Comparative analysis of molecular and histological glioblastomas: insights into prognostic variance.

PURPOSE: Whether molecular glioblastomas (GBMs) identify with a similar dismal prognosis as a "classical" histological GBM is controversial. This study aimed to compare the clinical, molecular, imaging, surgical factors, and prognosis between molecular GBMs and histological GBMs. METHODS: Retrospective chart and imaging review was performed in 983 IDH-wildtype GBM patients (52 molecular GBMs and 931 histological GBMs) from a single institution between 2005 and 2023. Propensity score-matched analysis was additionally performed to adjust for differences in baseline variables between molecular GBMs and histological GBMs. RESULTS: Molecular GBM patients were substantially younger (58.1 vs. 62.4, P = 0.014) with higher rate of TERTp mutation (84.6% vs. 50.3%, P < 0.001) compared with histological GBM patients. Imaging showed higher incidence of gliomatosis cerebri pattern (32.7% vs. 9.2%, P < 0.001) in molecular GBM compared with histological GBM, which resulted in lesser extent of resection (P < 0.001) in these patients. The survival was significantly better in molecular GBM compared to histological GBM (median OS 30.2 vs. 18.4 months, P = 0.001). The superior outcome was confirmed in propensity score analyses by matching histological GBM to molecular GBM (P < 0.001). CONCLUSION: There are distinct clinical, molecular, and imaging differences between molecular GBMs and histological GBMs. Our results suggest that molecular GBMs have a more favorable prognosis than histological GBMs.

Dose-response relationship in patients with newly diagnosed atypical meningioma treated with adjuvant radiotherapy.

PURPOSE: This study aimed to identify the radiation dose-response relationship in patients with newly diagnosed atypical meningioma (AM) treated with adjuvant radiotherapy (ART) using conventional fractionation. METHODS: In total, 158 patients who underwent surgery and ART between 1998 and 2018 were reviewed. Among these patients, 135 with complete information on radiotherapy (RT) dose/fractionation and pathological reports were analyzed. We entered RT dose as a continuous variable into the Cox regression model using penalized spline to allow for a nonlinear relationship between RT dose and events. Local control (LC), progression-free survival (PFS), and overall survival (OS) were evaluated. The corresponding biological equivalent dose in 2 Gy fractions (EQD2) was calculated using an α/ß ratio of 4 Gy. RESULTS: The median follow-up duration was 56.0 months. The median ART dose delivered was 61.2 Gy in 24-34 daily fractions, corresponding to a median EQD2 of 59.16 Gy. In multivariate analysis, larger size and higher mitotic count were associated with significantly reduced LC (P < 0.001 and P = 0.002, respectively), PFS (P < 0.001 and P = 0.006, respectively), and OS (P = 0.006 and P = 0.001, respectively). Meanwhile, a higher RT dose was significantly associated with improved LC, PFS, and OS. Moreover, RT showed a dose-dependent effect on LC, PFS, and OS; local failure, tumor progression, and death were reduced by 12%, 12%, and 16%, respectively, per 1 Gy increase in the dose (EQD2). CONCLUSION: The dose of ART in AM has a dose-response relationship with LC and survival outcomes.

Impact of boost sequence in concurrent chemo-radiotherapy on newly diagnosed IDH-wildtype glioblastoma multiforme.

BACKGROUND: The standard of care for glioblastoma multiforme (GBM) is maximal surgical resection followed by conventional fractionated concurrent chemoradiotherapy (CCRT) with a total dose of 60 Gy. However, there is currently no consensus on the optimal boost technique for CCRT in GBM. METHODS: We conducted a retrospective review of 398 patients treated with CCRT between 2016 and 2021, using data from two institutional databases. Patients were divided into two groups: those receiving sequential boost (SEB, N = 119) and those receiving simultaneous integrated boost (SIB, N = 279). The primary endpoint was overall survival (OS). To minimize differences between the SIB and SEB groups, we conducted propensity score matching (PSM) analysis. RESULTS: The median follow-up period was 18.6 months. Before PSM, SEB showed better OS compared to SIB (2-year, 55.6% vs. 44.5%, p = 0.014). However, after PSM, there was no significant difference between two groups (2-year, 55.6% vs. 51.5%, p = 0.300). The boost sequence was not associated with inferior OS before and after PSM (all p-values > 0.05). Additionally, the rates of symptomatic pseudo-progression were similar between the two groups (odds ratio: 1.75, p = 0.055). CONCLUSIONS: This study found no significant difference in OS between SEB and SIB for GBM patients treated with CCRT. Further research is needed to validate these findings and to determine the optimal boost techniques for this patient population.

