Lomustine with or without reirradiation for first progression of glioblastoma, LEGATO, EORTC-2227-BTG: study protocol for a randomized phase III study.

BACKGROUND: Chemotherapy with lomustine is widely considered as standard treatment option for progressive glioblastoma. The value of adding radiotherapy to second-line chemotherapy is not known. METHODS: EORTC-2227-BTG (LEGATO, NCT05904119) is an investigator-initiated, pragmatic (PRECIS-2 score: 34 out of 45), randomized, multicenter phase III trial in patients with first progression of glioblastoma. A total of 411 patients will be randomized in a 1:1 ratio to lomustine (110 mg/m2 every 6 weeks) or lomustine (110 mg/m2 every 6weeks) plus radiotherapy (35 Gy in 10 fractions). Main eligibility criteria include histologic confirmation of glioblastoma, isocitrate dehydrogenase gene (IDH) wild-type per WHO 2021 classification, first progression at least 6 months after the end of prior radiotherapy, radiologically measurable disease according to RANO criteria with a maximum tumor diameter of 5 cm, and WHO performance status of 0-2. The primary efficacy endpoint is overall survival (OS) and secondary endpoints include progression-free survival, response rate, neurocognitive function, health-related quality of life, and health economic parameters. LEGATO is funded by the European Union's Horizon Europe Research program, was activated in March 2024 and will enroll patients in 43 sites in 11 countries across Europe with study completion projected in 2028. DISCUSSION: EORTC-2227-BTG (LEGATO) is a publicly funded pragmatic phase III trial designed to clarify the efficacy of adding reirradiation to chemotherapy with lomustine for the treatment of patients with first progression of glioblastoma. TRIAL REGISTRATION: ClinicalTrials.gov NCT05904119. Registered before start of inclusion, 23 May 2023.

11C-methionine in the diagnostics and management of glioblastoma patients with rapid early progression: nonrandomized, open label, prospective clinical trial (GlioMET).

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary brain cancer. The treatment of GBM consists of a combination of surgery and subsequent oncological therapy, i.e., radiotherapy, chemotherapy, or their combination. If postoperative oncological therapy involves irradiation, magnetic resonance imaging (MRI) is used for radiotherapy treatment planning. Unfortunately, in some cases, a very early worsening (progression) or return (recurrence) of the disease is observed several weeks after the surgery and is called rapid early progression (REP). Radiotherapy planning is currently based on MRI for target volumes definitions in many radiotherapy facilities. However, patients with REP may benefit from targeting radiotherapy with other imaging modalities. The purpose of the presented clinical trial is to evaluate the utility of 11C-methionine in optimizing radiotherapy for glioblastoma patients with REP. METHODS: This study is a nonrandomized, open-label, parallel-setting, prospective, monocentric clinical trial. The main aim of this study was to refine the diagnosis in patients with GBM with REP and to optimize subsequent radiotherapy planning. Glioblastoma patients who develop REP within approximately 6 weeks after surgery will undergo 11C-methionine positron emission tomography (PET/CT) examinations. Target volumes for radiotherapy are defined using both standard planning T1-weighted contrast-enhanced MRI and PET/CT. The primary outcome is progression-free survival defined using RANO criteria and compared to a historical cohort with REP treated without PET/CT optimization of radiotherapy. DISCUSSION: PET is one of the most modern methods of molecular imaging. 11C-Methionine is an example of a radiolabelled (carbon 11) amino acid commonly used in the diagnosis of brain tumors and in the evaluation of response to treatment. Optimized radiotherapy may also have the potential to cover those regions with a high risk of subsequent progression, which would not be identified using standard-of-care MRI for radiotherapy planning. This is one of the first study focused on radiotherapy optimization for subgroup of patinets with REP. TRIAL REGISTRATION: NCT05608395, registered on 8.11.2022 in clinicaltrials.gov; EudraCT Number: 2020-000640-64, registered on 26.5.2020 in clinicaltrialsregister.eu. Protocol ID: MOU-2020-01, version 3.2, date 18.09.2020.

