A New Option for Pain Prevention Using a Therapeutic Virtual Reality Solution for Bone Marrow Biopsy (REVEH Trial): Open-Label, Randomized, Multicenter, Phase 3 Study.

BACKGROUND: Evidence regarding the analgesic effect of distraction through immersion in virtual reality (VR) for care-induced pain has been documented in several phase 2 trials, but comparison with standard treatments in large, randomized studies is needed. OBJECTIVE: In this open-label, multicenter, randomized, phase 3 trial, we evaluated the safety and efficacy of a novel VR therapy solution for distraction in the context of bone marrow biopsy. METHODS: Bliss is a VR software with 4 imaginary interactive environments in 3 dimensions with binaural sound (head-mounted display). Efficacy regarding pain intensity was evaluated using a visual analog scale (VAS; score from 0 to 10) immediately after the biopsy. Secondary end points were anxiety and tolerance. Modified intention-to-treat analysis was performed. RESULTS: Overall, 126 patients with previously documented untreated or suspected malignant hemopathy between September 6, 2018, and May 18, 2020, were randomly assigned in a 1:1 ratio to receive pain prevention with a mixture of nitrous oxide/oxygen (MEOPA; n=63) or VR (n=63) before and during the bone marrow biopsy. We excluded 8 patients from the final analysis (3 in the MEOPA group and 5 in the VR group). All patients received local anesthesia (lidocaine) before biopsy. Follow-up was limited to 1 month after the biopsy. Participants' median age was 65.5 (range 18-87) years, and 54.2% (64/118) of patients were male. The average pain intensity was 3.5 (SD 2.6, 95% CI -1.6 to 8.6) for the MEOPA group and 3.0 (SD 2.4, 95% CI -1.7 to 7.7) for the VR group, without any significant differences in age, sex, center, and hemopathy (P=.26). Concerning anxiety, 67.5% (79/117; fear of pain questionnaire) of the patients were afraid before the biopsy, and anxiety scores were moderate to very high in 26.3% (30/114; revised Spielberger State-Trait Anxiety Inventory questionnaire) of the patients before the biopsy and 9.0% (10/114) after the biopsy for all patients, without a significant difference between the 2 groups (P=.83). Immersion in VR was well tolerated by the majority (54/57, 95%) of patients in the VR group. CONCLUSIONS: The intensity of pain did not significantly differ between both arms. VR was well tolerated, and the satisfaction of patients, nurses, and physicians was very high. VR could be an alternative treatment in case of contraindication or intolerance to MEOPA. TRIAL REGISTRATION: ClinicalTrials.gov NCT03483194; https://clinicaltrials.gov/ct2/show/NCT03483194.

Assessing a New Prescreening Score for the Simplified Evaluation of the Clinical Quality and Relevance of eHealth Apps: Instrument Validation Study.

BACKGROUND: In 2020, more than 250 eHealth solutions were added to app stores each day, or 90,000 in the year; however, the vast majority of these solutions have not undergone clinical validation, their quality is unknown, and the user does not know if they are effective and safe. We sought to develop a simple prescreening scoring method that would assess the quality and clinical relevance of each app. We designed this tool with 3 health care stakeholder groups in mind: eHealth solution designers seeking to evaluate a potential competitor or their own tool, investors considering a fundraising candidate, and a hospital clinician or IT department wishing to evaluate a current or potential eHealth solution. OBJECTIVE: We built and tested a novel prescreening scoring tool (the Medical Digital Solution scoring tool). The tool, which consists of 26 questions that enable the quick assessment and comparison of the clinical relevance and quality of eHealth apps, was tested on 68 eHealth solutions. METHODS: The Medical Digital Solution scoring tool is based on the 2021 evaluation criteria of the French National Health Authority, the 2022 European Society of Medical Oncology recommendations, and other provided scores. We built the scoring tool with patient association and eHealth experts and submitted it to eHealth app creators, who evaluated their apps via the web-based form in January 2022. After completing the evaluation criteria, their apps obtained an overall score and 4 categories of subscores. These criteria evaluated the type of solution and domain, the solution's targeted population size, the level of clinical assessment, and information about the provider. RESULTS: In total, 68 eHealth solutions were evaluated with the scoring tool. Oncology apps (22%, 20/90) and general health solutions (23%, 21/90) were the most represented. Of the 68 apps, 32 (47%) were involved in remote monitoring by health professionals. Regarding clinical outcomes, 5% (9/169) of the apps assessed overall survival. Randomized studies had been conducted for 21% (23/110) of the apps to assess their benefit. Of the 68 providers, 38 (56%) declared the objective of obtaining reimbursement, and 7 (18%) out of the 38 solutions seeking reimbursement were assessed as having a high probability of reimbursement. The median global score was 11.2 (range 4.7-17.4) out of 20 and the distribution of the scores followed a normal distribution pattern (Shapiro-Wilk test: P=.33). CONCLUSIONS: This multidomain prescreening scoring tool is simple, fast, and can be deployed on a large scale to initiate an assessment of the clinical relevance and quality of a clinical eHealth app. This simple tool can help a decision-maker determine which aspects of the app require further analysis and improvement.

