Purpose The efficacy and lower neurotoxicity of normal brain-sparing radiotherapy (NBS-RT) with systemic therapy in treating multiple brain metastases from non–small cell lung cancer (NSCLC) is underexplored. This study compares whole brain radiotherapy (WBRT) and NBS-RT for multiple brain metastases in NSCLC, focusing on treatment outcomes and leukoencephalopathy.
Materials and Methods This retrospective study included 503 patients with NSCLC with multiple brain metastases at a single center, treated with either WBRT or NBS-RT. Post-RT treatments included chemotherapy, targeted therapy, or immunotherapy. Main outcomes measured were intracranial control, overall survival (OS), and leukoencephalopathy incidence.
Results In this study, 441 patients received WBRT and 62 received NBS-RT, with median ages of 62 and 61 years, respectively. A significant portion of both groups, 77.3% in WBRT and 80.6% in NBS-RT, received post-RT systemic therapy. The median number of brain metastases was 10 for WBRT and 12 for NBS-RT, with median maximal diameters of 11.7 mm in WBRT and 14.4 mm in NBS-RT. After a median follow-up of 10.9 months for WBRT and 11.8 months for NBS-RT, there were no significant differences in intracranial progression (p=0.516) or OS (p=0.492) between the groups. However, WBRT patients had a higher incidence of leukoencephalopathy than NBS-RT patients (p=0.013).
Conclusion NBS-RT combined with systemic therapy was as effective in treating multiple brain metastases as WBRT and was less toxic. NBS-RT-based strategies deserve further investigation in a prospective setting.
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Purpose This study aimed to identify a specific subgroup of patients among elderly glioblastoma patients aged 70 years or older with unmethylated O6-methylguanine-DNA methyltransferase promoters (eGBM-unmethylated) who would significantly benefit from the addition of temozolomide (TMZ) to radiotherapy (RT).
Materials and Methods Newly diagnosed patients with Isocitrate dehydrogenase wild-type eGBM-unmethylated treated with RT were included in this multicenter analysis (n=182). RT dose was 45 Gy in 15 fractions (62.3%), 60 Gy in 30 fractions, or 61.2 Gy in 34 fractions. For patients treated with RT plus TMZ (60.4%), TMZ was administered concurrently with RT, followed by six adjuvant cycles. The primary endpoint was overall survival.
Results During a median follow-up of 11.3 months for survivors, the median survival was 12.2 months. The median survival duration significantly improved with the addition of TMZ to RT compared with that with RT alone (13.6 months vs. 10.5 months, p=0.028). In the multivariable analysis adjusted for clinical, radiological, and genetic biomarkers, the addition of TMZ significantly improved overall survival (hazard ratio, 0.459; p=0.006). In subgroup analysis, median survival was especially improved by 4-5 months in patients with residual disease (p < 0.001), Karnofsky performance status ≥ 60 (p=0.033), and age ≤ 75 years (p=0.090). A significant benefit of TMZ was noted only in patients with two or three of the above factors (median survival, 14.1 months vs. 10.5 months; p=0.014).
Conclusion The addition of TMZ significantly improved the survival of patients with eGBM-unmethylated treated with RT. The suggested criteria for the specific subgroup in these patients warrant external validation for clinical application.
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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.
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Purpose This study aimed to develop a graded prognostic assessment (GPA) model integrating genomic characteristics for elderly patients with glioblastoma (eGBM), and to compare the efficacy of different radiotherapy schedules.
Materials and Methods This multi-institutional retrospective study included patients aged ≥ 65 years who underwent surgical resection followed by radiotherapy with or without temozolomide (TMZ) for newly diagnosed eGBM. Based on the significant factors identified in the multivariate analysis for overall survival (OS), the molecular GPA for eGBM (eGBM-molGPA) was established.
