Standard Radiation Research Articles

Reinforcement of Carbazole-Based Self-Assembled Monolayers in Inverted Perovskite Solar Cells.

Self-assembled monolayers (SAMs) with excellent hole conduction capabilities significantly improve the performance of inverted perovskite solar cells (PSCs). However, the amphiphilic nature of SAMs causes the spontaneous formation of spherical micelles in solution, limiting their surface coverage and uniformity on indium tin oxide (ITO) substrates. Furthermore, the distribution of the SAMs directly affects the morphology of perovskite films and the charges transfer properties at the buried interface. This study employs a cosolvent strategy combining n-butanol and dimethyl sulfoxide to improve the uniform spreading of SAMs on ITO. The synergistic interaction between the solvent molecules smooths the surface of [2-(3,6-dimethoxy-9H-carbazol-9-yl) ethyl] phosphonic acid (MeO-2PACz) and enhances its surface coverage. The cosolvent based MeO-2PACz has the characteristics of concentrated surface potential distribution and high work function, exhibiting uniform and enhanced P-type behavior. Additionally, the cosolvent-treated SAMs provide uniform nucleation sites for the crystallization of perovskite, effectively eliminating void defects at the buried interface and improving the crystallinity of perovskite films. Consequently, the optimized device achieves a power conversion efficiency (PCE) of 25.51% and a fill factor of 84.38%. Furthermore, the ordered SAMs improve the stability of PSCs, with encapsulated device retaining 92.63% of its initial PCE after operating for 1500 h under simulated AM 1.5G standard irradiation in air at 65 °C.

Online Radiotherapy: The Paradigm Shift to Real-Time Adaptive Radiotherapy.

Adaptive radiotherapy (ART) involves the continuous adaptation of the radiation plan according to patient- and tumor-specific feedback. In online ART, the plan is optimized in real time during the treatment; in offline ART, the plan is recalculated between treatment sessions. Hybrid linear accelerators with integrated CT, MRI, or PET are required to perform online ART. This review is based on clinically relevant studies on online ART (January 2019 - May 2024) that were retrieved by a selective search in PubMed. Online ART is a new technique for which no phase 3 trials have been published; in contrast, multiple randomized trials are already available for offline ART. The initial findings of a randomized phase 2 trial of online ART for head and neck cancer showed lower rates of G2 or higher radiation-induced dermatitis (8% vs. 31%, p = 0.05) and a lower dose to the parotid gland (mean dose: 11.5 Gy vs. 16.0 Gy, p = 0.02) with online ART compared to standard radiochemotherapy. Moreover, observational studies show that online ART is feasible and spares organs at risk in patients with esophageal, pancreatic, rectal, and prostatic cancer. Additionally, online ART can enable simulation-free treatment planning and faster initiation of radiotherapy. It is, however, more demanding of time and resources and more costly than standard radiotherapy, and no studies with long-term clinical endpoints are available to date. Initial studies confirm the feasibility of online ART and arouse the hope that it will enable more precise radiotherapy with less damage to surrounding structures. Phase 3 trials are needed so that the patient groups who stand to benefit most from online ART can be identified.

FLASH radiation reprograms lipid metabolism and macrophage immunity and sensitizes medulloblastoma to CAR-T cell therapy.

FLASH radiotherapy holds promise for treating solid tumors given the potential lower toxicity in normal tissues but its therapeutic effects on tumor immunity remain largely unknown. Using a genetically engineered mouse model of medulloblastoma, we show that FLASH radiation stimulates proinflammatory polarization in tumor macrophages. Single-cell transcriptome analysis shows that FLASH proton beam radiation skews macrophages toward proinflammatory phenotypes and increases T cell infiltration. Furthermore, FLASH radiation reduces peroxisome proliferator-activated receptor-γ (PPARγ) and arginase 1 expression and inhibits immunosuppressive macrophage polarization under stimulus-inducible conditions. Mechanistically, FLASH radiation abrogates lipid oxidase expression and oxidized low-density lipid generation to reduce PPARγ activity, while standard radiation induces reactive oxygen species-dependent PPARγ activation in macrophages. Notably, FLASH radiotherapy improves infiltration and activation of chimeric antigen receptor (CAR) T cells and sensitizes medulloblastoma to GD2 CAR-T cell therapy. Thus, FLASH radiotherapy reprograms macrophage lipid metabolism to reverse tumor immunosuppression. Combination FLASH-CAR radioimmunotherapy may offer exciting opportunities for solid tumor treatment.

