Radical Radiotherapy Research Articles

Radiotherapy improved the efficacy of immunotherapy for advanced esophageal cancer.

e16063 Background: The development of immunotherapy has changed treatment methods for advanced esophageal cancer (EC).However, the efficacy of ICIs in advanced EC is not ideal, and the clinical research on the combination of ICIs and Radiotherapy(RT) in advanced EC remains insufficient. This study aimed to evaluate the effectiveness and safety of radiation in first-line immunotherapy for advanced EC. Methods: We conducted 201 advanced EC patients who received first-line ICIs in West China Hospital. The enrolled patients were divided into 2 groups based on whether they received radiation therapy. Results: The analysis included data from 201 patients. The radiotherapy (RT) group had 103 patients (51.2%), whereas the non-radiotherapy (NRT) group included 98 individuals (48.8%). The RT sites include esophagus lesions (83, 80.6%), metastatic lymph nodes (11, 10.7%), liver metastases (4, 3.9%), bone metastases (2, 1.9%), brain metastases (2, 1.9%), lung metastases(1, 0.97%). The median radiation dose was 50.4 Gy (range, 12-68). The RT group had a median OS of 22.8 months (95% CI, 17.8-NA), which was longer than the NRT group's 14.6 months (95% CI, 12.8-26.5) (p = 0.038). And the median PFS was 12.9 months (95% CI, 11.2-14.0) in the RT group versus 7.3 months (95% CI, 6.3-9.7) in the NRT group (p = 0.006). Patients in the RT group had a higher disease control rate (DCR) (99.0% vs. 76.5%, P < 0.001). However, a higher proportion of patients in the RT group developed grade 3-4 myelosuppression (37.86% V.S. 20.20%, P = 0.006), and there was no significant difference in the other AEs. Conclusions: In the first-line immunotherapy for advanced esophageal cancer, radiotherapy has been attributed to improved survival with tolerable toxicity.

Effect of endoscopic surgery combined with chemotherapy and radiotherapy on prognosis of early nasopharyngeal carcinoma patients in high incidence area

Objective:To investigate the differences in the therapeutic effects of endoscopic surgery combined with chemotherapy and endoscopic surgery combined with radiotherapy in the treatment of early nasopharyngeal carcinoma, and to select individualized treatment strategy for early nasopharyngeal carcinoma. Methods:The clinical data of 68 patients with early nasopharyngeal carcinoma（T1-2N₀M₀） who received surgical treatment in a high-incidence area were retrospectively analyzed. According to different treatment methods, they were divided into the surgery + chemotherapy group（n=34, treated with endoscopic surgery combined with chemotherapy） and the surgery + radiotherapy group（n=34, treated with endoscopic surgery combined with radiotherapy）. Propensity score matching was used to match the patient data between the two groups at a 1∶1 ratio. Patients were followed up, and the survival rates and hematological toxicities were compared between the two groups. Results:Twenty-four cases in the surgery + chemotherapy group and 24 cases in the surgery + radiotherapy group were successfully matched. After matching, there was no statistically significant difference in T stage, and clinical stage between the two groups（all P>0.05）. The 3-year OS and DFS in the surgery + chemotherapy group were 100.0% and 95.8%, respectively, while the 3-year OS and DFS in the surgery + radiotherapy group were 100.0% and 100.0%, respectively, with no significant difference in survival rates between the two groups（both P>0.05）. After treatment, there was no statistically significant difference in bone marrow suppression between the surgery + chemotherapy group and the surgery + radiotherapy group （all P> 0.05） Conclusion:Endoscopic surgery combined with chemotherapy and surgery combined with radiotherapy have comparable clinical efficacy in the treatment of early nasopharyngeal carcinoma, but without radiotherapy-related complications, which is worth further investigation.

Reducing the risk of grade 3 or greater radiation pneumonitis after radical radiotherapy to the lung.

e20008 Background: Radiation pneumonitis (RP) is the most common adverse response in patients with lung cancer receiving thoracic radiotherapy. Higher grade RP is more likely to lead to mortality and poor quality of life, which could be abated by rigorous treatment standards formulated with individualized clinical characteristics. In this study, we aimed to identify the best clinical prognostic model for evaluating patients with lung cancer after radical radiotherapy. Methods: We collected information of RP patients in recent years and established the new consensus on the diagnosis and treatment of radiation-related pneumonitis. In a nutshell, clinical data of patients treated with radical radiotherapy were collected from August 2020 to August 2022, and part of patients from August 2021 to August 2022 was been intervented by treatment methods. The interventions included limited irradiation of the planning target volume (PTV), individualized lung dose limitation, and standardized steroid therapy. Clinical characteristics including baseline and treatment data were obtained from 693 patients, including 623 patients in the training cohort and 70 patients in the test cohort. Three models were built using different screening methods, including multivariate logistics regression (MLR), backward stepwise regression (BSR), and random forest regression (RFR), to evaluate their prognostic power. Overoptimism in the training cohorts was evaluated by four validation methods including hold-out, 10-fold, leave-one-out, and bootstrap methods, and extra data were used to evaluate the predictive performance of the model. Model calibration, Decision curve analysis (DCA), and evaluation of the nomograms for the three models were completed. Results: The incidence of RP was significantly decreased after the interventions compared to before (68.80% vs. 59.56%, P < 0.05), and the probability of grade 3 or higher RP also decreased from 11.97% to 6.67% (P < 0.05). A model of intervention, interstitial lung disease (ILD), concurrent chemoradiotherapy, standardized steroids, carbon monoxide diffusing capacity (DLCO) > 86.9%, and total lung volume exceeding 5 Gy (V5) > 35.2% for the radiological parameter had the best discriminative ability with an area under the curve of 0.963 (95% CI: 0.938–0.989) in the training chort . The calibration curve showed good agreement between the predicted and actual values, and the DCA showed a positive net benefit for the final model based on the nomogram. Conclusions: The implementation of standardized interventions for the prevention and treatment of RP accompanied with standardized use of steroids resulted in a significant decrease in the incidence of grade 3 or higher RP. Early intervention and methods for reducing the complications of high-dose steroids will be explored in future work.

