Concomitant Radiochemotherapy Research Articles

P09.05.A IMPACT OF A 16-WEEK SUPERVISED EXERCISE INTERVENTION ON CANCER-RELATED FATIGUE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA UNDERGOING ADJUVANT CHEMOTHERAPY

Abstract BACKGROUND Cancer-related fatigue (CRF) is considered one of the most prevalent symptoms in brain tumor patients undergoing concurrent chemoradiation (approx. 80 % of those affected). Several studies have identified beneficial effects of physical activity on reducing CRF. However, few studies have examined the reduction of CRF by exercise in glioma patients. Here we present prospective data showing the effect of an intensive 16-week supervised exercise intervention on CRF in neuro-oncological patients. MATERIAL AND METHODS Between July 2020 and April 2023, patients with newly diagnosed glioblastoma and after surgery and concomitant radiochemotherapy have been recruited for this single-arm trial in progress. Participants have received a 16-week supervised training intervention on a 1:1-basis consisting of two intensive 50-minute sessions per week (bicycle ergometry at an average of 75 % of maximum heart rate and progressive whole-body resistance training). CRF has been assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30). We calculated change scores (scores: 0-100; 100=max. fatigue) from baseline, after 8 weeks, and post-intervention (week 16). RESULTS So far, 26 glioblastoma patients (13 women) aged 35-84 years (mean 59 years) participated in the exercise intervention. All patients received adjuvant chemotherapy (50 % Stupp, 42 % CeTeG, 8 % other). Paired t-test indicated a statistically significant reduction in CRF from baseline to post-intervention (p=.030; 95 % CI: -0.5 - 24.2). Mean scores reduced from 40.4 to 36.2 (week 8) to 26.9 (week 16). However, the decrease between week 0 and week 8 was not yet significant (p=.281; 95 % CI: -7.6 - 13.6). CONCLUSION The present trial shows that a 16-week supervised exercise program can reduce CRF in glioblastoma patients despite adjuvant chemotherapy. Thus, and consistent with studies of exercise interventions in patients of other tumor types, glioblastoma patients have the opportunity to actively contribute to the reduction of tumor- and therapy-induced side effects through intensive physical training.

Significance of O6-methyl guanine methyltransferase promoter methylation in high grade glioma patients: optimal cutoff point, CpG locus, and genetic assay.

To evaluate O6-methyl guanine methyltransferase (MGMT) promoter methylation status in high grade glioma patients and to identify the best cutoff point as well as the most predictive CpG loci for patients survival. Consecutive high grade glioma patients treated with surgical gross total resection followed by concomitant radiochemotherapy and adjuvant chemotherapy were included in this retrospective observational study. Methylation status of MGMT promoter CpG island of resected tumor tissue were evaluated using next generation sequencing assay. The outcomes were grouped as CpG 70-78, CpG 79-83, CpG 84-87, CpG 70-87, and whole promoter. Quantitative analyses were dichotomized as methylated or unmethylated based on the cutoff points set to %10, and methylation was further graded as <%10 unmethylated, %10-30 low-methylated, and %30-100 high-methylated. Total of 95 patients with the mean age of 51.50 ± 12.36 years were included in the study. Overall survival (OS) and progression free survival (PFS) were 14.53 ± 1.92 (95% CI 10.77-18.30) and 10.90 ± 2.05 (95% CI 6.89-14.92) months, respectively. MGMT promoter was methylated in 38.2% of cases and high-methylated in 10.5% of cases. Methylation status of MGMT promoter was recognized as a very powerful predictor of OS and PFS. In particular, high-methylation of CpG 79-83 and CpG 84-87 islands at promoter region were strongly associated with better survival outcomes (p < 0.05). Our outcomes support the prognostic value of MGMT promoter methylation in patients with high grade glioma. Sequencing of whole promoter CpG islands demonstrated that methylation of particular CpG sites might predict clinical outcomes more precisely.