Real-world Implementation of an eHealth System Based on Artificial Intelligence Designed to Predict and Reduce Emergency Department Visits by Older Adults: Pragmatic Trial.

BACKGROUND: Frail older people use emergency services extensively, and digital systems that monitor health remotely could be useful in reducing these visits by earlier detection of worsening health conditions. OBJECTIVE: We aimed to implement a system that produces alerts when the machine learning algorithm identifies a short-term risk for an emergency department (ED) visit and examine health interventions delivered after these alerts and users' experience. This study highlights the feasibility of the general system and its performance in reducing ED visits. It also evaluates the accuracy of alerts' prediction. METHODS: An uncontrolled multicenter trial was conducted in community-dwelling older adults receiving assistance from home aides (HAs). We implemented an eHealth system that produces an alert for a high risk of ED visits. After each home visit, the HAs completed a questionnaire on participants' functional status, using a smartphone app, and the information was processed in real time by a previously developed machine learning algorithm that identifies patients at risk of an ED visit within 14 days. In case of risk, the eHealth system alerted a coordinating nurse who could then inform the family carer and the patient's nurses or general practitioner. The primary outcomes were the rate of ED visits and the number of deaths after alert-triggered health interventions (ATHIs) and users' experience with the eHealth system; the secondary outcome was the accuracy of the eHealth system in predicting ED visits. RESULTS: We included 206 patients (mean age 85, SD 8 years; 161/206, 78% women) who received aid from 109 HAs, and the mean follow-up period was 10 months. The HAs monitored 2656 visits, which resulted in 405 alerts. Two ED visits were recorded following 131 alerts with an ATHI (2/131, 1.5%), whereas 36 ED visits were recorded following 274 alerts that did not result in an ATHI (36/274, 13.4%), corresponding to an odds ratio of 0.10 (95% IC 0.02-0.43; P<.001). Five patients died during the study. All had alerts, 4 did not have an ATHI and were hospitalized, and 1 had an ATHI (P=.04). In terms of overall usability, the digital system was easy to use for 90% (98/109) of HAs, and response time was acceptable for 89% (98/109) of them. CONCLUSIONS: The eHealth system has been successfully implemented, was appreciated by users, and produced relevant alerts. ATHIs were associated with a lower rate of ED visits, suggesting that the eHealth system might be effective in lowering the number of ED visits in this population. TRIAL REGISTRATION: clinicaltrials.gov NCT05221697; https://clinicaltrials.gov/ct2/show/NCT05221697.

How Should Oncologists Choose an Electronic Patient-Reported Outcome System for Remote Monitoring of Patients With Cancer?

Electronic patient-reported outcome (ePRO) systems for symptom monitoring in patients with cancer have shown quality of life and survival benefits in controlled trials. They are beginning to be used in routine oncology practice. Many software developers provide software solutions for clinicians, but how should clinicians decide which system to use? We propose a synthesis of the main questions regarding the effectiveness, safety, and functionality of an ePRO system that a clinician should ask software providers to assist in the selection of a software product in order to obtain the best value tools for their patients and their practice.

Correction: Olfactory Training and Visual Stimulation Assisted by a Web Application for Patients With Persistent Olfactory Dysfunction After SARS-CoV-2 Infection: Observational Study.

[This corrects the article DOI: 10.2196/29583.].

Olfactory Training and Visual Stimulation Assisted by a Web Application for Patients With Persistent Olfactory Dysfunction After SARS-CoV-2 Infection: Observational Study.

