Descriptive epidemiology of 30,223 histopathologically confirmed meningiomas in France: 2006-2015.

BACKGROUND AND OBJECTIVES: Meningioma is one of the most common neoplasm of the central nervous system. To describe the epidemiology of meningioma operated in France and, to assess grading and histopathological variability among the different neurosurgical centres. METHODS: We processed the French Brain Tumour Database (FBTDB) to conduct a nationwide population-based study of all histopathologically confirmed meningiomas between 2006 and 2015. RESULTS: 30,223 meningiomas cases were operated on 28,424 patients, in 61 centres. The average number of meningioma operated per year in France was 3,022 (SD ± 122). Meningioma was 3 times more common in women (74.1% vs. 25.9%). The incidence of meningioma increased with age and, mean age at surgery was 58.5 ± 13.9 years. Grade 1, 2, and 3 meningiomas accounted for 83.9%, 13.91% and, 2.19% respectively. There was a significant variability of meningioma grading by institutions, especially for grade 2 which spanned from 5.1% up to 22.4% (p < 0.001). Moreover, the proportion of grade 2 significantly grew over the study period (p < 0.001). There was also a significant variation in grade 1 subtypes diagnosis among the institutions (p < 0.001). 89.05% of the patients had solely one meningioma surgery, 8.52% two and, 2.43% three or more. The number of surgeries was associated to the grade of malignancy (p < 0.001). CONCLUSION: The incidence of meningioma surgery increased with age and, peaked at 58.5 years. They were predominantly benign with meningothelial subtype being the most common. However, there was a significant variation of grade 1 subtypes diagnosis among the centres involved. The proportion of grade 2 meningioma significantly grew over the study time, on contrary to malignant meningioma proportion, which remained rare and, stable over time around 2%. Likewise, there was a significant variability of grade 2 meningioma rate among the institutions.

The Dual Role of Mesenchymal Stem Cells in Cancer Pathophysiology: Pro-Tumorigenic Effects versus Therapeutic Potential.

Mesenchymal stem/stromal cells (MSCs) are multipotent cells involved in numerous physiological events, including organogenesis, the maintenance of tissue homeostasis, regeneration, or tissue repair. MSCs are increasingly recognized as playing a major, dual, and complex role in cancer pathophysiology through their ability to limit or promote tumor progression. Indeed, these cells are known to interact with the tumor microenvironment, modulate the behavior of tumor cells, influence their functions, and promote distant metastasis formation through the secretion of mediators, the regulation of cell-cell interactions, and the modulation of the immune response. This dynamic network can lead to the establishment of immunoprivileged tissue niches or the formation of new tumors through the proliferation/differentiation of MSCs into cancer-associated fibroblasts as well as cancer stem cells. However, MSCs exhibit also therapeutic effects including anti-tumor, anti-proliferative, anti-inflammatory, or anti-oxidative effects. The therapeutic interest in MSCs is currently growing, mainly due to their ability to selectively migrate and penetrate tumor sites, which would make them relevant as vectors for advanced therapies. Therefore, this review aims to provide an overview of the double-edged sword implications of MSCs in tumor processes. The therapeutic potential of MSCs will be reviewed in melanoma and lung cancers.

[Gastrointestinal stromal tumors: a retrospective study]. / Tumeurs stromales gastro-intestinales: une étude rétrospective.

Introduction: although rare, gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the digestive tract. The aim of this work is to study the clinical, paraclinical, therapeutic and evolutionary features of GIST. Methods: we conducted a descriptive retrospective, monocentric study (April 2017-April 2021) collecting data from the medical records of all patients with GIST treated at the medical oncology department of the University Hospital of Mostaganem. Results: we collected data from the medical records of 23 patients, with a median age of 54.4 years, sex ratio 1.8, over a period of 4 years. Abdominal pain was the most frequent symptom (78.3%, n=18); 47.8% of patients (n=11) had a tumor in the small bowel. The diagnosis was made at an early stage in 69.6% of cases (n=16). Surgical treatment was performed in 20 of the 23 patients, 18 of whom with R0. Of the 15 operated patients with a localized tumor, 13 received adjuvant medical treatment (Imatinib). Disease progression was reported in three patients treated with imatinib, then 2nd line therapy (Sunitinib) was started. During the study period, all patients were alive except two who died due to disease progression. Conclusion: the diagnosis of GIST is mainly based on histology and immunohistochemistry, which is often not performed by our pathologists. Molecular biology makes it possible to predict the prognosis and consequently adapt the therapies. The outcome of patients with GIST is often favorable but marked by recurrences despite a supposedly curative treatment requiring prolonged monitoring.