Outcomes of intracranial non-germinomatous germ cell tumors: a retrospective Asian multinational study on treatment strategies and prognostic factors.

PURPOSE: Non-germinomatous germ cell tumors (NGGCTs) are rare pediatric conditions. This multicenter study using Asian multinational patient data investigated treatment outcomes and prognostic factors for NGGCTs. METHODS: Medical records of 251 patients with NGGCTs treated from 1995 to 2015 were retrospectively analyzed from participating centers in Asian countries (Korea, Taiwan, Singapore, and Japan). RESULTS: The median follow up was 8.5 years (95% CI 7.8-9.9). In the total cohort, 5-year event-free survival (EFS) and overall survival (OS) rates were 78.2% and 85.4%, respectively. In 17.9% of the patients, diagnosis was determined by tumor markers alone (alpha-fetoprotein ≥ 10 ng/mL (Korea) or > 25 ng/mL (Taiwan and Singapore), and/or ß-human chorionic gonadotropin (ß-hCG) ≥ 50 mIU/mL). Patients with immature teratomas and mature teratomas comprised 12.0% and 8.4%, respectively. The 5-year EFS rate was higher in patients with histologically confirmed germinoma with elevated ß-hCG (n = 28) than those in patients with malignant NGGCTs (n = 127). Among malignant NGGCTs, patients with choriocarcinoma showed the highest 5-year OS of 87.6%, while yolk sac tumors showed the lowest OS (68.8%). For malignant NGGCT subgroups, an increase in serum ß-hCG levels by 100 mIU/mL was identified as a significant prognostic factor associated with the EFS and OS. CONCLUSION: Our result shows excellent survival outcomes of overall CNS NGGCT. However, treatment outcome varied widely across the histopathologic subgroup of NGGCT. Hence, this study suggests the necessity for accurate diagnosis by surgical biopsy and further optimization of diagnosis and treatment according to the histopathology of NGGCTs. Future clinical trials should be designed for individualized treatments for different NGGCTs subsets.

Validation and optimization of a web-based nomogram for predicting survival of patients with newly diagnosed glioblastoma.

PURPOSE: To optimize and validate a current (NRG [a newly constituted National Clinical Trials Network group through National Surgical Adjuvant Breast and Bowel Project [NSABP], the Radiation Therapy Oncology Group [RTOG] and the Gynecologic Oncology Group (GOG)]) nomogram for glioblastoma patients as part of continuous validation. METHODS: We identified patients newly diagnosed with glioblastoma who were treated with temozolomide-based chemoradiotherapy between 2006 and 2016 at three large-volume hospitals. The extent of resection was determined via postoperative MRI. The discrimination and calibration abilities of the prediction algorithm were assessed; if additional factors were identified as independent prognostic factors, updated models were developed using the data from two hospitals and were externally validated using the third hospital. Models were internally validated using cross-validation and bootstrapping. RESULTS: A total of 837 patients met the eligibility criteria. The median overall survival (OS) was 20.0 (95% CI 18.5-21.5) months. The original nomogram was able to estimate the 6­, 12-, and 24-month OS probabilities, but it slightly underestimated the OS values. In multivariable Cox regression analysis, MRI-defined total resection had a greater impact on OS than that shown by the original nomogram, and two additional factors-IDH1 mutation and tumor contacting subventricular zone-were newly identified as independent prognostic values. An updated nomogram incorporating these new variables outperformed the original nomogram (C-index at 6, 12, 24, and 36 months: 0.728, 0.688, 0.688, and 0.685, respectively) and was well calibrated. External validation using an independent cohort showed C­indices of 0.787, 0.751, 0.719, and 0.702 at 6, 12, 24, and 36 months, respectively, and was well calibrated. CONCLUSION: An updated and validated nomogram incorporating the contemporary parameters can estimate individual survival outcomes in patients with glioblastoma with better accuracy.