Challenges with hippocampal MR spectroscopy as a surrogate for pre-radiotherapy assessment of neurocognitive impairment in patients with brain metastasis.

AIM: Patients with multiple brain metastases (BM) benefit from hippocampal-avoiding whole brain radiotherapy (HA-WBRT), the challenging and less available form of WBRT. This study explores potential of pre-radiotherapy (pre-RT) hippocampal magnetic resonance spectroscopy (MRS) measuring hippocampal neuronal density as an imaging surrogate and predictive tool for assessing neurocognitive functions (NCF). METHODS: 43 BM patients underwent pre-RT hippocampal MRS. N-acetyl aspartate (NAA) concentration, a marker for neuronal density (weighted by creatine (Cr) and choline (Cho) concentrations), and neurocognitive function (NCF) tests (HVLT and BVMT) performed by certified psychologists were evaluated. Clinical variables and NAA concentrations were correlated with pre-RT NCFs. RESULTS: HVLT and BVMT subtests showed pre-RT deterioration except for BVMT recognition. Significantly better NCFs were observed in women in HVLT subsets. Significantly higher NAA/Cr + Cho was measured in women (median 0.63 vs. 0.55; P=0.048) in the left hippocampus (no difference in the right hippocampus). In men, a positive correlation (0.51, P=0.018) between total brain volume and HVLT-TR, between left hippocampal NAA/Cr + Cho and HVLT-R (0.45, P=0.063), and between right hippocampal NAA/Cr + Cho and BVMT-recognition (0.49, P=0.054) was observed. In women, a borderline significant negative correlation was observed between left hippocampal NAA/Cr + Cho and BVMT-TR (-0.43, P=0.076) and between right NAA/Cr + Cho and HVLT-DR (-0.42, P=0.051). CONCLUSION: Borderline statistically significant correlations were observed with speculative interpretation underlying the challenges of hippocampal MRS as a surrogate for neurocognitive impairment. Further studies need to be done to ascertain the opportunities for imaging predictors of benefit from memory sparing radiotherapy.

Hippocampal subfield volumetric changes after radiotherapy for brain metastases.

Background: Changes in the hippocampus after brain metastases radiotherapy can significantly impact neurocognitive functions. Numerous studies document hippocampal atrophy correlating with the radiation dose. This study aims to elucidate volumetric changes in patients undergoing whole-brain radiotherapy (WBRT) or targeted stereotactic radiotherapy (SRT) and to explore volumetric changes in the individual subregions of the hippocampus. Method: Ten patients indicated to WBRT and 18 to SRT underwent brain magnetic resonance before radiotherapy and after 4 months. A structural T1-weighted sequence was used for volumetric analysis, and the software FreeSurfer was employed as the tool for the volumetry evaluation of 19 individual hippocampal subregions. Results: The volume of the whole hippocampus, segmented by the software, was larger than the volume outlined by the radiation oncologist. No significant differences in volume changes were observed in the right hippocampus. In the left hippocampus, the only subregion with a smaller volume after WBRT was the granular cells and molecular layers of the dentate gyrus (GC-ML-DG) region (median change -5 mm3, median volume 137 vs. 135 mm3; P = .027), the region of the presumed location of neuronal progenitors. Conclusions: Our study enriches the theory that the loss of neural stem cells is involved in cognitive decline after radiotherapy, contributes to the understanding of cognitive impairment, and advocates for the need for SRT whenever possible to preserve cognitive functions in patients undergoing brain radiotherapy.

Unilateral hippocampal sparing during whole brain radiotherapy for multiple brain metastases: narrative and critical review.

