Pharmaceutical management of acute radiation dermatitis in the German speaking radiation oncology community.

BACKGROUND: Radiation dermatitis (RD) remains the most common side effect in radiation therapy (RT) with various pharmaceutical options available for prevention and treatment. We sought to determine pharmaceutical management patterns of radiation dermatitis among radiation oncology professionals. METHODS: We conducted a survey on RD among the German-speaking community of radiation oncologists inquiring for their opinion on preventive and therapeutic pharmaceutical approaches for acute RD. RESULTS: 244 health professionals participated. Dexpanthenol lotion is the agent most widely used both for prevention (53.0%) and treatment (76.9%) of RD, followed by urea (29.8%) for prevention and corticosteroids (46.9%) for treatment. A wide range of substances is used by participants, though the overall experience with them is rather limited. 32.5% of participants do generally not recommend any preventative treatment. 53.4% of participants recommend alternative medicine for RD management. While seldomly used, corticosteroids were considered most effective in RD therapy, followed by dexpanthenol and low-level laser therapy. A majority of participants prefers moist over dry treatment of moist desquamation and 43.8% prescribe antiseptics. CONCLUSIONS: Pharmaceutical management of RD in the German-speaking radiation oncology community remains controversial, inconsistent, and partially not supported by evidence-based medicine. Stronger evidence level and interdisciplinary consensus is required amongst practitioners to improve these care patterns.

Electroanatomical mapping after cardiac radioablation for treatment of incessant electrical storm: a case report from the RAVENTA trial.

BACKGROUND: Electroanatomical mapping (EAM)-guided stereotactic arrhythmia radioablation (STAR) is a novel noninvasive therapy option for patients with monomorphic ventricular tachycardia (VT) refractory to antiarrhythmic drugs and/or urgent catheter ablation (CA). Data on success rates in an emergency situation such as electrical storm (ES) are rare. We present a case of a patient with an initially very poor life expectancy after extensive myocardial infarction with therapy-resistant ES, not amendable for further antiarrhythmic drug therapy, implantable cardioverter-defibrillator implantation, or repeated CA who was introduced to the radiation oncology department for emergency STAR as a bail-out therapy. METHODS: Target volume definition and transfer from EAM to CT were validated and quality assured with a semi-automatic, dedicated visualization tool (CARDIO-RT). Emergency STAR was performed with 25 Gy in the framework of the RAVENTA study. The VT burden gradually decreased after STAR; however, a second VT morphology occurred, which was successfully treated with EAM-guided CA 12 days after STAR. RESULTS: The second EAM-guided CA showed areas of low voltage in the irradiated segments, indicating a precise targeting and early functional response to STAR. The patient remained free of any VT recurrence or any radiation-related toxicities and in good general condition during the recent follow-up of 18 months. CONCLUSION: The case highlights the possible approach, caveats, difficulties, and prognosis of a patient severely affected by therapy-resistant VT in whom CA could not lead to VT suppression. Further studies of putative mechanisms of STAR in the acute and chronic phase of this novel therapy are warranted.

Mobile applications in radiation oncology-current choices and future potentials.

PURPOSE: To review existing scientific literature on mobile applications (apps) in the field of radiation oncology and to evaluate characteristics of commercially available apps across different platforms. METHODS: A systematic review of the literature for publications presenting apps in the field of radiation oncology was carried out using the PubMed database, Cochrane library, Google Scholar, and annual meetings of major radiation oncology societies. Additionally, the two major marketplaces for apps, App Store and Play Store, were searched for available radiation oncology apps for patients and health care professionals (HCP). RESULTS: A total of 38 original publications which met the inclusion criteria were identified. Within those publications, 32 apps were developed for patients and 6 for HCP. The vast majority of patient apps focused on documenting electronic patient-reported outcomes (ePROs). In the two major marketplaces, 26 apps were found, mainly supporting HCP with dose calculations. CONCLUSION: Apps used in (and for) scientific research in radiation oncology are rarely available for patients and HCP in common marketplaces.

Risk assessment, surveillance, and nonpharmaceutical prevention of acute radiation dermatitis: results of a multicentric survey among the German-speaking radiation oncology community.

