Survival Outcomes Associated With First-Line Procarbazine, CCNU, and Vincristine or Temozolomide in Combination With Radiotherapy in IDH-Mutant 1p/19q-Codeleted Grade 3 Oligodendroglioma.

PURPOSE: Patients with IDH-mutant 1p/19q-codeleted grade 3 oligodendroglioma (O3IDHmt/Codel) benefit from adding alkylating agent chemotherapy to radiotherapy (RT). However, the optimal chemotherapy regimen between procarbazine, 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine (PCV) and temozolomide (TMZ) remains unclear given the lack of randomized trial data comparing both regimens. METHODS: The objective was to assess the overall survival (OS) and progression-free survival (PFS) associated with first-line PCV/RT versus TMZ/RT in patients newly diagnosed with O3IDHmt/Codel. We included patients with histologically proven O3IDHmt/Codel (according to WHO criteria) from the French national prospective cohort Prise en charge des OLigodendrogliomes Anaplasiques (POLA). All tumors underwent central pathological review. OS and PFS from surgery were estimated using the Kaplan-Meier method and Cox regression model. RESULTS: 305 newly diagnosed patients with O3IDHmt/Codel treated with RT and chemotherapy between 2008 and 2022 were included, of which 67.9% of patients (n = 207) were treated with PCV/RT and 32.1% with TMZ/RT (n = 98). The median follow-up was 78.4 months (IQR, 44.3-102.7). The median OS was not reached (95% CI, Not reached [NR] to NR) in the PCV/RT group and was 140 months (95% CI, 110 to NR) in the TMZ/RT group (log-rank P = .0033). On univariable analysis, there was a significant difference in favor of PCV/RT in both 5-year (PCV/RT: 89%, 95% CI, 85 to 94; TMZ/RT: 75%, 95% CI, 66 to 84) and 10-year OS (PCV/RT: 72%, 95% CI, 61 to 85; TMZ/RT: 60%, 95% CI, 49 to 73), which was confirmed using the multivariable Cox model adjusted for age, type of surgery, gender, Eastern Cooperative Oncology Group performance status, and CDKN2A homozygous deletion (hazard ratio, 0.53 for PCV/RT, 95% CI, 0.30 to 0.92, P = .025). CONCLUSION: In patients with newly diagnosed O3IDHmt/Codel from the POLA cohort, first-line PCV/RT was associated with better OS outcomes compared with TMZ/RT. Our data suggest that the improved safety profile associated with TMZ comes at the cost of inferior efficacy in this population. Further investigation using prospective randomized studies is warranted.

Diagnosis and management of brain radiation necrosis.

Brain radiation necrosis (BRN) is a significant and complex side effect of stereotactic radiotherapy (SRT). Differentiating BRN from local tumor recurrence is critical, requiring advanced diagnostic techniques and a multidisciplinary approach. BRN typically manifests months to years post-treatment, presenting with radiological changes on MRI and may produce neurological symptoms. Key risk factors include the volume of irradiated brain tissue, the radiation dose, and prior radiotherapy history. This manuscript reviews the diagnostic process for BRN, emphasizing the importance of assessing baseline risk, clinical evaluation, and advanced imaging modalities. Multimodal imaging enhances diagnostic accuracy and aids in distinguishing BRN from tumor relapse. Therapeutic management varies based on symptoms. Asymptomatic BRN may be monitored with regular imaging, while symptomatic BRN often requires corticosteroids to reduce inflammation. Emerging therapies like bevacizumab have shown promise in clinical trials, with significant radiographic and symptomatic improvement. Surgical intervention may be necessary for histological confirmation and severe, treatment-resistant cases. Ongoing research aims to improve diagnostic accuracy and treatment efficacy, enhancing patient outcomes and quality of life. This review underscores the need for a multidisciplinary approach and continuous advancements to address the challenges posed by BRN in brain tumor patients.

The EORTC 22922/10925 trial investigating regional nodal irradiation in stage I-III breast cancer: Outcomes according to locoregional and systemic therapies.