Background: The landscape of brain metastases radiotherapy is evolving, with a shift away from whole-brain radiotherapy (WBRT) toward targeted stereotactic approaches aimed at preserving neurocognitive functions and maintaining overall quality of life. For patients with multiple metastases, especially in cases where targeted radiotherapy is no longer feasible due to widespread dissemination, the concept of hippocampal sparing radiotherapy (HA_WBRT) gains prominence. Methods: In this narrative review we explore the role of the hippocampi in memory formation and the implications of their postradiotherapy lateral damage. We also consider the potential advantages of selectively sparing one hippocampus during whole-brain radiotherapy (WBRT). Additionally, by systematic evaluation of relevant papers published on PubMed database over last 20 years, we provide a comprehensive overview of the various changes that can occur in the left or right hippocampus as a consequence of radiotherapy. Results: While it is important to note that various neurocognitive functions are interconnected throughout the brain, we can discern certain specialized roles of the hippocampi. The left hippocampus appears to play a predominant role in verbal memory, whereas the right hippocampus is associated more with visuospatial memory. Additionally, the anterior part of the hippocampus is more involved in episodic memory and emotional processing, while the posterior part is primarily responsible for spatial memory and pattern separation. Notably, a substantial body of evidence demonstrates a significant correlation between post-radiotherapy changes in the left hippocampus and subsequent cognitive decline in patients. Conclusion: In the context of individualized palliative radiotherapy, sparing the unilateral (specifically, the left, which is dominant in most individuals) hippocampus could expand the repertoire of strategies available for adapted WBRT in cases involving multiple brain metastases where stereotactic radiotherapy is not a viable option. Prospective ongoing studies assessing various memory-sparing radiotherapy techniques will define new standard of radiotherapy care of patients with multiple brain metastases.

Toxicity of external beam accelerated partial-breast irradiation (APBI) in adjuvant therapy of early-stage breast cancer: prospective randomized study.

BACKGROUND: Accelerated partial breast irradiation (APBI) is an alternative breast-conserving therapy approach where radiation is delivered in less time compared to whole breast irradiation (WBI), resulting in improved patient convenience, less toxicity, and cost savings. This prospective randomized study compares the external beam APBI with commonly used moderate hypofractionated WBI in terms of feasibility, safety, tolerance, and cosmetic effects. METHODS: Early breast cancer patients after partial mastectomy were equally randomized into two arms- external APBI and moderate hypofractionated WBI. External beam technique using available technical innovations commonly used in targeted hypofractionated radiotherapy to minimize irradiated volumes was used (cone beam computed tomography navigation to clips in the tumor bed, deep inspiration breath hold technique, volumetric modulated arc therapy dose application, using flattening filter free beams and the six degrees of freedom robotic treatment couch). Cosmetics results and toxicity were evaluated using questionnaires, CTCAE criteria, and photo documentation. RESULTS: The analysis of 84 patients with a median age of 64 years showed significantly fewer acute adverse events in the APBI arm regarding skin reactions, local and general symptoms during a median follow-up of 37 months (range 21-45 months). A significant difference in favor of the APBI arm in grade ≥ 2 late skin toxicity was observed (p = 0.026). Late toxicity in the breast area (deformation, edema, fibrosis, and pain), affecting the quality of life and cosmetic effect, occurred in 61% and 17% of patients in WBI and APBI arms, respectively. The cosmetic effect was more favorable in the APBI arm, especially 6 to 12 months after the radiotherapy. CONCLUSION: External APBI demonstrated better feasibility and less toxicity than the standard regimen in the adjuvant setting for treating early breast cancer patients. The presented study confirmed the level of evidence for establishing the external APBI in daily clinical practice. TRIAL REGISTRATION: NCT06007118.

Dosimetric patterns of failure in the era of novel chemoradiotherapy in newly-diagnosed glioblastoma patients.

