the time since the VTE event.

[Translation into French and republication of: "Central venous catheter associated upper extremity deep vein thrombosis in cancer patients: Diagnosis and therapeutic management"]. / Traduction et republication de : « Thrombose veineuse profonde du membre supérieur associée à un cathéter veineux central chez les patients cancéreux : diagnostic et prise en charge thérapeutique ¼.

Catheter-related thrombosis (CRT) is a relatively frequent and potentially fatal complication arising in patients with cancer who require a central catheter placement for intravenous treatment. In everyday practice, CRT remains a challenge for management; despite its frequency and its negative clinical impact, few data are available concerning diagnosis and treatment of CRT. In particular, no diagnostic studies or clinical trials have been published that included exclusively patients with cancer and a central venous catheter (CVC). For this reason, many questions regarding optimal management of CRT remain unanswered. Due to the paucity of high-grade evidence regarding CRT in cancer patients, guidelines are derived from upper extremity DVT studies for diagnosis, and from those for lower limb DVT for treatment. This article addresses the issues of diagnosis and management of CRT through a review of the available literature and makes a number of proposals based on the available evidence. In symptomatic patients, venous ultrasound is the most appropriate choice for first-line diagnostic imaging of CRT because it is noninvasive, and its diagnostic performance is high (which is not the case in asymptomatic patients). In the absence of direct comparative clinical trials, we suggest treating patients with CRT with a therapeutic dose of either a LMWH or a direct oral factor Xa inhibitor, with or without a loading dose. These anticoagulants should be given for a total of at least 3 months, including at least 1 month after catheter removal following initiation of therapy.

[Translation into French and republication of: "Recurrent venous thromboembolism in anticoagulated cancer patients: diagnosis and treatment"]. / Traduction et republication de : « Maladie thromboembolique veineuse récidivante chez les patients cancéreux anticoagulés : diagnostic et traitement ¼.

Patients with cancer are at significantly increased risk of venous thromboembolism (VTE), due both to the impact of malignant disease itself and to the impact of certain anticancer drugs on haemostasis. This is true both for first episode venous thromboembolism and recurrence. The diagnosis and management of VTE recurrence in patients with cancer poses particular challenges, and these are reviewed in the present article, based on a systematic review of the relevant scientific literature published over the last decade. Furthermore, it is uncertain whether diagnostic algorithms for venous thromboembolism, validated principally in untreated non-cancer patients, are also valid in anticoagulated cancer patients: the available data suggests that clinical decision rules and D-dimer testing perform less well in this clinical setting. In patients with cancer, computed tomography pulmonary angiography and venous ultrasound appear to be the most reliable diagnostic tools for diagnosis of pulmonary embolism and deep vein thrombosis respectively. Options for treatment of venous thromboembolism include low molecular weight heparins (at a therapeutic dose or an increased dose), fondaparinux or oral direct factor Xa inhibitors. The choice of treatment should take into account the nature (pulmonary embolism or VTE) and severity of the recurrent event, the associated bleeding risk, the current anticoagulant treatment (type, dose, adherence and possible drug-drug interactions) and cancer progression.

[Translation into French and republication of: "Anticoagulant treatment of cancer-associated thromboembolism"]. / Traduction et republication de : « Traitement anticoagulant de la maladie veineuse thromboembolique associée au cancer ¼.

Venous thromboembolism (VTE) is a frequent and potentially fatal complication in patients with cancer. During the initial period after the thromboembolic event, a patient receiving anticoagulant treatment is exposed both to a risk of VTE recurrence and also to an elevated bleeding risk conferred by the treatment. For this reason, the choice of anticoagulant is critical. The choice should take into account patient-related factors (such as functional status, age, body mass index, platelet count and renal function), VTE-related factors (such as severity or site), cancer-related factors (such as activity and progression) and treatment related factors (such as drug-drug interactions), which all potentially influence bleeding risk, and patient preference. These should be evaluated carefully for each patient during a multidisciplinary team meeting. For most patients, apixaban or a low molecular-weight heparin is the most appropriate initial choice for anticoagulant treatment. Such treatment should be offered to all patients with active cancer for at least 6months. The patient and treatment should be re-evaluated regularly, and anticoagulant treatment changed when necessary. Continued anticoagulant treatment beyond 6months is justified if the cancer remains active or if the patient experienced recurrence of VTE in the first 6months. In other cases, the interest of continued anticoagulant treatment may be considered on an individual patient basis in collaboration with oncologists.