BACKGROUND: Persistent olfactory dysfunction is a significant complication of SARS-CoV-2 infection. Olfactory training involving aromatic oils has been recommended to improve olfactory recovery, but quantitative data are missing. OBJECTIVE: We aimed to quantify the benefit of olfactory training and visual stimulation assisted by a dedicated web application for patients who experienced olfactory dysfunction for ≥1 month. METHODS: We performed an observational, real-life, data-based study on a cohort of patients who experienced at least 1 month of persistent olfactory dysfunction between January 30 and March 26, 2021. An analysis was performed after a mean olfactory training time of 4 weeks, and at least 500 patients were assessable for primary outcome assessment. Participants exposed themselves twice daily to odors from 4 high-concentration oils and visual stimulation assisted by a dedicated web application. Improvement was defined as a 2-point increase on a 10-point, self-assessed olfactory visual analogue scale. RESULTS: In total, 548 patients were assessable for primary outcome assessment. The mean baseline, self-assessed olfactory score was 1.9 (SD 1.7), and this increased to 4.6 (SD 2.8) after a mean olfactory training time of 27.7 days (SD 17.2). Olfactory training was associated with at least a 2-point increase in 64.2% (352/548) of patients. The rate of patients' olfactory improvement was higher for patients who trained for more than 28 days than that rate for patients who trained for less than 28 days (73.3% vs 59%; P=.002). The time to olfactory improvement was 8 days faster for patients with hyposmia compared to the time to improvement for patients with anosmia (P<.001). This benefit was observed regardless of the duration of the olfactory dysfunction. CONCLUSIONS: Olfactory training and visual stimulation assisted by a dedicated web application was associated with significant improvement in olfaction, especially after 28 days of olfactory training.

Analysis of COVID-19 Transmission Sources in France by Self-Assessment Before and After the Partial Lockdown: Observational Study.

BACKGROUND: We developed a questionnaire on a web application for analyzing COVID-19 contamination circumstances in France during the second wave of the pandemic. OBJECTIVE: This study aims to analyze the impact on contamination characteristics before and after the second partial lockdown in France to adapt public health restrictions to further prevent pandemic surges. METHODS: Between December 15 and 24, 2020, after a national media campaign, users of the sourcecovid.fr web application were asked questions about their own or a close relative's COVID-19 contamination after August 15, 2020, in France. The data of the contamination's circumstances were assessed and compared before and after the second partial lockdown, which occurred on October 25, 2020, during the second wave of the pandemic and was ongoing on December 24, 2020. RESULTS: As of December 24, 2020, 441,000 connections on the web application were observed. A total of 2218 questionnaires were assessable for analysis. About 61.8% (n=1309) of the participants were sure of their contamination origin, and 38.2% (n=809) thought they knew it. The median age of users was 43.0 (IQR 32-56) years, and 50.7% (n=1073) were male. The median incubation time of the assessed cohort was 4.0 (IQR 3-5) days. Private areas (family's or friend's house) were the main source of contamination (1048/2090, 50.2%), followed by work colleagues (579/2090, 27.7%). The main time of day for the contamination was the evening (339/961, 35.3%) before the lockdown and was reduced to 18.2% (86/473) after the lockdown (P<.001). The person who transmitted the virus to the user before and after the lockdown was significantly different (P<.001): a friend (382/1317, 29% vs 109/773, 14.1%), a close relative (304/1317, 23.1% vs 253/773, 32.7%), or a work colleague (315/1317, 23.9% vs 264/773, 34.2%). The main location where the virus was transmitted to the users before and after the lockdown was significantly different too (P<.001): home (278/1305, 21.3% vs 194/760, 25.5%), work (293/1305, 22.5% vs 225/760, 29.6%), collective places (430/1305, 33% vs 114/760, 15%), and care centers (58/1305, 4.4% vs 74/760, 9.7%). CONCLUSIONS: Modalities of transmissions significantly changed before and after the second lockdown in France. The main sources of contamination remained the private areas and with work colleagues. Work became the main location of contamination after the lockdown, whereas contaminations in collective places were strongly reduced. TRIAL REGISTRATION: ClinicalTrials.gov NCT04670003; https://clinicaltrials.gov/ct2/show/NCT04670003.

A Self-Assessment Web-Based App to Assess Trends of the COVID-19 Pandemic in France: Observational Study.