BACKGROUND: Patterns of failure (POF) may provide an alternative quantitative endpoint to overall survival for evaluation of novel chemoradiotherapy regimens with glioblastoma. MATERIALS AND METHODS: POF of 109 newly-diagnosed glioblastoma patients per 2016 WHO classification who received conformal radiotherapy with concomitant and adjuvant temozolomide were reviewed. Seventy-five of those patients also received an investigational chemotherapy agent (everolimus, erlotinib, or vorinostat). Recurrence volumes were defined with MRI contrast enhancement. POF at protocol (POFp), initial (POFi), and RANO (POFRANO) progression timepoints were characterized by the percentage of recurrence volume within the 95% dose region. POFp, POFi, and POFRANO of each patient were categorized (central, non-central, or both). RESULTS: POF of the temozolomide-only control cohort were unchanged (79% central, 12% non-central, and 9% both) across protocol, initial, and RANO progression timepoints. Unlike the temozolomide-only cohort, POF of the collective novel chemotherapy cohort appeared increasingly non-central when comparing POFi with POFp, with a non-central component increasing from 16% to 29% (p = 0.078). POF did not correlate with overall survival or time to progression. CONCLUSION: POF of patients receiving a novel chemotherapy appeared to be influenced by the timepoint of analysis and were increasingly non-central at protocol progression as compared with initial recurrence, suggesting that recurrence originates from the central region. Addition of everolimus and vorinostat appeared to influence POF, despite similar survival outcomes with the temozolomide-only control group. In studies dealing with novel therapeutic agents, robust and properly-timed dosimetric POF analysis may be helpful to evaluate biologic aspects of novel agents.

The effectiveness of three mobile-based psychological interventions in reducing psychological distress and preventing stress-related changes in the psycho-neuro-endocrine-immune network in breast cancer survivors: Study protocol for a randomised controlled trial.

Background: A growing body of literature shows that psychological distress is not only a major threat to psychological well-being but can also have a significant impact on physical health. In cancer patients, it can negatively affect prognosis and posttreatment recovery processes. Since face-to-face psychological interventions are often inaccessible to cancer patients, researchers have recently been focusing on the effectiveness of eHealth adaptations of well-established approaches. In this context, there has been a call for high-quality randomised controlled trials that would allow for a direct comparison of different approaches, potentially addressing different needs and preferences of patients, and also for more systematic research focusing on how psychological interventions affect not only psychological but also biological markers of stress. Both of these questions are addressed in the present study. Methods: A randomised controlled trial will be carried out to test and compare the effectiveness of three eight-week eHealth programmes for the mental health support of cancer patients. All programmes will be delivered through the same application for mobile devices MOU MindCare. N = 440 of breast cancer survivors will be recruited at the end of their adjuvant treatment (chemotherapy, radiotherapy, or both) and randomly assigned to one of the three interventions - Mindfulness-Based Cognitive Therapy for Cancer (MBCT-Ca), Positive Psychology (PP), or Autogenic Training (AT) - or the treatment-as-usual (TAU) control group. Psychological and biological markers of stress and adaptive functioning will be assessed at baseline (T0), post-treatment (T1), three-month follow-up (T2), and nine-month follow-up (T3). Primary outcomes will include heart-rate variability and self-report measures of depression, anxiety, perceived stress, general quality of life, and positive mental health. Secondary outcomes will include the levels of serum cortisol and immunomarkers, sleep quality, fatigue, common health symptoms, and several transdiagnostic psychological variables that are expected to be specifically affected by the MBCT-Ca and PP interventions, including dispositional mindfulness, emotion regulation, self-compassion, perceived hope, and gratitude. The data will be analysed using the mixed model repeated measures (MMRM) approach. Discussion: This trial is unique in comparing three different eHealth interventions for cancer patients based on three well-established approaches to mental health support delivered on the same platform. The study will allow us to examine whether different types of interventions affect different indicators of mental health. In addition, it will provide valuable data regarding the effects of stress-reducing psychological interventions on the biomarkers of stress playing an essential role in cancer recovery processes and general health.

Effects of Reoperation Timing on Survival among Recurrent Glioblastoma Patients: A Retrospective Multicentric Descriptive Study.