Predictors of time to brain metastasis and survival in patients diagnosed with breast cancer.

e13122 Background: Patients with breast cancer (BC) who develop brain metastases (BM) have poor survival outcomes. We aimed to identify significant predictors of time to develop BM and survival after diagnosis. Methods: Patient records were retrospectively reviewed from the Cleveland Clinic database between 2010-2020. Patients with a BC and a BM diagnosis were included for analysis. One way ANOVA was used to compare mean time to BM across subgroups (mean ± SE), and Kaplan-Meier method was used to compute median overall survival (mOS) after BM diagnosis (95% CI). Results: N=109 patients were included in the analysis with a mean age of 52 ± 13 years, mean time to developing BM of 42 ± 35 months, and mOS after BM of 12.00 months (8.99-15.01). The patients’ characteristics were as follows: female (98.2%), white (83.5%), married (56%), privately insured (43.1%), had a Karnofsky Performance Status (KPS) >80 (61.7%), and 21% had stage IV at initial diagnosis. In terms of BC characteristics, 80.4% of cases were ductal, 63.7% were Grade III, 52.3% were HR+, and 31.5% were HER2+, and 32.4% were triple negative. Most patients had extracranial metastases (ECM) at the time of BM diagnosis (67.8%), had at least 2 sites of BM (71.6%), parenchymal only BM (75%), and 10-30 mm BM (44.2%). 15.8% of patients underwent craniotomy and 86.2% received at least one form of radiotherapy (RT) for BM. The HR+/HER2- group had the longest time to BM compared to the shortest in the triple negative group (61.29 ± 6.95 vs 28.59 months ± 4.80, p<0.001). Patients receiving hormonal therapy had longer time to BM compared to those who didn’t (50.83 ± 5.04 vs 35.98 ± 4.67 months, p=0.034). Patients with Stage I disease had the longest time to develop BM (68.50 ± 13.66 months, p=0.009), while grade III status had the shortest time to BM (34.46 ± 3.46 months, p=0.002). Uninsured patients had the shortest time to BM (22.92 ± 4.09 months, p=0.003). After BM diagnosis, the HR+/HER2+ group achieved the best mOS at 35.00 months (14.20-55.80, p=0.040). Patients receiving Gamma Knife Radiosurgery (GKRS) achieved longer mOS than the other RT modalities at 30.00 months (11.46-48.51) vs 20.00 (1.26-38.74) in GKRS + Whole Brain RT (WBRT), 9.00 (3.43-14.57) in the WBRT, and 2.00 (1.12-2.88) in no RT group (p=0.022). Patients with a KPS of <80 had a shorter mOS compared to those with a KPS of >80 [5.00 (2.02-7.98) vs 17.00 (9.41-24.6), p=0.002]. Patients receiving hormonal therapy had longer mOS compared to those who did not [17.00 (6.58-27.43) vs 9.00 (3.72-14.28), p=0.016]. Patients with stage I disease had longer mOS compared to those with stage II-IV disease [41.00 (22.70-59.30) vs 10.00 (6.60-13.40), p=0.025]. Conclusions: This study identifies significant clinical predictors for BM development and survival in patients with BC including Hormone receptor status, treatment modalities, stage, and KPS. These findings emphasize the need for early BM screening in high-risk patients to improve survival.

A preliminary study on the timing of radiotherapy for chemoimmunotherapy in oligometastatic non-small-cell lung cancer with negative driver genes.

e20084 Background: Local radiotherapy (LRT) is reported to provide durable local and distant disease control for oligometastatic non-small cell lung cancer (NSCLC) in accumulating evidence, but research on the optimal initial time point remains scarce. We conducted a study to preliminarily evaluate the timing of radiotherapy for chemoimmunotherapy in Oligometastatic Non-small-cell lung cancer with negative driver genes. Methods: 50 patients diagnosed with Oligometastatic Non-small-cell lung cancer with negative driver genes who were treated with chemoimmunotherapy and radiotherapy were retrospectively recruited between January 2018 and October 2023. They were divided into two groups: one early to initiate radiotherapy group (≤2 cycles of immunotherapy, EAR group) and one deferred radiotherapy group (>2 cycles of immunotherapy, DEF group). The clinical efficacy and adverse reactions were compared between the two groups. Progression-free survival (PFS) and overall survival (OS) were evaluated by Kaplan-Meier curves, the Cox proportional hazard model was used to find out predictors of PFS and OS. Results: The tumor control rates had no significance was observed when comparing these two groups (50.0% and 26.9%, respectively, p = 0.093). The PFS in the RAE group was significantly higher than that in the DEF group (median PFS: 12.2 months vs 5.3 months, P<0.05). The OS in two groups were no significance (median OS: 20.5months vs 23.1months, P>0.05). The results of the Cox multivariate regression analysis revealed that the number of metastatic lesions and organs were independent prognostic factors for PFS. The number of metastatic lesions and organs, maintain therapy were independent predictors associated with OS. All patients well tolerated the treatments. Conclusions: Early initiation of local radiotherapy resulted in better PFS and no significant increase in adverse reactions was observed.

Differential expression of circRNAs during osteogenic/odontogenic differentiation of stem cells from apical papilla promoted by blue light-emitting diode.