The EORTC 22922/10925 trial aimed to investigate the impact on overall survival (OS) of elective internal mammary and medial supraclavicular (IM-MS) radiation therapy (RT) in breast cancer stage I-III. Surgery for the primary tumour and axillary lymph nodes, chest wall RT, boost RT after whole breast RT in breast conserving therapy (BCT), RT to operated axilla, and systemic therapy were per physician's preference. The aim of the current analysis is to assess breast cancer outcomes according to different locoregional and systemic therapy used in the trial. MATERIAL/METHODS: Data with a median follow-up of 15.7 years were extracted from the trial's case report forms. Kaplan-Meier curves of disease-free and OS and cumulative incidence curves of breast cancer events were produced. An exploratory analysis of the effect of the type of locoregional and systemic therapy on breast cancer outcomes was conducted using the Cox model or the Fine & Gray model accounting for competing risks, both models being adjusted for baseline patient and disease characteristics and treatment. The significance level was set at 5 %, 2-sided. RESULTS: Of the 4,004 patients included, 625 (16%) did not receive any postoperative systemic therapy, 1,185 (30%) received endocrine therapy only, 994 (25%) chemotherapy only, and 1,200 (30%) both chemotherapy and endocrine therapy, without differences between the randomisation arms. Administration and type of therapy was associated with age, menopausal status, clinical T- and N-stage and ER status (p < 0.0001). Local control was better with mastectomy (with/without postmastectomy RT) as compared to BCT, but mastectomy was associated with more distant metastasis (DM) as first event. Similarly, DM as first event occurred more in the BCT group that received a boost as compared to no boost and in those who received RT to the lower axillary level. IM-MS RT reduced significantly regional recurrences and improved disease-free survival in a sensitivity stratified analysis. OS was worse with mastectomy as compared to BCT and with irradiation of the axilla but better with sentinel node dissection and adjuvant combined chemo and hormonal therapy. CONCLUSION: Different components of therapy influenced the site of first event. IM-MS RT improved outcomes in different breast cancer outcomes were most probably related that the group were balanced due to the trial arms and stratification methods.

Overcoming the limits of pediatric brain tumor radiotherapy: The use of preclinical 3D models.

Radiotherapy (RT) is an integral part of managing pediatric brain tumors, yet many patients develop tumor radioresistance, leading to recurrence and poor clinical outcomes. In addition, neurocognitive impairment is a common long-term side effect of RT, significantly impairing quality of life. Indeed, increasing evidence suggests that the developing child's brain is particularly vulnerable to the neurotoxic effects of ionizing radiation. Consequently, developing novel preclinical models is crucial for studying radiation's impact on normal brain tissue and predicting patient-specific responses to RT, enabling the development of personalized therapies combined with RT. However, this area remains underexplored, primarily due to the transfer of results gathered from in vitro tumor models from adults to pediatric entities while the location and molecular characteristics of the brain tumor differ. Recent years have seen the emergence of patient-specific 3D in vitro models, which have been established for entities including glioblastoma and medulloblastoma. These models better mimic primary parenteral tumors more closely in their histological, transcriptional, and mutational characteristics, thus approximating their intratumoral heterogeneity more accurately than conventional 2D-models. In this review, we presented the main limits of pediatric brain tumor radiotherapy, including mechanisms of radioresistance, associated tumor relapse, and the side effects of irradiation on the central nervous system. We also conducted an exhaustive review to identify studies utilizing basic or advanced 3D models of pediatric brain tumors combined with irradiation and discussed how these models can overcome the limitations of RT.

Role of autophagy in modulating tumor cell radiosensitivity: Exploring pharmacological interventions for glioblastoma multiforme treatment.

Autophagy is an innate cellular process characterized by self-digestion, wherein cells degrade or recycle aged proteins, misfolded proteins, and damaged organelles via lysosomal pathways. Its crucial role in maintaining cellular homeostasis, ensuring development and survival is well established. In the context of cancer therapy, autophagy's importance is firmly recognized, given its critical impact on treatment efficacy. Following radiotherapy, several factors can modulate autophagy including parameters related to radiation type and delivery methods. The concomitant use of chemotherapy with radiotherapy further influences autophagy, potentially either enhancing radiosensitivity or promoting radioresistance. This review article discusses some pharmacological agents and drugs capable of modulating autophagy levels in conjunction with radiation in tumor cells, with a focus on those identified as potential radiosensitizers in glioblastoma multiforme treatment.

Tumor reirradiation: Issues, challenges and perspectives for radiobiology.