Glioblastoma inevitably recurs, but no standard regimen has been established for treating this recurrent disease. Several reports claim that reoperative surgery can improve survival, but the effects of reoperation timing on survival have rarely been investigated. We, therefore, evaluated the relationship between reoperation timing and survival in recurrent GBM. A consecutive cohort of unselected patients (real-world data) from three neuro-oncology cancer centers was analyzed (a total of 109 patients). All patients underwent initial maximal safe resection followed by treatment according to the Stupp protocol. Those meeting the following criteria during progression were indicated for reoperation and were further analyzed in this study: (1) The tumor volume increased by >20-30% or a tumor was rediscovered after radiological disappearance; (2) The patient's clinical status was satisfactory (KS ≥ 70% and PS WHO ≤ gr. 2); (3) The tumor was localized without multifocality; (4) The minimum expected tumor volume reduction was above 80%. A univariate Cox regression analysis of postsurgical survival (PSS) revealed a statistically significant effect of reoperation on PSS from a threshold of 16 months after the first surgery. Cox regression models that stratified the Karnofsky score with age adjustment confirmed a statistically significant improvement in PSS for time-to-progression (TTP) thresholds of 22 and 24 months. The patient groups exhibiting the first recurrence at 22 and 24 months had better survival rates than those exhibiting earlier recurrences. For the 22-month group, the HR was 0.5 with a 95% CI of (0.27, 0.96) and a p-value of 0.036. For the 24-month group, the HR was 0.5 with a 95% CI of (0.25, 0.96) and a p-value of 0.039. Patients with the longest survival were also the best candidates for repeated surgery. Later recurrence of glioblastoma was associated with higher survival rates after reoperation.

The risk of second primary malignancies in colorectal cancer patients using calcium channel blockers.

Calcium channel blockers are among the most commonly used agents in the treatment of cardiovascular diseases. There are several known side-effects associated with their long-term use, whereas other potential adverse effects are yet to be proven. This study aims to evaluate the association between calcium channel blockers exposure and the incidence of second primary malignancy. We established a cohort of 1401 patients with colorectal cancer diagnosed in our institution between January 2003 and December 2016. Patients were followed-up until December 2020. The tumor characteristics and basic clinical data including medication information were obtained from the hospital information system database. Second malignancy was detected in 301 patients (21.5%), and occurred in 27.8% of patients who used calcium channel blockers compared to only 19.9% among non-users. Their use was associated with an increased incidence of bladder cancer in particular. Subanalysis of patients with second malignancy displayed a higher proportion of right-sided colon cancer compared to rectal carcinoma in non-users. Survival analysis revealed significantly better outcomes in early-stage colorectal cancer patients without a history of calcium channel blockers treatment or second primary malignancy.

Sr(II) and Ba(II) Alkaline Earth Metal-Organic Frameworks (AE-MOFs) for Selective Gas Adsorption, Energy Storage, and Environmental Application.

Two new alkaline earth metal-organic frameworks (AE-MOFs) containing Sr(II) (UPJS-15) or Ba(II) (UPJS-16) cations and extended tetrahedral linker (MTA) were synthesized and characterized in detail (UPJS stands for University of Pavol Jozef Safarik). Single-crystal X-ray analysis (SC-XRD) revealed that the materials are isostructural and, in their frameworks, one-dimensional channels are present with the size of ~11 × 10 Å2. The activation process of the compounds was studied by the combination of in situ heating infrared spectroscopy (IR), thermal analysis (TA) and in situ high-energy powder X-ray diffraction (HE-PXRD), which confirmed the stability of compounds after desolvation. The prepared compounds were investigated as adsorbents of different gases (Ar, N2, CO2, and H2). Nitrogen and argon adsorption measurements showed that UPJS-15 has SBET area of 1321 m2 g-1 (Ar) / 1250 m2 g-1 (N2), and UPJS-16 does not adsorb mentioned gases. From the environmental application, the materials were studied as CO2 adsorbents, and both compounds adsorb CO2 with a maximum capacity of 22.4 wt.% @ 0 °C; 14.7 wt.% @ 20 °C and 101 kPa for UPJS-15 and 11.5 wt.% @ 0°C; 8.4 wt.% @ 20 °C and 101 kPa for UPJS-16. According to IAST calculations, UPJS-16 shows high selectivity (50 for CO2/N2 10:90 mixture and 455 for CO2/N2 50:50 mixture) and can be applied as CO2 adsorbent from the atmosphere even at low pressures. The increased affinity of materials for CO2 was also studied by DFT modelling, which revealed that the primary adsorption sites are coordinatively unsaturated sites on metal ions, azo bonds, and phenyl rings within the MTA linker. Regarding energy storage, the materials were studied as hydrogen adsorbents, but the materials showed low H2 adsorption properties: 0.19 wt.% for UPJS-15 and 0.04 wt.% for UPJS-16 @ -196 °C and 101 kPa. The enhanced CO2/H2 selectivity could be used to scavenge carbon dioxide from hydrogen in WGS and DSR reactions. The second method of applying samples in the area of energy storage was the use of UPJS-15 as an additive in a lithium-sulfur battery. Cyclic performance at a cycling rate of 0.2 C showed an initial discharge capacity of 337 mAh g-1, which decreased smoothly to 235 mAh g-1 after 100 charge/discharge cycles.

