Efficacy and Safety of Adjuvant Radiotherapy in Re-excised Soft-tissue Sarcoma After Unplanned Resection.

INTRODUCTION: The objective of this study was to evaluate the efficacy and safety of adjuvant radiotherapy (aRT) in patients with soft-tissue sarcoma (STS) re-excised after unplanned tumor resection (UPR). MATERIALS AND METHODS: From 2000 to 2015, we retrospectively evaluated patients with STS of limb or trunk who underwent post-UPR re-excision in our expert center and received or not aRT. RESULTS: Median follow-up was 121 months (IQR 94-165). Among the 145 patients, 37 were not treated with aRT (no-RT) and 108 received aRT with a median radiation dose of 50 Gy (IQR 50-60). At 10 years, patients in the aRT and no-RT groups showed a cumulative incidence of local failure (10y-LF) of 14.7% and 37.7%, and a local recurrence-free survival (10y-LRFS) of 61.3% and 45.8%, respectively. Multivariate analysis identified aRT and age ≥70 years as independent predictors of both LF and LRFS, while grade 3 and deep-seated tumor were independent predictors of LRFS. In overall population, 10-year distant metastasis-free survival (10y-DMFS) and overall survival (10y-OS) were 63.7% and 69.4%. In multivariate analyses, age ≥70 years, grade 3, and deep-seated lesion were associated with shorter DMFS and OS. Acute severe adverse events were not significantly increased in aRT group (14.8% vs. 18.1%, P = .85) but dramatically increased if radiation dose exceeded 50 Gy (risk ratio 2.96 compared to ≤50 Gy, P = .04). CONCLUSION: In STS patients re-excised after UPR, 50 Gy aRT was safe and associated with reduced LF and longer LRFS. It seems to be beneficial even in absence of residual disease or in absence of initial adverse prognostic factors.

Long-term outcomes after definitive radiotherapy with modern techniques for unresectable soft tissue sarcoma.

INTRODUCTION: The use of definitive radiotherapy (dRT) in unresectable soft-tissue sarcomas (STS) is still controversial and recent data are scarce. We report clinical results of this therapeutic option. METHODS: We retrospectively included STS patients treated between 2009 and 2020, with dRT for unresectable or with a measurable residual disease after R2 surgery. Response rate, local failure (LF), progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: 116 patients with localized/locally advanced STS were treated from 2009 to 2020, with a median age of 71 years (range 18-92). Most tumors were deep-seated (96.6%), grade 2-3 (85.1%), located in the trunk or extremities (74.2%). Helical tomotherapy, volumetric modulated arc therapy, or stereotactic radiotherapy was performed in 39.7%, 19% and 8.6% of patients, respectively. The median equivalent dose in 2 Gy fractions (EQD2) was 60 Gy (IQR 52-65). At first follow-up, 66 (58.9%) and 25 (22%) patients had stable disease and partial response. After a median follow-up of 54.8 months (IQR 40.3-95.4), 3-year LF, PFS and OS were 43.2%, 16.6% and 34%, respectively. Median OS was 21.4 months (95%CI 14-26). The multivariate analysis identified grade 3 and AJCC T3-T4 stage to be associated with both shorter PFS and OS (all p < 0.001). Macroscopically incomplete resection and EQD2 ≥ 64 Gy were associated with better OS (p = 0.016 and p = 0.007). Acute and late severe adverse events occurred in 24 (19.7%) and 5 (4.3%) patients. CONCLUSION: In unresectable STS patients, definitive modern radiotherapy is a safe and effective treatment yielding long term control in selected patients.

Toxicity and efficacy of stereotactic body radiotherapy for ultra-central lung tumours: a single institution real life experience.