Temozolomide regulates primary central nerve system lymphoma, being resistant to high dose methotrexate-based chemotherapy and radiation

Introduction: Primary central nerve system lymphoma (PCNSL) is an intracranial malignancy. Combined chemotherapy with methotrexate, procarbazine, vincristine, and Rituximab, following radiation, sometimes results in partial response or progressive disease. Temozolomide (TMZ) administration has been proposed to salvage therapy. Case Report: A 72-year-old man had headache and forgetfulness. Mild disorientation was observed. Head magnetic resonance image revealed a mass lesion in the right frontal lobe. Pathological examination after an incisional biopsy revealed a diagnosis of diffuse large B cell lymphoma. Standard treatment consisted of 6 cycles of high-dose methotrexate-based chemotherapy with procarbazine and vincristine. Three cycles of high-dose methotrexate-based chemotherapy with procarbazine and vincristine, combined with Rituximab. Further, focal radiation therapy against core lesion with marginal area irradiation was performed. In spite of total standard treatment, the lesion was not under regulation. The patient continued TMZ therapy 29 cycles on an outpatient basis due to psychiatric complications that made it difficult to continue intravenous treatment in the hospital. The tumor mass and surrounding edematous lesions decreased. Conclusion: Oral TMZ administration was effective in an elderly patient with PCNSL, who had failed standard chemotherapy and radiation therapy. It was less invasive, allowed for transition to outpatient management, and provided adequate therapeutic benefit. Future indications for similar cases should be considered.

Patient-Reported Outcomes: Comparing Functional Avoidance and Standard Thoracic Radiation Therapy in Lung Cancer.

Novel methods generate functional images using image processing techniques combined with four-dimensional computed tomography (4DCT) data (4DCT-ventilation). 4DCT-ventilation was implemented in a phase II, multicenter functional avoidance clinical trial. The work compares functional avoidance patient-reported outcomes (PROs) against historical standards. Patients with locally advanced lung cancer undergoing curative-intent chemoradiation were accrued. 4DCT-ventilation imaging was generated and functional avoidance treatment plans created reduced dose to functional lung. PRO instruments included Functional Assessment of Cancer Therapy Lung questionnaire and accompanying subscales (including the Trial Outcome Index [TOI]), EuroQol-5 Dimension (EQ-5D), and EQ-Visual Analog Scale (EQ-VAS). The average change from baseline and percentage of clinically meaningful declines were calculated. We compared results against PROs from RTOG 0617 and PACIFIC trial data using Student t-tests and chi-square tests. Fifty-nine patients completed baseline PRO surveys. The median age was 65 (44-86) years, non-small cell lung cancer comprised 83%, and median dose was 60 Gy in 30 fractions. The percent of patients with clinically meaningful decline in FACT-TOI at 12 months was 47.8% for RTOG 0617% and 26.8% for functional avoidance (P = .03). The functional avoidance cohort demonstrated a significantly (P = .012) higher change in EQ-VAS score at 12 months (9.9 ± 3.3; average ± SE) compared with the PACIFIC cohort (1.6 ± 0.6). The current work demonstrates improved PROs from a phase II functional avoidance trial in certain subscales (FACT-TOI and EQ-VAS) compared with PROs from seminal studies (RTOG 0617 and PACIFIC). The presented data support investigation of 4DCT functional avoidance in a phase III setting.

Preliminary results of the ALTER-E009 study: Efficacy and safety of anlotinib combined with radiotherapy in patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC)—A multicenter, multi-cohort retrospective exploratory study.