Spinal Metastasis in a Patient with Supratentorial Glioblastoma with Primitive Neuronal Component: A Case Report with Clinical and Molecular Evaluation.

Glioblastoma (GBM) is regarded as an aggressive brain tumor that rarely develops extracranial metastases. Despite well-investigated molecular alterations in GBM, there is a limited understanding of these associated with the metastatic potential. We herein present a case report of a 43-year-old woman with frontal GBM with primitive neuronal component who underwent gross total resection followed by chemoradiation. Five months after surgery, the patient was diagnosed with an intraspinal GBM metastasis. Next-generation sequencing analysis of both the primary and metastatic GBM tissues was performed using the Illumina TruSight Tumor 170 assay. The number of single nucleotide variants observed in the metastatic sample was more than two times higher. Mutations in TP53, PTEN, and RB1 found in the primary and metastatic tissue samples indicated the mesenchymal molecular GBM subtype. Among others, there were two inactivating mutations (Arg1026Ile, Trp1831Ter) detected in the NF1 gene, two novel NOTCH3 variants of unknown significance predicted to be damaging (Pro1505Thr, Cys1099Tyr), one novel ARID1A variant of unknown significance (Arg1046Ser), and one gene fusion of unknown significance, EIF2B5-KIF5B, in the metastatic sample. Based on the literature evidence, the alterations of NF1, NOTCH3, and ARID1A could explain, at least in part, the acquired invasiveness and metastatic potential in this particular GBM case.

Small RNA Sequencing Identifies a Six-MicroRNA Signature Enabling Classification of Brain Metastases According to their Origin.

BACKGROUND/AIM: Brain metastases (BMs) are the most frequent intracranial tumors in adults and one of the greatest challenges for modern oncology. Most are derived from lung, breast, renal cell, and colorectal carcinomas and melanomas. Up to 14% of patients are diagnosed with BMs of unknown primary, which are commonly characterized by an early and aggressive metastatic spread. It is important to discover novel biomarkers for early identification of BM origin, allowing better management of patients with this disease. Our study focused on microRNAs (miRNAs), which are very stable in frozen native and FFPE tissues and have been shown to be sensitive and specific diagnostic biomarkers of cancer. We aimed to identify miRNAs with significantly different expression in the five most frequent groups of BMs and develop a diagnostic classifier capable of sensitive and specific classification of BMs. MATERIALS AND METHODS: Total RNA enriched for miRNAs was isolated using the mirVana miRNA Isolation Kit from 71 fresh-frozen histopathologically confirmed BM tissues originating in 5 cancer types. Sequencing libraries were prepared using the QIAseq miRNA Library Kit and sequenced on the NextSeq 500 platform. MiRNA expression was further validated by RT-qPCR. RESULTS: Differential analysis identified 373 miRNAs with significantly different expression between 5 BM groups (p<0.001). A classifier model was developed based on the expression of 6 miRNAs (hsa-miR-141-3p, hsa-miR-141-5p, hsa-miR-146a-5p, hsa-miR-194-5p, hsa-miR-200b-3p and hsa-miR-365b-5p) with the ability to correctly classify 91.5% of samples. Subsequent validation confirmed both significantly different expression of selected miRNAs in 5 BM groups as well as their diagnostic potential. CONCLUSION: To date, our study is the first to analyze miRNA expression in various types of BMs using small RNA sequencing to develop a diagnostic classifier and, thus, to help stratify BMs of unknown primary. The presented results confirm the importance of studying the dysregulated expression of miRNAs in BMs and the diagnostic potential of the validated 6-miRNA signature.