PURPOSE: Radiation dermatitis (RD) represents one of the most frequent side effects in radiotherapy (RT). Despite technical progress, mild and moderate RD still affects major subsets of patients and identification and management of patients with a high risk of severe RD is essential. We sought to characterize surveillance and nonpharmaceutical preventive management of RD in German-speaking hospitals and private centers. METHODS: We conducted a survey on RD among German-speaking radiation oncologists inquiring for their evaluation of risk factors, assessment methods, and nonpharmaceutical preventive management of RD. RESULTS: A total of 244 health professionals from public and private institutions in Germany, Austria, and Switzerland participated in the survey. RT-dependent factors were deemed most relevant for RD onset followed by lifestyle factors, emphasizing the impact of treatment conceptualization and patient education. While a broad majority of 92.8% assess RD at least once during RT, 59.0% of participants report RD at least partially arbitrarily and 17.4% stated to classify RD severity solely arbitrarily. 83.7% of all participants were unaware of patient-reported outcomes (PROs). Consensus exists on some lifestyle recommendations like avoidance of sun exposure (98.7%), hot baths (95.1%), and mechanical irritation (91.8%) under RT, while deodorant use (63.4% not at all, 22.1% with restrictions) or application of skin lotion (15.1% disapproval) remain controversial and are not recommended by guidelines or evidence-based practices. CONCLUSION: Identification of patients at an increased risk of RD and subsequent implementation of adequate preventive measures remain relevant and challenging aspects of clinical routines. Consensus exists on several risk factors and nonpharmaceutical prevention recommendations, while RT-dependent risk factors, e.g., the fractionation scheme, or hygienic measures like deodorant use remain controversial. Surveillance is widely lacking methodology and objectivity. Intensifying outreach in the radiation oncology community is needed to improve practice patterns.

Safety and efficacy of helical tomotherapy following lung-sparing surgery in locally advanced malignant pleural mesothelioma.

PURPOSE: To assess the value of radiation therapy (RT) with helical tomotherapy (HT) in the management of locally advanced malignant pleural mesothelioma (MPM) receiving no or lung-sparing surgery. METHODS: Consecutive MPM cases not undergoing extrapleural pneumonectomy and receiving intensity-modulated (IM) HT were retrospectively evaluated for local control, distant control, progression-free survival (PFS), and overall survival (OS). Impact of age, systemic treatment, RT dose, and recurrence patterns was analyzed by univariate and multivariate analysis. As a secondary endpoint, reported toxicity was assessed. RESULTS: A total of 34 localized MPM cases undergoing IMHT were identified, of which follow-up data were available for 31 patients. Grade 3 side effects were experienced by 26.7% of patients and there were no grade 4 or 5 events observed. Median PFS was 19 months. Median OS was 20 months and the rates for 1­ and 2­year OS were 86.2 and 41.4%, respectively. OS was significantly superior for patients receiving adjuvant chemotherapy (p = 0.008). CONCLUSION: IMHT of locally advanced MPM after lung-sparing surgery is safe and feasible, resulting in satisfactory local control and survival. Adjuvant chemotherapy significantly improves OS. Randomized clinical trials incorporating modern RT techniques as a component of trimodal treatment are warranted to establish an evidence-based standard of care pattern for locally advanced MPM.

Outcome assessment of intraoperative radiotherapy for brain metastases: results of a prospective observational study with comparative matched-pair analysis.