361 Background: Therapeutic options for metastatic esophageal squamous cell carcinoma (ESCC) primarily involve immunotherapy combined with chemotherapy. For locally advanced ESCC, concurrent chemoradiotherapy (CRT) or radiotherapy is the standard, though outcomes remain suboptimal. Targeted therapies, particularly anti-angiogenic agents, hold promise to enhance CRT efficacy. Anlotinib, a multi-target anti-angiogenic agent inhibiting VEGFR, PDGFR, FGFR, and c-KIT, has shown potential to enhance radiotherapy by alleviating tumor hypoxia. This multicenter, retrospective study evaluates the efficacy and safety of anlotinib combined with radiotherapy in locally advanced or metastatic ESCC. Methods: This study screened patients (pts) with locally advanced or metastatic ESCC treated with anlotinib (8-12 mg, p.o., qd, d1-14, q3w) and radiotherapy from June 2018 to June 2024. Two cohorts were included: Cohort 1 (metastatic ESCC) and Cohort 2 (locally advanced ESCC). Cohort 2 was divided into an observational group (OG, anlotinib + radiotherapy ± chemotherapy) and a control group (CG, radiotherapy ± chemotherapy). Radiotherapy doses for primary lesions were 45-60 Gy (1.8-2.2 Gy per fraction), while metastatic lesions received either standard fractionation (≥45 Gy) or stereotactic body radiotherapy (SBRT, ≥3 Gy per fraction, total dose ≥30 Gy). Chemotherapy regimens were not restricted. Cohort 1 aimed to enroll 50 pts, while Cohort 2 included 100 in the OG and 200 in the CG. The primary endpoint was overall survival (OS), with secondary endpoints including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), and safety. Results: By September 10, 2024, 128 pts had been enrolled: 34 in Cohort 1 and 94 in the OG of Cohort 2. In Cohort 1, all 34 pts (100%) were stage IVB, with a median OS of 24.0 months (95% CI: 12.44-35.60) and a median PFS of 9.2 months (95% CI: 7.60-10.80). The 24-month OS and PFS rates were 54.0% (95% CI: 27.20-74.73) and 30.8% (95% CI: 10.21-54.53), respectively. ORR was 52.9% (95% CI: 35.1-70.2), with 1 complete response (CR) and 17 partial responses (PR), DCR was 88.2% (95% CI: 72.5-96.7). In Cohort 2, 50 pts (53.2%) were stage III, and 28 (29.8%) were stage IVA. The median OS is not yet mature, but the median PFS was 20.1 months. The 36-month OS and PFS rates were 61.9% (95% CI: 46.12-74.34) and 48.4% (95% CI: 29.58-64.87). ORR was 46.8% (95% CI: 36.4-57.4), with 6 CRs and 38 PRs, DCR was 95.7% (95% CI: 89.5-98.8). Safety data collection is ongoing. Conclusions: Anlotinib combined with radiotherapy exhibited promising efficacy in locally advanced or metastatic ESCC, though further data are needed to confirm these preliminary findings.

Multienergy Barrier Anti-/Deicing Surface with Excellent Photothermal Effect.

Superhydrophobic surfaces are considered to be an effective method for anti-icing, but passive anti-icing alone is not as effective as it should be, so it is crucial to develop effective anti-icing techniques. In this study, a photothermal anti-icing structure with multienergy barriers was designed by combining active and passive anti-icing technologies and prepared by a three-step method of laser etching, hydrothermal growth of nanostructures, and chemical modification based on the Cassie-Baxter-Wenzel transition theory. The experimental results show that the static water contact angle of the prepared surface is up to 160°, the sliding angle is less than 3.6°, and the surface temperature is 25 °C higher than that of the original control group over 100 s under standard solar irradiation. The multienergy barrier design greatly prolongs the time of the anti-icing, and the durability test shows that the surface maintains superhydrophobicity even after the abrasion of sandpaper and the impact of sand. This superhydrophobic photothermal coating has great potential for anti-icing and deicing applications.

Intraindividual Comparison of Image Quality Between Low-Dose and Ultra-Low-Dose Abdominal CT With Deep Learning Reconstruction and Standard-Dose Abdominal CT Using Dual-Split Scan.