OBJECTIVES: The use of stereotactic body radiotherapy (SBRT) to treat ultra-central lung tumours remains more controversial than for peripheral and central tumours. Our objective was to assess toxicities, local control (LC) rate and survival data in patients with ultra-central lung tumours treated with SBRT. METHODS: We conducted a retrospective and monocentric study about 74 patients with an ultra-central lung tumour, consecutively treated between 2012 and 2018. Ultra-central tumours were defined as tumours whose planning target volume overlapped one of the following organs at risk (OARs): the trachea, right and left main bronchi, intermediate bronchus, lobe bronchi, oesophagus, heart. RESULTS: Median follow-up was 25 months. Two patients (2.7%) showed Grade 3 toxicity. No Grade 4 or 5 toxicity was observed. 11% of patients experienced primary local relapse. LC rate was 96.7% at 1 year and 87.6% at 2 years. Median progression free survival was 12 months. Median overall survival was 31 months. CONCLUSION: SBRT for ultra-central tumours remains safe and effective as long as protecting organs at risk is treatment-planning priority. ADVANCES IN KNOWLEDGE: The present study is one of the rare to describe exclusively ultra-central tumours through real-life observational case reports. Globally, literature analysis reveals a large heterogeneity in ultra-central lung tumours definition, prescribed dose, number of fractions. In our study, patients treated with SBRT for ultra-central lung tumours experienced few Grade 3 toxicities (2.7%) and no Grade 4 or 5 toxicities, due to the highest compliance with dose constraints to OARs. LC remained efficient.

Impact of histological subtype on radiological and pathological response after neoadjuvant radiotherapy in soft tissue sarcoma.

BACKGROUND: Evaluation of response to neoadjuvant radiotherapy (NART) does not consider soft tissue sarcoma (STS) heterogeneity. We aimed to investigate radiological and pathological response of 4 major histotypes. METHODS: Extremity or trunk STS patients who received 50 Gy NART between 2009 and 2020 were retrospectively included. Relative variation in tumor size (RVTS) and pathological response were reported in the overall population and in undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), myxoid liposarcoma (MLS) and synovial sarcoma (SS) patients to identify response modalities of each histotype. RESULTS: Among the 121 included patients, 49, 19, 13 and 11 presented UPS, MFS, MLS and SS. Median RVTS were 0% (IQR -18-+18), +8% (IQR 0-+24), -12% (IQR -20-3) and -11% (IQR -15-9), respectively (p = 0.001). Median viable cells were 10%, 60%, 20% and 70% (p = 0.007). In overall population, pathological complete response and median necrosis were 27.7% and 10% without significant correlation to histotype (p = 0.18 and 0.06). Nineteen (38.8%) UPS specimens presented cysts that were emptied during the sampling process and distorted the microscopic response evaluation. Infiltrative growth pattern was observed in 28% and 38.9% UPS and MFS patients. Five (38.5%) MLS presented mature adipocytes without proven prognostic value. Cysts were observed in 36% of SS specimens. In the absence of initial tumor limits, the great viable cellularity of SS may be overestimated by their nodular aspect. CONCLUSION: After NART, we highlighted disparate response of UPS, frequent progression of MFS, and confirmed MLS and SS radiosensitivity. Response must be interpreted with caution and consider the histotype-specific patterns.

Carbon ion irradiation withstands cancer stem cells' migration/invasion process in Head and Neck Squamous Cell Carcinoma (HNSCC).

Cancer Stem Cells (CSCs) in Head and Neck Squamous Cell Carcinoma (HNSCC) have extremely aggressive profile (high migratory and invasive potential). These characteristics can explain their resistance to conventional treatment. Efficacy of photon and carbon ion irradiation with addition of cetuximab (5 nM) is studied on clonogenic death, migration and invasion of two HNSCC populations: SQ20B and SQ20B/CSCs. SQ20B express E-cadherin and overexpress EGFR while SQ20B/CSCs express N-cadherin and low EGFR. Cetuximab strongly inhibits SQ20B proliferation but has no effect on SQ20B/CSCs. 2 Gy photon irradiation enhances migration and invasiveness in both populations (p < 0.05), while cetuximab only stops SQ20B migration (p < 0.005). Carbon irradiation significantly inhibits invasion in both populations (p < 0.05), and the association with cetuximab significantly inhibits invasion in both populations (p < 0.005). These results highlight CSCs characteristics: EGFRLow, cetuximab-resistant, and highly migratory. Carbon ion irradiation appears to be a very promising therapeutic modality counteracting migration/invasion process in both parental cells and CSCs in contrast to photon irradiation.

Intensity-modulated radiotherapy or volumetric-modulated arc therapy in patients with head and neck cancer: Focus on salivary glands dosimetry.