The radiobiology of tumor reirradiation is poorly understood. It pertains to tumors and their sensitivity at the time of relapse, encompassing primary tumors, metastases, or secondary cancers developed in or proximal to previously irradiated tissues. The ability to control the pathology depends, in part, on understanding this sensitivity. To date, literature data remains limited regarding changes in the radiosensitivity of tissues after initial irradiation, and most proposals are based on conjecture. The response of healthy tissues at the site of irradiation raises concerns about radio-induced complications. Cumulative dose is likely a major factor in this risk, thus using equivalent dose calculations might help reduce the risk of complications. However, the correlation between mathematical equivalence formulas and clinical effects of radiobiological origin is weak, and the lack of knowledge of the alpha/beta (α/ß) ratio of healthy tissues remains an obstacle to the extensive use of these formulas. However, tissues exposed to recovery dose may have a tolerance to irradiation much higher than assumed, thus further biological work remains to be developed. Also, the functionality of previously irradiated tissues could be useful in selecting the most suitable irradiation beams. Finally, research on the genomics of irradiated healthy tissues could improve the prediction of side effects and personalize radiotherapy.

A 3D Convolutional Neural Network Based on Non-enhanced Brain CT to Identify Patients with Brain Metastases.

Dedicated brain imaging for cancer patients is seldom recommended in the absence of symptoms. There is increasing availability of non-enhanced CT (NE-CT) of the brain, mainly owing to a wider utilization of Positron Emission Tomography-CT (PET-CT) in cancer staging. Brain metastases (BM) are often hard to diagnose on NE-CT. This work aims to develop a 3D Convolutional Neural Network (3D-CNN) based on brain NE-CT to distinguish patients with and without BM. We retrospectively included NE-CT scans for 100 patients with single or multiple BM and 100 patients without brain imaging abnormalities. Patients whose largest lesion was < 5 mm were excluded. The largest tumor was manually segmented on a matched contrast-enhanced T1 weighted Magnetic Resonance Imaging (MRI), and shape radiomics were extracted to determine the size and volume of the lesion. The brain was automatically segmented, and masked images were normalized and resampled. The dataset was split into training (70%) and validation (30%) sets. Multiple versions of a 3D-CNN were developed, and the best model was selected based on accuracy (ACC) on the validation set. The median largest tumor Maximum-3D-Diameter was 2.29 cm, and its median volume was 2.81 cc. Solitary BM were found in 27% of the patients, while 49% had > 5 BMs. The best model consisted of 4 convolutional layers with 3D average pooling layers, dropout layers of 50%, and a sigmoid activation function. Mean validation ACC was 0.983 (SD: 0.020) and mean area under receiver-operating characteristic curve was 0.983 (SD: 0.023). Sensitivity was 0.983 (SD: 0.020). We developed an accurate 3D-CNN based on brain NE-CT to differentiate between patients with and without BM. The model merits further external validation.

Radiotherapy for central neurocytoma: A multicentric retrospective study in France.

PURPOSE: Neurocytomas represent 0.25 to 0.5% of primary brain tumours and are mainly found in young adults. These tumours have neuronal differentiation. The cornerstone treatment is neurosurgery. The efficacy of other therapies, including radiotherapy, is still unclear. The objective of this study was to evaluate the management of central neurocytomas and the role of radiotherapy. MATERIALS AND METHODS: All adult patients (age 18 years or older) newly diagnosed with a histologically confirmed neurocytoma between 2006 and 2015 in France were included. RESULTS: One hundred and sixteen patients were diagnosed with a central neurocytoma during the study period. All patients underwent surgical resection, and six received adjuvant radiotherapy. Eleven patients received radiotherapy due to progression. After a median follow-up of 68.7 months, local failure occurred in 29 patients. The 5-year local control rate was 73.4%. According to univariate analysis, marker of proliferation Ki67 index greater than 2% (hazard ratio [HR]: 1.48; confidence interval [CI]: 1.40-1.57; P=0.027) and subtotal resection (HR: 8.48; CI: 8.01-8.99; P<0.001) were associated with an increase in local failure. Gross total resection was associated with a higher risk of sequelae epilepsy (HR: 3.62; CI: 3.42-3.83; P<0.01) and memory disorders (HR: 1.35; CI: 1.07-1.20; P<0.01). Ten patients (8.6%) died during the follow-up. The 10-year overall survival rate was 89.0%. No prognostic factors for overall survival were found. CONCLUSION: The analysis showed that patients who underwent subtotal surgical resection, particularly when the tumour had a Ki67 index greater than 2%, had an increased risk of local recurrence. These patients could benefit from adjuvant radiotherapy.