The aim of this study was to intraindividually compare the conspicuity of focal liver lesions (FLLs) between low- and ultra-low-dose computed tomography (CT) with deep learning reconstruction (DLR) and standard-dose CT with model-based iterative reconstruction (MBIR) from a single CT using dual-split scan in patients with suspected liver metastasis via a noninferiority design. This prospective study enrolled participants who met the eligibility criteria at 2 tertiary hospitals in South Korea from June 2022 to January 2023. The criteria included (a) being aged between 20 and 85 years and (b) having suspected or known liver metastases. Dual-source CT scans were conducted, with the standard radiation dose divided in a 2:1 ratio between tubes A and B (67% and 33%, respectively). The voltage settings of 100/120 kVp were selected based on the participant's body mass index (<30 vs ≥30 kg/m2). For image reconstruction, MBIR was utilized for standard-dose (100%) images, whereas DLR was employed for both low-dose (67%) and ultra-low-dose (33%) images. Three radiologists independently evaluated FLL conspicuity, the probability of metastasis, and subjective image quality using a 5-point Likert scale, in addition to quantitative signal-to-noise and contrast-to-noise ratios. The noninferiority margins were set at -0.5 for conspicuity and -0.1 for detection. One hundred thirty-three participants (male = 58, mean body mass index = 23.0 ± 3.4 kg/m2) were included in the analysis. The low- and ultra-low- dose had a lower radiation dose than the standard-dose (median CT dose index volume: 3.75, 1.87 vs 5.62 mGy, respectively, in the arterial phase; 3.89, 1.95 vs 5.84 in the portal venous phase, P < 0.001 for all). Median FLL conspicuity was lower in the low- and ultra-low-dose scans compared with the standard-dose (3.0 [interquartile range, IQR: 2.0, 4.0], 3.0 [IQR: 1.0, 4.0] vs 3.0 [IQR: 2.0, 4.0] in the arterial phase; 4.0 [IQR: 1.0, 5.0], 3.0 [IQR: 1.0, 4.0] vs 4.0 [IQR: 2.0, 5.0] in the portal venous phases), yet within the noninferiority margin (P < 0.001 for all). FLL detection was also lower but remained within the margin (lesion detection rate: 0.772 [95% confidence interval, CI: 0.727, 0.812], 0.754 [0.708, 0.795], respectively) compared with the standard-dose (0.810 [95% CI: 0.770, 0.844]). Sensitivity for liver metastasis differed between the standard- (80.6% [95% CI: 76.0, 84.5]), low-, and ultra-low-doses (75.7% [95% CI: 70.2, 80.5], 73.7 [95% CI: 68.3, 78.5], respectively, P < 0.001 for both), whereas specificity was similar (P > 0.05). Low- and ultra-low-dose CT with DLR showed noninferior FLL conspicuity and detection compared with standard-dose CT with MBIR. Caution is needed due to a potential decrease in sensitivity for metastasis (clinicaltrials.gov/ NCT05324046).

Randomized Evaluation of the PET-Adjusted IMRT for NSCLC Trial (REPAINT).

Standard radiotherapy (RT) for locally advanced NSCLC (LA-NSCLC) employs a uniform dose of approximately 60 Gy. Recent trials demonstrated that radiotherapy dose escalation may not improve outcomes and may cause added toxicity. XXX previously performed a single-arm trial testing a personalized, risk-adapted, and de-intensified RT strategy. We now report findings from a randomized trial testing this novel approach. LA-NSCLC patients with ECOG performance status 0-2 were eligible for this trial. Metabolic tumor volume (MTV) for each pulmonary tumor and involved lymph node was calculated using FDG-PET. Participants were randomized 1:1 to receive standard RT (60 Gy in 30 fractions delivered to pulmonary tumors and involved lymph nodes) versus dose-painted RT (55 Gy delivered to tumors and lymph nodes with metabolic volume exceeding 20 cm3 and 44-48 Gy to other lesions, all in 20 fractions). Concurrent chemotherapy and standard adjuvant therapy were given in both arms. The primary objective was to characterize patient-reported outcomes utilizing PRO-CTCAE. Secondary objectives included comparing outcomes between study arms. Fifty patients were enrolled. The most common grade 3 patient-reported adverse events within 90 days of RT completion were dysphagia (38%), fatigue (38%), cough (32%), and wheezing (28%). The median progression-free survival (PFS) duration is 18 months, and the median overall survival (OS) duration is 42 months. PFS and OS rates are similar across study arms (logrank p=0.562 and 0.765, respectively). There have been three cases of in-field disease progression, with one in the control arm and two in the dose-painted arm. Grade 3-4 lymphopenia was reduced with dose-painted RT (48% v. 81%, chi-square p=0.012). High-grade patient-reported toxicity in LA-NSCLC patients who are treated with concurrent chemoradiotherapy is common. We found no evidence that risk-adapted radiotherapy de-escalation compromises clinical outcomes. Follow-up studies testing the ability of this approach to improve the safety profile of chemoradiotherapy are warranted.

99mTc-FAPI-46 Scan and 177Lu-FAPI-2286 Treatment in a Patient With Nasopharyngeal Carcinoma.