Circular RNA (circRNA) is a key player in regulating the multidirectional differentiation of stem cells. Previous research by our group found that the blue light-emitting diode (LED) had a promoting effect on the osteogenic/odontogenic differentiation of human stem cells from apical papilla (SCAPs). This research aimed to investigate the differential expression of circRNAs during the osteogenic/odontogenic differentiation of SCAPs regulated by blue LED. SCAPs were divided into the irradiation group (4J/cm2) and the control group (0J/cm2), and cultivated in an osteogenic/odontogenic environment. The differentially expressed circRNAs during osteogenic/odontogenic differentiation of SCAPs promoted by blue LED were detected by high-throughput sequencing, and preliminarily verified by qRT-PCR. Functional prediction of these circRNAs was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the circRNA-miRNA-mRNA networks were also constructed. It showed 301 circRNAs were differentially expressed. GO and KEGG analyses suggested that these circRNAs were associated with some signaling pathways related to osteogenic/odontogenic differentiation. And the circRNA-miRNA-mRNA networks were also successfully constructed. CircRNAs were involved in the osteogenic/odontogenic differentiation of SCAPs promoted by blue LED. In this biological process, circRNA-miRNA-mRNA networks served an important purpose, and circRNAs regulated this process through certain signaling pathways.

SUNRAY-01, a pivotal, global study of olomorasib (LY3537982) in combination with pembrolizumab with or without chemotherapy for 1L treatment in KRAS G12C-mutant advanced NSCLC.

TPS8649 Background: Mutations in KRAS are among the most frequent oncogenic drivers with the G12C variant found in ~13% of NSCLC. Outcomes for KRAS G12C-mutant NSCLC may be improved by combining KRAS G12C inhibitors with current 1L standard of care (SOC). Olomorasib is a potent and highly selective second-generation inhibitor of KRAS G12C, which delivers >90% sustained target occupancy in preclinical models. In the LOXO-RAS-20001 phase 1/2 study, olomorasib in combination with pembrolizumab demonstrated preliminary efficacy and a favorable safety profile.1 Methods: SUNRAY-01 (NCT06119581) is a pivotal, global, phase 3 study in 1L advanced KRAS G12C-mutated NSCLC designed to seamlessly 1) optimize the dosing of olomorasib in combination with 1L SOC, and then 2) compare efficacy and safety of olomorasib plus SOC with placebo plus SOC. In the open-label randomized dose optimization (pembrolizumab plus olomorasib 50 mg vs 100 mg BID) and single arm safety lead-in (olomorasib plus pembrolizumab, pemetrexed, platinum), the optimal dose of olomorasib for combination therapy will be determined before the phase 3 study (parts A and B) is opened for enrollment. In part A, 384 participants with PD-L1 expression ≥50% are randomized (1:1) to pembrolizumab plus olomorasib or placebo. In part B, 552 participants are randomized (1:1) to pembrolizumab, pemetrexed, platinum plus olomorasib or placebo regardless of PD-L1 expression. Allocation of participants with PD-L1 expression ≥50% to either part A or part B will be at the discretion of the investigator. The primary objective is to compare efficacy based on PFS per RECIST v1.1 by blinded independent central review. Secondary endpoints include OS, ORR, DOR, DCR, TTR, PFS2, safety and tolerability, and patient-reported outcomes. Eligible participants (≥18 years) must have a KRAS G12C mutation in tumor or blood and known PD-L1 expression (0-100%), stage IIIB, IIIC, or IV NSCLC not suitable for curative intent radical surgery or radiation therapy, measurable disease per RECIST v1.1, and an ECOG PS 0-1. Participants can be enrolled based on local KRAS and PD-L1 testing results. Participants should not have received prior systemic therapy for advanced or metastatic NSCLC, however 1 cycle of SOC treatment prior to enrollment is allowed if immediate treatment is clinically indicated. Participants with asymptomatic (lesions ≤1.5 cm) or previously treated radiographically stable brain metastases are eligible. Key exclusion criteria include history of pneumonitis/interstitial lung disease and clinically significant active cardiovascular disease or malabsorption syndrome. The study opened for enrollment in December 2023. 1Murciano-Goroff et al. 2023 Cancer Res 83 (8 Suppl): CT028. Clinical trial information: NCT06119581 .

A phase II exploratory trial of adebrelimab in combination with chemotherapy and concurrent radiotherapy as a first-line treatment for oligo-metastatic extensive-stage small-cell lung cancer.

TPS8131 Background: Oligometastasis of extensive-stage small-cell lung cancer (ES-SCLC) is an intermediate state between local and extensive metastasis, characterized by reduced metastatic potential and a limited number of metastatic sites, which makes local treatment of each lesion possible. Multiple clinical studies have shown that adding local therapy to standard systemic therapy can improve the prognosis of patients with oligometastatic disease. The PD-L1 inhibitor adebrelimab combined with chemotherapy has become one of the standard regimens for first-line treatment of ES-SCLC. Based on these, we hypothesize that in patients with oligometastatic ES-SCLC at risk of early progression, the early addition of chest radiotherapy and stereotactic radiotherapy (SBRT) for metastatic lesions to first-line treatment with adebrelimab combined with chemotherapy may be expected to achieve local control, thereby improving survival benefits. Methods: This is a prospective, single-arm, multicenter, phase II exploratory trial. Patients will be eligible if they are 18 to 75 years of age; have histopathologically or cytologically confirmed ES-SCLC with the number of metastatic lesions of ≤ 5 and organ metastasis of ≤ 3 (i.e. oligometastases); have an ECOG PS of 0-1; and have no previous systemic treatment. The treatment period in this trial is subdivided into induction therapy, concurrent chemoradiotherapy, and consolidation and maintenance therapy. In the induction setting, patients will receive two 3-week cycles of adebrelimab (20 mg/kg on day 1), carboplatin (AUC of 5 mg/mL per min on day 1)/cisplatin (75 mg/m2 on day 1), and etoposide (100 mg/m2 on days 1-3). Patients who achieve partial response or stable disease after induction therapy will then receive concurrent chemoradiotherapy, of which chemotherapy regimen is the same as the induction setting. Radical IMRT radiotherapy (2.5-3 Gy/f, total dose 45-55 Gy) will be performed for the primary tumor in the chest and lymph node region, and SBRT radiotherapy will be given to metastatic lesions. Prophylactic cranial irradiation is optional. After the end of chemoradiotherapy, patients will receive 1-2 cycles of consolidation treatment with the same regimen as induction treatment, followed by adebrelimab monotherapy (20 mg/kg on day 1, q3w) as maintenance treatment until disease progression, intolerance toxicity, or up to 2 years of adebrelimab. The total cycle number of chemotherapy is 4-6. The primary endpoint is progression-free survival (PFS), and secondary endpoints are objective response rate, duration of response, overall survival (OS), 6-month and 1-year PFS rates, 1-year and 2-year OS rates, and safety. The trial is under recruitment, and a total of 62 patients are planned to be enrolled. Clinical trial information: NCT06177925 .