Rendimiento del ASAS Health Index en pacientes con Espondiloartritis de la vida real / Performance of ASAS Health Index in real life spondyloarthritis patients

Introducción: El cuestionario "Assessment of Spondyloarthritis International Society Health Index" (ASAS-HI) fue desarrollado para medir de manera global la funcionalidad y el estado de salud en pacientes con espondiloartritis (EspA). Se han propuesto puntos de corte para determinar diferentes estados de salud que fueron poco evaluados en pacientes de la vida real. Objetivos: Describir el estado de salud medido por ASAS-HI en pacientes argentinos con EspA axial (EspAax) y periférica (EspAp) en la práctica diaria y evaluar los factores asociados al pobre estado de salud. Materiales y métodos: Estudio de corte transversal, analítico y multicéntrico. Se incluyeron consecutivamente pacientes con EspAax y EspAp según criterios ASAS, de 15 centros argentinos. Análisis estadístico: Se realizó estadística descriptiva, análisis bivariado y multivariado (regresión logística múltiple) para evaluar los factores asociados al pobre estado de salud (ASAS-HI ≥12). Para analizar la validez de constructo de la herramienta se realizó correlación de Spearman entre el ASAS-HI y otros parámetros de evaluación de la enfermedad. Resultados: Se incluyeron 274 pacientes con EspA, con una edad media de 49 (±14) años y una duración mediana de la enfermedad de 62 meses (p25-75: 24-135), 155 (56,6%) de los pacientes eran de sexo masculino, 129 pacientes (47%) con EspAax y 145 (52,9%) EspAp. Según el ASAS-HI 119 pacientes (43,4%) presentaban buen estado de salud, 117 (42,7%) tenían estado de salud moderado y 38 (13.9%) pobre estado de salud. En los pacientes con EspAp el valor de ASAS-HI mediano fue de 7 (p25-75: 3-10). El ASAS-HI correlacionó positivamente con: DAS28: rho: 0.5 (p<0.001) y HAQ: rho: 0.54 (p<0.001). La variable asociada de manera independiente con pobre estado de salud fue el DAS28 (OR: 1.9, IC95% 1.1-3.4, p: 0.029). En los pacientes con EspAax el valor de ASAS-HI mediano fue de 6 (p25-75: 2.75-10). El ASAS-HI mostró correlación con: BASDAI: rho: 0.7 (p<0.001), ASDAS-ERS: rho: 0.7 (p<0,001), ASQoL: rho: 0.8 (p<0.001), BASFI rho: 0.75 (p<0.001). La variable que se asoció de manera independiente a pobre estado de salud fue el ASDAS-ERS (OR 6.6, IC95% 2-22, p 0.002). Conclusión: Un pobre estado de salud se asoció independientemente a mayor actividad de la enfermedad en pacientes con EspAax y EspAp. El ASAS-HI correlacionó con otros parámetros de la enfermedad, lo que refuerza la validez de constructo de esta nueva herramienta.