Comprehensive Immuno-Molecular Profiles for Liposarcoma: Roles of Programmed Death Ligand 1, Microsatellite Instability, and PIK3CA.

BACKGROUND: Developing personalized strategies for cancer has shown good efficacies. METHODS: We assessed the molecular targets programmed death ligand 1 (PD-L1), microsatellite instability (MSI), and PIK3CA. Seventy-four patients with liposarcomas who underwent curative resection were assessed for PD-L1 expression in the tumor and tumor-infiltrating lymphocytes (TILs), mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemistry, MSI using polymerase chain reaction, and PIK3CA mutation/amplification using pyrosequencing and fluorescence in situ hybridization. RESULTS: Seventeen (23%) cases were TIL+ (≥1 + expression) and associated with longer 5-year overall survival than those with TIL- tumors (84.4 vs. 60.8%, p = 0.007). Six (35.3%) PD-L1+ tumors were detected only in TIL+ cases, with none detected in tumor cells. Two well-differentiated liposarcomas showed MSI, one low and one high with concurrent loss of MLH1, MSH6, and PMS2. PIK3CA mutation was detected in 7 (9.5%) [exon 9 (n = 4) and exon 20 (n = 3)] and only 1 Q546K mutation was a PD-L1+ tumor. PIK3CA copy number gain was detected in 18 (24.4%) and was associated with TIL+ tumors (p = 0.045). CONCLUSIONS: Our comprehensive immuno-molecular panel suggests that liposarcoma should be categorized based on the molecular genomic subtype for precision medicine.

Simple calculation using anatomical features on pre-treatment verification CT for bladder volume estimation during radiation therapy for rectal cancer.

BACKGROUND: Despite detailed instruction for full bladder, patients are unable to maintain consistent bladder filling during a 5-week pelvic radiation therapy (RT) course. We investigated the best bladder volume estimation procedure for verifying consistent bladder volume. METHODS: We reviewed 462 patients who underwent pelvic RT. Biofeedback using a bladder scanner was conducted before simulation and during treatment. Exact bladder volume was calculated by bladder inner wall contour based on CT images (Vctsim). Bladder volume was estimated either by bladder scanner (Vscan) or anatomical features from the presacral promontory to the bladder base and dome in the sagittal plane of CT (Vratio). The feasibility of Vratio was validated using daily megavoltage or kV cone-beam CT before treatment. RESULTS: Mean Vctsim was 335.6 ± 147.5 cc. Despite a positive correlation between Vctsim and Vscan (R2 = 0.278) and between Vctsim and Vratio (R2 = 0.424), Vratio yielded more consistent results than Vscan, with a mean percentage error of 26.3 (SD 19.6, p < 0.001). The correlation between Vratio and Vctsim was stronger than that between Vscan and Vctsim (Z-score: - 7.782, p < 0.001). An accuracy of Vratio was consistent in megavoltage or kV cone-beam CT during treatment. In a representative case, we can dichotomize for clinical scenarios with or without bowel displacement, using a ratio of 0.8 resulting in significant changes in bowel volume exposed to low radiation doses. CONCLUSIONS: Bladder volume estimation using personalized anatomical features based on pre-treatment verification CT images was useful and more accurate than physician-dependent bladder scanners. TRIAL REGISTRATION: Retrospectively registered.

Treatment outcomes of radiotherapy for primary spinal cord glioma.