Induction therapy with PD-1 antibody combined with platinum-based doublet chemotherapy for locally-advanced non-small cell lung cancer: A randomised controlled, open-label, phase 2 trial.

8044 Background: Chemoradiotherpay plus immunotherapy is recommended for unresectable locally-advanced non-small cell lung cancer (NSCLC) based on PACIFIC trial. However, it is unclear whether surgery can provide survival benefit for patients with tumors initially unresectable transformed into resectable ones after chemoimmunotherapy. This trial aims to investigate the efficacy and safety of the therapeutic regimen of chemoimmunotherapy plus surgery or radiotherapy. Methods: Patients with unresectable stage IIIB-IIIC NSCLC were enrolled to receive 4 cycles (q21d) of PD-1 antibody (Serplulimab, 4.5mg/kg) and platinum-based doublet chemotherapy. After the induction therapy, those with disease downstaged to IIIA or lower stage and resectable were randomized to receive radical surgery or radiotherapy with a ratio of 1:1, and those with stage IIIB or higher stage or unresectable disease after induction therapy were then treated by oncologists. Primary endpoint was event-free survival (EFS). Secondary endpoints included objective response rate (ORR), major pathologic response (MPR), pathologic complete response (pCR), progression-free survival (PFS), disease-free survival (DFS), overall survival (OS), R0 rate of resection, severe adverse event (SAE) rate, and health related quality of life (HRQol). Preliminary short-term results were collected. Results: One hundred patients will be enrolled as planned, and a total of 82 patients were enrolled by the data cutoff date (January 6, 2024). Fifty-four and 28 patients were diagnosed with stage IIIB and IIIC disease, respectively. The percentage of squamous carcinomas, adenocarcinomas, and NSCLCs not otherwise specified were 68.3% (56/82), 15.9% (13/82), and 15.9% (13/82), respectively. ORR in 73 evaluable patients was 74.0% (54/73). Twenty-six of them are still in induction therapy phase, and the other 47 and 9 patients received 4 cycles and 1-3 cycles of induction therapy, respectively. Thirty-one patients had downstaged and resectable disease after 4 cycles of induction therapy, and 26 of them were randomized to arm A (n = 13) and arm B (n = 13), and 5 refused randomization (3 received surgery). One patient received surgery after 2 cycles of induction therapy. In 56 patients finished 1-4 cycles of induction therapy, the rate of conversion to resectability was 57.1% (32/56). In total, 17 patients received surgery, and the MPR and pCR rate in 16 evaluable patients were 62.5% (10/16) and 31.3% (5/16), respectively. The grade 3-5 adverse event rate in 56 patients finished induction therapy was 50.0% (28/56). One patient died of immune-related pneumonia. Conclusions: Induction therapy with PD-1 antibody (Serplulimab) and chemotherapy could transform half of unresectable stage IIIB-IIIC NSCLC into resectable, and the efficacy and safety were satisfactory. Clinical trial information: NCT05766800 .

Lactobacillus rhamnosus GG alleviates radiation-induced intestinal injury by modulating intestinal immunity and remodeling gut microbiota

Radiation injury to the intestine is one of the most common complications in patients undergoing abdominal or pelvic cavity radiotherapy. In this study, we investigated the potential protective effect of Lactobacillus rhamnosus GG (LGG) on radiation-induced intestinal injury and its underlying mechanisms. Mice were assigned to a control group, a 10 Gy total abdominal irradiation (TAI) group, or a group pretreated with 108 CFU LGG for three days before TAI. Small intestine and gut microbiota were analyzed 3.5 days post-exposure. LGG intervention improved intestinal structure, reduced jejunal DNA damage, and inhibited the inflammatory cGAS/STING pathway. Furthermore, LGG reduced M1 proinflammatory macrophage and CD8+ T cell infiltration, restoring the balance between Th17 and Treg cells in the inflamed jejunum. LGG also partially restored the gut microbiota. These findings suggest the possible therapeutic radioprotective effect of probiotics LGG in alleviating radiation-induced intestinal injury by maintaining immune homeostasis and reshaping gut microbiota.