Introduction: The "Assessment of Spondyloarthritis International Society Health Index" (ASAS-HI) questionnaire was developed to globally measure function and health status in patients with spondyloarthritis (SpA). Cut-off points have been proposed to determine different health states that were poorly evaluated in real-life patients. Objectives: To describe the health status measured by ASAS-HI in Argentine patients with axial SpA (AxSpA) and peripheral SpA (SpAp) in daily practice and to evaluate the factors associated with poor health. Materials and methods: Cross-sectional, analytical and multicenter study. Patients with SpAax and SpAp were consecutively included according to ASAS criteria, from 15 Argentine centers. Statistical analysis: Descriptive statistics, bivariate and multivariate analysis (multiple logistic regression) were performed to evaluate the factors associated with poor health status (ASAS-HI ≥12). To analyze the construct validity of the tool, Spearman correlation was performed between the ASAS-HI and other disease evaluation parameters. Results: 274 patients with SpA were included, with a mean age of 49 (± 14) years and a median duration of the disease of 62 months (p25-75: 24-135), 155 (56.6%) were male, 129 patients (47%) with AxSpA and 145 (52.9%) SpAp. According to the ASAS-HI, 119 patients (43.4%) had good health, 117 (42.7%) had moderate health and 38 (13.9%) had poor health. In patients with SpAp, the mean ASAS-HI value was 7 (p25-75: 3-10). The ASAS-HI positively correlated with: DAS28: rho: 0.5 (p <0.001) and HAQ: rho: 0.54 (p <0.001). The variable independently associated with poor health status was DAS28 (OR: 1.9, 95% CI 1.1-3.4, p: 0.029). In patients with AxSpA, the mean ASAS-HI value was 6 (p25-75: 2.75-10). The ASAS-HI showed correlation with: BASDAI: rho: 0.7 (p <0.001), ASDAS-ERS: rho: 0.7 (p <0.001), ASQoL: rho: 0.8 (p <0.001), BASFI rho: 0.75 (p <0.001). The variable that was independently associated with poor health was the ASDAS-ERS (OR 6.6, 95% CI 2-22, p 0.002). Conclusion: Poor health status was independently associated with higher disease activity in patients with AxSpA and SpAp. The ASAS-HI correlated with other parameters of the disease, which reinforces the construct validity of this new tool.

[Plastic surgery and fighting: Our experience during Nagorno-Karabakh war in 2020]. / Chirurgie plastique et conflit armé : notre expérience lors du conflit au Haut-Karabakh en 2020.

INTRODUCTION: This work relates the experience of three French surgical missions in the care of the war wounded during the armed conflict in Nagorno Karabakh which took place from September 27 to November 10, 2020. MATERIALS AND METHODS: Three surgical missions were carried out in Armenia between October 2020 and January 2021. Surgeons intervened in different hospitals, at different times of the conflict and on various war wounds. RESULTS: The presence of a plastic surgeon proved to be essential in the care of war wounded, especially in delayed emergency and secondary care. The ortho-plastic treatment offered during these missions has proven to be effective in the reconstruction of limbs. These missions made it possible to introduce the induced membrane technique of Masquelet AC in Armenia. During our visit to the Yerevan burn center, we mentioned the very probable use of white phosphorus as an etiology in several of the cases analyzed. CONCLUSION: We relate the particular experience of civilian surgeons in the context of a modern armed conflict. The presence of a plastic surgeon proved to be indispensable in the care of war wounded and especially in their secondary reconstructions.

A Randomized Placebo-Controlled Efficacy Study of a Prime Boost Therapeutic Vaccination Strategy in HIV-1-Infected Individuals: VRI02 ANRS 149 LIGHT Phase II Trial.

In this placebo-controlled phase II randomized clinical trial, 103 human immunodeficiency virus type 1 (HIV-1)-infected patients under cART (combined antiretroviral treatment) were randomized 2:1 to receive either 3 doses of DNA GTU-MultiHIV B (coding for Rev, Nef, Tat, Gag, and gp160) at week 0 (W0), W4, and W12, followed by 2 doses of LIPO-5 vaccine containing long peptides from Gag, Pol, and Nef at W20 and W24, or placebo. Analytical treatment interruption (ATI) was performed between W36 to W48. At W28, vaccinees experienced an increase in functional CD4+ T-cell responses (P < 0.001 for each cytokine compared to W0) measured, predominantly against Gag and Pol/Env, and an increase in HIV-specific CD8+ T cells producing interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-α) (P = 0.001 and 0.013, respectively), predominantly against Pol/Env and Nef. However, analysis of T-cell subsets by mass cytometry in a subpopulation showed an increase in the W28/W0 ratio for memory CD8+ T cells coexpressing exhaustion and senescence markers such as PD-1/TIGIT (P = 0.004) and CD27/CD57 (P = 0.044) in vaccinees compared to the placebo group. During ATI, all patients experienced viral rebound, with the maximum observed HIV RNA level at W42 (median, 4.63 log10 copies [cp]/ml; interquartile range [IQR], 4.00 to 5.09), without any difference between arms. No patient resumed cART for CD4 cell count drop. Globally, the vaccine strategy was safe. However, a secondary HIV transmission during ATI was observed. These data show that the prime-boost combination of DNA and LIPO-5 vaccines elicited broad and polyfunctional T cells. The contrast between the quality of immune responses and the lack of potent viral control underscores the need for combined immunomodulatory strategies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01492985.)IMPORTANCE In this placebo-controlled phase II randomized clinical trial, we evaluated the safety and immunogenicity of a therapeutic prime-boost vaccine strategy using a recombinant DNA vaccine (GTU-MultiHIV B clade) followed by a boost vaccination with a lipopeptide vaccine (HIV-LIPO-5) in HIV-infected patients on combined antiretroviral therapy. We show here that this prime-boost strategy is well tolerated, consistently with previous studies in HIV-1-infected individuals and healthy volunteers who received each vaccine component individually. Compared to the placebo group, vaccinees elicited strong and polyfunctional HIV-specific CD4+ and CD8+ T-cell responses. However, these immune responses presented some qualitative defects and were not able to control viremia following antiretroviral treatment interruption, as no difference in HIV viral rebound was observed in the vaccine and placebo groups. Several lessons were learned from these results, pointing out the urgent need to combine vaccine strategies with other immune-based interventions.