BACKGROUND: Despite radiotherapy (RT) technical improvements, high salivary dysfunction rates are still reported in patients with head and neck squamous cell carcinoma (HNSCC). The purpose of the present study was to report salivary glands dosimetry with volumetric-modulated arc therapy (VMAT) and intensity-modulated RT (IMRT). METHODS: Dosimetry of consecutive patients receiving IMRT or VMAT for proven HNSCC between 2007 and 2013 were retrospectively reviewed. RESULTS: Data of 609 patients were studied. Mean dose, mean maximum dose, and mean percentage of salivary gland volume receiving at least 26 Gy (V26) of the contralateral parotid were 24.50 Gy (range, 0-70.4 Gy), 39.08 Gy (range, 0.38-76.45 Gy), and 40.92% (range, 0% to 100%), respectively. Mean and maximum dose on contralateral submandibular gland were 48.18 Gy (range, 0.19-70.73 Gy), and 61.25 Gy (range, 0-75.8 Gy), respectively. CONCLUSION: Target volume coverage still has to be prioritized over organs at risk (OAR) sparing with new RT techniques. Submandibular glands are not sufficiently taken into account in guidelines. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1028-1034, 2016.

Influence of Nucleoshuttling of the ATM Protein in the Healthy Tissues Response to Radiation Therapy: Toward a Molecular Classification of Human Radiosensitivity.

PURPOSE: Whereas post-radiation therapy overreactions (OR) represent a clinical and societal issue, there is still no consensual radiobiological endpoint to predict clinical radiosensitivity. Since 2003, skin biopsy specimens have been collected from patients treated by radiation therapy against different tumor localizations and showing a wide range of OR. Here, we aimed to establish quantitative links between radiobiological factors and OR severity grades that would be relevant to radioresistant and genetic hyperradiosensitive cases. METHODS AND MATERIALS: Immunofluorescence experiments were performed on a collection of skin fibroblasts from 12 radioresistant, 5 hyperradiosensitive, and 100 OR patients irradiated at 2 Gy. The numbers of micronuclei, γH2AX, and pATM foci that reflect different steps of DNA double-strand breaks (DSB) recognition and repair were assessed from 10 minutes to 24 hours after irradiation and plotted against the severity grades established by the Common Terminology Criteria for Adverse Events and the Radiation Therapy Oncology Group. RESULTS: OR patients did not necessarily show a gross DSB repair defect but a systematic delay in the nucleoshuttling of the ATM protein required for complete DSB recognition. Among the radiobiological factors, the maximal number of pATM foci provided the best discrimination among OR patients and a significant correlation with each OR severity grade, independently of tumor localization and of the early or late nature of reactions. CONCLUSIONS: Our results are consistent with a general classification of human radiosensitivity based on 3 groups: radioresistance (group I); moderate radiosensitivity caused by delay of nucleoshuttling of ATM, which includes OR patients (group II); and hyperradiosensitivity caused by a gross DSB repair defect, which includes fatal cases (group III).

Real-life assessment of Volumetric Modulated Arc Therapy (VMAT) toxicity in Head and Neck Squamous Cell Carcinoma (HNSCC) treatment.

CONCLUSION: The present study demonstrates the feasibility of VMAT in association with platin or cetuximab in HNSCC and reports VMAT-related acute and late toxicities for the first time. OBJECTIVES: New radiotherapy techniques, such as Volumetric Modulated Arc Therapy (VMAT) were developed to lower RT-related toxicity. The aim of the present study was to investigate acute and late toxicities of head and neck squamous cell carcinoma (HNSCC) patients treated using VMAT. METHODS: This study investigated retrospectively all patients with HNSCC who received VMAT in curative intent. RESULTS: From 2010-2013, 150 patients were treated. Seventy-five patients (50%) received concurrent chemotherapy with VMAT, 51 patients (34%) received VMAT alone and 24 patients (16%) received concurrent cetuximab with VMAT. Mean delivered dose to planning target volume tumor (PTV T), high risk nodes (PTV HNR), low risk nodes (PTV LNR) and prophylactic nodes (PTV PN) were: 65.2 Gy, 62.9 Gy, 55.4 Gy, and 51.5 Gy, respectively. PTV mean coverages were higher than 96.5%. Most common grade 3/4 acute infield toxicities were mucosis (n = 28, 19%), dysphagia (n = 24, 16%), and dermatitis (n = 24, 16%). With a median follow-up of 16.0 months, most common late toxicities were dysphagia (n = 30, 20%), xerostomia (n = 28, 19%), larynx stiff (n = 17, 11%), and skin fibrosis (n = 14, 9%).