Synchronous Laryngeal Primary Cancer in a Patient with Esophageal Squamous Carcinoma Cell: A Case Report

Unexpected diagnosis of primary synchronous cancer in a patient with esophageal squamous carcinoma cell makes therapeutic management difficult. The careful evaluation of synchronous tumors is a primority aspect of management. we present the unusual case of an individual with esophageal squamous carcinomas cell synchronously associated with another primary laryngeal tumor. Initial clinical assessment was performed and consisting in a pan endoscopy and FDG-Pet scan / CT revealed the presence of Synchronous Head and Neck and Esophageal Carcinoma (SHNEC). As recommended in the literature, surgical resection was not indicated. In this case radio chemotherapy often remains the only therapeutic alternative which guarantees a better result and improves the prognosis. The patient progressed well under concomitant radio chemotherapy even if complications inherent to this treatment required the cessation of treatment for a short period.

Synchronous Laryngeal Primary Cancer in a Patient with Esophageal Squamous Carcinoma Cell . A Case Report

Unexpected diagnosis of primary synchronous cancer in a patient with esophageal squamous carcinoma cell makes therapeutic management difficult. the careful evaluation of synchronous tumors is a primority aspect of management. we present the unusual case of an individual with esophageal squamous carcinomas cell synchronously associated with another primary laryngeal tumor. Initial clinical assessment was performed and consisting in a pan endoscopy and FDG-Pet scan / CT revealed the presence of synchronous head and neck and esophageal carcinoma (SHNEC). As recommended in the literature, surgical resection was not indicated. In this case radio chemotherapy often remains the only therapeutic alternative which guarantees a better result and improves the prognosis. The patient progressed well under concomitant radio chemotherapy even if complications inherent to this treatment required the cessation of treatment for a short period.

Phase I/II study testing the combination of AGuIX nanoparticles with radiochemotherapy and concomitant temozolomide in patients with newly diagnosed glioblastoma (NANO-GBM trial protocol)

BackgroundDespite standard treatments including chemoradiotherapy with temozolomide (TMZ) (STUPP protocol), the prognosis of glioblastoma patients remains poor. AGuIX nanoparticles have a high radiosensitizing potential, a selective and long-lasting accumulation in tumors and a rapid renal elimination. Their therapeutic effect has been proven in vivo on several tumor models, including glioblastoma with a potential synergetic effect when combined with TMZ based chemoradiotherapy, and they are currently evaluated in 4 ongoing Phase Ib and II clinical trials in 4 indications (brain metastases, lung, pancreatic and cervix cancers) (> 100 patients received AGuIX). Thus, they could offer new perspectives for patients with newly diagnosed glioblastoma. The aim of this study is to determine the recommended dose of AGuIX as a radiosensitizer in combination with radiotherapy and TMZ during the concurrent radio-chemotherapy period for phase II (RP2D) and to estimate the efficacy of the combination.MethodsNANO-GBM is a multicenter, phase I/II, randomized, open-label, non-comparative, therapeutic trial. According to a dose escalation scheme driven by a TITE-CRM design, 3 dose levels of AGuIX (50, 75 and 100 mg/kg) will be tested in phase I added to standard concomitant radio-chemotherapy. Patients with grade IV glioblastoma, not operated or partially operated, with a KPS ≥ 70% will be eligible for the study. The primary endpoints are i) for phase I, the RP2D of AGuIX, with DLT defined as any grade 3–4 NCI-CTCAE toxicity and ii) for phase II, the 6-month progression-free survival rate. The pharmacokinetics, distribution of nanoparticles, tolerance of the combination, neurological status, overall survival (median, 6-month and 12-month rates), response to treatment, and progression-free survival (median and 12-month rates) will be assessed as secondary objectives. Maximum sixty-six patients are expected to be recruited in the study from 6 sites.DiscussionThe use of AGuIX nanoparticles could allow to overpass the radioresistance to the reference treatment of newly diagnosed glioblastomas that have the poorest prognosis (incomplete resection or biopsy only).Trial registrationClinicaltrials.gov: NCT04881032, registered on April 30, 2021. Identifier with the French National Agency for the Safety of Medicines and Health Products (ANSM): N°Eudra CT 2020-004552-15. Protocol: version 3, 23 May 2022.