Results A total of 334 and 239 patients who underwent conventionally fractionated radiotherapy (CFRT) and hypofractionated radiotherapy (HFRT) were included, respectively, with 86% of patients receiving TMZ-based chemoradiation. With a median follow-up of 17.4 months (range, 3.3 to 149.9 months), the median OS was 18.7 months for CFRT+TMZ group, 15.1 months for HFRT+TMZ group, and 10.4 months for radiotherapy alone group (CFRT+TMZ vs. HFRT+TMZ: hazard ratio [HR], 1.52; p < 0.001 and CFRT+TMZ vs. radiotherapy alone: HR, 2.52; p < 0.001). In a combined analysis with the NOA-08 and Nordic trials, CFRT+TMZ group exhibited the highest survival rates among all treatment groups. The eGBM-molGPA, which integrated four clinical and three molecular parameters, stratified patients into low-, intermediate-, and high-risk groups. CFRT+TMZ significantly improved OS compared to HFRT+TMZ or radiotherapy alone in the low-risk (p=0.023) and intermediate-risk groups (p < 0.001). However, in the high-risk group, there was no significant difference in OS between treatment options (p=0.770).
Conclusion CFRT+TMZ may be more effective than HFRT+TMZ or radiotherapy alone for selected eGBM patients. The novel eGBM-molGPA model can guide treatment selection for this patient population.
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Cancer Res Treat. 2022;54(4):1191-1199. Published online December 7, 2021
Purpose This study proposed the optimal definition of biochemical recurrence (BCR) after salvage radiotherapy (SRT) following radical prostatectomy for prostate cancer.
Materials and Methods Among 1,117 patients who had received SRT, data from 205 hormone-naïve patients who experienced post-SRT prostate-specific antigen (PSA) elevation were included in a multi-institutional database. The primary endpoint was to determine the PSA parameters predictive of distant metastasis (DM). Absolute serum PSA levels and the prostate-specific antigen doubling time (PSA-DT) were adopted as PSA parameters.
Results When BCR was defined based on serum PSA levels ranging from 0.4 ng/mL to nadir+2.0 ng/mL, the 5-year probability of DM was 27.6%-33.7%. The difference in the 5-year probability of DM became significant when BCR was defined as a serum PSA level of 0.8 ng/ml or higher (1.0-2.0 ng/mL). Application of a serum PSA level of ≥ 0.8 ng/mL yielded a c-index value of 0.589. When BCR was defined based on the PSA-DT, the 5-year probability was 22.7%-39.4%. The difference was significant when BCR was defined as a PSA-DT ≤ 3 months and ≤ 6 months. Application of a PSA-DT ≤ 6 months yielded the highest c-index (0.660). These two parameters complemented each other; for patients meeting both PSA parameters, the probability of DM was 39.5%-44.5%; for those not meeting either parameter, the probability was 0.0%-3.1%.
Conclusion A serum PSA level > 0.8 ng/mL was a reasonable threshold for the definition of BCR after SRT. In addition, a PSA-DT ≤ 6 months was significantly predictive of subsequent DM, and combined application of both parameters enhanced predictability.
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Cancer Res Treat. 2020;52(4):1041-1049. Published online April 23, 2020
Purpose
The aim of this study is to evaluate the survival rate and prognostic factors of anaplastic gliomas according to the 2016 World Health Organization classification, including extent of resection (EOR) as measured by contrast-enhanced T1-weighted magnetic resonance imaging (MRI) and the T2-weighted MRI.
Materials and Methods
The records of 113 patients with anaplastic glioma who were newly diagnosed at our institute between 2000 and 2013 were retrospectively reviewed. There were 62 cases (54.9%) of anaplastic astrocytoma, isocitrate dehydrogenase (IDH) wild-type (AAw), 18 cases (16.0%) of anaplastic astrocytoma, IDH-mutant, and 33 cases (29.2%) of anaplastic oligodendroglioma, IDH-mutant and 1p/19q-codeleted.