Case report: radiation-induced lumbosacral plexopathy - a very late complication of radiotherapy for cervical cancer.

BACKGROUND: Lumbosacral plexopathy caused by radiotherapy is a rare but severe consequence of cancer treatment. This condition often leads to varying degrees of sensory and motor impairment. Neurological complications, which are typically permanent, manifest a long period after irradiation. CASE PRESENTATION: We describe a case of progressive lower extremity weakness and sensory impairment in a woman who had been effectively treated with radiotherapy for cervical cancer with development 36 years after irradiation. The electrophysiological assessment revealed a subacute bilateral axonal lesion of the lumbosacral plexus. None of the clinical manifestations, serology, cerebrospinal fluid or imaging data discovered an explanation other than radiation-induced lumbosacral plexopathy (RILP). CONCLUSIONS: This case demonstrates that RILP may emerge more than 30 years after the radiotherapy.

Human Papillomavirus-Related Non-Metastatic Oropharyngeal Carcinoma: Current Local Treatment Options and Future Perspectives.

Over the last two decades, human papillomavirus (HPV) has caused a new pandemic of cancer in many urban areas across the world. The new entity, HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), has been at the center of scientific attention ever since, not only due to its distinct biological behavior, but also because of its significantly better prognosis than observed in its HPV-negative counterpart. The very good treatment outcomes of the disease after primary therapy (minimally-invasive surgery, radiation therapy with or without chemotherapy) resulted in the creation of a separate staging system, reflecting this excellent prognosis. A substantial proportion of newly diagnosed HPV-driven OPSCC is diagnosed in stage I or II, where long-term survival is observed worldwide. Deintensification of the primary therapeutic methods, aiming at a reduction of long-term toxicity in survivors, has emerged, and the quality of life of the patient after treatment has become a key-point in many clinical trials. Current treatment recommendations for the treatment of HPV-driven OPSCC do not differ significantly from HPV-negative OPSCC; however, the results of randomized trials are eagerly awaited and deemed necessary, in order to include deintensification into standard clinical practice.

Stereotactic Body Radiotherapy (SBRT) of Pancreatic Cancer-A Critical Review and Practical Consideration.

Pancreatic cancer is the third leading cause of cancer death in the developed world and is predicted to become the second by 2030. A cure may be achieved only with surgical resection of an early diagnosed disease. Surgery for more advanced disease is challenging and can be contraindicated for many reasons. Neoadjuvant therapy may improve the probability of achieving R0 resection. It consists of systemic treatment followed by radiation therapy applied concurrently or sequentially with cytostatics. A novel approach to irradiation, stereotactic body radiotherapy (SBRT), has the potential to improve treatment results. SBRT can deliver higher doses of radiation to the tumor in only a few treatment fractions. It has attracted significant interest for pancreatic cancer patients, as it is completed quickly, requires less time away from full-dose chemotherapy, and is well-tolerated than conventional radiotherapy. In this review, we aim to provide the reader with a basic overview of current evidence for SBRT indications in the treatment of pancreatic tumors. In the second part of the review, we focus on practical information with respect to SBRT treatment plan preparation the performance of such therapy. Finally, we discuss future directions related to the use of magnetic resonance linear accelerators.

Post-synthetically modified metal-porphyrin framework GaTCPP for carbon dioxide adsorption and energy storage in Li-S batteries.