PURPOSE: Intraoperative radiation therapy (IORT) is an emerging alternative to adjuvant stereotactic external beam radiation therapy (EBRT) following resection of brain metastases (BM). Advantages of IORT include an instant prevention of tumor regrowth, optimized dose-sparing of adjacent healthy brain tissue and immediate completion of BM treatment, allowing an earlier admission to subsequent systemic treatments. However, prospective outcome data are limited. We sought to assess long-term outcome of IORT in comparison to EBRT. METHODS: A total of 35 consecutive patients, prospectively recruited within a study registry, who received IORT following BM resection at a single neuro-oncological center were evaluated for radiation necrosis (RN) incidence rates, local control rates (LCR), distant brain progression (DBP) and overall survival (OS) as long-term outcome parameters. The 1 year-estimated OS and survival rates were compared in a balanced comparative matched-pair analysis to those of our institutional database, encompassing 388 consecutive patients who underwent adjuvant EBRT after BM resection. RESULTS: The median IORT dose was 30 Gy prescribed to the applicator surface. A 2.9% RN rate was observed. The estimated 1 year-LCR was 97.1% and the 1 year-DBP-free survival 73.5%. Median time to DBP was 6.4 (range 1.7-24) months in the subgroup of patients experiencing intracerebral progression. The median OS was 17.5 (0.5-not reached) months with a 1 year-survival rate of 61.3%, which did not not significantly differ from the comparative cohort (p = 0.55 and p = 0.82, respectively). CONCLUSION: IORT is a safe and effective fast-track approach following BM resection, with comparable long-term outcomes as adjuvant EBRT.

Intraoperative or postoperative stereotactic radiotherapy for brain metastases: time to systemic treatment onset and other patient-relevant outcomes.

PURPOSE: Intraoperative radiotherapy (IORT) has become a viable treatment option for resectable brain metastases (BMs). As data on local control and radiation necrosis rates are maturing, we focus on meaningful secondary endpoints such as time to next treatment (TTNT), duration of postoperative corticosteroid treatment, and in-hospital time. METHODS: Patients prospectively recruited within an IORT study registry between November 2020 and June 2023 were compared with consecutive patients receiving adjuvant stereotactic radiotherapy (SRT) of the resection cavity within the same time frame. TTNT was defined as the number of days between BM resection and start of the next extracranial oncological therapy (systemic treatment, surgery, or radiotherapy) for each of the groups. RESULTS: Of 95 BM patients screened, IORT was feasible in 84 cases (88%) and ultimately performed in 64 (67%). The control collective consisted of 53 SRT patients. There were no relevant differences in clinical baseline features. Mean TTNT (range) was 36 (9 - 94) days for IORT patients versus 52 (11 - 126) days for SRT patients (p = 0.01). Mean duration of postoperative corticosteroid treatment was similar (8 days; p = 0.83), as was mean postoperative in-hospital time (11 versus 12 days; p = 0.97). Mean total in-hospital time for BM treatment (in- and out-patient days) was 11 days for IORT versus 19 days for SRT patients (p < 0.001). CONCLUSION: IORT for BMs results in faster completion of interdisciplinary treatment when compared to adjuvant SRT, without increasing corticosteroid intake or prolonging in-hospital times. A randomised phase III trial will determine the clinical effects of shorter TTNT.

Long-term characterization of MRI-morphologic alterations after active motion-compensated liver SBRT: a multi-institutional pooled analysis.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an effective therapeutic approach in patients with liver metastases. However, long-term changes in hepatic normal tissue have to be taken into account in multimodal treatment regimes. Magnetic-resonance-imaging (MRI) based morphologic liver alterations (MMA) after liver SBRT have been analyzed longitudinally. MATERIAL AND METHODS: 57 patients treated with gantry-based or robotic-based SBRT of 69 treatment volumes of liver metastases, who had long-term follow-up (FU) ≥6 months were included in this retrospective analysis. Post-SBRT MMAs were contoured on each contrast-enhanced-T1-weighted (T1w) MRI-sequence. Morphologic/volumetric data of the liver and MMAs were evaluated longitudinally, including the dependency on treatment-related factors of the planning target volume (PTV) and liver. RESULTS: The median FU time was 1 year [6-48 months]. 66 of 69 treatment volumes developed MMAs (mean 143.8 ± 135.1 ccm at first appearance). 31.8% of MMAs resolved completely during FU. Of the persisting MMAs 82.2%/13.3% decreased/increased in size until last available FU. Morphological characterization of the MMAs at first appearance included 75% hypointense and 25% hyperintense T1w-MRI-based appearances. Hypointense as compared to hyperintense appearance was significantly associated with a higher mean liver dose EQD2α/ß=3 Gy (p = 0.0212) and non-significantly greater MMA size. Variance analysis demonstrated a significant reduction of MMA and total liver volume after SBRT (p < 0.0001). The volume reduction decelerated longitudinally for both MMA (p < 0.0001) and liver size (p = 0.0033). Radiation doses (PTV-BEDα/ß=3 Gy and 10 Gy) were not significantly associated with MMA volume reduction. SBRT of liver metastases with mean liver dose EQD2α/ß=3 Gy > 18 Gy were characterized by greater MMA volumes (p = 0.0826) and steeper MMA reduction gradients during FU than those with EQD2α/ß=3 Gy ≤ 18 Gy (p < 0.0001). CONCLUSION: Radiogenic MMAs either completely resolve or usually decrease in volume with pronounced reduction during short-term FU. This course was independent of the MMA's morphological appearance. Further, increased mean liver dose was associated with greater MMA size and a greater gradient of MMA size reduction during FU.

