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Background: Study RTOG 9802 in high-risk diffuse low-grade gliomas (DLGGs) showed the potential synergistic effect on survival of the procarbazine, CCNU, and vincristine (PCV) radiotherapy (RT) combination. Limited data on long-term neurocognitive impact and quality of life (QoL) have yet been reported. Patients and Methods: We described a monocentric series of patients treated at first line by the combination of PCV immediately followed by RT between January 01, 1982 and January 01, 2017. Radiological data were collected and included volume, velocity of diametric expansion (VDE), and MRI aspects. Long-term neurocognitive and QoL were analyzed. Results: Twenty patients fulfilled the eligibility criteria. The median response rate was 65.1% (range, 9.6%–99%) at the time of maximal VDE decrease corresponding to a median volume reduction of 79.7 cm3 (range, 3.1 to 174.2 cm3), which occurred after a median period of 7.2 years (range, 0.3–21.9) after the end of RT. An ongoing negative VDE was measured in 13/16 patients after the end of RT, with a median duration of 6.7 years (range, 9 months–21.9 years). The median follow-up since radiological diagnosis was 17.5 years (range, 4.8 to 29.5). Estimated median survival was 17.4 years (95% CI: 12; NR). After a long-term follow-up, substantial neurotoxicity was noticed with dementia in six progression-free patients (30%), leading to ventriculo-peritoneal shunt procedures in three, and premature death in five. Thirteen patients (65%) were unable to work with disability status. Successive longitudinal neurocognitive assessments for living patients showed verbal episodic memory deterioration. Conclusions: PCV-RT combination seems to have not only an oncological synergy but also a long-term neurotoxic synergy to consider before initial therapeutic decision. [ABSTRACT FROM AUTHOR]

Background Diffuse low-grade gliomas (DLGGs) are rare and incurable tumors. Whereas maximal safe, functional-based surgical resection is the first-line treatment, the timing and choice of further treatments (chemotherapy, radiation therapy, or combined treatments) remain controversial. Methods An online survey on the management of DLGG patients was sent to 28 expert centers from the European Low-Grade Glioma Network (ELGGN) in May 2015. It contained 40 specific questions addressing the modalities of use of chemotherapy in these patients. Results The survey demonstrated a significant heterogeneity in practice regarding the initial management of DLGG patients and the use of chemotherapy. Interestingly, radiation therapy combined with the procarbazine, CCNU (lomustine), and vincristine regimen has not imposed itself as the gold-standard treatment after surgery, despite the results of the Radiation Therapy Oncology Group 9802 study. Temozolomide is largely used as first-line treatment after surgical resection for high-risk DLGG patients, or at progression. Conclusions The heterogeneity in the management of patients with DLGG demonstrates that many questions regarding the postoperative strategy and the use of chemotherapy remain unanswered. Our survey reveals a high recruitment potential within the ELGGN for retrospective or prospective studies to generate new data regarding these issues. [ABSTRACT FROM AUTHOR]

Diffuse low-grade gliomas are highly epileptogenic brain tumours. Pallud et al. examine the predictors and prognostic significance of epileptic seizures in 1509 patients harbouring these tumours. Time to treatment and extent of resection are predictors of seizure control, arguing for early and maximal resection.Diffuse low-grade gliomas are highly epileptogenic brain tumours. We aimed to explore the natural course of epileptic seizures, their predictors and the prognostic significance of their occurrence in adult patients harbouring a diffuse low-grade glioma. An observational retrospective multicentre study examined 1509 patients with diffuse low-grade gliomas to identify mutual interactions between tumour characteristics, tumour course and epileptic seizures. At diagnosis, 89.9% of patients had epileptic seizures. Male gender (P = 0.003) and tumour location within functional areas (P = 0.001) were independent predictors of a history of epileptic seizures at diagnosis. Tumour volume, growth velocity, cortical location, histopathological subtype or molecular markers did not significantly affect epileptic seizure occurrence probability. Prolonged history of epileptic seizures (P < 0.001), insular location (P = 0.003) and tumour location close to functional areas (P = 0.038) were independent predictors of uncontrolled epileptic seizures at diagnosis. Occurrence of epileptic seizures (P < 0.001), parietal (P = 0.029) and insular (P = 0.002) locations were independent predictors of uncontrolled epileptic seizures after oncological treatment. Patient age (P < 0.001), subtotal (P = 0.007) and total (P < 0.001) resections were independent predictors of total epileptic seizure control after oncological treatment. History of epileptic seizures at diagnosis and total surgical resection were independently associated with increased malignant progression-free (P < 0.001 and P < 0.001) and overall (P < 0.001 and P = 0.016) survivals. Epileptic seizures are independently associated with diffuse low-grade glioma prognosis. Patients diagnosed with epileptic seizures and those with complete and early surgical resections have better oncological outcomes. Early and maximal surgical resection is thus required for diffuse low-grade gliomas, both for oncological and epileptological purposes. [ABSTRACT FROM AUTHOR]