We present a 24-year-old man with a history of metastatic nasopharyngeal cancer. Despite receiving standard treatments, including surgery, radiotherapy, and chemotherapy, he has shown progression. Consequently, he has been referred to the nuclear medicine department for theranostic purposes. The 99mTc-FAPI-46 whole-body scan showed tracer uptake in mediastinal large mass, both external lymph nodes and osseous metastases. Treatment with 177Lu-FAPI-2286 initiated, with subsequent planar scans revealing sustained uptake up to day 10, particularly in the large mediastinal mass. This case indicates promising FAPI-targeted theranostic potential in metastatic nasopharyngeal carcinoma and proper retention of 177Lu-FAPI-2286 in metastatic lesions.

Extensive small cell lung cancer treated by integrated traditional Chinese and Western medicine: A case report.

Patients with extensive small cell lung cancer (SCLC) generally have a dismal survival rate and are conventionally treated with chemotherapy. This study aimed to explore an alternative treatment approach by combining traditional Chinese medicine (TCM) with radiotherapy and chemotherapy. A 68-year-old male was diagnosed with extensive-stage SCLC. Positron emission tomography/computed tomography scans indicated a high metabolism mass in the left hilar region, along with multiple lymph node metastases and metastatic tumors in both lungs. A left lung biopsy verified small cell carcinoma. The patient was confirmed to have extensive stage SCLC based on imaging and biopsy results. The patient received a comprehensive treatment regimen. TCM herbal prescriptions such as Qianjin Weijing Decoction, Wuwei Xiaodu Decoction, Xiaoxianxiong Decoction, and Xiaochengqi Decoction were administered. In parallel, standard Western medicine therapies, including chemotherapy (intravenous cisplatin and etoposide) and radiotherapy, were carried out. Oral ondansetron was given to alleviate nausea and vomiting caused by chemotherapy and radiotherapy. After 30 months, follow-up positron emission tomography/computed tomography demonstrated the complete disappearance of all cancerous lesions. The patient regained normal daily activities and experienced a substantially enhanced quality of life. Four years after the initial treatment, there has been no recurrence, and the patient persists in taking the original TCM decoction. The combination of TCM and Western medicine in treating SCLC proves effective in managing systemic symptoms, mitigating bone marrow suppression, gastrointestinal reactions, immunosuppression, and other chemotherapy-induced adverse reactions. It also significantly prolongs the survival period, suggesting it as a preferable treatment option for SCLC.

Advancements in targeted and immunotherapy strategies for glioma: toward precision treatment.

In recent years, significant breakthroughs have been made in cancer therapy, particularly with the development of molecular targeted therapies and immunotherapies, owing to advances in tumor molecular biology and molecular immunology. High-grade gliomas (HGGs), characterized by their high malignancy, remain challenging to treat despite standard treatment regimens, including surgery, radiotherapy, chemotherapy, and tumor treating fields (TTF). These therapies provide limited efficacy, highlighting the need for novel treatment strategies. Molecular targeted therapies and immunotherapy have emerged as promising avenues for improving treatment outcomes in high-grade gliomas. This review explores the current status and recent advancements in targeted and immunotherapeutic approaches for high-grade gliomas.

Disease stage-specific role of the mitochondrial pyruvate carrier suppresses differentiation in temozolomide and radiation-treated glioblastoma.

The mitochondrial pyruvate carrier (MPC), a central metabolic conduit linking glycolysis and mitochondrial metabolism, is instrumental in energy production. However, the role of the MPC in cancer is controversial. In particular, the importance of the MPC in glioblastoma (GBM) disease progression following standard temozolomide (TMZ) and radiation therapy (RT) remains unexplored. Leveraging in vitro and in vivo patient-derived models of TMZ-RT treatment in GBM, we characterize the temporal dynamics of MPC abundance and downstream metabolic consequences using state-of-the-art molecular, metabolic, and functional assays. Our findings unveil a disease stage-specific role for the MPC, where in post-treatment GBM, but not therapy-naïve tumors, the MPC acts as a central metabolic regulator that suppresses differentiation. Temporal profiling reveals a dynamic metabolic rewiring where a steady increase in MPC abundance favors a shift towards enhanced mitochondrial metabolic activity across patient GBM samples. Intriguingly, while overall mitochondrial metabolism is increased, acetyl-CoA production is reduced in post-treatment GBM cells, hindering histone acetylation and silencing neural differentiation genes in an MPC-dependent manner. Finally, the therapeutic translations of these findings are highlighted by the successful pre-clinical patient-derived orthotopic xenograft (PDOX) trials utilizing a blood-brain-barrier (BBB) permeable MPC inhibitor, MSDC-0160, which augments standard TMZ-RT therapy to mitigate disease relapse and prolong animal survival. Our findings demonstrate the critical role of the MPC in mediating GBM aggressiveness and molecular evolution following standard TMZ-RT treatment, illuminating a therapeutically-relevant metabolic vulnerability to potentially improve survival outcomes for GBM patients.