Antisecretory factor is safe to use as add-on treatment in newly diagnosed glioblastoma

PurposeGlioblastoma (GBM) is the most common primary malignant brain tumor in adults. Despite the best available treatment, prognosis remains poor. Current standard therapy consists of surgical removal of the tumor followed by radiotherapy and chemotherapy with the alkylating agent temozolomide (TMZ). Experimental studies suggest that antisecretory factor (AF), an endogenous protein with proposed antisecretory and anti-inflammatory properties, may potentiate the effect of TMZ and alleviate cerebral edema. Salovum is an egg yolk powder enriched for AF and is classified as a medical food in the European Union. In this pilot study, we evaluate the safety and feasibility of add-on Salovum in GBM patients.MethodsEight patients with newly diagnosed, histologically confirmed GBM were prescribed Salovum during concomitant radiochemotherapy. Safety was determined by the number of treatment-related adverse events. Feasibility was determined by the number of patients who completed the full prescribed Salovum treatment.ResultsNo serious treatment-related adverse events were observed. Out of 8 included patients, 2 did not complete the full treatment. Only one of the dropouts was due to issues directly related to Salovum, which were nausea and loss of appetite. Median survival was 23 months.ConclusionsWe conclude that Salovum is safe to use as an add-on treatment for GBM. In terms of feasibility, adherence to the treatment regimen requires a determined and independent patient as the large doses prescribed may cause nausea and loss of appetite.Trial registrationClinicalTrials.gov NCT04116138. Registered on 04/10/2019.

Natural Course and Prognosis of Primary Spinal Glioblastoma: A Nationwide Study.

Primary spinal glioblastoma (PsGBM) is extremely rare. The dramatic neurologic deterioration and unresectability of PsGBM makes it a particularly disabling malignant neoplasm. Because it is a rare and heterogeneous disease, the assessment of prognostic factors remains limited. PsGBMs were identified from the French Brain Tumor Database and the Club de Neuro-Oncologie of the Société Française de Neurochirurgie retrospectively. Inclusion criteria were age 18 years or older at diagnosis, spinal location, histopathologic diagnosis of newly glioblastoma according to the 2016 World Health Organization classification, and surgical management between 2004 and 2016. Diagnosis was confirmed by a centralized neuropathologic review. The primary outcome was overall survival (OS). Therapeutic interventions and neurologic outcomes were also collected. Thirty-three patients with a histopathologically confirmed PsGBM (median age 50.9 years) were included (27 centers). The median OS was 13.1 months (range 2.5-23.7), and the median progression-free survival was 5.9 months (range 1.6-10.2). In multivariable analyses using Cox model, Eastern Cooperative Oncology Group (ECOG) performance status at 0-1 was the only independent predictor of longer OS (hazard ratio [HR] 0.13, 95% CI 0.02-0.801; p = 0.02), whereas a Karnofsky performance status (KPS) score <60 (HR 2.89, 95% CI 1.05-7.92; p = 0.03) and a cervical anatomical location (HR 4.14, 95% CI 1.32-12.98; p = 0.01) were independent predictors of shorter OS. The ambulatory status (Frankel D-E) (HR 0.38, 95% CI 0.07-1.985; p = 0.250) was not an independent prognostic factor, while the concomitant standard radiochemotherapy with temozolomide (Stupp protocol) (HR 0.35, 95% CI 0.118-1.05; p = 0.06) was at the limit of significance. Preoperative ECOG performance status, KPS score, and the location are independent predictors of OS of PsGBMs in adults. Further analyses are required to capture the survival benefit of concomitant standard radiochemotherapy with temozolomide.

Prognostic impact of tumor size reduction assessed by magnetic resonance imaging after radiochemotherapy in patients with locally advanced cervical cancer.