[Oncogenetics in the French overseas departments and regions: Situation in Reunion Island]. / Oncogénétique dans les départements et régions d'Outre-mer français : situation à La Réunion.

In view of the use of oncogenetics as a lever for proposing new-targeted therapies whose indications are expanding, this article provides an overview of this discipline in the French overseas departments and regions (DROM). Contrary to the metropolitan departments, where the number of consultations exceeds 100 consultations per 100,000 inhabitants for most centres in 2019, the number of consultations in the DROMs remains insufficient to meet the national average of 117 per 100,000 inhabitants. The financial and structural support offered by the INCa and the DGOS since 2003 has contributed favourably to the deployment of this activity in metropolitan France. This activity, which seems to be suffering in the DROMs, probably requires particular attention in order to understand the difficulties encountered and thus to meet the INCa's objective as well as possible: to identify and support patients with mutations by providing them with appropriate care.

Complement Activation and Up-Regulated Expression of Anaphylatoxin C3a/C3aR in Glioblastoma: Deciphering the Links with TGF-ß and VEGF.

The complement (C) innate immune system has been shown to be activated in the tumor microenvironment of various cancers. The C may support tumor growth by modulating the immune response and promoting angiogenesis through the actions of C anaphylatoxins (e.g., C5a, C3a). The C has important double-edged sword functions in the brain, but little is known about its role in brain tumors. Hence, we analyzed the distribution and the regulated expression of C3a and its receptor C3aR in various primary and secondary brain tumors. We found that C3aR was dramatically upregulated in Grade 4 diffuse gliomas, i.e., glioblastoma multiforme, IDH-wildtype (GBM) and astrocytoma, IDH-mutant, Grade 4, and was much less expressed in other brain tumors. C3aR was observed in tumor-associated macrophages (TAM) expressing CD68, CD18, CD163, and the proangiogenic VEGF. Robust levels of C3a were detected in the parenchyma of GBM as a possible result of Bb-dependent C activation of the alternative C pathway. Interestingly, in vitro models identified TGF-ß1 as one of the most potent growth factors that upregulate VEGF, C3, and C3aR in TAM (PMA-differentiated THP1) cell lines. Further studies should help to delineate the functions of C3a/C3aR on TAMs that promote chemotaxis/angiogenesis in gliomas and to explore the therapeutic applications of C3aR antagonists for brain tumors.

Bevacizumab in real-life patients with recurrent glioblastoma: benefit or futility?

PURPOSE: Angiogenesis plays a key role in glioblastoma, but most anti-angiogenic therapy trials have failed to change the poor outcome of this disease. Despite this, and because bevacizumab is known to alleviate symptoms, it is used in daily practice. We aimed to assess the real-life benefit in terms of overall survival, time to treatment failure, objective response, and clinical benefit in patients with recurrent glioblastoma treated with bevacizumab. METHODS: This was a monocentric, retrospective study including patients treated between 2006 and 2016 in our institution. RESULTS: 202 patients were included. The median duration of bevacizumab treatment was 6 months. Median time to treatment failure was 6.8 months (95%CI 5.3-8.2) and median overall survival was 23.7 months (95%CI 20.6-26.8). Fifty percent of patients had a radiological response at first MRI evaluation, and 56% experienced symptom amelioration. Grade 1/2 hypertension (n = 34, 17%) and grade one proteinuria (n = 20, 10%) were the most common side effects. CONCLUSIONS: This study reports a clinical benefit and an acceptable toxicity profile in patients with recurrent glioblastoma treated with bevacizumab. As the panel of therapies is still very limited for these tumors, this work supports the use of bevacizumab as a therapeutic option.

[Impact of digital pathology implementation in Reunion Island]. / Intérêt de la pathologie numérique à La Réunion.

In recent decades, the major scientific advances in oncology have complexified anatomic pathology practice. Collaboration with local and national pathologists is essential for ensuring a high-quality diagnosis. Anatomic pathology is undergoing a digital revolution that implements whole slide imaging in routine pathologic diagnosis. Digital pathology improves diagnostic efficiency, allows remote peer review and consultations (telepathology), and enables the use of artificial intelligence. The implementation of digital pathology is of particular interest in isolated territories, facilitating access to expertise and therefore to specialized diagnosis. This review discusses the impact of digital pathology implementation in French overseas territories, particularly in Reunion Island.