BACKGROUND: We developed a self-assessment and participatory web-based triage app to assess the trends of the COVID-19 pandemic in France in March 2020. OBJECTIVE: We compared daily large-scale RT-PCR test results to monitor recent reports of anosmia through a web-based app to assess the dynamics of emergency department visits, hospitalizations, and intensive care unit (ICU) admissions among individuals with COVID-19 in France. METHODS: Between March 21 and November 18, 2020, users of the maladiecoronavirus.fr self-triage app were asked questions about COVID-19 symptoms. Data on daily hospitalizations, large-scale positive results on RT-PCR tests, emergency department visits, and ICU admission of individuals with COVID-19 were compared to data on daily reports of anosmia on the app. RESULTS: As of November 18, 2020, recent anosmia was reported 575,214 times from among approximately 13,000,000 responses. Daily anosmia reports during peak engagement with the app on September 16, 2020, were spatially correlated with the peak in daily COVID-19-related hospitalizations in November 2020 (Spearman rank correlation coefficient [ρ]=0.77; P<.001). This peak in daily anosmia reports was observed primarily among young adults (age range 18-40 years), being observed 49 days before the peak of hospitalizations that corresponded to the first wave of infections among the young population, followed by a peak in hospitalizations among older individuals (aged ≥50 years) in November 2020. The reduction in the daily reports of anosmia associated with the peaks in the number of cases preceded the reduction in daily hospitalizations by 10 and 9 days during the first and the second waves of infection, respectively, although the reduction in the positivity rates on RT-PCR tests preceded the reduction in daily hospitalizations by only 2 days during the second wave of infections. CONCLUSIONS: Data on daily reports of anosmia collected through a nationwide, web-based self-assessment app can be a relevant tool to anticipate surges in outbreaks, hospitalizations, and ICU admission during the COVID-19 pandemic. TRIAL REGISTRATION: ClinicalTrials.gov NCT04331171; https://clinicaltrials.gov/ct2/show/NCT04331171.

Implementation of a Self-Triage Web Application for Suspected COVID-19 and Its Impact on Emergency Call Centers: Observational Study.

BACKGROUND: We developed a self-triage web application for COVID-19 symptoms, which was launched in France in March 2020, when French health authorities recommended all patients with suspected COVID-19 call an emergency phone number. OBJECTIVE: Our objective was to determine if a self-triage tool could reduce the burden on emergency call centers and help predict increasing burden on hospitals. METHODS: Users were asked questions about their underlying conditions, sociodemographic status, postal code, and main COVID-19 symptoms. Participants were advised to call an emergency call center if they reported dyspnea or complete loss of appetite for over 24 hours. Data on COVID-19-related calls were collected from 6 emergency call centers and data on COVID-19 hospitalizations were collected from Santé Publique France and the French Ministry of Health. We examined the change in the number of emergency calls before and after the launch of the web application. RESULTS: From March 17 to April 2, 2020, 735,419 questionnaires were registered in the study area. Of these, 121,370 (16.5%) led to a recommendation to call an emergency center. The peak number of overall questionnaires and of questionnaires leading to a recommendation to call an emergency center were observed on March 22, 2020. In the 17 days preceding the launch of the web application, emergency call centers in the study area registered 66,925 COVID-19-related calls and local hospitals admitted 639 patients for COVID-19; the ratio of emergency calls to hospitalizations for COVID-19 was 104.7 to 1. In the 17 days following the launch of the web application, there were 82,347 emergency calls and 6009 new hospitalizations for COVID-19, a ratio of 13.7 calls to 1 hospitalization (chi-square test: P<.001). CONCLUSIONS: The self-triage web application launch was followed by a nearly 10-fold increase in COVID-19-related hospitalizations with only a 23% increase in emergency calls. The peak of questionnaire completions preceded the peak of COVID-19-related hospitalizations by 5 days. Although the design of this study does not allow us to conclude that the self-triage tool alone contributed to the alleviation of calls to the emergency call centers, it does suggest that it played a role, and may be used for predicting increasing burden on hospitals. TRIAL REGISTRATION: ClinicalTrials.gov NCT04331171; https://clinicaltrials.gov/ct2/show/NCT04331171.

Epidemiological Observations on the Association Between Anosmia and COVID-19 Infection: Analysis of Data From a Self-Assessment Web Application.