Chasing a rarity: a retrospective single-center evaluation of prognostic factors in primary gliosarcoma.

BACKGROUND AND PURPOSE: Primary gliosarcoma (GS) is a rare variant of IDH-wildtype glioblastoma multiforme. We performed a single-center analysis to identify prognostic factors. PATIENTS AND METHODS: We analyzed the records of 26 patients newly diagnosed with primary WHO grade IV GS. Factors of interest were clinical and treatment data, as well as molecular markers, time to recurrence, and time to death. RESULTS: Median follow-up was 9 months (range 5-21 months). Gross total resection did not lead to improved survival, most likely due to the relatively small sample size. Low symptom burden at the time of diagnosis was associated with longer PFS (P = 0.023) and OS (P = 0.018). Median OS in the entire cohort was 12 months. Neither MGMT promoter hypermethylation nor adjuvant temozolomide therapy influenced survival, consistent with some previous reports. CONCLUSION: In this retrospective study, patients exhibiting low symptom burden at diagnosis showed improved survival. None of the other factors analyzed were associated with an altered outcome.

Drug repurposing using transcriptome sequencing and virtual drug screening in a patient with glioblastoma.

Background Precision medicine and drug repurposing are attractive strategies, especially for tumors with worse prognosis. Glioblastoma is a highly malignant brain tumor with limited treatment options and short survival times. We identified novel BRAF (47-438del) and PIK3R1 (G376R) mutations in a glioblastoma patient by RNA-sequencing. Methods The protein expression of BRAF and PIK3R1 as well as the lack of EGFR expression as analyzed by immunohistochemistry corroborated RNA-sequencing data. The expression of additional markers (AKT, SRC, mTOR, NF-κB, Ki-67) emphasized the aggressiveness of the tumor. Then, we screened a chemical library of > 1500 FDA-approved drugs and > 25,000 novel compounds in the ZINC database to find established drugs targeting BRAF47-438del and PIK3R1-G376R mutated proteins. Results Several compounds (including anthracyclines) bound with higher affinities than the control drugs (sorafenib and vemurafenib for BRAF and PI-103 and LY-294,002 for PIK3R1). Subsequent cytotoxicity analyses showed that anthracyclines might be suitable drug candidates. Aclarubicin revealed higher cytotoxicity than both sorafenib and vemurafenib, whereas idarubicin and daunorubicin revealed higher cytotoxicity than LY-294,002. Liposomal formulations of anthracyclines may be suitable to cross the blood brain barrier. Conclusions In conclusion, we identified novel small molecules via a drug repurposing approach that could be effectively used for personalized glioblastoma therapy especially for patients carrying BRAF47-438del and PIK3R1-G376R mutations.

Implementation, relevance, and virtual adaptation of neuro-oncological tumor boards during the COVID-19 pandemic: a nationwide provider survey.