Effectiveness of Therapeutic Patient Education Interventions for Older Adults with Cancer: A Systematic Review.

The incidence of cancer increases with age and demographics shows that the population of western countries is dramatically ageing. The new discipline of Geriatric Oncology is emerging aiming at providing tailored and patient-centred support to older adults with cancer. With the development of oral cancer therapy and outpatient treatments, Therapeutic Patient Education (TPE), aiming at enabling the patient and their relatives to cope with the disease in partnership with health professionals, appears to be an interesting and useful tool. The purpose of this paper is to search for evidence of the effectiveness of educational interventions for patients in older adults with cancer. The first screening found 2,617 articles, of which 150 were eligible for review. Among them, fourteen finally met the inclusion criteria: experimental and quasi-experimental studies enrolling older adults (over 65 years old), suffering from cancer and receiving an educational intervention. The types of educational intervention were diverse in these studies (support by phone and web base material). The results appear to be positive on anxiety, depression and psychological distress, patient knowledge and pain. However, data currently available on the effectiveness of a TPE program in Geriatric Oncology is lacking. Further studies are needed to assess the effectiveness of TPE programs adapted to the specific circumstances of the older adult.

[The role of electromagnetic navigation bronchoscopy in the diagnosis of peripheral pulmonary lesions]. / Place de la navigation électromagnétique endobronchique pour le diagnostic de lésions pulmonaires périphériques.

INTRODUCTION: Electromagnetic navigation bronchoscopy (ENB) is a recent, minimally invasive procedure utilized to guide endoscopic diagnostic tools to peripheral pulmonary nodules. The place of this technology among other diagnostic procedures remains uncertain. METHOD: We analyzed our 30 first months of ENB used in the diagnosis of 106 lesions in 101 patients, from June 2016 to December 2018. Follow-up and final diagnosis was completed for 95 lesions (90%). RESULTS: ENB was performed for 3.5% of all patients referred for abnormal findings on pulmonary imaging, and represented 19% of second line procedures for peripheral pulmonary lesions. Procedures were performed under general anesthesia, with a mean duration of 35min. The sensitivity of ENB was 64% (95%CI: 52-74%) for lesions with a mean diameter of 21mm, with an improvement over time (sensitivity 69% in the last 18 months). The presence of a bronchus within the lesion (bronchus sign) was associated with an increased sensitivity of 74%. Pneumothorax occurred in 5 patients (5%) of which 4 required drainage. There was no hemoptysis, and no death related to the procedure. CONCLUSION: ENB is a minimally invasive procedure reaching acceptable sensitivity in the most difficult patients. ENB can be recommended for the diagnosis of peripheral pulmonary nodules when no other procedure is successful or possible. Its use as a first choice procedure is, for the moment, limited by the cost, but must be weighed against that of non-diagnostic procedures, and the cost of complications of trans-thoracic lung biopsies.

[Endobronchial ultrasonography (EBUS) for the internist]. / Écho-endoscopie bronchique (EBUS) pour l'interniste.