Survival of adult patients with solid cancer in Reunion Island, 1998-2014.

INTRODUCTION: Population-based cancer survival is a major indicator of effectiveness of cancer management. This study is the first population-based study to estimate the net survival (NS) of adult cancer patients in Reunion Island, a French overseas department with distinctive epidemiological, cultural, and sociodemographic characteristics. METHODS: All adult incident cases (n=23,055) of invasive solid tumors diagnosed between 1998 and 2014 and registered in the Reunion Island Cancer Registry were included in the study. The Pohar-Perme estimator was used to estimate 1-, 3-, 5-, and 10-year NS. RESULTS: 5-year NS ranged from 7% (liver in women) to 97% (thyroid cancer in women) for cancers diagnosed between 2006 and 2014. For the most common cancers, the age-standardized 5-year NS of women was 81% for breast cancer, 58% for colorectal cancer and 62% for cervical cancer. For men, the age-standardized 5-year NS was 85% for prostate cancer, 12% for lung cancer, and 52% for colorectal cancer. Age-standardized 5-year NS increased slightly with the period of diagnosis (from 1998-2005 to 2006-2014) for prostate, breast, head and neck, lung, colorectal (women), and stomach (men) cancers, remained stable for colorectal (men) cancer, and decreased slightly for cervical and stomach (women) cancers. DISCUSSION: Overall, NS was lower in Reunion Island than in mainland France. While the epidemiological, cultural, and sociodemographic characteristics of the Reunionese population likely explain some of the observed differences compared to mainland France, site-specific studies are needed to explore the different determinants of survival in Reunion Island.

Health, illness and cancer in Mayotte: Multicultural experiences in a medically underserved French Territory.

The island of Mayotte is part of the French territory and one of the European Union's Outermost Regions but there is a significant lack of data and research on health and cancers in Mayotte. This article reviews the literature on health, disease and cancer in Mayotte, from the perspectives of social science and epidemiology. It starts by shedding light on the specificities of Mahoran demography and society, and shows the healthcare infrastructure is insufficient to meet the population's needs. It then reviews social science studies on health and illness in Mayotte and shows that the political issue of migration permeates the management and the experiences of health on the island. It ends with a focus on the epidemiology of cervical cancer and a review of the available data on screening, treatment and prevention. The article concludes with a quick review of ongoing research and urgently calls for more data and research on this critical public health issue.

[The oncology residency program in French overseas]. / L'internat d'oncologie en outre-mer français.

Once his specialty has been chosen, and according to his ranking, the new resident in oncology decides on the subdivision in which he wishes to be among the 28 existing subdivisions. Two concern overseas departments and territories: the Antilles-Guyana subdivision and the Indian Ocean subdivision. The oncology residency has its own particularities because of the demographic characteristics and epidemiology of cancers in these areas, but also because of a particular organization of care and university teaching. The training of residents in these subdivisions is little known. Over the past ten years, most of the residents have been trained in oncology-radiotherapy in these subdivisions and some of them in medical oncology. The residency program is however experiencing a revival in terms of university education in parallel with the development of technical and human equipment in the centres of these regions. This article details the training of residents in oncology in French overseas territories by contextualizing it with epidemiological data and the characteristics of the oncology care offer in these territories.

Health, illness and cancer in Reunion Island: Health services in a diverse but aging French territory.

The major social, cultural, economic and demographic changes in Reunion Island in the last 70 years have had effects on its population and the evolution of its public health issues. The demographic transition and changes in lifestyle have led to a rapidly aging population with increased needs for care for dependency and chronic illness such as cancers. The aim of this paper is to offer a review of the literature and ongoing research on health and cancer in Reunion Island. It reviews the recent literature on these changes, including the socio-demography of the population, the medical demography and cancer care infrastructure. It highlights the significant social inequalities of the island, and shows its medical demography and healthcare services are close to national averages. It then offers a review of publications on the experiences of health and illness in Reunion Island in a multicultural and postcolonial context, between medical pluralism and biomedicine. It then offers a focus on the epidemiology of three cancers, namely breast, cervical and prostate cancers. It concludes with a review of known ongoing research, and calls for a rapid adaptation of the organization of the medico-social system, in order to face Reunion Island's most pressing healthcare issues: chronic illnesses such as cancers, and dependency.