Initial Age and Performans Status: Predicators for Re-Irradiation Ability in Patients with Relapsed Brain Metastasis after Initial Stereotactic Radiotherapy.

BACKGROUND: Brain metastases (BMs) frequently occur in cancer patients, and stereotactic radiation therapy (SRT) is a preferred treatment option. In this retrospective study, we analyzed patients treated by SRT for a single BM during their first SRT session and we compared two subgroups: "Cohort 1" with patients did not undergo cerebral re-irradiation and "Cohort 2" with patients received at least one subsequent SRT session for cerebral recurrence. METHODS: We included patients who received SRT for a single BM between January 2010 and June 2020. Cohort 1 comprised 152 patients, and Cohort 2 had 46 patients. RESULTS: Cohort 2 exhibited younger patients with higher Karnofsky performance status (KPS). Median overall survival was considerably longer in Cohort 2 (21.8 months) compared to Cohort 1 (6.1 months). Local and cerebral recurrence rates were significantly higher in Cohort 2 (p < 0.001), attributed to patient selection and longer survival. The combined score of age and KPS proved to be a predictive factor for survival, with patients under 65 years of age and KPS > 80 showing the best survival rates in the overall population. CONCLUSION: This retrospective study highlights that the combined score of age and KPS can predict better survival, especially for patients under 65 years with a KPS score above 80. Further research involving larger and more diverse populations is essential to validate and expand upon these findings.

Preclinical and clinical advances to overcome hypoxia in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most common adult primary brain tumor. The standard clinical treatment of GBM includes a maximal surgical resection followed by concomitant radiotherapy (RT) and chemotherapy sessions with Temozolomide (TMZ) in addition to adjuvant TMZ cycles. Despite the severity of this protocol, GBM is highly resistant and recurs in almost all cases while the protocol remains unchanged since 2005. Limited-diffusion or chronic hypoxia has been identified as one of the major key players driving this aggressive phenotype. The presence of hypoxia within the tumor bulk contributes to the activation of hypoxia signaling pathway mediated by the hypoxia-inducing factors (HIFs), which in turn activate biological mechanisms to ensure the adaptation and survival of GBM under limited oxygen and nutrient supply. Activated downstream pathways are involved in maintaining stem cell-like phenotype, inducing mesenchymal shift, invasion, and migration, altering the cellular and oxygen metabolism, and increasing angiogenesis, autophagy, and immunosuppression. Therefore, in this review will discuss the recent preclinical and clinical approaches that aim at targeting tumor hypoxia to enhance the response of GBM to conventional therapies along with their results and limitations upon clinical translation.

Complications and Risk Factors in Patients with Soft Tissue Sarcoma of the Extremities Treated with Radiotherapy.

INTRODUCTION: Soft tissue sarcomas of the extremities (ESTSs) pose significant challenges in treatment and management due to their diverse nature and potential complications. This study aimed to assess complications associated with multimodal treatments involving surgery and radiotherapy (RT) and to identify potential risk factors. METHODS: We retrospectively analyzed nonmetastatic ESTS patients treated with surgery and pre- or post-operative RT between 2007 and 2020 in Strasbourg, France. Complications, including wound complications (WCs), lymphedema, acute and chronic RT-related complications, and fractures, were meticulously evaluated. RESULTS: A total of 169 patients diagnosed with localized ESTSs were included, with a median age of 64 years (range 21-94 years). ESTSs primarily occurred proximally (74.6%) and in the lower limbs (71%). The median follow-up was 5.5 years. WCs occurred in 22.5% of patients, with proximal and lower extremity tumors being significant risk factors. Acute RT-related complications included radiodermatitis, with grade ≥ 2 occurring in 43.1% of patients, which was associated with superficial tumors. Three patients had an edema grade ≥ 2. Chronic complications included telangiectasias (21.7%) and fibrosis (38.7%), with higher rates associated with larger PTVs and higher RT doses, respectively. Fractures occurred in 5 patients, mainly in the tibia (40%). CONCLUSIONS: Multimodal treatment of ESTSs demonstrated excellent tolerance, with manageable side effects. Numerous risk factors have been highlighted, providing insights for optimizing treatment strategies and enhancing patient care in this rare disease.

Comparative study of dynamic conformal arc therapy and volumetric modulated arc therapy for treating single brain metastases: A retrospective analysis of dosimetric and clinical outcomes.