PURPOSE: Neuro-oncology tumor boards (NTBs) hold an established function in cancer care as multidisciplinary tumor boards. However, NTBs predominantly exist at academic and/or specialized centers. In addition to increasing centralization throughout the healthcare system, changes due to the COVID-19 pandemic have arguably resulted in advantages by conducting clinical meetings virtually. We therefore asked about the experience and acceptance of (virtualized) NTBs and their potential benefits. METHODS: A survey questionnaire was developed and distributed via a web-based platform. Specialized neuro-oncological centers in Germany were identified based on the number of brain tumor cases treated in the respective institution per year. Only one representative per center was invited to participate in the survey. Questions targeted the structure/organization of NTBs as well as changes due to the COVID-19 pandemic. RESULTS: A total of 65/97 institutions participated in the survey (response rate 67%). In the context of the COVID-19 pandemic, regular conventions of NTBs were maintained by the respective centers and multi-specialty participation remained high. NTBs were considered valuable by respondents in achieving the most optimal therapy for the affected patient and in maintaining/encouraging interdisciplinary debate/exchange. The settings of NTBs have been adapted during the pandemic with the increased use of virtual technology. Virtual NTBs were found to be beneficial, yet administrative support is lacking in some places. CONCLUSIONS: Virtual implementation of NTBs was feasible and accepted in the centers surveyed. Therefore, successful implementation offers new avenues and may be pursued for networking between centers, thereby increasing coverage of neuro-oncology care.

Intracellular Delivery of Doxorubicin by Iron Oxide-Based Nano-Constructs Increases Clonogenic Inactivation of Ionizing Radiation in HeLa Cells.

In this study, we determined the potential of polyethylene glycol-encapsulated iron oxide nanoparticles (IONPCO) for the intracellular delivery of the chemotherapeutic doxorubicin (IONPDOX) to enhance the cytotoxic effects of ionizing radiation. The biological effects of IONP and X-ray irradiation (50 kV and 6 MV) were determined in HeLa cells using the colony formation assay (CFA) and detection of γH2AX foci. Data are presented as mean ± SEM. IONP were efficiently internalized by HeLa cells. IONPCO radiomodulating effect was dependent on nanoparticle concentration and photon energy. IONPCO did not radiosensitize HeLa cells with 6 MV X-rays, yet moderately enhanced cellular radiosensitivity to 50 kV X-rays (DMFSF0.1 = 1.13 ± 0.05 (p = 0.01)). IONPDOX did enhance the cytotoxicity of 6 MV X-rays (DMFSF0.1 = 1.3 ± 0.1; p = 0.0005). IONP treatment significantly increased γH2AX foci induction without irradiation. Treatment of HeLa cells with IONPCO resulted in a radiosensitizing effect for low-energy X-rays, while exposure to IONPDOX induced radiosensitization compared to IONPCO in cells irradiated with 6 MV X-rays. The effect did not correlate with the induction of γH2AX foci. Given these results, IONP are promising candidates for the controlled delivery of DOX to enhance the cytotoxic effects of ionizing radiation.

Protective Effects of Flavonoids Against Mitochondriopathies and Associated Pathologies: Focus on the Predictive Approach and Personalized Prevention.

Multi-factorial mitochondrial damage exhibits a "vicious circle" that leads to a progression of mitochondrial dysfunction and multi-organ adverse effects. Mitochondrial impairments (mitochondriopathies) are associated with severe pathologies including but not restricted to cancers, cardiovascular diseases, and neurodegeneration. However, the type and level of cascading pathologies are highly individual. Consequently, patient stratification, risk assessment, and mitigating measures are instrumental for cost-effective individualized protection. Therefore, the paradigm shift from reactive to predictive, preventive, and personalized medicine (3PM) is unavoidable in advanced healthcare. Flavonoids demonstrate evident antioxidant and scavenging activity are of great therapeutic utility against mitochondrial damage and cascading pathologies. In the context of 3PM, this review focuses on preclinical and clinical research data evaluating the efficacy of flavonoids as a potent protector against mitochondriopathies and associated pathologies.

Low-dose radiotherapy for COVID-19 pneumonia treatment: case report, procedure, and literature review.

BACKGROUND: The COVID-19 pandemic outbreak has set the emergency services in developing countries on major alert, as the installed response capacities are easily overwhelmed by the constantly increasing high demand. The deficit of intensive care unit beds and ventilators in countries like Peru is forcing practitioners to seek preventive or early interventional strategies to prevent saturating these chronically neglected facilities. CASE PRESENTATION: A 64-year-old patient is reported after presenting with COVID-19 pneumonia and rapidly progressing to deteriorated ventilatory function. Compassionate treatment with a single 1­Gy dose to the bilateral whole-lung volume was administered, with gradual daily improvement of ventilatory function and decrease in serum inflammatory markers and oxygen support needs, including intubation. No treatment-related toxicity developed. Procedures of transport, disinfection, and treatment planning and delivery are described. CONCLUSION: Whole-lung low-dose radiotherapy seems to be a promising approach for avoiding or delaying invasive respiratory support. Delivered low doses are far from meeting toxicity ranges. On-going prospective trials will elucidate the effectiveness of this approach.