The involvement of eloquent brain areas may preclude the total/subtotal surgical resection of diffuse low-grade gliomas (DLGGs). The feasibility and functional tolerance of neoadjuvant chemotherapy have been demonstrated in such cases. The present study assesses the clinical and radiological impact of neoadjuvant chemotherapy on the natural course of DLGG. Seventeen patients without feasible surgical resection (infiltration of functional areas and/or large contralateral extension) were retrospectively selected. Temozolomide based neoadjuvant chemotherapy was initiated, inducing a tumor volume decrease and allowing a functional based maximal surgical resection. The median follow-up since initial radiological diagnosis was 5.9 years (range, 1.4-11). The median time to malignant transformation was 5.9 years. Six patients (35 %) had 1p19q codeletion, 12 patients (70 %) with IDH mutation and MGMT promoter methylation, and eight patients (47 %) had p53 overexpression. Chemotherapy reduced tumor volume (median −35.6 %, range −61.6 to −5.1 %) in contralateral hemisphere through the corpus callosum in seven cases (41 %) and in ipsi-lesional functional areas in ten cases (59 %). Chemotherapy significantly decreased the imaging tumor growth (measured by the velocity of diametric expansion VDE) with a median of −3.2 mm/year (range, −29.8 to −0.9 mm/year) ( p < 0.001). A tumor volume decrease of more than 20 % was correlated with a lower postoperative residual tumor (median 2 cc, p = 0.04), a greater extent of resection (93.1 vs. 89.5 %), a higher probability of total/subtotal removal. Neoadjuvant chemotherapy with Temozolomide could optimize the surgical resection of DLGGs and could impact their natural history. Further large prospective studies with long-term follow-up are needed. [ABSTRACT FROM AUTHOR]

Context. Hadrontherapy is an innovative form of radiotherapy using beams of protons or carbon ions able to destroy some radio resistant tumours. Because these tumours are highly specific amongst all cancerous tumours, it is impossible to determine the incidence of these diseases from surveillance registries. Goal. To assess, within the Rhône-Alpes region, the incidence of cancers being hadrontherapy indications. Method. Prospective, multicentre continuous data collection during 1 year, by practitioners participating to multidisciplinary tumor board. Tumours are inoperable, radio resistant, at primary stage of development, or locally recurrent, with low metastatic potential. Results. Study involved 27 healthcare centres, 52 groups of specialist practitioners. The estimated incidence of cancers eligible for hadrontherapy in the Rhône-Alpes region in 2010, that is, for 34 locations in all, is of 8.5/100 000 inhabitants. Appraisal of the low potential of metastatic progression is impeded, because these are rare diseases, whose outcome is unfamiliar to investigators. Conclusion. Future epidemiological studies will need to focus on prognosis and on the metastatic progression rate of these diseases. Indeed, there are few information available on this subject in the literature that could be used to improve preventive measures, medical care, and the surveillance of these rare cancers. [ABSTRACT FROM AUTHOR]