Pelvic magnetic resonance imaging (MRI) is a key exam used for the initial assessment of loco-regional involvement of cervical cancer. In patients with locally advanced cervical cancer, MRI is used to evaluate the early response to radiochemotherapy before image-guided brachytherapy, the prognostic impact of which we aimed to study. Patients with locally advanced cervical cancer treated using concomitant radiochemotherapy followed by closure treatment between January 2010 and December 2015 were included in this study. Clinical, anatomopathological, radiological, therapeutic, and follow-up data were evaluated. After applying the inclusion and exclusion criteria to the initially chosen 310 patients, 232 were included for evaluation (median follow-up period, 5.3 years). The median age was 50 years (range, 25-83 years), and the median tumor size was 47.5mm (range, 0-105 mm). Based on the International Federation of Gynaecology and Obstetrics classification system, 9 patients were in stage IB2; 20, IB3; 2, IIA; 63, IIB; 4, IIIA; 7, IIIB; and 127, IIIC1 or higher. The re-evaluation MRI was performed at the median dose of 55.5 Gy, and median reduction in tumor size was 55.2% (range, -20-100%). There was a difference between the disease-free and overall survival rates of the patients with a tumor response greater or lesser than 50%. The risk of recurrence or death reduced by 39% in patients with a tumor size reduction >50%. The overall 5-year survival rate of patients with a response greater and lesser than 50% were 77.7% and 61.5%, respectively. The 5-year disease-free survival rate for these two groups of patients were 68.8% and 51.5%, respectively. Our study confirms the prognostic impact of tumor size reduction using MRI data obtained after radiochemotherapy in patients with locally advanced cervical cancer.

Molecular Characterization of the Dual Effect of the GPER Agonist G-1 in Glioblastoma.

Glioblastoma (GBM) is the most common primary brain tumor in adults. Despite conventional treatment, consisting of a chirurgical resection followed by concomitant radio-chemotherapy, the 5-year survival rate is less than 5%. Few risk factors are clearly identified, but women are 1.4-fold less affected than men, suggesting that hormone and particularly estrogen signaling could have protective properties. Indeed, a high GPER1 (G-protein-coupled estrogen receptor) expression is associated with better survival, especially in women who produce a greater amount of estrogen. Therefore, we addressed the anti-tumor effect of the GPER agonist G-1 in vivo and characterized its molecular mechanism of action in vitro. First, the antiproliferative effect of G-1 was confirmed in a model of xenografted nude mice. A transcriptome analysis of GBM cells exposed to G-1 was performed, followed by functional analysis of the differentially expressed genes. Lipid and steroid synthesis pathways as well as cell division processes were both affected by G-1, depending on the dose and duration of the treatment. ANGPTL4, the first marker of G-1 exposure in GBM, was identified and validated in primary GBM cells and patient samples. These data strongly support the potential of G-1 as a promising chemotherapeutic compound for the treatment of GBM.

QOL-02. FACTORS INFLUENCING COMPLIANCE IN TTF TREATMENT – THE COMPTUNE STUDY

Abstract INTRODUCTION Recently, tumor treating fields (TTFields) were established for the treatment of newly diagnosed glioblastoma (nGBM). A crucial parameter for TTFields efficacy is compliance to treatment. In this prospective study, we assessed 5 psychological domains known to influence treatment compliance using a standardized interview in nGBM patients. The results of this psychological assessment were correlated to TTF compliance. METHODS A cohort of 49 nGBM patients (female 22; male 27, median age 62 years) were recruited. Most patients received a gross total resection (51%), the postsurgical treatment consisted of concomitant radiochemotherapy plus TTF in most cases (81%), only 2 patients received chemotherapy only, and 7 patients were additionally enrolled in clinical drug trials. The psychological assessment system consisted of 5 domains: Social support, confidence in treatment efficacy, communication status about treatment, anxiety, and depression. The interview was repeated every 8 weeks over a period of 8 months or if patients stopped treatment or developed second tumor progression. Additional phone interviews were conducted every 4 weeks. RESULTS Median and mean compliance was 98% and 81.6%, respectively (range 5%-100%), drops of compliance below 75%, which were classified as a threshold value, occurred 2259 times. Over-dispersed Poisson and multivariate negative binomial regression analysis revealed depression to be significantly correlated with the number of drops below 75% and with the mean compliance in the first 4 months of treatment. In addition, at later time points, confidence in treatment efficacy significantly correlated with the number of drops below 75%. All other domains did not appear to be associated with TTF treatment compliance. CONCLUSION Overall, compliance to TTF was high, however, drops below 75% of compliance occurred frequently during the measurement periods. In the initial treatment phase, depression was associated with these events, whereas confidence in treatment efficacy was correlated at later time points.

Pituitary carcinoma - case series and review of the literature.