Background and purpose: Stereotactic radiation therapy (SRT) is commonly used to treat brain metastases (BMs). This retrospective study compared two SRT techniques, dynamic conformal arc therapy (DCAT) and volumetric modulated arc therapy (VMAT), for single BM treatments. Material and methods: Data of patients treated between January 2010 and June 2020 were considered. Patients with multiple BMs, resected BMs, reirradiation, whole-brain radiation therapy and brainstem metastases were excluded. We focused our analysis on 97 patients who received 23.1 Gy in three fractions. Acute toxicities and follow-up outcomes were recorded. Dosimetric data were analyzed in two subgroups (PTV ≤ 10 cc and PTV > 10 cc). Results: DCAT and VMAT were used in 70 (72.2 %) and 27 (27.8 %) patients, respectively. Acute toxicities were not significantly different between groups (p = 0.259), and no difference was detected in the incidence rate of radionecrosis, local recurrence and cerebral recurrence (p > 0.999, p > 0.999 and p = 0.682, respectively). PTV coverage was better with DCAT for small volumes (PTV ≤ 10 cc). Mean conformity index (CI) was significantly higher with VMAT and mean gradient index (GI) was significantly lower with DCAT whatever volume subgroups (p < 0.001). DCAT had more heterogeneous plans and VMAT required more monitor units. DCAT resulted in reduced low and intermediate doses, whereas VMAT led to decreased high doses. Conclusion: DCAT and VMAT are two effective and safe SRT techniques for BMs treatment. In the era of re-irradiation, it is important to reduce the doses delivered to healthy tissues. Further prospective studies are needed to validate these findings.

Factors Influencing Long-Term Local Recurrence, Distant Metastasis, and Survival in Patients with Soft Tissue Sarcoma of the Extremities Treated with Radiotherapy.

INTRODUCTION: The prognostic factors for extremity soft-tissue sarcomas (ESTSs) treated with multimodal surgery and radiotherapy (RT) remain a subject of debate across diverse and heterogeneous studies. METHODS: We retrospectively analyzed nonmetastatic ESTS patients treated with RT between 2007 and 2020 in Strasbourg, France. We assessed local control (LC), distant control (DC), overall survival (OS), and complications. RESULTS: A total of 169 patients diagnosed with localized ESTS were included. The median age was 64 years (range 21-94 years). ESTS primarily occurred proximally (74.6%) and in the lower limbs (71%). Most tumors were grade 2-3 (71.1%), deep-seated (86.4%), and had R0 margins (63.9%). Most patients were treated with helical tomotherapy (79.3%). The median biologically effective dose (BED) prescribed was 75 BEDGy4 (range 45.0-109.9). The median follow-up was 5.5 years. The 5- and 10-year LC, DC, and OS rates were 91.7%, 76.8%, and 83.8% and 84.2%, 74.1%, and 77.6%, respectively. According to the univariate analysis, LC was worse for patients who received less than 75 BEDGy4 (p = 0.015). Deep tumors were associated with worse OS (p < 0.05), and grade 2-3 and undifferentiated pleomorphic sarcoma (UPS) were linked to both shorter DC and shorter OS (p < 0.05). IMRT was associated with longer LC than 3DRT (p = 0.018). Multivariate analysis revealed that patients with liposarcoma had better OS (p < 0.05) and that patients with distant relapse had shorter OS (p < 0.0001). CONCLUSION: RT associated with surgical resection was well tolerated and was associated with excellent long-term rates of LC, DC, and OS. Compared with 3DRT, IMRT improved local control. Liposarcoma was a favorable prognostic factor for OS. Intermediate- and high-grade tumors and deep tumors were associated with lower DC and OS.

Randomized phase III trial of metabolic imaging-guided dose escalation of radio-chemotherapy in patients with newly diagnosed glioblastoma (SPECTRO GLIO trial).