ИЗУЧЕНИЕ КЛИНИКО-ГЕМАТОЛОГИЧЕСКИХ И ИММУНОЛОГИЧЕСКИХ ПОКАЗАТЕЛЕЙ ПРИ ОЦЕНКЕ ПРОТИВОРАДИАЦИОННОЙ ЭФФЕКТИВНОСТИ ТЕРАПЕВТИЧЕСКОГО СРЕДСТВА НА ОСНОВЕ МИКРООРГАНИЗМА FUSOBACTERIUM NECROPHORUM

Purpose: To study clinical, hematologic and immunologic parameters in assessing the anti-radiation efficacy of the therapeutic agent based on the microorganism Fusobacterium necrophorum. Material and methods: The studies on determination of the anti-radiation efficacy of the strains of microorganisms killed by gamma-irradiation were carried out on sexually mature sexless white mice and white rats with live weight of 18–20 and 180–200 g, respectively, divided into experimental and control groups according to the principle of analogs. Modeling of acute radiation sickness was carried out on a Puma gamma unit with a radioactive source of cesium-137 at a dose of LD100/30. As potential anti-radiation drugs we used inactivated by irradiation on the gamma unit Explorer preparations of microbial origin F. necrophorum strain 8. necrophorum strain 8TS630501 at doses of 15, 20, 25 and 30 kGy. The tested preparations were injected subcutaneously in the volume of 0.2 cm3 to white mice and 2.0 cm3 to white rats 3 days after radiation exposure. Results: It was experimentally established that complete sterilization of the microbe occurs at doses of 25 and 30 kGy. The culture of F. necrophorum, irradiated at doses of 25 and 30 kGy and administered to animals 3 days after external radiation exposure, promoted survival, preservation of 60 to 80 % of lethally irradiated white mice and rats. At the same time the recovery of leukocytes and hemoglobin number was slow and continued until the end of the study. In animals treated with the developed therapeutic agents, there was also a decrease in the number of T-cells, but it was less pronounced than in the irradiation control group. The number of B-lymphocytes was affected similarly to T-lymphocytes. The minimum of the number of B-lymphocytes in the experimental groups was noted at 14 days. Studies on the intensity of the process of lipid peroxidation (LPO) in the content of malonic dialdehyde in peripheral blood of gamma-irradiated, treated and intact rats, it was found that in the irradiated control group there is a significant increase in the LPO index in blood in relation to biological control and treatment groups. Conclusion: It has been established that the highest anti-radiation efficacy is possessed by a therapeutic agent of microbial origin (RNF-30), which was obtained by gamma-irradiation at a dose of 30 kGy of the culture of F. necrophorum.

The impact of adjuvant radiation therapy on disease-specific survival in stage I and II Merkel cell carcinoma: A SEER database analysis.

9593 Background: Merkel Cell Carcinoma (MCC) is a rare, cutaneous neuroendocrine tumor associated with poor prognosis. Adjuvant radiation therapy (RT) is commonly used for the treatment of locoregional disease, but the impact on survival remains controversial. Previous studies from the Survival, Epidemiology, and End Results (SEER) database have shown an overall survival benefit to adjuvant RT without controlling for important prognostic differences in comparison groups such as age. To better control for these variables, we examined the impact of postoperative adjuvant radiation therapy on stage I and II disease-specific survival using the SEER database. Methods: SEERStat was used to obtain and analyze the outcomes of 2423 histologically confirmed MCC patients treated with surgery monotherapy or surgery with postoperative radiation therapy between 2004 and 2020 in the 17-registry (November 2021) SEER database. We compared the 5-year disease-specific survival (DSS) between the surgery monotherapy and adjuvant RT groups for stage I (n=1697) and stage II (n=726) MCC patients. Results: Patients treated with surgery and adjuvant RT were younger than those who received surgery monotherapy (median age 72 versus 77, respectively). Adjuvant RT was not associated with an increase in disease-specific survival. In contrast, adjuvant RT was associated with a statistically significant decrease in 5-year DSS among stage I patients (82.8% for those treated with RT versus 87.5% for those treated with surgery monotherapy, p = 0.023). Additionally, RT was not associated with a significant increase in DSS among stage II patients (77.0% versus 74.4% for patients treated with surgery monotherapy, p=0.490). Conclusions: This study demonstrates that there is no statistically significant disease-specific survival benefit from adjuvant radiation therapy for stage I and II MCC in the SEER database. Interestingly, in stage I patients we find a significant negative association between adjuvant RT and DSS. Younger patients are more likely to receive adjuvant RT, which likely contributes to higher overall survival previously reported from the SEER database, but the explanation for decreased DSS in patients who received RT remains unclear. Further studies regarding the effect of radiation therapy on local disease control and tumor microenvironment are needed to establish the appropriate role of RT in stage I-II MCC patients. [Table: see text]

Predictors of time to diagnosis and treatment: A retrospective cohort study of patients with clinically localized prostate cancer in Nigeria.

e23123 Background: Equitable access to the management of early-stage prostate cancer is important for optimal outcome in the diagnostic and curative treatment pathway of patients. This study aimed to identify the predictors of time to treatment and time to diagnosis in these patients. Methods: This was a cohort study of 110 patients with clinically localized prostate cancer (T1-T3a, N0, M0) in three government-funded tertiary hospitals in Nigeria. Retrospective data on sociodemographic status, co-morbid conditions, clinical, pathological and radiological quality metrics, date of first presentation for cancer-related complaint in the tertiary hospital, date of diagnosis of prostate cancer, and the date of commencement of first cancer-directed treatment were collected. Primary endpoint was the time from diagnosis to treatment and the secondary endpoint was the time from presentation to diagnosis. Predictors were determined by Cox proportional hazards using Stata software, version 18.0 with a p-value of less than 0.05 considered significant. Results: Twelve percent (n = 13) of the patients had a family history of prostate cancer. Fifty-four percent (n = 59) had other co-morbid conditions. Nearly one-third, 29% (n = 32) had retired from their primary occupation and 10% (n = 11) were covered by health insurance. The overall median time to diagnosis was 30 (interquartile range (IQR) 10 - 48) days. The median time to treatment commencement was 32 (IQR 19 - 82) days for ADT; 57 (IQR 50 - 63) days for active surveillance; 45 (IQR 21 - 78) days for radical radiotherapy; and 100 (IQR 0 - 127) days for radical prostatectomy. Diagnostic PSA documentation independently predicted delayed time to diagnosis (adjusted HR = 0.22 with 95% CI [0.05,0.97]) while those with guideline concordant imaging investigations independently predicted longer time to treatment (adjusted HR = 0.63 with 95% CI [0.40,0.99]). Conclusions: The documentation of PSA level and use of guideline concordant imaging investigations were significantly associated with delayed time to care. Studies on interventions to reduce barriers associated with these factors is warranted to strengthen equitable access to care in this setting.