BACKGROUND: We developed a self-assessment and participatory surveillance web application for coronavirus disease (COVID-19), which was launched in France in March 2020. OBJECTIVE: Our objective was to determine if self-reported symptoms could help monitor the dynamics of the COVID-19 outbreak in France. METHODS: Users were asked questions about underlying conditions, sociodemographic status, zip code, and COVID-19 symptoms. Depending on the symptoms reported and the presence of coexisting disorders, users were told to either stay at home, contact a general practitioner (GP), or call an emergency phone number. Data regarding COVID-19-related hospitalizations were retrieved from the Ministry of Health. RESULTS: As of March 29, 2020, the application was opened 4,126,789 times; 3,799,535 electronic questionnaires were filled out; and 2,477,174 users had at least one symptom. In total, 34.8% (n=1,322,361) reported no symptoms. The remaining users were directed to self-monitoring (n=858,878, 22.6%), GP visit or teleconsultation (n=1,033,922, 27.2%), or an emergency phone call (n=584,374, 15.4%). Emergency warning signs were reported by 39.1% of participants with anosmia, a loss of the sense of smell (n=127,586) versus 22.7% of participants without anosmia (n=1,597,289). Anosmia and fever and/or cough were correlated with hospitalizations for COVID-19 (Spearman correlation coefficients=0.87 and 0.82, respectively; P<.001 for both). CONCLUSIONS: This study suggests that anosmia may be strongly associated with COVID-19 and its severity. Despite a lack of medical assessment and virological confirmation, self-checking application data could be a relevant tool to monitor outbreak trends. TRIAL REGISTRATION: ClinicalTrials.gov NCT04331171; https://clinicaltrials.gov/ct2/show/NCT04331171.

Parameter identification of a model for prostate cancer treated by intermittent therapy.

Adenocarcinoma is the most frequent cancer affecting the prostate walnut-size gland in the male reproductive system. Such cancer may have a very slow progression or may be associated with a "dark prognosis" when tumor cells are spreading very quickly. Prostate cancers have the particular properties to be marked by the level of prostate specific antigen (PSA) in blood which allows to follow its evolution. At least in its first phase, prostate adenocarcinoma is most often hormone-dependent and, consequently, hormone therapy is a possible treatment. Since few years, hormone therapy started to be provided intermittently for improving patient's quality of life. Today, durations of on- and off-treatment periods are still chosen empirically, most likely explaining why there is no clear benefit from the survival point of view. We therefore developed a model for describing the interaction between the tumor environment, the PSA produced by hormone-dependent and hormone-independent tumor cells, respectively, and the level of androgens. Model parameters were identified using a genetic algorithm applied to the PSA time series measured in a few patients who initially received prostatectomy and were then treated by intermittent hormone therapy (LHRH analogs and anti-androgen). The measured PSA time series is quite correctly reproduced by free runs over the whole follow-up. Model parameter values allow for distinguishing different types of patient (age and Gleason score) meaning that the model can be individualized. We thus showed that the long-term evolution of the cancer can be affected by durations of on- and off-treatment periods.

Prospective study of a web-mediated management of febrile neutropenia related to chemotherapy (Bioconnect).

BACKGROUND: We aimed to investigate whether patient self-evaluated symptoms transmitted via Internet is feasible between planned visits to provide an early management of fever and neutropenia induced by chemotherapy, and if it can reduce hospitalizations for severe neutropenia. METHODS: Patients who received a chemotherapy regimen with an overall risk of febrile neutropenia ≥ 20% had to report daily temperature between physician planned visits using a web application. Fever and clinical signs of seriousness were reported to the physician (if some criteria were fulfilled in a specific algorithm) via automatic email notifications by the web application. Patients could be hospitalized quickly or could take over at home, make blood count, and take predefined oral antibiotics if indicated. Primary outcome was patient's compliance and satisfaction. The number and the cost of hospitalization were also assessed and compared with an historical cohort of patients with similar clinical conditions and treatment. RESULTS: Among the 41 patients included, 36 (87.8%) used the web application with 88% of daily compliance and 90% (28/33) of satisfaction. One patient (2.7%) had planned hospitalization after the web application alert. In the historical cohort, the rate of unplanned hospitalization for febrile neutropenia was 17% (6 patients) and 2.7% (1 patient) in users of the web application cohort. The cumulative cost of hospitalization for neutropenia was USD 28,827 in the historical cohort and USD 6563 in the web application cohort. CONCLUSION: Web-mediated follow-up of febrile neutropenia is feasible. It led to high patient satisfaction, high compliance, and a possible reduction of the number and the cost of hospitalizations.