PURPOSE: Spinal cord gliomas are rare, and there is no consensus on the optimal radiotherapy (RT) regimen. Herein, we investigated therapeutic outcomes in spinal cord gliomas to obtain clues for the optimal RT regimen. METHODS: We assessed 45 patients who received RT for primary spinal cord non-ependymoma gliomas between 2005 and 2017: 37 (82%) received postoperative RT, 6 (13%) underwent definitive RT without surgery, and 2 (5%) received salvage RT for recurrent tumors. Craniospinal irradiation (CSI; median, 40 Gy) was administered in 4 patients with seeding at diagnosis; all other patients received local RT only (median, 50.4 Gy). RESULTS: In all 23 failures occurred (20 in patients without initial seeding +3 in patients with initial seeding and CSI; median follow-up, 33 months). The 2­year overall survival and progression-free survival rates were 74 and 54%, respectively. Overall, 13 (32%) new seeding events outside the local RT field developed either first or subsequently. Tumor grade was significantly associated with survival endpoints (p = 0.009, 0.028) and overall seeding rates (p = 0.042). In grade II tumors, seeding developed in 23%, with a dismal prognosis (median, 10 months after RT). In grade III tumors, seeding developed in 45% with diverse prognosis. In grade IV tumors, seeding developed in 45%. The survival of patients with newly developed seeding was significantly worse than the others (2-year 50%, p < 0.001). CONCLUSION: To encompass a considerable rate of progressive disease seeding, aggressive treatment such as pre-emptive application of CSI needs to be considered for high-grade spinal cord gliomas with adverse features. Prophylactic CSI could be an option for survival prolongation and requires prospective validation.

Analysis of patterns of failure and appraisal of postoperative radiation field for grade II-III meningioma.

PURPOSE: To analyze patterns of failure according to treatment modalities and evaluate the adequacy of an institution's current volume of postoperative radiotherapy (PORT) for World Health Organization (WHO) grade II or III meningiomas. PATIENTS AND METHODS: Data of 98 patients treated by either surgery and PORT (PORT group, n = 53) or surgery alone (surgery group, n = 45) between March 2000 and December 2013 were reviewed. Clinical target volume of PORT was delineated as a 1.5-2-cm expansion from the tumor bed. Local failure (LF) was defined as recurrence within a 2-cm margin from the tumor bed. Failures other than LF were defined as out-field failure (OFF). Median total dose of PORT was 59.4 (range 45.0-69.0) Gy. RESULTS: The PORT group had larger proportions of grade III meningiomas (18/53, 34.0%) than the surgery group (8/46, 15.6%) (p = 0.037). After a median 73.4-month follow-up, 29 patients experienced LF and 5 developed OFF. The actuarial 5-year local control (LC) rates were 86.7% and 59.3% in the PORT and surgery groups, respectively (p = 0.002). PORT was a significant factor of LC in the univariate (p = 0.003, hazard ratio [HR] 3.449, 95% confidence interval [CI] 1.516-7.846) and multivariate analyses (p < 0.001, HR 5.486, 95% CI 2.178-13.820). CONCLUSIONS: Despite the larger proportion of grade III meningiomas in the PORT group, PORT reduced LF in patients with WHO grade II or III meningiomas compared with the surgery group. The current PORT field seems reasonable because LF was the dominant pattern of failure in patients treated by surgery alone.

Clinical outcomes of radiotherapy for spinal cord ependymoma with adverse prognostic features: a single-center study.

PURPOSE: This study evaluated the outcomes of radiotherapy (RT) for spinal ependymoma with adverse features, such as incomplete resection or disseminated disease. METHODS: Twenty-five patients underwent RT for spinal cord ependymoma during 1991-2016. Twenty-four patients had gross disease on the pre-RT spinal magnetic resonance images. Six patients (24%) had disseminated disease. The World Health Organization grades were I (12 patients), II (12 patients), and III (1 patient). The RT fields were the tumor bed plus margin in 19 patients (76%), the entire craniospinal axis in 5 patients (20%), and the entire spinal canal with posterior cranial fossa in 1 patient (4%). The median RT dose was 50.4 Gy (range 44.0-59.4 Gy). RESULTS: The median follow-up was 49 months (range 9-321 months), with 5-year overall and progression-free survival rates of 83.7% and 70.8%, respectively. Relative to patients with grade II/III ependymoma, patients with grade I ependymoma had higher 5-year rates of overall survival (100% vs. 69.4%, P = .088) and progression-free survival (100% vs. 42.3%, P = .02). Disease progression was observed in 4 patients who had grade II ependymoma, including 2 of 6 patients with disseminated disease and 2 of 19 patients with localized disease. Twelve patients (48%) exhibited improved neurological function. One patient who underwent craniospinal irradiation developed late hypopituitarism. No other RT-related late toxicities were observed. CONCLUSIONS: Favorable survival outcomes were achieved using RT for spinal ependymoma with adverse prognostic features. Thus, RT may be an effective treatment option when complete tumor removal cannot be achieved.