[Intercontinental Multidisciplinary Oncology Videoconferencing between the South Pacific and the French mainland: Results after one year and 323 cases of rare or complex cancers discussed]. / RCP Pacifique : bilan après un an et 323 cancers rares et/ou complexes discutés.

INTRODUCTION: Overseas France represents 18 % of French territory and is home to 4 % of its population for whom there is unequal treatment in the field of rare/complex cancer. AIM: To report our experience of intercontinental multidisciplinary videoconferencing between the French mainland and Pacific territories. METHODS: Every other friday, three centers located in Papeete, Nouméa and Paris-Villejuif connected between 6:30 AM and 8:00 AM GMT to discuss cases of rare/complex cancers. RESULTS: Between November 2019 and December 2020, 323 presentations implicating 233 patients involved sarcoma (n=93), digestive pathology (n=60), neuroendocrine tumors (n=35), urology (n=24), gynecology (n=24), neurology (n=16), thyroid pathology (n=14), dermatology (n=14), senology (n=11), hematology (n=11), ENT pathology (n=10), pathology thoracic (n=10) and pediatrics (n=1). Of the 233 patients, 134 (57.5 %) living in New Caledonia and 99 (42.5 %) in French Polynesia, 117 (50.5 %) had metastatic disease. 39 patients (16.7 %) were transferred to French mainland (EVASAN), for surgery (n=25), vectorized radiotherapy (n=7), biopsy (n=5), chemotherapy (n=1) or inclusion in a clinical trial (n=1). 195 patients (83.7 %) were treated at home, 15 (6.4 %) are still awaiting a decision and 4 (1.7 %) lost to follow-up. CONCLUSION: The use of videoconferencing to discuss rare/complex cancer cases was effective in guaranteeing French overseas population access to innovative therapies and clinical trials, limiting the need for intercontinental transfer to 16.7 %.

A Predictive Clinical-Radiomics Nomogram for Survival Prediction of Glioblastoma Using MRI.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adult patients with a median survival of around one year. Prediction of survival outcomes in GBM patients could represent a huge step in treatment personalization. The objective of this study was to develop machine learning (ML) algorithms for survival prediction of GBM patient. We identified a radiomic signature on a training-set composed of data from the 2019 BraTS challenge (210 patients) from MRI retrieved at diagnosis. Then, using this signature along with the age of the patients for training classification models, we obtained on test-sets AUCs of 0.85, 0.74 and 0.58 (0.92, 0.88 and 0.75 on the training-sets) for survival at 9-, 12- and 15-months, respectively. This signature was then validated on an independent cohort of 116 GBM patients with confirmed disease relapse for the prediction of patients surviving less or more than the median OS of 22 months. Our model insured an AUC of 0.71 (0.65 on train). The Kaplan-Meier method showed significant OS difference between groups (log-rank p = 0.05). These results suggest that radiomic signatures may improve survival outcome predictions in GBM thus creating a solid clinical tool for tailoring therapy in this population.

Machine-Learning-Based Radiomics MRI Model for Survival Prediction of Recurrent Glioblastomas Treated with Bevacizumab.

Anti-angiogenic therapy with bevacizumab is a widely used therapeutic option for recurrent glioblastoma (GBM). Nevertheless, the therapeutic response remains highly heterogeneous among GBM patients with discordant outcomes. Recent data have shown that radiomics, an advanced recent imaging analysis method, can help to predict both prognosis and therapy in a multitude of solid tumours. The objective of this study was to identify novel biomarkers, extracted from MRI and clinical data, which could predict overall survival (OS) and progression-free survival (PFS) in GBM patients treated with bevacizumab using machine-learning algorithms. In a cohort of 194 recurrent GBM patients (age range 18-80), radiomics data from pre-treatment T2 FLAIR and gadolinium-injected MRI images along with clinical features were analysed. Binary classification models for OS at 9, 12, and 15 months were evaluated. Our classification models successfully stratified the OS. The AUCs were equal to 0.78, 0.85, and 0.76 on the test sets (0.79, 0.82, and 0.87 on the training sets) for the 9-, 12-, and 15-month endpoints, respectively. Regressions yielded a C-index of 0.64 (0.74) for OS and 0.57 (0.69) for PFS. These results suggest that radiomics could assist in the elaboration of a predictive model for treatment selection in recurrent GBM patients.

Interaction between the Number of Chemotherapy Cycles and Brachytherapy Dose/Volume Parameters in Locally Advanced Cervical Cancer Patients.