Endobronchial ultrasonography (EBUS) is a recent mini-invasive technique allowing transbronchial needle aspiration (TBNA) of mediastinal lymph nodes as well as peribronchial lesions. EBUS was initially developed for lung cancer mediastinal staging. Over the years, indications for EBUS have been progressively extended to the scope of inflammatory disorders, mediastinal lymphomas, and infectious diseases. Particularly in immunosuppressed patients, including HIV-infected patients, EBUS allows the diagnosis of several diseases that involve the mediastinum, avoiding invasive surgical explorations such as mediastinoscopy or thoracoscopy. This review aims at discussing the technical aspects, and specifies indications, results, and limits of EBUS for the internist.

[Malignant infantile osteopetrosis: Case report of a 5-month-old boy]. / Ostéopétrose maligne infantile : à propos d'un cas chez un nourrisson de 5 mois.

Malignant infantile osteopetrosis is a rare congenital disease characterized by a dysfunction of osteoclasts followed by an abnormal bone densification. We report the case of a 5-month-old infant in whom this disease was suspected because of the clinical (hepatosplenomegaly, gingival hypertrophy), hematological (pancytopenia and hypocalcemia), and radiological criteria (abnormal bone density, periosteal reaction). The genetic investigation confirmed the diagnosis. Compound heterozygous mutations in the CLCN7 gene were identified, including an as yet undescribed mutation. The second mutation had already been described as being responsible for severe and irreversible neurological damage in patients with osteopetrosis. Since this patient presented severely delayed development, he was not eligible for bone marrow transplantation.

[Script concordance test for knowledge assessment of lung cancer screening]. / Évaluation des connaissances sur le dépistage du cancer par test de concordance de script.

BACKGROUND: Annual screening for lung cancer using low-dose CT-scans is associated with decreased mortality. A survey conducted in Rhône-Alpes area in France found that clinicians need education and information on this topic. Script concordance tests (SCT) are a tool for assessing clinical reasoning in situations of uncertainty. They have not previously been used in France in the context of continuing medical education. METHOD: We created a questionnaire with 5 multiple-choice questions (MCQ) and two SCT scenarios. The questionnaire was sent to all clinicians and residents who are members of French-Speaking Respiratory Society or the French Young Pulmonologist Association. RESULTS: One hundred and ninety answers were analyzed. Seventy percent stated that decreasing mortality was the best criterion for assessing the effectiveness of a cancer screening policy, and 75% that low-dose CT scan was the best test to achieve this in lung cancer screening. Forty-five percent knew the eligibility criteria of the population, and 62% that low-dose CT scan should be performed annually. Participation in tumor boards and certification in oncology were significantly associated with a better score at MCQ and SCT. SCT and MCQ scores were significantly correlated (Spearman's Rho 0.339; P<0.0001). CONCLUSION: SCT are feasible by electronic survey and seem relevant. Improving knowledge of clinicians on lung cancer screening is still critical.

[Study of parenteral iron use in a health facility and its impact in terms of hospital economics]. / Étude de l'usage du fer injectable en établissement de santé et de son impact en terme d'économie hospitalière.

INTRODUCTION: Administration of parenteral iron is a mainstay of iron deficiency treatment. Evaluation and control of this element is an issue for healthcare facilities. Study of parenteral iron use is thus to be evaluated in its impact in terms of hospital economics. MATERIALS AND METHODS: Parenteral iron administrations that took place on 2014 in our healthcare facility were retrospectively identified by pharmacists. Following data were extracted from Pharma™ and Crossway™ softwares: indication, diagnostic coding and total dose of iron received. They were then compared to the summary of product characteristics. RESULTS: Of 198 analyzed prescriptions, iron deficiency was known or suspected for 97% of patients. However, the total dose of iron administered was not in compliance for three quarters of prescriptions. Sixty-eight percent of patients appear under-dosed. Administration's traceability was found for two-thirds. Eighty-five hospital discharges did not have the right coding and 34 stays were charged like an external act instead sessions. Financial loss for the hospital is estimated at 49,300 euros. DISCUSSION AND CONCLUSION: As part of improving practice, close pharmaceutical monitoring of parenteral iron prescribed dosing regimen is essential. Effective communication with the medical information department and regular awareness raising of prescribers should also allow to give more value to this act. Hospital economics is a real tool to aid decision-making.

Medial thighplasty: Current concepts and practices.