Chemotherapy Regimen in Nonagenarian Cancer Patients: A Bi-Institutional Experience.

BACKGROUND: The elderly population in Western countries is growing and constitutes a public health issue. Concomitantly, age-related diseases such as cancer increase. There are few data on the efficacy, tolerability and toxicity of specific anticancer therapy in the very elderly patients; therefore, their management is not standardized. METHODS: In this bi-institutional study, we reviewed medical records of patients who received or continued specific anticancer therapy beyond the age of 90 years. Geriatric assessment was not reported for our patients. Twelve patients were enrolled. Their general health condition was good, and half of them were living in elderly institutions. Ten patients had a solid tumor and 2 were treated for hematological malignancies. Most were diagnosed with a locally advanced or metastatic disease, and the goal of treatment was curative for only 1 patient. Six patients received chemotherapy as first-line treatment, 4 patients received targeted therapy and 2 received concomitant chemoradiation. Four patients received a second-line treatment. RESULTS: Despite a significant reduction in treatment posology in half of the patients, 8 acute grade 3/4 toxicities were reported and 2 patients died of treatment-related septic shock. Median duration of first-line treatment was 3.2 months, and progression-free survival ranged from 18 to 311 days. Overall survival ranged from 18 days to 11 years. CONCLUSION: Aging is a heterogeneous process, and management of elderly patients is a multidisciplinary approach. Geriatric assessment helps to identify older patients with a higher risk of morbidity/mortality and allows to assess the risks and benefits of specific anticancer therapy. The choice of treatment should be based primarily on the expected symptomatic benefit, and treatment should not compromise the quality of life.

Hypofractionated radiation therapy for treatment of bladder carcinoma in patients aged 90 years and more: A new paradigm to be explored?

INTRODUCTION: There are only scarce data on the optimal management of patients who present with a bladder carcinoma and who are aged 90 years and older. PATIENTS AND METHODS: We retrospectively reviewed records from radiotherapy departments from two university hospitals, two private centers and one public center to identify patients who underwent radiotherapy for bladder cancer over the past decade and who were aged 90 years or older. From 2003 to 2013, 14 patients aged 90 years or older receiving RT for bladder malignant tumors were identified. RESULTS: Mean age was 92.7 years. Ten patients (71 %) had a general health status altered (PS 2-3) at the beginning of RT. A total of 14 RT courses were delivered, including six treatments (43 %) with curative intent and eight treatments (57 %) with palliative intent. Palliative intent mainly encompassed hemostatic RT (36 %). At last follow-up, two patients (14 %) experienced complete response, one patient (7 %) experienced partial response, three patients (21 %) had their disease stable, and three patients (21 %) experienced tumor progression, of whom two patients with the progression of symptoms. There was no reported high-grade acute local toxicity in 14 patients (100 %). One patient experienced delayed grade 2 toxicity with pain and lower urinary tract symptoms. At last follow-up, seven patients (50 %) were deceased. Cancer was the cause of death for five patients. CONCLUSION: Hypofractionated radiotherapy remains feasible for nonagenarians with bladder cancer. Further investigations including analysis of geriatric comorbidities and impact of treatments on quality of life should be conducted.

Radiotherapy for head and neck cancer in nonagenarian patients: a possible cornerstone?

In the field of radiotherapy, there is very little scientific data on the management of nonagenarians, especially in patients aged 90 years or more and with head and neck cancer (HNC). We made one of the first retrospective study of the feasibility and safety of radiotherapy in this population with HNC. Records of radiotherapy coming from four health facilities were studied to include all nonagenarian patients with HNC in the last 10 years and who received radiation therapy. We analyzed patient characteristics and primary cancers, as well as objective of the treatment (curative or palliative), efficacy and toxicity. Twenty patients receiving radiotherapy were identified; mean age was 93.2 years (standard deviation 2.8). Treatment was given with curative and palliative intent in 40 and 60 % of cases, respectively. The most common primary tumors were tumors of the salivary glands (30 % of cases), oral cavity tumors (25 % of cases) and thyroid tumors (15 % of cases). Median total prescribed dose was 47.5 Gy (12-70 Gy). Median number of delivered fractions was 18.5 (2-35 fractions). All patients received intensive supportive care during radiotherapy. Toxicities were mild to moderate. Radiotherapy could not be completed for four patients (20 % of cases). One patient developed grade 1-2 delayed toxicities. At the last follow-up, only four patients (20 % of cases) were alive. Cancer was cause of death in most cases. Radiotherapy may be performed for the nonagenarians with HNC. The total dose and fractionation must be adjusted to optimize the tolerance. However, the prognosis remains very poor, cancer being the main cause of death. Research of geriatric vulnerabilities prior to any treatment, in the context of a comprehensive geriatric assessment, is still recommended to select patients for radiotherapy.