Scarce data exist on concurrent chemotherapy in locally advanced cervical cancer (LACC) patients (pts) treated with image-guided adaptive brachytherapy (IGABT). We examined the effect of a number of chemotherapy cycles and their interaction with brachytherapy dose/volume parameters. Clinical records of 209 consecutive pts treated for a LACC were reviewed. Pts received CRT concurrently with cisplatin 40 mg/m² or carboplatin AUC2. An additional cycle could have been delivered during the pulse-dose rate (PDR)-IGABT. The impact of a number of chemotherapy cycles on outcome was examined, as well as the interactions with dose volume parameters. The number of cycles was four in 55 (26.3%) pts, five in 154 (73.7%) including 101 receiving the fifth cycle during IGABT. Median follow-up was 5.5 years. Pts receiving five cycles had a better outcome on all survival endpoints, including three year local control rate (93.9% vs. 77.2%; p < 0.05). In the subgroup, only pts with tumor FIGO (Fédération Internationale de Gynécologie Obstétrique) stage ≤IIB or with CTVHR > 25 cm3 had a better outcome. Pts receiving four cycles with D90CTVHR > 80GyEQD2 had the same locoregional control-(LRC) as those receiving five cycles and achieving D90CTVHR ≤ 80 GyEQD2 (p = 0.75). An optimal propensity score matching the balance for the FIGO stage, CTVHR volume and D90CTVHR confirmed the effect, with the largest life expectancy benefit for locoregional failure-free survival (absolute gain: 1.5 years; p = 0.017). Long-term radiation-induced toxicity was not increased. Increasing the total number of cycles from 4 to 5 improved LFS, suggesting a place for systemic strategies aimed at in-field cooperation. Delivering an additional cycle at the time of brachytherapy did not increase morbidity and there permitted an increase in chemotherapy dose intensity.

Risk of Late Urinary Complications Following Image Guided Adaptive Brachytherapy for Locally Advanced Cervical Cancer: Refining Bladder Dose-Volume Parameters.

PURPOSE: To study correlations between dose-volume parameters of the whole bladder and bladder trigone and late urinary toxicity in locally advanced cervical cancer patients treated with pulsed-dose-rate brachytherapy. METHODS AND MATERIALS: Patients with locally advanced cervical cancer treated with chemoradiation therapy and pulsed-dose-rate brachytherapy from 2004 to 2015 were included. Cumulative dose-volume parameters of the whole bladder and bladder trigone were converted into 2-Gy/fraction equivalents (EQD2, with α/ß = 3 Gy); these parameters, as well as clinical factors, were analyzed as predictors of toxicity in patients without local relapse. RESULTS: A total of 297 patients fulfilled the inclusion criteria. The median follow-up period was 4.9 years (95% confidence interval 4.5-5.3 years). In patients without local relapse (n = 251), the Kaplan-Meier estimated grade 2 or higher urinary toxicity rates at 3 years and 5 years were 25.4% and 32.1%, respectively. Minimal dose to the most exposed 2 cm3 of the whole bladder [Formula: see text] , bladder International Commission on Radiation Units & Measurements (ICRU) (BICRU) dose, and trigone dose-volume parameters correlated with grade 2 or higher toxicity. At 3 years, the cumulative incidence of grade 2 or higher complications was 22.8% (standard error, 2.9%) for bladder [Formula: see text]  < 80 GyEQD2 versus 61.8% (standard error, 12.7%) for [Formula: see text]  ≥ 80 GyEQD2 (P = .001). In the subgroup of patients with bladder [Formula: see text]  ≤ 80 GyEQD2, a trigone dose delivered to 50% of the volume (D50%) > 60 GyEQD2 was significant for grade 2 or higher toxicity (P = .027). The probability of grade 3 or higher toxicities increased with bladder [Formula: see text]  > 80 GyEQD2 (16.7% vs 1.6%; hazard ratio [HR], 5.77; P = .039), BICRU dose > 65 GyEQD2 (4.9% vs 1.3%; HR, 6.36; P = .018), and trigone D50% > 60 GyEQD2 (3.1% vs 1.2%; HR, 6.29; P = .028). Pearson correlation coefficients showed a moderate correlation between bladder [Formula: see text] , BICRU dose, and bladder trigone D50% (P < .0001). CONCLUSIONS: These data suggest that [Formula: see text]  ≤ 80 GyEQD2 should be advised for minimizing the risk of severe urinary complications (<15%). Bladder trigone dose was also predictive of severe late urinary toxicity. These constraints need further confirmation in a multicenter prospective setting.