Although pituitary adenomas (PAs) account for 15% of intracranial tumors, pituitary carcinomas (PCs) are a rare entity. Most commonly, PCs evolve from aggressive PAs invading the surrounding structures and eventually leading to metastatic lesions. Due to the low incidence, the diagnosis and treatment remains challenging. We report a case series of five patients with pituitary carcinoma (PC) treated in our center. At first diagnosis 3 patients had an ACTH-producing adenoma, 1 a prolactinoma and 1 a double secreting adenoma (GH and prolactin). The mean time interval from initial diagnosis to diagnosis of PC was 10.7 years (range 5-20 years). All patients underwent multiple surgical resections and radiotherapy. Four patients were treated with temozolomide for metastatic disease. One patient with concomitant radiochemotherapy for local recurrence. Temozolomide led to a stable disease in 2 patients. One patient had a progressive disease after 9 cycles of temozolomide. In absence of standard treatment, immunotherapy was initiated, resulting in a stable disease.We report five cases of PCs. Three patients obtained a stable disease after tailored multidisciplinary treatment. Additionally, one patient was treated with immunotherapy, opening a new treatment option in PCs. Overall, PCs are rare intracranial neoplasms occurring several years after the initial diagnosis of aggressive PAs. Currently, the absence of predictive factors for an aggressive clinical course, provokes a challenging management.

P11.02.A Gliotarget: a Danish nationwide phase I/II platform trial focusing on individualized targeted treatment for newly diagnosed glioblastoma patients based on genomic profiling

Abstract INTRODUCTION The survival in glioblastoma has been unchanged since 2005. The introduction of targeted treatments, which have improved survival in several cancers has yet to influence the treatment of glioblastoma. In Gliotarget, we will individualize the targeted treatment, and give it in the primary setting alongside standard therapy with the intention to improve the likelihood of effect. METHODS Gliotarget is a biomarker enriched phase I/II platform trial with initially 4 predefined biomarker selected arms and one control arm. All patients receive standard therapy with concomitant radiochemotherapy and adjuvant temozolomide. The experimental treatment is given alongside the adjuvant temozolomide. Molecular analysis, including Whole Genome Sequencing, is performed on all patients, to identify actionable biomarkers. Gliotarget includes newly diagnosed IDH-wt glioblastoma patients. In addition, to exclude the patients where the inherent poor prognosis might conceal the drug efficacy, the patients must have a 50% probability of being alive 12 months after initial surgery, according to a prognostic model developed in our institution. The sample size is calculated with Simon’s two-stage design using treatment effect at 9-months progression free survival (PFS9). We anticipate 9 patients for stage one and 24 in total, for each arm. Treatment effect is defined as 65% of the patients in an experimental arm reaching PFS9. For the survival analysis, supplementing the control arm data with leveraged external controls taken from our prospectively registered database will decrease the probability of false positive results. CONCLUSION Gliotarget complements the field of ongoing platform trials with its distinctive trial design. The chosen biomarkers and treatments will be presented at the 2022 EANO meeting. Enrollment is set to open in Q4 2022.

P15.06.B Influence of arterial transit time delays on the differentiation between tumor progression and pseudo-progression in glioblastoma by arterial spin labeling MRI