Long-term outcome after intraoperative radiotherapy as a boost in breast cancer.

PURPOSE: To investigate long-term oncological outcome and incidence of chronic side effects in patients with breast cancer and intraoperative radiotherapy given as an upfront boost (IORT boost). METHODS: Retrospective analysis of 400 patients with an IORT boost with low-energy X­rays (20 Gy), subsequent whole-breast irradiation (46-50 Gy), and annual oncological follow-up. Side effects were prospectively evaluated (LENT-SOMA scales) over a period of up to 15 years. Side effects scored ≥grade 2 at least three times during follow-up were judged to be chronic. RESULTS: The median age was 63 years (30-85) and the median follow-up was 78 months (2-180) after IORT boost. In 15 patients a local recurrence occurred, resulting in a local recurrence rate at 5, 10, and 15 years of 2.0%, 6.6%, and 10.1%, respectively. The overall survival rates at 5, 10, and 15 years were 92.1%, 81.8%, and 80.7%, respectively. The most common high-grade side effects were fibrosis (21%) and pain (8.6%). The majority of side effects occurred within the first 3 years. The actuarial rates of chronic fibrosis were 19.1% and 21.1% at 5 and ≥8 years, of chronic pain 8.6% at ≥4 years, of chronic edema of the breast 2.4% at ≥2 years, of chronic lymphedema 0.0% at 5 and 10 years, and of chronic hyperpigmentation 0.5% at ≥2 years. Side effects were similar or less than expected from an external beam boost. CONCLUSION: IORT boost appears to be a highly efficient and safe method for upfront delivery of the tumor bed boost in high-risk breast cancer patients.

Oncology Informatics: Status Quo and Outlook.

Oncology has undergone rapid progress, with emerging developments in areas including cancer stem cells, molecularly targeted therapies, genomic analyses, and individually tailored immunotherapy. These advances have expanded the tools available in the fight against cancer. Some of these have seen broad media coverage resulting in justified public attention. However, these achievements have only been possible due to rapid developments in the expanding field of biomedical informatics and information technology (IT). Artificial intelligence, radiomics, electronic health records, and electronic patient-reported outcome measures (ePROMS) are only a few of the developments enabling further progress in oncology. The promising impact of IT in oncology will only become reality through a multidisciplinary approach to the complex challenges ahead.

Digital Follow-Up and the Perspective of Patient-Centered Care in Oncology: What's the PROblem?

There is accumulating evidence from randomized trials suggesting that digital patient-centered care allows a more reliable detection of tumour-related symptoms and adverse events - with a direct impact on overall survival. Consequently, a variety of unsynchronized approaches were kicked off to (electronically) measure patient-reported outcomes (PROs). Despite increasing evidence that PRO data are highly relevant for patient care, the data generated in these initial projects lack standardized processing pathways in order to impact clinical routine; therefore, potential future routine PRO assessments require adequate analysis, storage and processing to allow a robust, reproducible and reliable incorporation into routine clinical decision-making. Here, we discuss relevant challenges of digital follow-up that need to be tackled to render PRO data as relevant to physicians as laboratory or biomarker data.

Open-Label Phase II Evaluation of Imatinib in Primary Inoperable or Incompletely Resected and Recurrent Glioblastoma.