Multifunctional Organic Molecule for Defect Passivation of Perovskite for High-Performance Indoor Solar Cells.

Perovskite solar cells (PSCs) can utilize the residual photons from indoor light and continuously supplement the energy supply for low-power electron devices, thereby showing the great potential for sustainable energy ecosystems. However, the solution-processed perovskites suffer from serious defect stacking within crystal lattices, compromising the low-light efficiency and operational stability. In this study, we designed a multifunctional organometallic salt named sodium sulfanilate (4-ABS), containing both electron-donating amine and sulfonic acid groups to effectively passivate the positively-charged defects, like under-coordinated Pb ions and iodine vacancies. The strong chemical coordination of 4-ABS with the octahedra framework can further regulate the crystallization kinetics of perovskite, facilitating the enlarged crystal sizes with mitigated grain boundaries within films. The synergistic optimization effects on trap suppression and crystallization modulation upon 4-ABS addition can reduce energy loss and mitigate ionic migration under low-light conditions. As a result, the optimized device demonstrated an improved power conversion efficiency from 22.48% to 24.34% and achieved an impressive efficiency of 41.11% under 1000 lux weak light conditions. This research provides an effective defect modulation strategy for synergistically boosting the device efficiency under standard and weak light irradiations.

Brachytherapy Seed Placement by Robotic Bronchoscopy with Cone-Beam CT Guidance for Peripheral Lung Cancer: A Human Cadaveric Feasibility Pilot.

This study evaluates the feasibility of utilizing robotic-assisted bronchoscopy with cone beam computed tomography (RB-CBCT) platform to perform low-dose-rate brachytherapy implants (LDR-BT) in a mechanically ventilated human cadaveric model. Post-implant dosimetry was compared to standard stereotactic body radiation therapy plans (SBRT). The RB-CBCT platform was used to place inert LDR-BT seeds into mechanically ventilated human cadavers with percutaneously injected pseudotumors. LDR-BT dosimetry plans were created a priori with a prescription dose of 100 Gy to the pseudotumor plus a 3mm margin to define a planning target volume (PTV). Implant quality was assessed by post-implant dosimetry and seed placement accuracy. Brachytherapy dosimetry was compared to standard SBRT treatment plans for the same cadaveric tumor volumes. Eight pseudotumors were planned with a total of 41 LDR-BT seeds, with a median of 5 seeds to achieve appropriate target coverage. All 41 LDR-BT seeds were successfully implanted in the 8 pseudotumors using RB-CBCT. On post-implant analysis, the average (± standard deviation) dosimetry to the pseudotumor was a V95% of 99.4 ± 3.3% and D90% of 128 ± 23Gy. The average distance between the planned and delivered seed location was 3.8 ± 1.1 mm. In comparison to SBRT plans, LDR-BT dose conformity was superior for the ratio of the V50% to the volume of the PTV (2.3 to 4.0, p < 0.001) and V25% (5.0 vs 17.5, p < 0.001). RB-CBCT may be a feasible technology for implantation of LDR-BT seeds in peripheral lung tumors and can achieve pre-planned dosimetry goals with better dose conformity compared to SBRT. Further clinical studies are indicated to demonstrate safety and efficacy of LDR-BT delivered by RB-CBCT for treating early-stage lung cancer.

FLASH proton reirradiation, with or without hypofractionation, reduces chronic toxicity in the normal murine intestine, skin, and bone.