NRG-BR007: A phase III trial evaluating de-escalation of breast radiation (DEBRA) following breast-conserving surgery of stage 1, HR+, HER2-, RS ≤18 breast cancer.

TPS622 Background: Approximately 50% of newly diagnosed invasive breast cancers are stage 1, with the majority being ER/PR-positive, HER2-negative. Genomic assays such as the Oncotype DX have identified patients (pts) with reduced risk of distant metastasis and without benefit from chemotherapy added to endocrine therapy, freeing them from excess toxicity. Genomic assays are also recognized as prognostic for in-breast recurrence (IBR) after BCS and could similarly allow de-escalation of adjuvant radiotherapy (RT). Reducing overtreatment is of interest to pts, providers, and payers. Methods: We hypothesize that breast-conserving surgery (BCS) alone is non-inferior to BCS plus RT for IBR and breast preservation in women intending endocrine therapy (ET) for stage 1 invasive breast cancer (ER and/or PR-positive, HER2-negative with an Oncotype DX Recurrence Score [RS] of ≤18). Stratification is by age (<60; ≥60), tumor size (≤1 cm; >1-2cm), and RS (≤11, >11-18/MammaPrint Low). Pts are randomized post-BCS to Arm 1 with breast RT using standard methods (moderate or ultra hypo- or conventional-fractionated whole breast RT with/without boost, or APBI) with ≥5 yrs of ET (tamoxifen or AI) or Arm 2 with ≥5 yrs of ET (tamoxifen or AI) alone. The specific regimen of ET in both arms is at the treating physician’s discretion. Eligible pts are stage 1: pT1 (≤2 cm), pN0, age ≥50 to <70 yrs, s/p BCS with negative margins (no ink on tumor), s/p axillary nodal staging (SNB or ALND), ER and/or PR-positive (ASCO/CAP), HER2-negative (ASCO/CAP), and Oncotype DX RS ≤18 (diagnostic core biopsy or resected specimen); (a “low risk” MammaPrint is permissible if completed as part of usual care prior to screening). Primary endpoint is IBR (invasive breast cancer or DCIS). Secondary endpoints are breast conservation rate, invasive in-breast recurrence, relapse-free interval, distant disease-free survival, overall survival, patient-reported breast pain, patient-reported worry about recurrence, and adherence to ET. We assume a clinically acceptable difference in IBR of 4% at 10 yrs to judge omission of RT as non-inferior (10-yr event-free survival for RT group is 95.6% v 91.6% for the omission-of-RT group). BR007 is powered to detect non-inferiority with 80% power and a one-sided α=0.025, assuming that there would be a ramp-up in accrual in the first two years (leveling off in yrs 3-5); 1,670 pts (835 per arm) are required for randomization. Conservative loss to follow-up is 1%/yr. Some T1a pts screened may have Oncotype DX scores >18, making them ineligible for the study. In the accrual process, 1,714 pts will be required to register to ensure that our final randomized cohort is 1,670 pts. Current accrual (02-05-2024) is 805 screened and 716 randomly assigned. Clinical trial information: NCT04852887 .

Obstacles to receiving postoperative radiation therapy following separation surgery for metastatic spine disease.

Obtaining timely postoperative radiotherapy (RT) following separation surgery is critical to avoid local recurrence of disease yet can be a challenge due to scheduling conflicts, insurance denials, and travel arrangements. In patients undergoing metastatic spine surgery for spinal cord compression, the authors sought to: 1) report the rate of postoperative RT, 2) describe reasons for patients not receiving postoperative RT, and 3) investigate factors that may predict whether a patient receives postoperative RT. A single-center retrospective case series was undertaken of all patients who underwent metastatic spine surgery for extradural disease between January 2010 and January 2021. Inclusion criteria were patients with intermediate or radioresistant tumors with evidence of spinal cord compression who underwent surgery. The primary outcome was the occurrence of RT within 3 months following surgery. Multivariable logistic regression analysis was performed controlling for age, BMI, race, total number of decompressed levels, tumor size, other organ metastasis, and preoperative RT or chemotherapy to predict patients receiving postoperative RT. Of 239 patients undergoing spine surgery for metastatic disease, 113 (47.3%) received postoperative RT while 126 (52.7%) did not. In the postoperative RT group, 24 (21.2%) received stereotactic body radiation therapy while 89 (78.8%) received conventional external-beam radiation therapy. The most common reasons for patients not receiving postoperative RT included death or transfer to hospice (31.0%), RT not being recommended by radiation oncology (30.2%), and loss to follow-up (23.8%). On critical review with the radiation oncology department, the authors estimated that 101 of 126 (80.2%) patients who did not receive postoperative RT were potential candidates for postoperative RT. Patients who received postoperative RT had more documented inpatient (48.7% vs 32.5%, p < 0.001) and outpatient (100.0% vs 65.1%, p < 0.001) radiation oncology consultations than those who did not. Additionally, patients who received postoperative RT had a higher rate of postoperative chemotherapy (53.1% vs 25.4%, p < 0.001), while patients who did not receive postoperative RT had a higher rate of preoperative RT (7.1% vs 31.0%, p < 0.001). Multivariable analysis confirmed that patients who received preoperative RT had lower odds of undergoing postoperative RT (OR 0.14, 95% CI 0.06-0.34; p < 0.001), and patients who underwent postoperative chemotherapy had higher odds of undergoing postoperative RT (OR 3.83, 95% CI 2.05-7.17; p < 0.001). In the current study reflecting real-world care of patients with metastatic spine disease after undergoing separation surgery, 47% of patients did not receive postoperative RT, and 80% of those patients were potential candidates for postoperative RT. Radiation oncology consultation and postoperative chemotherapy were significantly associated with receiving postoperative RT, whereas preoperative RT was significantly associated with not receiving postoperative RT. The lack of timely postoperative RT highlights a potential gap in metastatic spine tumor care and underscores the necessity for prompt radiation oncology consultation and effective planning.