The role of endoscopic evaluation for radiation proctitis in patients receiving intermediate-dose postoperative radiotherapy for rectal cancer.

OBJECTIVES: High-dose pelvic radiotherapy (RT) is known to be associated with chronic radiation proctitis (RP). However, the effects of intermediate radiation doses are unknown. We assessed the incidence of late clinical RP among patients with rectal cancer receiving intermediate-dose postoperative RT, as well as the role of early endoscopic abnormalities in predicting RP development. METHODS: We retrospectively reviewed 153 patients with rectal cancer who received postoperative RT at a median dose of 54 Gy between 2005 and 2009 and who underwent endoscopic examination within 12 months thereafter. Endoscopic RP was assessed using the Vienna rectoscopy score (VRS). Late clinical RP toxicity was evaluated, as was its correlation with endoscopic RP. RESULTS: All patients underwent an endoscopic examination at a median of 9 months after postoperative pelvic RT. Endoscopic RP was detected in 45 patients (29.4%); the predominant patterns were telangiectasia and congested mucosa. During the median 88-month follow-up period, 29 patients (19.0%) experienced late clinical RP; only 3 (2.0%) had Grade 3 or above. The VRS predicted the development of late clinical RP as well as its cumulative incidence (P < 0.001). Endoscopic evidence of telangiectasia was significantly associated with the development of late clinical RP (P < 0.001). CONCLUSIONS: Early endoscopic findings using VRS are useful for predicting the possibility of late clinical RP, although the incidences of severe cases were low. Patients with endoscopic abnormalities should be followed closely owing to their susceptibility to clinical RP.

Slitrks control excitatory and inhibitory synapse formation with LAR receptor protein tyrosine phosphatases.

The balance between excitatory and inhibitory synaptic inputs, which is governed by multiple synapse organizers, controls neural circuit functions and behaviors. Slit- and Trk-like proteins (Slitrks) are a family of synapse organizers, whose emerging synaptic roles are incompletely understood. Here, we report that Slitrks are enriched in postsynaptic densities in rat brains. Overexpression of Slitrks promoted synapse formation, whereas RNAi-mediated knockdown of Slitrks decreased synapse density. Intriguingly, Slitrks were required for both excitatory and inhibitory synapse formation in an isoform-dependent manner. Moreover, Slitrks required distinct members of the leukocyte antigen-related receptor protein tyrosine phosphatase (LAR-RPTP) family to trigger synapse formation. Protein tyrosine phosphatase σ (PTPσ), in particular, was specifically required for excitatory synaptic differentiation by Slitrks, whereas PTPδ was necessary for inhibitory synapse differentiation. Taken together, these data suggest that combinatorial interactions of Slitrks with LAR-RPTP family members maintain synapse formation to coordinate excitatory-inhibitory balance.

Multimodality treatment involving radiotherapy for advanced liver-confined hepatocellular carcinoma.

BACKGROUND: Advanced-stage hepatocellular carcinoma (HCC) has an extremely poor prognosis although sorafenib, which is the treatment of choice, has provided survival benefits. Among advanced diseases, liver-confined HCC, which invades the vasculature without extrahepatic metastasis, requires novel therapeutic management beyond using sorafenib alone. Currently, the Korean Liver Cancer Study Group and National Comprehensive Cancer Network guidelines recommend combined radiotherapy (RT) and chemotherapy for some selected cases. For advanced liver-confined HCC, focal liver irradiation, RT technological development, and optimal selection of RT-suitable patients enable clinicians to use RT-involving multimodality treatments based on oncologic principles, such as concurrent chemoradiotherapy, which represent effective multimodality treatments for several types of malignancy. SUMMARY: In this review, we discuss the need to develop novel therapeutic approaches for liver-confined HCC and clinical applications of RT-involving multimodality treatments for advanced liver-confined HCC. CONCLUSION: RT-involving multimodality treatments can enhance the overall therapeutic successes for advanced liver-confined HCC and also provide potential cures to some patients via conversion to a resectable condition.