The normal tissue sparing afforded by FLASH radiotherapy is being intensely investigated for potential clinical translation. Here, we studied the effects of FLASH proton radiotherapy (F-PRT) in the reirradiation setting, with or without hypofractionation. Chronic toxicities in three murine models of normal tissue toxicity including the intestine, skin, and bone were investigated. In studies of the intestine, single-dose irradiation was performed with 12 Gy of standard proton RT (S-PRT), followed by a second dose of 12 Gy of F-PRT or S-PRT. Additionally, a hypofractionation scheme was applied in the reirradiation setting (3 x 6.4 Gy of F-PRT or S-PRT, given every 48 hrs). In studies of skin/bone of the murine leg, 15 Gy of S-PRT was followed by hypofractionated reirradiation with F-PRT or S-PRT (3 x 11 Gy). Compared to reirradiation with S-PRT, F-PRT induced less intestinal fibrosis and collagen deposition that was accompanied by significantly increased survival rate, demonstrating its protective effects on intestinal tissues in the reirradiation setting. In previously irradiated leg tissues, reirradiation with hypofractionated F-PRT created transient dermatitis that fully resolved in contrast to reirradiation with hypofractionated S-PRT. Lymphedema was also alleviated after a second course of radiation with F-PRT, along with significant reductions in the accumulation of fibrous connective tissue in the skin, compared to mice reirradiated with S-PRT. The delivery of a second course of fractionated S-PRT induced tibial fractures in 83.3% of the mice, whereas only 20% of mice reirradiated with F-PRT presented with fractures. These studies provide the first evidence of the sparing effects of F-PRT in the setting of hypofractionated reirradiation. The results support FLASH as highly relevant to the reirradiation regimen where it exhibits significant potential to minimize chronic complications for patients undergoing RT.

PARP inhibition radiosensitizes BRCA1 wildtype and mutated breast cancer to proton therapy

Aggressive breast cancers often fail or acquire resistance to radiotherapy. To develop new strategies to improve the outcome of aggressive breast cancer patients, we studied how PARP inhibition radiosensitizes breast cancer models to proton therapy, which is a radiotherapy modality that generates more DNA damage in the tumor than standard radiotherapy using photons. Two human BRCA1-mutated breast cancer cell lines and their isogenic BRCA1-recovered pairs were treated with a PARP inhibitor and irradiated with photons or protons. Protons (9.9 and 3.85 keV/µm) induced higher cell kill independent of BRCA1 status. PARP inhibition amplified the cell kill effect to both photons and protons (9.9 and 3.85 keV/µm) independent of BRCA1 status. Numbers of γH2AX foci, micronuclei, and cGAS-positive micronuclei were significantly higher in BRCA1-mutated cells. Cell cycle distribution and stress-induced senescence were not affected by PARP inhibition in our cell lines. In vivo, the combination of protons (3.99 keV/µm) and PARP inhibition induced the greatest tumor growth delay and the highest survival. We found that PARP inhibition increases radiosensitization independent of BRCA1 status for both protons and photons. The combination of protons and PARP inhibition was the most effective in decreasing clonogenic cell survival, increasing DNA damage, and delaying tumor growth.

Dosimetric Planning Comparison for Left Ventricle Avoidance in Non-small Cell Lung Cancer Radiotherapy.

Radiation may unintentionally injure myocardial tissue, potentially leading to radiation-induced cardiac disease (RICD), with the net benefit of non-small cell lung cancer (NSCLC) radiotherapy (RT) due to the proximity of the lung and heart. RTOG-0617 showed a greater reduction in overall survival (OS) comparing higher doses to standard radiation doses in NSCLC RT. V5GyHeart has been reported as an OS predictor in the first- and fifth-year follow-ups. A worsening OS trend was reported in another study where the mean left ventricle dose (mean LV) was ≥14.5 Gy. It is therefore important to spare the heart, specifically the LV, from radiation. Furthermore, dose-limiting factors toward the normal lung should be accounted for to prevent radiation-induced lung injury. The LV and left anterior descending artery (LAD) were also contoured on the average four-dimensional computed tomography (4D-CT) dataset that contained clinically defined targets and normal structures for stage III NSCLC RT. The prescribed treatment plans (n=15) were retrospectively optimized with the clinical goals of minimizing the mean LV and mean heart dose while maintaining the dose constraint of V20GyLung ≤30% and V95%PTV ≥95%. Dose-volume histograms were used to compare the heart and lung dosimetric parameters between the delivered and reoptimized RT plans. A significant reduction (p≤0.044) was observed in the mean LV, mean heart dose, mean LAD dose, max LADdose, and V5GyHeart from the reoptimized RT plans. V20GyLung ≤30% and V95%PTV ≥95% were maintained, and no differences were observed in the mean lung, V5GyLung, V20GyLung, mean esophagus, and max cord. Minimizing the LV dose in NSCLC RT plans is achievable and dosimetrically advantageous for the heart while maintaining dose constraints to the normal lung and maximizing tumor control. Radiation dose reduction to cardiac substructures may decrease the RICD risk in NSCLC patients.