[Radiation-induces increased tumor cell aggressiveness of tumors of the glioblastomas?]. / La radiothérapie induit-elle une agressivité accrue des cellules tumorales du glioblastome ?

Glioblastoma multiform is the most common and aggressive brain tumor with a worse prognostic. Ionizing radiation is a cornerstone in the treatment of glioblastome with chemo-radiation association being the actual standard. As a paradoxal effect, it has been suggested that radiotherapy could have a deleterious effect on local recurrence of cancer. In vivo studies have studied the effect of radiotherapy on biological modification and pathogenous effect of cancer cells. It seems that ionizing radiations with photon could activate oncogenic pathways in glioblastoma cell lines. We realized a review of the literature of photon-enhanced effect on invasion and migration of glioblastoma cells by radiotherapy.

[Carcinosarcomas in female genital tracts: general review]. / Carcinosarcomes gynécologiques: revue générale et principes de prise en charge.

Carcinosarcoma, also known as mixed mesodermal tumor or malignant mixed Mullerian tumor (MMMT) is a pathological entity combining a sarcomatous and a carcinomatous component. Found in thoracic, digestive, genitourinary, liver or skin locations, the most common location is the female genital tract. In gynecological tumors, carcinosarcoma accounts for about 2-5% of endometrial cancers, and 1% of ovarian cancers. To date, there is no consensus on the therapeutic strategy. It relies mostly on maximum cytoreductive surgery. Adjuvant therapy remains controversial, and few prospective studies investigating its interest. Retrospective studies show the benefits of adjuvant chemotherapy based on platinum in most cases. Radiation therapy has a place in the adjuvant situations of endometrial and cervical carcinosarcoma. A more detailed pathological knowledge, and the use of targeted therapies may be promising in this histological subtype whose prognosis remains very poor. The objective of this study is to present the main principles of carcinosarcoma management in female genital tracts, describing pathological and prognostic features at the same time.

Radiation-enhanced cell migration/invasion process: a review.

Radiation therapy is a keystone treatment in cancer. Photon radiation has proved its benefits in overall survival in many clinical studies. However, some patients present local recurrences or metastases when cancer cells survive to treatment. Metastasis is a process which includes adhesion of the cell to the extracellular matrix, degradation of the matrix by proteases, cell motility, intravasation in blood or lymphatic vessels, extravasation in distant parenchyma and development of cell colonies. Several studies demonstrated that ionizing radiation might promote migration and invasion of tumor cells by intricate implications in the micro-environment, cell-cell junctions, extracellular matrix junctions, proteases secretion, and induction of epithelial-mesenchymal transition. This review reports various cellular pathways involved in the photon-enhanced cell invasion process for which potential therapeutic target may be employed for enhancing antitumor effectiveness. Understanding these mechanisms could lead to therapeutic strategies to counter the highly invasive cell lines via specific inhibitors or carbon-ion therapy.

[Melanomas of the female genital tract: state of the art]. / Mélanomes du tractus génital féminin : état des lieux.

Melanoma of the female genital tract is a rare location (less than 2% of melanomas all sites combined). These cancers have a very poor prognosis, due to the delay in diagnosis. Vulvar location is about 1% of melanomas then the vaginal location, uterine and ovarian. There is no consensus to date regarding their care, due to the rarity of the lesions. Their treatment must however be based on the current data concerning gynaecological cancers as well as standard management of cutaneous melanoma. The treatment is often based on conservative surgery, because radical resection does not improve survival. For the vulva and vagina, reconstructive surgery is possible. Treatment is sometimes supplemented by chemotherapy or radiotherapy, which could improve local control. The interest in the use of targeted therapy in these locations is not well known because of their rarity, but the study of genes c-Kit and BRAF provides new prospects for treatment. The objective of this review is to describe and report the current state of knowledge about gynaecologic melanomas.