BACKGROUND: Glioblastoma (GBM) systematically recurs after a standard 60 Gy radio-chemotherapy regimen. Since magnetic resonance spectroscopic imaging (MRSI) has been shown to predict the site of relapse, we analyzed the effect of MRSI-guided dose escalation on overall survival (OS) of patients with newly diagnosed GBM. METHODS: In this multicentric prospective phase III trial, patients who had undergone biopsy or surgery for a GBM were randomly assigned to a standard dose (SD) of 60 Gy or a high dose (HD) of 60 Gy with an additional simultaneous integrated boost totaling 72 Gy to MRSI metabolic abnormalities, the tumor bed and residual contrast enhancements. Temozolomide was administered concomitantly and maintained for 6 months thereafter. RESULTS: One hundred and eighty patients were included in the study between March 2011 and March 2018. After a median follow-up of 43.9 months (95% CI [42.5; 45.5]), median OS was 22.6 months (95% CI [18.9; 25.4]) versus 22.2 months (95% CI [18.3; 27.8]) for HD, and median progression-free survival was 8.6 (95% CI [6.8; 10.8]) versus 7.8 months (95% CI [6.3; 8.6]), in SD versus HD, respectively. No increase in toxicity rate was observed in the study arm. The pseudoprogression rate was similar across the SD (14.4%) and HD (16.7%) groups. For O(6)-methylguanine-DNA methyltransferase (MGMT) methylated patients, the median OS was 38 months (95% CI [23.2; NR]) for HD patients versus 28.5 months (95% CI [21.1; 35.7]) for SD patients. CONCLUSION: The additional MRSI-guided irradiation dose totaling 72 Gy was well tolerated but did not improve OS in newly diagnosed GBM. TRIAL REGISTRATION: NCT01507506; registration date: December 20, 2011. https://clinicaltrials.gov/ct2/show/NCT01507506?cond=NCT01507506&rank=1.

Prospective results for 5-year survival and toxicity of moderately hypofractionated radiotherapy with simultaneous integrated boost (SIB) in (very) high-risk prostate cancer.

Purpose: High-risk (HR) prostate cancer patients usually receive high-dose radiotherapy (RT) using a two-phase sequential technique, but data on a simultaneous integrated boost (SIB) technique are lacking. We prospectively evaluated the long-term results of urinary (GU) and digestive (GI) toxicity and survival data for high-dose RT using a SIB technique in HR and very high-risk (VHR) prostate cancer. Methods: Patients were treated using an SIB technique in 34 fractions, at a dose of 54.4 Gy to the pelvis and seminal vesicles and 74.8 Gy to the prostate, combined with 36 months of androgen-depriving therapy in a prospective multicenter study. Acute and late GU and GI toxicity data were collected. Overall survival (OS), biochemical-relapse-free survival (bRFS), loco-regional-relapse-free survival (LRRFS), metastasis-free-survival (MFS) and disease-free-survival (DFS) were assessed. Results: We recruited 114 patients. After a median follow-up of 62 months, very few patients experienced acute (M0-M3) (G3-4 GU = 3.7 %; G3-4 GI = 0.9 %) or late (M6-M60) severe toxicity (G3-4 GU = 5.6 %; G3-4 GI = 2.8 %). The occurrence of acute G2 + GU or GI toxicity was significantly related to the consequential late G2 + toxicity (p < 0.01 for both GU and GI). Medians of OS, bRFS, LRRFS, MFS and DFS were not reached. At 60 months, OS, bRFS, LRRFS, MFS and DFS were 88.2 % [82.1; 94.7], 86.0 % [79.4 %;93.2 %], 95.8 % [91.8 %;99.9 %], 87.2 % [80.9 %;94.0 %] and 84.1 % [77.2 %;91.6 %] respectively. Conclusion: SIB RT at a dose of 54.4 Gy to the pelvis and 74.8 Gy to the prostate is feasible, leading to satisfying tumor control and reasonable toxicity in HR and VHR prostate cancer.

Nuclear medicine imaging methods of early radiation-induced cardiotoxicity: a ten-year systematic review.

Introduction: Radiotherapy has significantly improved cancer survival rates, but it also comes with certain unavoidable complications. Breast and thoracic irradiation, for instance, can unintentionally expose the heart to radiation, leading to damage at the cellular level within the myocardial structures. Detecting and monitoring radiation-induced heart disease early on is crucial, and several radionuclide imaging techniques have shown promise in this regard. Method: In this 10-year review, we aimed to identify nuclear medicine imaging modalities that can effectively detect early cardiotoxicity following radiation therapy. Through a systematic search on PubMed, we selected nineteen relevant studies based on predefined criteria. Results: The data suggest that incidental irradiation of the heart during breast or thoracic radiotherapy can cause early metabolic and perfusion changes. Nuclear imaging plays a prominent role in detecting these subclinical effects, which could potentially serve as predictors of late cardiac complications. Discussion: However, further studies with larger populations, longer follow-up periods, and specific heart dosimetric data are needed to better understand the relationship between early detection of cardiac abnormalities and radiation-induced heart disease.