Digestive toxicities after palliative three-dimensional conformal radiation therapy (3D-CRT) for cervico-thoracic spinal metastases.

OBJECTIVE: The palliative treatment for cervico-thoracic spinal metastases is based on a three-dimensional conformal radiation therapy (3D-CRT). Digestive toxicities are common and cause a clinical impact frequently underestimated in patients. We performed a retrospective study of digestive side effects occurring after palliative 3D-CRT for cervico-thoracic spinal metastases. PATIENTS AND METHODS: All patients receiving palliative 3D-CRT at Jean Bernard Center from January 2013 to December 2014 for spinal metastases between the 5th cervical vertebra (C5) and the 12th thoracic vertebra (T12) were eligible. Three-dimensional conformal RT was delivered by a linear accelerator (CLINAC, Varian). Premedication to prevent digestive toxicities was not used. Adverse events ("esophagitis" and "nausea and/or vomiting") were evaluated according to the NCI-CTCae (version 4). RESULTS: From January 2013 to December 2014, 128 patients met the study criteria. The median age was 68.6 years [31.8; 88.6]. Most patients (84.4%) received 30 Gy in 10 fractions. The median overall time of treatment was 13 days [3-33]. Forty patients (31.3%) suffered from grade ≥ 2 of "esophagitis" (35 grade 2 (27.4%) and 5 grade 3 (3.9%)). Eight patients (6.3%) suffered from grade ≥ 2 of "nausea and/or vomiting" (6 grade 2 (4.7%), 1 grade 3 (0.8%), and 1 grade 4 (0.8%)). CONCLUSION: The high incidence of moderate to severe digestive toxicities after palliative 3D-CRT for cervico-thoracic spinal metastases led to consider static or dynamic intensity-modulated radiation therapy (IMRT) to reduce the dose to organ at risk (the esophagus and stomach). Dosimetric studies and implementation in the clinic should be the next steps.

Totally implantable venous access ports: a prospective long-term study of early and late complications in adult patients with cancer.

PURPOSE: Totally implantable venous access ports (TIVAP) have been widely used for many years in the management of patients suffering from cancer. The implantation and long-term use of TIVAPs are associated with mechanical, thrombotic, and infectious complications. This is the first exhaustive prospective study of all complications occurring in a whole population on long-term follow-up and therefore allows an objective assessment to be made of the safety of TIVAPs. METHODS: We carried out a prospective single-center observational study. All adult patients with cancer who had a TIVAP implanted between January 1 and December 31, 2006 were registered. Early and late complications were recorded until the removal of the device, the patient's death, or until December 31, 2013. Exhaustive data concerning patients and TIVAP was recorded at time of implantation. RESULTS: Four hundred and ninety-three TIVAPs were implanted in 483 adult cancer patients and were followed during a period from 1 to 94 months (median = 18 months) representing a global quantity of 367,359 catheter-days. Eighty-seven complications were recorded (0.237/1000 catheter-days), including 37 infections (0.101/1000 catheter-days), 17 thrombotic events (0.046/1000 catheter-days), and 9 extravasations. Out of the 87 events, 62 (71.3%) occurred during the first year after implantation. Events were therefore extremely rare after 1 year. Thromboembolic and infectious complications were rare and no risk factors for these were found. CONCLUSIONS: This study demonstrates excellent tolerability, with only occasional complications. Most of these occurred during the year following implantation. A TIVAP may also be left in place for an extremely long time.

Spatial avascular growth of tumor in a homogeneous environment.

Describing tumor growth is a key issue in oncology for correctly understanding the underlying mechanisms leading to deleterious cancers. In order to take into account the micro-environment in tumor growth, we used a model describing - at the tissue level - the interactions between host (non malignant), effector immune and tumor cells to simulate the evolution of cancer. The spatial growth is described by a Laplacian operator for the diffusion of tumor cells. We investigated how the evolution of the tumor diameter is related to the dynamics (periodic or chaotic oscillations, stable singular points) underlying the interactions between the different populations of cells in proliferation sites. The sensitivity of this evolution to the key parameter responsible for the immuno-evasion, namely the growth rate of effector immune cells and their inhibition rate by tumor cells, is also investigated.

How the growth rate of host cells affects cancer risk in a deterministic way.