Reduced-dose radiotherapy for stage IE gastric mucosa-associated lymphoid tissue lymphoma: a multi-institutional prospective study (KROG 16-18).

PURPOSE: Definitive radiotherapy (RT) of 30 Gy or higher is commonly recommended to treat Helicobacter pylori-independent gastric mucosa-associated lymphoid tissue (MALT) lymphoma with an excellent disease control rate. However, the efficacy of reduced-dose RT has not yet been evaluated in a prospective cohort study. This multi-institutional study aimed to determine the role of reduced-dose RT in the treatment of stage IE gastric MALT lymphoma. METHODS: Between March 2017 and June 2022, 62 patients with histologically confirmed stage IE gastric MALT lymphoma without evidence of H. pylori infection were enrolled. The patients were treated with reduced-dose RT at a total dose of 24-25.5 Gy to the entire stomach. The response to therapy was evaluated by endoscopy with a biopsy of suspicious lesions if necessary. The primary endpoints were 6-month complete remission (CR) and local failure-free survival (LFFS). RESULTS: Among 62 patients, 32 (51.6%) were previously treated for H. pylori eradication. Radiotherapy was delivered using 3D-conformal (n=20, 32.3%) or intensity-modulated radiotherapy (n=42, 67.7%). The median follow-up duration was 34.5 months (range, 9.6-68.8 months). The 6-month CR rate was 96.7%. The 5-year LFFS and progression-free survival rates were 92.0% and 90.4%, respectively. None of the patients experienced grade 3 or worse acute toxicities, and grade 2 acute toxicities were reported in 17 patients (27.4%). CONCLUSION: Reduced-dose RT exhibited excellent response rates in stage IE gastric MALT lymphoma, comparable to historical controls of standard dose (≥ 30 Gy) radiotherapy, with a minimal toxicity profile. Current prospective evidence strongly supports the use of definitive radiotherapy (24-25.5 Gy) for the treatment of H. pylori-independent stage IE gastric MALT lymphoma.

Integrative prediction model for radiation pneumonitis incorporating genetic and clinical-pathological factors using machine learning.

Purpose: We aimed to develop a machine learning-based prediction model for severe radiation pneumonitis (RP) by integrating relevant clinicopathological and genetic factors, considering the associations of clinical, dosimetric parameters, and single nucleotide polymorphisms (SNPs) of genes in the TGF-ß1 pathway with RP. Methods: We prospectively enrolled 59 primary lung cancer patients undergoing radiotherapy and analyzed pretreatment blood samples, clinicopathological/dosimetric variables, and 11 functional SNPs in TGFß pathway genes. Using the Synthetic Minority Over-sampling Technique (SMOTE) and nested cross-validation, we developed a machine learning-based prediction model for severe RP (grade ≥ 2). Feature selection was conducted using four methods (filtered-based, wrapper-based, embedded, and logistic regression), and performance was evaluated using three machine learning models. Results: Severe RP occurred in 20.3 % of patients with a median follow-up of 39.7 months. In our final model, age (>66 years), smoking history, PTV volume (>300 cc), and AG/GG genotype in BMP2 rs1979855 were identified as the most significant predictors. Additionally, incorporating genomic variables for prediction alongside clinicopathological variables significantly improved the AUC compared to using clinicopathological variables alone (0.822 vs. 0.741, p = 0.029). The same feature set was selected using both the wrapper-based method and logistic model, demonstrating the best performance across all machine learning models (AUC: XGBoost 0.815, RF 0.805, SVM 0.712, respectively). Conclusion: We successfully developed a machine learning-based prediction model for RP, demonstrating age, smoking history, PTV volume, and BMP2 rs1979855 genotype as significant predictors. Notably, incorporating SNP data significantly enhanced predictive performance compared to clinicopathological factors alone.