Repeated Stereotactic Radiotherapy for Local Brain Metastases Failure or Distant Brain Recurrent: A Retrospective Study of 184 Patients.

BACKGROUND: The main advantages of stereotactic radiotherapy (SRT) are to delay whole-brain radiotherapy (WBRT) and to deliver ablative doses. Despite this efficacy, the risk of distant brain metastases (BM) one year after SRT ranges from 26% to 77% and 20 to 40% of patients required salvage treatment. The role and consequences of reirradiation remain unclear, particularly in terms of survival. The objective was to study overall survival (OS) and neurological death-free survival (NDFS) and to specify the prognostic factors of long-term survival. METHODS: we retrospectively reviewed the data of patients treated between 2010 and 2020 with at least two courses of SRT without previous WBRT. RESULTS: In total, 184 patients were treated for 915 BMs with two-to-six SRT sessions. Additional SRT sessions were provided for local (5.6%) or distant (94.4%) BM recurrence. The median number of BMs treated per SRT was one with a median of four BMs in total. The mean time between the two SRT sessions was 8.9 months (95%CI 7.7-10.1) and there was no significant difference in the delay between the two sessions. The 6-, 12- and 24-month NDFS rates were 97%, 82% and 52%, respectively. The 6-, 12- and 24-month OS rates were 91%, 70% and 38%, respectively. OS was statistically related to the number of SRT sessions (HR = 0.48; p < 0.01), recursive partitioning analysis (HR = 1.84; p = 0.01), salvage WBRT (HR = 0.48; p = 0.01) and brain metastasis velocity (high: HR = 13.83; p < 0.01; intermediate: HR = 4.93; p < 0.01). CONCLUSIONS: Lung cancer and melanoma were associated with a lower NDFS compared to breast cancer. A low KPS, a low number of SRT sessions, synchronous extracerebral metastases, synchronous BMs, extracerebral progression at SRT1, a high BMV grade, no WBRT and local recurrence were also associated with a lower NDFS. A high KPS at SRT1 and low BMV grade are prognostic factors for better OS, regardless of the number of BM recurrence events.

Prognostic Factors in Extremity Soft Tissue Sarcomas Treated with Radiotherapy: Systematic Review of the Literature.

Soft tissue sarcomas of the extremities are rare tumors with various prognostic factors. Their management is debatable due to their inconsistent results within the literature and the lack of large prospective studies. The objective of this systematic review is to analyze the available scientific data on prognostic factors concerning the characteristics of the patients, the disease and the treatments performed, as well as their potential complications, on studies with a median follow-up of 5 years at minimum. A search of articles following the "PRISMA method" and using the PubMed search engine was conducted to select the most relevant studies. Twenty-five articles were selected, according to preestablished criteria. This review provides a better understanding of the prognosis and disease outcome of these tumors. Many factors were described comparing the frequency of occurrence according to the studies, which remain heterogeneous between them. Significant factors that could orient patients to radiotherapy were highlighted. These positive prognostic factors provide valuable insight to optimize radiotherapy treatments for patients treated for soft tissue sarcoma of the extremities.

Second Cancer Affecting the Central Nervous System: Systematic Literature Review Exploring the Link Between Malignant Melanoma and Glioblastoma.

BACKGROUND: Glioblastoma (GBM) is a malignant primary brain cancer, among the most devastating and lethal diseases of the central nervous system. Similarly, malignant melanoma (MM) is responsible for most skin cancer-related deaths. A link between those 2 aggressive cancers has not yet been established. We present here a systematic review of the literature and an exemplificative case. METHODS: A systematic review of the literature was conducted to assess possible commonalities between MM and GBM. An exemplificative surgical vignette of a 73-year-old patient with the occurrence of a frontobasal GBM after surgical removal of a metastasis of MM in the same location was then detailed. RESULTS: Fifteen studies published in the English international literature support a link between MM and GBM, both based on epidemiologic and pathophysiologic/genetic aspects. This theory is reinforced by our surgical vignette of a collision tumor with the occurrence of both tumors in the same location several years apart. CONCLUSIONS: The evidence reported in the literature, as well as our surgical vignette, support a likely link between the pathogenesis of GBM and MM.