Objective: Seizure is the presenting symptom in most of World Health Organization grade II gliomas (GIIGs). Rarely, a GIIG is discovered incidentally on imaging. Little is known about the natural course and prognosis of incidental GIIGs. The aim of the present study is to characterize their natural history and to investigate whether their clinical and radiological behaviors differ from those of symptomatic GIIGs. Methods: The clinical and radiological findings, treatments, and outcomes of 47 histologically-proven incidental GIIGs were compared with those of 1249 symptomatic GIIGs. Results: Incidental GIIGs differ significantly from symptomatic GIIGs: they have a female predominance ( p = 0.05), smaller initial tumor volumes ( p < 0.001), lower incidence of contrast enhancement ( p = 0.009), and are more likely to undergo gross total surgical removal ( p < 0.001). Proliferation rates were similar to that observed among symptomatic GIIGs. Younger age at the time of discovery, frontal lobes, and noneloquent brain regions were associated with incidental GIIGs, as compared to their symptomatic counterparts. When not treated, incidental GIIGs demonstrated radiological growth (median velocity of diametric expansion at 3.5 mm/year), and became symptomatic at a median interval of 48 months after radiological discovery. Overall, incidental discovery was associated with a significant survival benefit ( p = 0.04). Interpretation: Incidental GIIGs are progressive tumors leading to clinical transformation toward symptomatic GIIGs. They may represent an earlier step in the natural history of a glioma than the symptomatic GIIGs. ANN NEUROL 2010;68:727-733 [ABSTRACT FROM AUTHOR]

Grade II gliomas grow slowly and linearly (at rates about 4 mm/year) before undergoing anaplastic transformation. In order to analyze how surgery may affect radiological grade II glioma kinetics, we restrospectively reviewed our national database searching for patients operated on for a supratentorial grade II glioma between 1997 and 2007. We selected patients with at least two postoperative MRI with a minimal delay of 6 months. For each patient, postoperative residues were segmented on successive MRIs. Velocities of diameter expansion were estimated by linear regression of mean diameter evolution for each patient. Fifty-four patients fulfilled inclusion criteria. Median postoperative follow-up was 1.6 years with, on average, 3.4 MRI examinations per patient. Postoperative growth rates of mean diameter were normally distributed, around a mean value of 4.3 mm/year (SD = 3.2 mm/year). Statistical analysis showed no difference between this distribution and the distribution of preoperative growth rates in a previous series of 143 grade II gliomas. For a subset of 23 patients, delay between first MRI and surgery made it possible to estimate also preoperative growth rates. Intrapatient comparison revealed that growth rates were grossly unchanged for 80% of cases. In summary, inter- and intrapatient comparison of pre- and postoperative growth rates proves that surgery does not change grade II glioma dynamics, thus, acting as a cytoreduction. [ABSTRACT FROM AUTHOR]

The c-erbB-2 proto-oncogene encodes a transmembrane protein tyrosine kinase receptor of 185 kDa (p185) and has been associated with several types of human cancers. In human breast cancer, overexpression of p185 occurs in 15–30% of cases, correlates with poor prognostic factors and characterizes breast cancers with a more aggressive behavior. Overexpression of p185 is usually associated with c-erbB-2 amplification, though it may occur independently and thus define subpopulations of breast cancers which might be of clinical interest. p185 expression is usually detected by immunohistochemistry (IHC) and few studies have been carried out to evaluate the p185 content of breast cancers with an ELISA technique. In this context, we showed, in 106 breast cancer samples, that p185 was expressed at high levels in 13.2%, intermediate levels in 55.7% and negative ones in 31.1% of cases. All p185 positive samples showed a c-erbB-2 oncogene amplification while none of the p185 negative samples and only 4% of p185 imtermediate samples had an amplification of c-erbB-2. p185 expression is significantly correlated with the negativity of estrogen and progestrone receptors, with high levels of cathepsin D and in some conditions with axillary nodal involvement. Thus, using the p185 ELISA assay, the c-erbB-2 status of breast cancers can be defined and moreover a subset can be discriminated which is characterized by intermediate levels of p185 and absence of c-erbB-2 amplification. The quantitative approach towards p185 in breast cancers affords the possibility of identifying more appropriately patients with high or low risk and thus permits adaptation of therapeutic regimens. [ABSTRACT FROM AUTHOR]