Unraveling the Impact of Sarcopenia-Induced Lymphopenia on Treatment Response and Prognosis in Patients with Stage III Non-Small Cell Lung Cancer: Insights for Optimizing Chemoradiation and Immune Checkpoint Inhibitor.

PURPOSE: Sarcopenia is a poor prognostic factor in non-small cell lung cancer (NSCLC). However, its prognostic significance in patients with NSCLC receiving immune checkpoint inhibitors (ICIs) and its relationship with lymphopenia remain unclear. We aimed to investigate the prognostic role of sarcopenia and its effect on lymphocyte recovery in patients with stage III NSCLC treated with concurrent chemoradiotherapy (CCRT) followed by ICI. MATERIALS AND METHODS: We retrospectively evaluated 151 patients with stage III NSCLC who received definitive CCRT followed by maintenance ICI between January 2016 and June 2022. Sarcopenia was evaluated by measuring the skeletal muscle area at the L3 vertebra level using computed tomography scans. Lymphocyte level changes were assessed based on measurements taken before and during CCRT and at 1, 2, 3, 6, and 12 months post-CCRT completion. RESULTS: Even after adjusting for baseline absolute lymphocyte count through propensity score-matching, patients with pre-radiotherapy (RT) sarcopenia (n=86) exhibited poor lymphocyte recovery and a significantly high incidence of grade ≥3 lymphopenia during CCRT. Pre-RT sarcopenia and grade ≥3 lymphopenia during CCRT emerged as prognostic factors for overall survival and progression-free survival, respectively. Concurrent chemotherapy dose adjustments, objective response after CCRT, and discontinuation of maintenance ICI were also analyzed as independent prognostic factors. CONCLUSION: Our results demonstrated an association between pre-RT sarcopenia and poor survival, concurrent chemotherapy dose adjustments, and impaired lymphocyte recovery after definitive CCRT. Moreover, CCRT-induced lymphopenia not only contributed to poor prognosis but may have also impaired the therapeutic efficacy of subsequent maintenance ICI, ultimately worsening treatment outcomes.

Aggressive Local Ablative Radiotherapy Mitigates Progression Risk in Oligometastatic Lung Adenocarcinoma.

PURPOSE: This study aimed to determine the role of local ablative radiotherapy (LART) in oligometastatic/oligoprogressive lung adenocarcinoma. MATERIALS AND METHODS: Patients (n=176) with oligometastatic lung adenocarcinoma treated with LART were identified, and those treated with LART at the initial diagnosis of synchronous oligometastatic disease (OMD group) or treated with LART when they presented with repeat oligoprogression (OPD group) were included. RESULTS: In the OMD group (n=54), the 1- and 3-year progression-free survival (PFS) were 50.9% and 22.5%, respectively, whereas the 1- and 3-year overall survival in the OPD group were 75.9% and 58.1%, respectively. Forty-one patients (75.9%) received LART at all gross disease sites. Tyrosine kinase inhibitor (TKI) use and all-metastatic site LART were significant predictors of higher PFS (p=0.018 and p=0.046, respectively). In patients treated with TKIs at the time of LART (n=23) and those treated with all-metastatic site LART, the 1-year PFS was 86.7%, while that of patients not treated with all-metastatic site LART was 37.5% (p=0.006). In the OPD group (n=122), 67.2% of the patients (n=82) maintained a systemic therapy regimen after LART. The cumulative incidence of changing systemic therapy was 39.6%, 62.9%, and 78.5% at 6 months, 1 year, and 2 years after LART, respectively. CONCLUSION: Aggressive LART can be an option to improve survival in patients with oligometastatic disease. Patients with synchronous oligometastatic disease receiving TKI and all-metastatic site LART may have improved PFS. In patients with repeat oligoprogression, LART might potentially extend survival by delaying the need to change the systemic treatment regimen.