It is well known that cancers are significantly more often encountered in some tissues than in other ones. In this paper, by using a deterministic model describing the interactions between host, effector immune and tumor cells at the tissue level, we show that this can be explained by the dependency of tumor growth on parameter values characterizing the type as well as the state of the tissue considered due to the "way of life" (environmental factors, food consumption, drinking or smoking habits, etc.). Our approach is purely deterministic and, consequently, the strong correlation (r = 0.99) between the number of detectable growing tumors and the growth rate of cells from the nesting tissue can be explained without evoking random mutation arising during DNA replications in nonmalignant cells or "bad luck". Strategies to limit the mortality induced by cancer could therefore be well based on improving the way of life, that is, by better preserving the tissue where mutant cells randomly arise.

A cancer model for the angiogenic switch.

The occurrence of metastasis is an important feature in cancer development. In order to have a one-site model taking into account the interactions between host, effector immune and tumor cells which is not only valid for the early stages of tumor growth, we developed in this paper a new model where are incorporated interactions of these three cell populations with endothelial cells. These latter cells are responsible for the neo-vascularization of the tumor site which allows the migration of tumor cells to distant sites. It is then shown that, for some parameter values, the resulting model for the four cell populations reproduces the angiogenic switch, that is, the transition from avascular to vascular tumor.

Detecting lung cancer relapse using self-evaluation forms weekly filled at home: the sentinel follow-up.

PURPOSE: We aimed to assess if patients' ratings of symptoms can be used to provide an early indication of disease recurrence or progression in lung cancer. We proposed a simple self-evaluation form made of six clinical parameters weekly scored by patients at home as a follow-up--here named sentinel--to improve relapse detection. Its performances were compared to those of a routine imaging follow-up. METHODS: Patients with lung cancer were prospectively recruited to weekly fill a form at home for self-assessing weight, fatigue, pain, appetite, cough, and breathlessness during at least 4 months. Each patient reported weight and assessed the severity of each symptom by grading it from 0 (no symptom) to 3 (major symptom). A score was retrospectively designed for discriminating patients with relapse from those without. Accuracy of relapse detection was then compared to values of the routine planned imaging. RESULTS: Forty-three patients were included in our center and recruited for 16 weeks or more follow-up during which at least one tumor imaging assessment was performed (CT scan or PET-CT). Forty-one completed the form weekly. Sensitivity, specificity, and positive and negative predictive values of sentinel were high (86, 93, 86 % and 93 vs 79, 96, 92, and 90 % for routine imaging--p = ns) and well correlated with relapse (pχ2 > 0.001). Moreover, relapses were detectable with sentinel on average 6 weeks earlier than the planned imaging. CONCLUSION: This study suggests that a personalized cancer follow-up based on a weekly self-evaluation of six symptoms is feasible and may be accurate for earlier detection of lung cancer relapse, allowing integration in electronic devices for real-time patient outcome follow-up.

Detection of lung cancer relapse using self-reported symptoms transmitted via an internet web-application: pilot study of the sentinel follow-up.

PURPOSE: We aimed to investigate whether patient self-evaluated symptoms transmitted via Internet can be used between planned visits to provide an early indication of disease relapse in lung cancer. METHODS: Between 2/2013 and 8/2013, 42 patients with lung cancer having access to Internet were prospectively recruited to weekly fill a form of 11 self-assessed symptoms called "sentinel follow-up". Data were sent to the oncologist in real-time between planned visits. An alert email was sent to oncologist when self-scored symptoms matched some predefined criteria. Follow-up visit and imaging were then organized after a phone call for confirming suspect symptoms. Weekly and monthly compliances, easiness with which patients used the web-application and the accuracy of the sentinel follow-up for relapse detection were assessed and compared to a routine visit and imaging follow-up. RESULTS: Median follow-up duration was 18 weeks (8-32). Weekly and monthly average compliances were 79 and 94 %, respectively. Sixty percents of patients declared to be less anxious during the few days before planned visit and imaging with the sentinel follow-up than without. Sensitivity, specificity, positive, and negative predictive values provided by the sentinel (planned imaging) follow-up were 100 %(84 %), 89 %(96 %), 81 %(91 %), and 100 %(93 %), respectively and well correlated with relapse (pχ (2) < 0.001). On average, relapses were detectable 5 weeks earlier with sentinel than planned visit. CONCLUSION: An individualized cancer follow-up that schedule visit and imaging according to the patient status based on weekly self-reported symptoms transmitted via Internet is feasible with high compliance. It may even provide earlier detection of lung cancer relapse and care.