Abstract Background Perfusion MRI by Arterial Spin Labeling (ASL) and Dynamic Susceptibility Contrast (DSC) has shown its potential for differentiating tumor progression from pseudo-progression in glioblastoma patients. The ASL scans can be affected by arterial transit time (ATT) delays, which could be caused by treatment effects due to concomitant radiochemotherapy. A prolonged ATT is present as apparent signal increase in the large arteries due to labeled spins still residing within the vasculature, leading to underestimation of tissue perfusion and thus potentially affecting clinical decision-making. The research questions were: 1) Do delayed ATTs lead to a difference in the visual assessment of ASL perfusion (normal/increased) maps compared to DSC-MRI?; 2) Does the radiological evaluation (progression vs. pseudo-progression) of ASL and DSC perfusion maps differ when ATT artifacts are present?; 3) Do delayed ATTs affect the predictive value of ASL-MRI scans 3 months post-radiotherapy for detecting true disease progression? Material and Methods This retrospective, single-center study included 68 adult patients with histologically confirmed glioblastoma who received postoperative radio(chemo)therapy. ASL and DSC scans were acquired 3 months post-radiotherapy as part of routine clinical follow-up. The perfusion data were visually scored by a neuroradiologist who determined presence/absence of ATT artifacts and their severity (%), perfusion of the enhancing tumor lesion and the radiological evaluation of tumor progression versus pseudo-progression. Presence of true disease progression was determined by follow-up of clinical data until 9 months post-radiotherapy available for 49/68 patients. Logistic regression was performed with gender, age, treatment type and tumor genetic status as covariates to assess the predictive value of ASL. Results In 78% of the patients ATT artifacts were present. No statistically significant association between the agreement of the perfusion maps and presence of ATT artifacts was found, but presence of ATT artifacts lowered the agreement between the DSC and ASL radiological evaluation. The logistic regression analysis showed that the ASL-based radiological score could not predict true disease progression, whereas higher age and unmethylated MGMT gene were associated with progression. Presence of ATT artifacts was not associated with tumor progression. Conclusion The presence of delayed ATT in ASL data seems to impact the radiological evaluation of ASL data, steering interpretation towards tumor progression (as compared to the DSC evaluation), whereas in patients without ATT artifacts ASL and DSC provide more similar radiological scores. Therefore, it is highly recommended to consider these artifacts when interpreting ASL perfusion MRI to differentiate between tumor progression and pseudo-progression in glioblastoma patients.

Strahlentherapie endokriner Tumoren

BackgroundEven with the advent of new systemic therapy options, radiotherapy keeps its place for the treatment of endocrine and neuroendocrine tumors. The advancement of radiotherapy technology has enabled its advent into the treatment of rare tumor entities.Materials and methodsA selective PubMed search was performed and national and international guidelines were taken into consideration.ResultsEndocrine and neuroendocrine tumors are rarely treated by definitive radiotherapy. For anaplastic thyroid carcinomas and aggressive pituitary tumors, radiotherapy represents a cornerstone of multimodal treatment. Locally advanced neuroendocrine tumors (NET) can be treated with concomitant radiochemotherapy. Stereotactic ablative radiotherapy is applied in oligometastatic cases. In palliative situations, radiotherapy is successfully used for symptom relief.ConclusionDespite advances in systemic therapy options for treatment of endocrine and neuroendocrine tumors, the field of radiation therapy continues to offer a broad spectrum of therapies from curative to palliative situations, including oligometastasis. The decision for radiotherapy treatment should be made by a multidisciplinary team.

The Routine Application of Tumor-Treating Fields in the Treatment of Glioblastoma WHO° IV

Introduction:Tumor-treating fields (TTFs) are a specific local oncological treatment modality in glioblastoma multiforme WHO° IV (GBM). Their mechanism of action is based on the effect of electrical fields interfering with the mitotic activity of malignant cells. Prospective studies have demonstrated efficacy, but TTF benefits are still controversially discussed. This treatment was implemented in our center as the standard of care in January 2016. We thus discuss the current state of the art and our long-term experience in the routine application of TTF.MethodsThe data of 48 patients suffering from GBM and treated with TTF were assessed and compared with previously published studies. Up-to-date information from open sources was evaluated.ResultsA total of 31 males and 17 females harboring a GBM were treated with TTF, between January 2016 and August 2021, in our center. In 98% of cases, TTFs were started within 6 weeks after concomitant radiochemotherapy (Stupp protocol). Mean overall survival was 22.6 months (95% CI: 17.3–27.9). Current indications, benefits, and restrictions were evaluated. Future TTF opportunities and ongoing studies were reviewed.ConclusionTTFs are a feasible and routinely applicable specific oncological treatment option for glioblastoma multiforme WHO° IV. Further research is ongoing to extend the indications and the efficacy of TTF.

HGG-16. Final analysis of the HIT-HGG-2007 trial (ISRCTN19852453): Significant survival benefit for pontine and non-pontine pediatric high-grade gliomas in comparison to previous HIT-GBM-C/-D trials.