Medial thighplasty, also known as medial thigh lift, is a procedure that has been carried out for five decades. The original "Lewis" technique has undergone many changes, and thereby been rendered widely available to plastic surgeons. Given the increasingly high number of surgical reconstructions after massive weight loss, this technique is now an integral part of a surgeon's therapeutic arsenal as he strives to meet the evolving demands of patients. The objective of this article, which is based on a comprehensive review of the literature, is to summarize current knowledge on medial thighplasty and thereby allow plastic surgeons to adopt the operating technique best suited to the deformations presented by their patients and to the overall context. The different techniques, outcomes and complications are successively discussed.

Should busulfan therapeutic range be narrowed in pediatrics? Experience from a large cohort of hematopoietic stem cell transplant children.

Busulfan, the corner stone of hematopoietic stem cell transplantation regimens, has a narrow therapeutic window. Therapeutic drug monitoring (TDM)-guided dosing to reach the conventional area under the concentration-time curve (AUC) target range of 900-1500 µmol min/L is associated with better outcomes. We report our experience with busulfan TDM in a large cohort of children. The aims were to investigate the relevance of using a more restricted therapeutic range and investigate the association between busulfan therapeutic range and clinical outcome. This study includes 138 children receiving 16 doses of intravenous busulfan, with the first dose assigned based on weight and doses adjusted to a local AUC target range of 980-1250 µmol min/L. Busulfan TDM combined with model-based dose adjustment was associated with an increased probability of AUC target attainment, for both target range: 90.8% versus 74.8% for the conventional target range and 66.2% versus 43.9% for the local target range (P<0.001). The median follow-up was 56.2 months. Event-free survival was 88.5%, overall survival was 91.5% and veno-occlusive disease occurred in 18.3% of patients. No difference was observed for clinical outcomes depending on the selected target range. Pharmacokinetic monitoring and individualization of busulfan dosage regimen are useful in improving target attainment, but using a restricted target range has no impact on clinical outcomes.

Negative prognostic value of high levels of intracellular poly(ADP-ribose) in non-small cell lung cancer.

BACKGROUND: Cisplatin-resistant non-small cell lung cancer (NSCLC) cells are often characterized by alterations in vitamin B-related metabolic processes, including the overexpression and hyperactivation of poly(ADP-ribose) polymerase 1 (PARP1) and the downregulation of pyridoxal kinase (PDXK), correlating with elevated apoptosis resistance. Low PDXK expression is an established negative prognostic factor in NSCLC. PATIENTS AND METHODS: We determined by immunohistochemistry the expression of PARP1 and the level of its product, poly(ADP-ribose) (PAR), in two independent cohorts of patients with resected NSCLC. RESULTS: Intratumoral high levels (above median) of PAR (but not PARP1 protein levels) had a negative prognostic impact in both the training (92 stage I subjects) and validation (133 stage I and II subjects) cohorts, as determined by univariate and multivariate analyses. The simultaneous assessment of PAR and PDXK protein levels improved risk stratification. CONCLUSION: NSCLC patients with high intratumoral PARP1 activity (i.e. elevated PAR levels above median) and low PDXK expression (below median) had a dismal prognosis, while patients with low PARP1 activity and high PDXK expression had a favorable outcome. Altogether, these results underscore the clinical potential and possible therapeutic relevance of these biomarkers.

Resistance Development: A Major Piece in the Jigsaw Puzzle of Tumor Size Modeling.

Mathematical models of tumor size (TS) dynamics and tumor growth inhibition (TGI) need to place more emphasis on resistance development, given its relevant implications for clinical outcomes. A deeper understanding of the underlying processes, and effective data integration at different complexity levels, can foster the incorporation of new mechanistic aspects into modeling approaches, improving anticancer drug effect prediction. As such, we propose a general framework for developing future semi-mechanistic TS/TGI models of drug resistance.

A review of mixed-effects models of tumor growth and effects of anticancer drug treatment used in population analysis.

Population modeling of tumor size dynamics has recently emerged as an important tool in pharmacometric research. A series of new mixed-effects models have been reported recently, and we present herein a synthetic view of models with published mathematical equations aimed at describing the dynamics of tumor size in cancer patients following anticancer drug treatment. This selection of models will constitute the basis for the Drug Disease Model Resources (DDMoRe) repository for models on oncology.