Exploring the role of Disulfidptosis in glioma progression: insights into tumor heterogeneity and therapeutic potential through single-cell RNA sequencing.

Gliomas, particularly glioblastoma (GBM), are the most common and aggressive primary brain tumors in adults, characterized by high malignancy and frequent recurrence. Despite standard treatments, including surgery, radiotherapy, and chemotherapy, the prognosis for GBM remains poor, with a median survival of less than 15months and a five-year survival rate below 10%. Tumor heterogeneity and resistance to treatment create significant challenges in controlling glioma progression. Therefore, there is an urgent need for new therapeutic targets and strategies. This study investigates the role of Disulfidptosis, a recently discovered form of programmed cell death, in gliomas. Unlike apoptosis and necrosis, Disulfidptosis is driven by the abnormal accumulation of intracellular disulfide bonds, leading to protein misfolding and cytoskeletal collapse, particularly in cancer cells with metabolic dysregulation. We aim to explore how glioma cells respond to Disulfidptosis and identify potential therapeutic targets by analyzing the heterogeneity of gliomas at the single-cell level using single-cell RNA sequencing (scRNA-seq). scRNA-seq data from glioma patients were analyzed to uncover differences in ferroptosis-related pathways, including iron metabolism and lipid peroxidation. Cellular subpopulations within gliomas were profiled to assess their sensitivity to Disulfidptosis and the underlying mechanisms. Survival analysis was conducted to evaluate the clinical relevance of Disulfidptosis-related gene expression. Multiple cell subpopulations within gliomas exhibit varying sensitivities to Disulfidptosis, influenced by their metabolic properties. Dysregulated iron metabolism and antioxidant mechanisms were identified as key factors impacting Disulfidptosis sensitivity. Glioma microenvironment signaling pathways also play a role in regulating Disulfidptosis. These findings suggest that activating Disulfidptosis pathways may provide novel therapeutic strategies to overcome treatment resistance in gliomas. This study offers new insights into the role of Disulfidptosis in glioma progression and highlights its potential as a therapeutic target. By leveraging single-cell sequencing data, the research uncovers tumor heterogeneity and identifies specific cell populations resistant to Disulfidptosis. These findings may pave the way for personalized treatment strategies to improve survival outcomes in glioma patients.

Comparative Study to Evaluate Irradiated Small Bowel Volume with or Without Using Belly Board During Treating Pelvic Malignancy in 3dcrt Technique

Gastrointestinal (GI) toxicity is the most frequently encountered complication of pelvic radiotherapy with clinically significant acute and late toxicity occurring in up to 60% and 20% of patients, respectively. The current study was conducted to assess and compare irradiated small bowel volume and dose between prone position using belly board and supine position without belly board in pelvic radiotherapy. Methods: It was a quasi-experimental study conducted at the department of Radiation Oncology of NICRH. Sixty patients of rectal and cervical malignancy were included in the study. They were enrolled in either arm A or arm B to receive radiotherapy to pelvis in supine position or prone position with belly board, respectively by 3DCRT technique. Results: There were no statistically significant differences in distributions of the patients across the two arms regarding age and other various demographic data, abdominal girth etc. Irradiated volume was significantly low in arm-B (5189cm3 vs. 3485cm3, &amp;lt;i&amp;gt;p-value&amp;lt;/i&amp;gt;&amp;lt;0.001). Small bowel volume which received 45Gy was also significantly low in arm-B (351cm3 vs. 191cm3, &amp;lt;i&amp;gt;p-value&amp;lt;/i&amp;gt;&amp;lt;0.001). Radiation dose to 195cm3 of small bowel volume was 53Gy vs. 36Gy in arm-A and arm-B respectively (&amp;lt;i&amp;gt;p-value&amp;lt;/i&amp;gt;&amp;lt;0.001). Conclusion: Using belly board in prone position is comfortable, inexpensive, highly reproducible, and permits maximal bowel displacement from standard pelvic radiotherapy fields.