Results
The median overall survival (OS) was 48.4 months in the whole anaplastic glioma group and 21.5 months in AAw group. In multivariate analysis, age, preoperative Karnofsky Performance Scale score, O6-methylguanine-DNA methyltransferase (MGMT) methylation status, postoperative tumor volume, and EOR measured from the T2 MRI sequence were significant prognostic factors. The EOR cut-off point for OS measured in contrast-enhanced T1-weighted MRI and T2-weighted MRI were 99.96% and 85.64%, respectively.
Conclusions
We found that complete resection of the contrast-enhanced portion (99.96%) and more than 85.64% resection of the non-enhanced portion of the tumor have prognostic impacts on patient survival from anaplastic glioma.
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Cancer Res Treat. 2020;52(1):167-180. Published online June 25, 2019
Purpose
The purpose of this study was to investigate the clinical outcomes of postoperative radiotherapy (PORT) patients who underwent radical prostatectomy for localized prostate cancer.
Materials and Methods
Localized prostate cancer patients who received PORT after radical prostatectomy between 2001 and 2012 were identified retrospectively in a multi-institutional database. In total, 1,117 patients in 19 institutions were included. Biochemical failure after PORT was defined as prostate-specific antigen (PSA) ≥ nadir+2 after PORT or initiation of androgen deprivation therapy (ADT) for increasing PSA regardless of its value.
Results
Ten-year biochemical failure-free survival, clinical failure-free survival, distant metastasisfree survival, overall survival (OS), and cause-specific survival were 60.5%, 76.2%, 84.4%, 91.1%, and 96.6%, respectively, at a median of 84 months after PORT. Pre-PORT PSA ≤ 0.5 ng/ml and Gleason’s score ≤ 7 predicted favorable clinical outcomes, with 10-year OS rates of 92.5% and 94.1%, respectively. The 10-year OS rate was 82.7% for patients with a PSA > 1.0 ng/mL and 86.0% for patients with a Gleason score of 8-10. The addition of longterm ADT (≥ 12 months) to PORT improved OS, particularly in those with a Gleason score of 8-10 or ≥ T3b.
Conclusion
Clinical outcomes of PORT in a Korean prostate cancer population were very similar to those in Western countries. Lower Gleason score and serum PSA level at the time of PORT were significantly associated with favorable outcomes. Addition of long-term ADT (≥ 12 months) to PORT should be considered, particularly in unfavorable risk patients with Gleason scores of 8-10 or ≥ T3b.
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Purpose The purpose of this study is to investigate the long-term results and appropriateness of radiation therapy (RT) for medulloblastoma (MB) at a single institution. Materials and Methods We analyzed the clinical outcomes of 106 patients with MB who received RT between January 1992 and October 2009. The median age was 7 years (range, 0 to 50 years), and the proportion of M0, M1, M2, and M3 stages was 60.4%, 8.5%, 4.7%, and 22.6%, respectively. The median total craniospinal irradiation (CSI) and posterior fossa tumor bed dose in 102 patients (96.2%) treated with CSI was 36 Gy and 54 Gy, respectively. Results The median follow-up period in survivors was 132 months (range, 31 to 248 months). A gradual improvement in survival outcomes was observed, with 5-year overall survival rates of 61.5% in 1990s increasing to 73.6% in 2000s. A total of 29 recurrences (27.4%) developed at the following sites: five (17.2%) in the tumor bed; five (17.2%) in the posterior fossa other than the tumor bed; nine (31%) in the supratentorium; and six (20.7%) in the spinal subarachnoid space only. The four remaining patients showed multiple site recurrences. Among 12 supratentorial recurrences, five cases recurred in the subfrontal areas. Although the frequency of posterior fossa/tumor bed recurrences was significantly high among patients treated with subtotal resection, other site (other intracranial/spinal) recurrences were more common among patients treated with gross tumor removal (p=0.016). There was no case of spinal subarachnoid space relapse from desmoplastic/extensive nodular histological subtypes. Conclusion Long-term follow-up results and patterns of failure confirmed the importance of optimal RT dose and field arrangement. More tailored multimodal strategies and proper CSI technique may be the cornerstones for improving treatment outcomes in MB patients.
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