Lithium-sulphur batteries attract increasing interest due to their high theoretical specific capacity, advantageous economy, and "eco-friendliness". In this study, a metal-organic framework (MOF) GaTCPP containing a porphyrinic base ligand was used as a conductive additive for sulphur. GaTCPP was synthesized, characterized, and post-synthetically modified by the transition metal ions (Co2+/Ni2+). The doping of GaTCPP ensured an increase in the carbon dioxide adsorption capacities, which were measured under different conditions. Post-synthetic modification of GaTCPP with Co2+/Ni2+ ions has been shown to increase carbon dioxide storage capacity from 22.8 wt% for unmodified material to 23.1 wt% and 26.5 wt% at 0 °C and 1 bar for Co2+ and Ni2+-doped analogues, respectively. As a conductive part of cathode material, MOFs displayed successful sulphur capture and encapsulation proven by stable charge/discharge cycle performances, high-capacity retention, and coulombic efficiency. The electrodes with pristine GaTCPP showed a discharge capacity of 699 mA h g-1 at 0.2C in the fiftieth cycle. However, the doping of GaTCPP by Ni2+ has a positive impact on the electrochemical properties, the capacity increased to 778 mA h g-1 in the fiftieth cycle at 0.2C.

Identification of AGR2 Gene-Specific Expression Patterns Associated with Epithelial-Mesenchymal Transition.

The TGF-ß signaling pathway is involved in numerous cellular processes, and its deregulation may result in cancer development. One of the key processes in tumor progression and metastasis is epithelial to mesenchymal transition (EMT), in which TGF-ß signaling plays important roles. Recently, AGR2 was identified as a crucial component of the cellular machinery responsible for maintaining the epithelial phenotype, thereby interfering with the induction of mesenchymal phenotype cells by TGF-ß effects in cancer. Here, we performed transcriptomic profiling of A549 lung cancer cells with CRISPR-Cas9 mediated AGR2 knockout with and without TGF-ß treatment. We identified significant changes in transcripts associated with focal adhesion and eicosanoid production, in particular arachidonic acid metabolism. Changes in transcripts associated with the focal adhesion pathway were validated by RT-qPCR of COL4A1, COL4A2, FLNA, VAV3, VEGFA, and VINC mRNAs. In addition, immunofluorescence showed the formation of stress fibers and vinculin foci in cells without AGR2 and in response to TGF-ß treatment, with synergistic effects observed. These findings imply that both AGR2 downregulation and TGF-ß have a role in focal adhesion formation and cancer cell migration and invasion. Transcripts associated with arachidonic acid metabolism were downregulated after both AGR2 knockout and TGF-ß treatment and were validated by RT-qPCR of GPX2, PTGS2, and PLA2G4A. Since PGE2 is a product of arachidonic acid metabolism, its lowered concentration in media from AGR2-knockout cells was confirmed by ELISA. Together, our results demonstrate that AGR2 downregulation and TGF-ß have an essential role in focal adhesion formation; moreover, we have identified AGR2 as an important component of the arachidonic acid metabolic pathway.

FMISO-Based Adaptive Radiotherapy in Head and Neck Cancer.

Concurrent chemoradiotherapy represents one of the most used strategies in the curative treatment of patients with head and neck (HNC) cancer. Locoregional failure is the predominant recurrence pattern. Tumor hypoxia belongs to the main cause of treatment failure. Positron emission tomography (PET) using hypoxia radiotracers has been studied extensively and has proven its feasibility and reproducibility to detect tumor hypoxia. A number of studies confirmed that the uptake of FMISO in the recurrent region is significantly higher than that in the non-recurrent region. The escalation of dose to hypoxic tumors may improve outcomes. The technical feasibility of optimizing radiotherapeutic plans has been well documented. To define the hypoxic tumour volume, there are two main approaches: dose painting by contour (DPBC) or by number (DPBN) based on PET images. Despite amazing technological advances, precision in target coverage, and surrounding tissue sparring, radiation oncology is still not considered a targeted treatment if the "one dose fits all" approach is used. Using FMISO and other hypoxia tracers may be an important step for individualizing radiation treatment and together with future radiomic principles and a possible genome-based adjusting dose, will move radiation oncology into the precise and personalized era.