PURPOSE: Preclinical studies indicated that imatinib may have single-agent activity in glioblastoma through inhibition of tyrosine kinase activity and also that it might enhance the efficacy of radiotherapy. We therefore sought to investigate clinical efficacy in patients with newly diagnosed and recurrent glioblastoma in combination with radiotherapy. METHODS: We conducted a nonrandomized, 2-arm, open-label phase II trial including patients aged 18 years or older with an ECOG performance status of 0-2 that were either newly diagnosed (arm A) with a measurable tumor (i.e., after incomplete resection or biopsy) or that were diagnosed with progression of a glioblastoma after initial therapy (arm B). Patients in arm A received 600 mg/day imatinib in combination with hypofractionated radiotherapy (2.5 Gy per fraction, 22 fractions). Patients in arm B received 600 mg/day imatinib alone or in combination with re-irradiation at various doses. In case tumor progression occurred, CCNU was added (2 cycles, 100 mg/m2) to imatinib. The primary end point was progression-free survival (PFS). The secondary end point was safety, defined as per Common Terminology Criteria for Adverse Events (version 2.0). Overall survival (OS) was analyzed as an exploratory end point. RESULTS: Fifty-one patients were enrolled, of which 19 were included in arm A and 32 in arm B. The median follow-up was 4 (0.5-30) months in arm A and 6.5 (0.3-51.5) months in arm B. The median PFS was 2.8 months (95% CI 0-8.7) in arm A and 2.1 months (95% CI 0-11.8) in arm B. The median OS was 5.0 (0.8-30) months (95% CI 0-24.1) in arm A and 6.5 (0.3-51.5) months (95% CI 0-32.5) in arm B. The major grade 3 events were seizure (present in 17 patients), pneumonia (11 patients), and vigilance decrease (7 patients). CONCLUSIONS: Imatinib showed no measurable activity in patients with newly diagnosed or recurrent glioblastoma.

Response of advanced HCC to pembrolizumab and lenvatinib combination therapy despite monotherapy failure.

In recent years, immune checkpoint inhibitors (ICIs) were successfully introduced to cancer therapy, and these drugs have already become essential for the treatment of various noncurable tumors. However, monotherapy in advanced hepatocellular carcinoma (aHCC) failed to show statistically significant improvement.Recently, the combination of atezolizumab and bevacizumab demonstrated efficacy of combining ICI and VEGF inhibition, further substantiating previous data on synergistic mechanisms among respective substance classes.As TKI treatment is currently standard of care for aHCC, and ICIs are approved by the FDA and available in many areas of the world, numerous patients may have been treated with monotherapy of those drugs. However, it remains unclear if failure to monotherapy has an impact on combination therapy. We therefore report a patient well responding to combination therapy despite previous failures to TKI and ICI monotherapy.

Longitudinal MRI findings in patients with newly diagnosed glioblastoma after intraoperative radiotherapy.

BACKGROUND AND PURPOSE: Post-radiation treatment effects (pseudoprogression/radionecrosis) may bias MRI-based tumor response evaluation. To understand these changes specifically after high doses of radiotherapy, we analyzed MRIs of patients enrolled in the INTRAGO study (NCT02104882), a phase I/II dose-escalation trial of intraoperative radiotherapy (20-40 Gy) in glioblastoma. METHODS: INTRAGO patients were evaluated and compared to control patients who received standard therapy with focus on contrast enhancement patterns/volume, T2 lesion volume, and mean rCBV. RESULTS: Overall, 11/15 (73.3%) INTRAGO patients (median age 60 years) were included. Distant failure was observed in 7/11 (63.6%) patients, local tumor recurrence in one patient (9.1%). On the first follow-up MRI all but one patient demonstrated enhancement of varying patterns around the resection cavity which were: in 2/11 (18.2%) patients thin and linear, in 7/11 (63.6%) combined linear and nodular, and in 1/11 (9.1%) voluminous, indistinct, and mesh-like. In the course of treatment, most patients developed the latter two patterns (8/11 [72.7%]). INTRAGO patients demonstrated more often combined linear and nodular and/or voluminous, indistinct, mesh-like components (8/11 [72.7%]) in comparison to control patients (3/12 [25%], P = 0.02). INTRAGO patients demonstrated significantly increasing enhancing lesion (P = 0.001) and T2 lesion volumes (P < 0.001) in the longitudinal non-parametric analysis in comparison to the control group. rCBV showed no significant differences between both groups. CONCLUSIONS: High doses of radiotherapy to the tumor cavity result in more pronounced enhancement patterns/volumes and T2 lesion volumes. These results will be useful for the response evaluation of patients exposed to high doses of radiotherapy in future studies.