A randomised, controlled, multicentre trial of imiquimod versus radiotherapy for lentigo maligna.

9502 Background: Lentigo maligna (LM) is a form of melanoma in situ that occurs mainly on sun exposed skin. For patients with LM who are not suitable for surgery due to location, size, patient preference or co-morbidities, topical imiquimod or radiotherapy are alternative non-surgical treatments. There are no prospective randomized controlled trial data to form the basis of any recommendations for the management of LM. This multi-institutional, international randomized phase 3 trial evaluated the efficacy and safety of imiquimod verus radiotherapy for patients with LM. The primary hypothesis was that treatment of LM with topical imiquimod would result in fewer treatment failures than radiotherapy. Methods: Patients aged &gt; 18 years old with LM not suitable for surgery were randomly assigned (1:1) to imiquimod or radiotherapy. The primary endpoint was treatment failure within 24 months. Secondary endpoints included development of invasive disease within the area, side effects and patient-reported quality of life (QOL) assessed with validated questionnaires (skin-specific Skindex-16 and generic EQ-5D-5L). Results: Between August 2015 and November 2021, 126 patients were randomised from 8 centres (imiquimod 60, radiotherapy 58 in final analysis). The median age was 72 years and 94.9% of lesions were on the head and neck area. Median follow-up was 27 months (range 3-62 months). Six (10.5%) patients in the imiquimod group and 12 (24.0%) patients in the radiotherapy group developed recurrence within 24 months (OR 2.68, 95% CI, 0·92-7.8, p = 0.063). Median time to recurrence was not reached in either group. Treatment failure was significantly different within the subgroup of patients who had reflectance confocal microscopy (RCM) follow up of the LM (imiquimod 4/46, 8.7% radiotherapy 13/52 25.0%; OR 3.50 95% CI 1.05-11.65, p = 0.033). Only one RCM feature was associated with failure at 24 months and significantly different between treatment groups : the presence of atypical round cells at the dermal-epidermal junction (6.9 % of imiquimod failure and 27% of radiotherapy failure: p = 0.035). There were no differences between trial groups in patient-reported skin symptoms (itching, burning/stinging, pain, irritation), skin-specific emotional and functional QOL impacts, or generic QOL at any time points. Conclusions: Both imiquimod and radiotherapy are valid, well-tolerated and efficient non-surgical options for LM. There is no significant difference in the acute or long term QoL for the two treatments. Clinical trial information: NCT02394132 .

Preclinical analysis of the efficacy of near-infrared photoimmunotherapy and anti-PD-1 antibody combination therapy for treating CD73-positive lung cancer.

e14521 Background: The CD73/adenosine pathway, which converts extracellular ATP to adenosine, is emerging as a promising target for immunotherapy in various cancers. In the tumor microenvironment, hypoxia triggers upregulation of adenosine-activating molecules, including CD73, a membrane-anchored enzyme expressed on cancer cells. CD73 induces the expression of PD-1 and CTLA4, and all of this leads to immunosuppression. Therefore, we focused utilizing near-infrared photoimmunotherapy (NIR-PIT) to kill CD73-expressing cells and alleviate immunosuppression. NIR-PIT is an innovative cancer treatment approach which involves irradiating NIR light after the administrated antibody-photosensitizer conjugate binds to the target cells. Methods: In vitro, anti-CD73 antibody-IR700 conjugate was prepared and added to the CMT167 and LLC cell lines, which were irradiated with NIR light under a microscope. In vivo, a mouse model was established using the CMT167 cell line. The mice were divided into 6 groups: 1) NIR-PIT group against CD73; 2) anti-PD-1 antibody group; 3) combined treatment group of 1) and 2); 4) control group; 5) anti-CD73 antibody-IR700 conjugate group; and 6) near-infrared light irradiation group. Tumor volume and survival rate were compared among these groups. Additionally, after 2 weeks of treatment, tumors in the four groups 1) to 4) above were pathologically evaluated using two different AI-equipped software programs. Results: Microscope observation revealed that NIR-PIT induced immunogenic cell death of CD73-positive mouse lung cancer cell lines in vitro. In vivo, the effect of NIR-PIT on this mouse model was also demonstrated. Although previous studies have shown the efficacy of treatment with anti-CD73 antibodies, the present study compared the CD73-IR700 conjugate group to the NIR-PIT to CD73 group, and the latter group showed better therapeutic outcomes. Additionally, the combined treatment group displayed the highest anti-tumor efficacy in terms of survival and tumor volume. Pathological evaluation of the tumor interior showed a significant increase in tumor-infiltrating lymphocytes compared to the other groups. Additionally, the percentage of tumor cells was significantly reduced, while the percentage of stroma, including fibrous tissue, was significantly increased. In line with other studies that have already reported the additive effect of combination therapy with anti-CD73 antibodies and immune checkpoint inhibitors, the present study showed that the combination therapy resulted in further activation of immune cells and enhanced the therapeutic effect. Conclusions: CD73 represents a promising target for NIR-PIT, with potential for enhanced effectiveness when used in combination with immune checkpoint inhibitors.