[Management of vaginal carcinoma in patients over 70 years old: advantage of a radiotherapy-brachytherapy association]. / Prise en charge du cancer primitif du vagin chez la femme de plus de 70ans: intérêt d'une association radiothérapie-curiethérapie.

OBJECTIVE: Report and discuss the management of the primitive vaginal cancer in elderly adults at a single institute. PATIENTS AND METHODS: Data from patients more than 70 year-old treated for a primitive vaginal cancer at the Institut de Cancérologie de la Loire Lucien-Neuwirth was retrospectively collected. RESULTS: From August 1999 to January 2009, 9/24 patients treated for a primitive vaginal cancer had more than 70 year-old. The median age was 81 years (7-94 years). Most patients had a performance status less or equal to 1 (n=6), a squamous cell carcinoma (n=7) and a FIGO stage less or equal to II (n=6). All patients were treated with 3D external beam radiation, 3 received concurrent chemotherapy, 3 had a supplementary brachytherapy, and 6 had a colpohysterectomy. Among 7 evaluable patients, there were 4 complete responses, 2 partial responses and one progression. Main acute toxicities were gastrointestinal (n=5), urinary (n=3), general (n=3) and cutaneous (n=2). Three patients experienced late toxicities. Four patients had a local recurrence after a mean delay of 10.8 months. At last news, 4 patients were still alive and 4/5 deaths were related to the cancer. All (n=3) patients who received the combination of radiotherapy - brachytherapy were alive and disease-free. Median overall survival was 18 months. DISCUSSION AND CONCLUSIONS: Primitive vaginal cancers are rare and aggressive tumours. Our results suggested the feasibility of the combination of radiotherapy and brachytherapy for elderly patients. Prospective trials remain needed to better define and validate the optimal strategy, especially in elderly adults.

Volumetric modulated arc radiotherapy for limited osteosclerotic myeloma.

AIM: To assess the feasibility of volumetric intensity-modulated arc radiotherapy (VMAT) in patients with limited polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome. METHODS: A 70-year-old male with histologically confirmed osteosclerotic myeloma was treated in our department in July 2010 with VMAT. Fourty-six Gray in 23 fractions were given on three bone lesions. Doses delivered to target volume and critical organs were compared with a tridimensional conformal radiotherapy (3D-RT) plan. Treatment was well tolerated without any side effects. RESULTS: VMAT improved dose homogeneity within the target volume, as compared to 3D-RT (standard deviations: 2.9 Gy and 1.6 Gy for 3D and VMAT, respectively). VMAT resulted in a better sparing of critical organs. Dose delivered to 20% of organ volume (D20) was reduced from 22 Gy (3D-RT) to 15 Gy (VMAT) for small bowel, from 24 Gy (3D-RT) to 17 Gy (VMAT) for bladder and from 47 Gy (3D-RT) to 3 Gy (VMAT) for spinal cord. Volumes of critical organs that received at least 20 Gy (V20) were decreased by the use of VMAT, as compared to 3D-RT (V20 bladder: 10% vs 99%; V20 small bowel: 6% vs 21%). One year after treatment completion, no tumor progression has been reported. CONCLUSION: VMAT improved dose distribution as compared to 3D-RT for limited osteosclerotic myeloma, with better saving of critical organs.

[Cancer stem cells, cornerstone of radioresistance and perspectives for radiosensitization: glioblastoma as an example]. / Facteurs de radiorésistance des cellules souches cancéreuses et perspectives de radiosensibilisation : l'exemple du glioblastome.

Cancer stem cells are a subject of increasing interest in oncology. In particular, several data suggest that cancer stem cells are involved in the mechanisms of tumor radioresistance, and may explain the therapeutic failures after radiotherapy. Because of its poor prognosis and high recurrence rate after irradiation, glioblastoma model is often studied in the search for new radiosensitizers. There are several preclinical data suggesting that cancer stem cells could be a potential therapeutic target for improving the biological effectiveness of radiation therapy. Through the example of glioblastoma, we review the main signaling pathways involved in the mechanisms of radiation resistance of cancer stem cells and for which pharmacological targeting could potentially enhance tumor radiosensitivity.