The aim of the HIT-HGG-2007 trial (ISRCTN19852453) was to demonstrate therapeutic non-inferiority of temozolomide radiochemotherapy for pediatric patients (3-18 years) with high-grade gliomas (pedHGG) in comparison to the cisplatinum-based radiochemotherapy of the two previous clinical trials HIT-GBM-C/-D. Between 06/2009 and 12/2016, 456 patients were enrolled at 79 centers in Germany, Austria, and Switzerland (n=18 dropouts, remaining patients for confirmatory analysis: n=438). 438 patients from HIT-GBM-C/-D served as historical control. All pedHGG diagnoses had been confirmed by central neuroradiological and neuropathological review. Primary objective was achieved since non-inferiority of HIT-HGG-2007 in comparison to HIT-GBM-C/-D as indicated by 6 months event-free survival (EFS) was statistically confirmed (p=0.0125). Statistical survival analyses even revealed a better overall survival (OS) and EFS for HIT-HGG-2007 patients in comparison to their HIT-GBM-C/-D counterparts (EFS: p<0.0001; OS: p=0.0328). While EFS subgroup analyses for pontine and non-pontine pedHGG also showed a better survival of HIT-HGG-2007 patients (median EFS pontine pedHGG: 8.2 (n=152; confidence interval (CI): 7.6-9.4) versus 6.2 (n=170; CI: 5.5-6.9) months, p=0.0079; median EFS non-pontine pedHGG: 10.7 (n=276; CI: 9.6-12.4) versus 7.4 (n=267; CI: 6.4-9.2) months, p<0.0001), OS was only improved in HIT-HGG-2007 patients with non-pontine pedHGG (median OS non-pontine pedHGG: 19.3 (CI: 16.8-23.3) versus 16.2 (CI: 14.2-19.1) months; p=0.0181) but not with pontine pedHGG (median OS pontine pedHGG: 11.4 months versus 11.3 months, p=0.4021) Toxicity profile of HIT-HGG-2007 seemed very favorable with most CTCAE (common toxicity criteria adverse event) ≥ grade 3 as hematological toxicity, hepatotoxicity, and neurotoxicity. Less toxicity was observed during concomitant radiochemotherapy in comparison to HIT-GBM-C/-D. Further subgroup survival analyses as well as the assessment of the impact of MGMT promoter methylation are ongoing. In conclusion, our data show non-inferiority of the HIT-HGG-2007 trial with increased survival and less toxicity when compared with previous trials HIT-GBM-C/-D.

Impact of therapeutic strategy on disease-free and overall survival of early-stage cervical cancer: Surgery alone versus preoperative radiotherapy.

e17517 Background: At present, there is no international consensus for management of early-stage cervical cancer. This study aimed to retrospectively investigate disease-free survival (DFS) and overall survival (OS) in patients with early cervical cancer according to the therapeutic strategy used, surgery alone versus pre-operative radiotherapy following by surgery. Methods: Data from patients with early-stage cervical cancer were retrospectively collected from January 1998 to December 2015 using the Breast &amp; Gynecological Cancer Registry of the Côte d’Or, regrouping data from 7 centers. The inclusion criteria were: FIGO 2009 stage IB1 or lower; epidermoid, adenocarcinoma or adenosquamous type. The exclusion criteria were: history of pelvic radiation; concomitant radiochemotherapy; adjuvant radiotherapy; total radiation dose less than 50 Gy, or more than 66 Gy or not documented. In the surgery group, patients had only a surgical treatment for early-stage cervical cancer. The surgical treatment was either a hysterectomy, a trachelectomy or a conization. In the radiation group; patients had radiotherapy, brachytherapy and/or radiotherapy followed by surgery. DFS and OS were determined using the Kaplan-Meier method .Survival curves were compared using the log-rank test. Results: A total of 126 patients were included. Median survival in the whole population was 90 months (47-148); 72 months for those receiving primary surgery, and 135.5 months for those receiving primary radiation therapy. There was no significant difference in DFS between the surgery and radiation groups (HR=2.82, 95%CI (0.82-9.65), p=0.08). Similarly, there was no significant difference in OS between groups (HR=1.35, 95%CI (0.6-3.05), p=0.5). In the sub-group of patients with stage IB1 (FIGO 2009), there was no significant difference in DFS (HR=3.26, 95%CI (0.4-26.76), p=0.2) or in OS (HR=3.87, 95%CI (0.49-30.35), p=0.2) between groups. Conclusions: Cervical cancer counts among the only solid tumors for which increasing mortality has been observed in recent years. Radiation therapy is still a major source of morbidity for young patients. Therefore, key issues remain outstanding for the future management of young patients with cervical cancer and include reducing the morbidity of existing therapeutic options by identifying subgroups of patients at low or intermediate risk, and facilitating fertility-sparing surgery.