A Thorough Examination of the Variables Affecting the Quantum Efficiency of Radiative Decay of Trichlorotriphenylmethyl Radicals.

Fluorescence quantum efficiency is determined by the competition between radiation and nonradiation processes of the excited states. Understanding the factors affecting the radiation and nonradiative decay rates is of great significance for the design of luminescent materials. The excitation state deactivation mechanisms of singlet and triplet states have been extensively studied, providing a comprehensive understanding of the processes involved in the relaxation of these states. However, research on free radical systems involving doublet states is relatively scarce. Therefore, in this study, radiation and nonradiative decay rates and the mechanism of a series of trichlorotriphenylmethyl-based radicals were investigated theoretically. The results indicate that the relative rotations of electron donor and acceptor, as well as the internal rotations of trichlorotriphenylmethyl moiety, play important roles in energy dissipation through nonradiative channels. The effect of a solid-state environment on the radiation and nonradiative decay rates of radicals was investigated using a combination of quantum mechanics and molecular mechanics methods. The results indicate that the solid-state environment restricts the expansion of the conjugated system in the excited state of radicals, leading to a slight decrease in radiative decay rate. In addition, the solid-state environment reduces the reorganization energy and also affects the adiabatic excitation energy of radicals. The reduction in reorganization energy results in a decrease in nonradiative rate, while the opposite effect is observed for adiabatic excitation energy. The nonradiative rate of radicals in a solid-state environment is thus inflected by a combination of molecular geometric structure relaxation and ground-excited state energy gap.

The role of adjuvant radiotherapy for intracranial malignant meningiomas: analysis of a nationwide database.

This study aimed to examine the effect of postoperative radiotherapy on survival outcomes in patients with malignant meningiomas. We identified patients with malignant meningioma diagnosed between 2007 and 2018 using the Taiwan Cancer Registry and followed them up using the death registry. Survival was compared between patients with and without adjuvant radiotherapy. The potential confounding factors evaluated in this study included age, sex, comorbidities, and the Charlson Comorbidity Index (CCI). The analysis included 204 patients; 94 (46%) received adjuvant radiotherapy. The two groups had similar sex distributions (p = 0.53), mean age (p = 0.33), histologic subtype (p = 0.13), and CCI (p = 0.62). The prognosis of malignant meningioma was poor, with a median overall survival (OS) of 2.4 years. The median OS was 3.0 years (interquartile range (IQR) [1.4-6.1], and 2.0 years (IQR [0.5-3.9]) in the radiotherapy and non-radiotherapy groups, respectively (p = 0.001). However, Kaplan-Meier curves with the log-rank test showed no significant difference in OS between the two groups (p = 0.999). Controlling for age group, sex, histologic subtype, treatment, comorbidities, and CCI, adjuvant radiotherapy did not impart a survival benefit (hazard ratio [HR] = 0.87; 95% confidence interval [CI]: 0.6‒1.26); however, only factor of higher comorbidity score (HR = 2.03, 95%CI: 1.04‒3.94) was associated with unfavorable survival. This population-based retrospective analysis suggests that the role of radiotherapy remains unclear and underscores the need for randomized clinical trials to assess the usefulness of adjuvant radiotherapy in malignant meningioma.

Anti‑epidermal growth factor receptor monoclonal antibody therapy in locally advanced head and neck cancer: A systematic review of phase III clinical trials.

The present systematic review evaluated the effectiveness of anti-EGFR therapy in combination with radiotherapy (RT) or with chemoradiation compared with the existing standard of care for the treatment of locally advanced head and neck squamous cell carcinoma (LAHNSCC). The PubMed, SCOPUS, EMBASE and COCHRANE databases were searched and 12 phase III randomized controlled trials were included. The effectiveness of the anti-EGFR monoclonal antibody cetuximab was evaluated in nine trials. Nimotuzumab (one trial), zalutumumab (one trial) and panitumumab (one trial) were the monoclonal antibodies evaluated in the remaining three trials. One study tested the effectiveness of adding cetuximab to radical RT and found that patients with LAHNSCC exhibited improvement in locoregional control (LRC), overall survival (OS) and progression-free survival (PFS) compared with those of patients treated with RT alone. A total of three studies tested the effectiveness of adding an anti-EGFR agent to chemoradiation. Of these, a single institution study in which patients received cisplatin at 30 mg/m2 weekly, instead of the standard doses of 100 mg/m2 every 3 weeks or 40 mg/m2 every week, reported significant improvement in PFS with the addition of nimotuzumab to chemoradiotherapy without an improvement in overall survival. However, the other two studies indicated that, when added to standard chemoradiation, the anti-EGFR monoclonal antibodies cetuximab or zalutumumab did not improve survival outcomes. Two phase III trials evaluated RT plus an anti-EGFR agent compared with chemoradiation alone. Of these, one study reported inferior outcomes with cetuximab-RT in terms of OS and LRC, whereas the other study with panitumumab plus RT failed to prove the non-inferiority. Two trials evaluated induction chemotherapy followed by cetuximab-RT compared with chemoradiotherapy and reported no benefits in terms of OS or PFS. Furthermore, one study evaluated induction chemotherapy followed by cetuximab-RT compared with induction chemotherapy followed by chemoradiotherapy and found no improvement in OS or PFS. Finally, three phase III trials tested the effectiveness of cetuximab plus RT in the treatment of human papillomavirus-positive oropharyngeal carcinoma, and found it to be inferior compared with cisplatin-RT in terms of OS, PFS and failure-free survival. Based on the aforementioned findings, it is difficult to conclude that anti-EGFR therapy in any form has an advantage over conventional chemoradiation in the treatment of LAHNSCC.