First Report of Tumor Treating Fields (TTFields) Therapy for Glioblastoma in Comorbidity with Multiple Sclerosis.

Tumor Treating Fields (TTFields) therapy is FDA approved and has the CE mark for treatment of newly diagnosed and recurrent glioblastoma. To our knowledge, to date TTFields therapy remains unstudied in glioblastoma patients with multiple sclerosis (MS) as a comorbidity. Here, we present a patient who was diagnosed with MS at the age of 34. Treatment included several corticoid pulse treatments and therapies with interferon beta-1a and sphingosine-1-phosphate receptor modulator fingolimod. At the age of 52 the patient was diagnosed with glioblastoma, after experiencing worsening headaches which could not be attributed to the MS condition. After subtotal resection and concomitant radiochemotherapy, the patient received temozolomide in combination with TTFields therapy. For two years, the tumor condition remained stable while the patient showed high adherence to TTFields therapy with low-grade skin reactions being the only therapy-related adverse events. After two years, the tumor recurred. The patient underwent re-resection and radiotherapy and restarted TTFields therapy together with chemotherapy and is currently still on this therapy regime. Although having not been studied systematically, the case presented here demonstrates that TTFields therapy may be considered for newly diagnosed and recurrent glioblastoma patients with previously diagnosed multiple sclerosis.

Sex-Dependent Analysis of Temozolomide-Induced Myelosuppression and Effects on Survival in a Large Real-life Cohort of Patients With Glioma.

To investigate the association of radiochemotherapy-induced cytopenia with sex and its potential effect on survival in patients with glioma. We retrospectively analyzed cytopenia during temozolomide-based concomitant radiochemotherapy in 492 patients with glioma. Histologic grading, molecular pathology, surgical procedures, adjuvant chemotherapy subsequent to the radiochemotherapy phase, and overall survival (OS) were recorded. The extent of cytopenia was correlated with sex and outcome. Treatment-induced severe cytopenia (leukocytopenia, lymphocytopenia, neutropenia, and thrombocytopenia) was more frequent in women than men (44 vs 18%; p = 0.0002). In women with IDH-wt high-grade astrocytomas, there was a negative correlation of severe cytopenia in general and thrombocytopenia in particular during temozolomide radiochemotherapy with OS independent from other predictors (92 [77-111] vs 73 [21-127] weeks; p < 0.05). In men, there was also a trend for this unfavorable effect. In addition, severe cytopenia in all blood cell lineages correlated with reduced temozolomide dose exposure during radiochemotherapy (all p < 0.05 in the total cohort) and reduced dose exposure was independently associated with worse OS (hazard ratios for OS in complete vs reduced temozolomide dose in the total and female cohort 0.66 [0.47-0.92] and 0.4 [0.24-0.69], p < 0.05). Our analysis of treatment-induced cytopenia in a large cohort of patients with glioma confirms that women are at higher risk and demonstrates an association of cytopenia with shortened survival in women. This study provides Class II evidence that women with glioma treated with temozolomide-based concomitant radiochemotherapy have more frequent treatment-induced severe cytopenia than men and that severe myelosuppression correlates with worse OS in women.

État des lieux et perspectives thérapeutiques pour les carcinomes nasopharyngés localement évolués

Nasopharyngeal carcinoma diagnosis is often made at a locally advanced stage (75 to 90% of cases) due to its deep localization. Concomitant radio-chemotherapy is the cornerstone of the treatment of locally advanced forms. The advent of intensity-modulated radiotherapy has improved oncological outcomes and reduced toxicity and is currently the gold standard for irradiation technique. For the locally advanced stage, the addition of induction chemotherapy has become the new standard care according to the latest international recommendations to reduce tumor volumes and act early on micro-metastases. Despite these therapeutic advances, the local and especially distant failure rate remains high. This article reviews current treatment strategies and discuss new approaches and perspectives of locoregional and systemic treatment to reduce treatment failures.