Comparison of initial and sequential salvage brain-directed treatment in patients with 1-4 vs. 5-10 brain metastases from breast cancer (KROG 16-12).

PURPOSE: We aimed to compare the initial and salvage brain-directed treatment and overall survival (OS) between patients with 1-4 brain metastases (BMs) and those with 5-10 from breast cancer (BC). We also organized a decision tree to select the initial whole-brain radiotherapy (WBRT) for these patients. METHODS: Between 2008 and 2014, 471 patients were diagnosed with 1-10 BMs. They were divided into two groups based on the number of BM: 1-4 BMs (n = 337) and 5-10 BMs (n = 134). Median follow-up duration was 14.0 months. RESULTS: Stereotactic radiosurgery (SRS)/fractionated stereotactic radiotherapy (FSRT) was the most common treatment modality (n = 120, 36%) in the 1-4 BMs group. In contrast, 80% (n = 107) of patients with 5-10 BMs were treated with WBRT. The median OS of the entire cohort, 1-4 BMs, and 5-10 BMs was 18.0, 20.9, and 13.9 months, respectively. In the multivariate analysis, the number of BM and WBRT were not associated with OS, whereas triple-negative BC and extracranial metastasis decreased OS. Physicians determined the initial WBRT based on four variables in the following order: number and location of BM, primary tumor control, and performance status. Salvage brain-directed treatment (n = 184), mainly SRS/FSRT (n = 109, 59%), prolonged OS by a median of 14.3 months. CONCLUSION: The initial brain-directed treatment differed notably according to the number of BM, which was chosen based on four clinical factors. In patients with ≤ 10 BMs, the number of BM and WBRT did not affect OS. The major salvage brain-directed treatment modality was SRS/FSRT and increased OS.

PIVKA-II as a surrogate marker for prognosis in patients with localized hepatocellular carcinoma receiving stereotactic body radiotherapy.

PURPOSE: This study aimed to determine the correlation between protein induced by vitamin K absence or antagonist-II (PIVKA-II) and stereotactic body radiotherapy (SBRT) in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Sixty-one patients received SBRT between 2015 and 2020 with a median dose of 48 Gy (range, 39 to 60 Gy) with a median of 4 fractions. Changes in tumor markers before and after SBRT were analyzed. RESULTS: The median follow-up period was 31 months (range, 12 to 64 months). The estimated 2-year in-field failure-free survival, progression-free survival (PFS), and overall survival rates were 82.0%, 39.3%, and 96.7%, respectively. Patients with decreased PIVKA-II levels through SBRT had significantly few in-field failures (p = 0.005). Patients with PIVKA-II levels of ≤25 mAU/mL after SBRT had significantly long PFS (p = 0.004). CONCLUSION: PIVKA-II could be a useful surrogate marker for response or survival outcomes in patients with localized HCC receiving SBRT.

The Pattern of Care for Brain Metastasis from Breast Cancer over the Past 10 Years in Korea: A Multicenter Retrospective Study (KROG 16-12).

PURPOSE: We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea. MATERIALS AND METHODS: We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008], 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014], 302 patients). RESULTS: Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance. CONCLUSION: The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years.

Novel prognostic classification predicts overall survival of patients receiving salvage whole-brain radiotherapy for recurrent brain metastasis from breast cancer: A recursive partitioning analysis (KROG 16-12).

BACKGROUND: To investigate outcomes of salvage whole-brain radiotherapy (WBRT) for recurrent brain metastases (BM) from breast cancer (BC), to identify prognostic factors of overall survival (OS), and to propose a novel prognostic classification for OS in these patients. MATERIALS AND METHODS: We identified 54 patients who had received salvage WBRT as the second brain-focused treatment for recurrent BM from BC (2000-2014). The median follow-up duration was 4.9 months. A recursive partitioning analysis (RPA) was conducted to develop a model to predict OS at the time of salvage WBRT. RESULTS: The median OS was 6.8 months. OS according to BC-specific graded prognostic assessment (breast-GPA), modified breast-GPA, and updated breast-GPA did not represent our cohort. In the multivariate analysis, a long time before salvage WBRT (≥16 months), control of primary BC or extracranial metastases, systemic treatment after salvage WBRT, and administration of a biologically effective dose for an α/ß of 10 Gy (BED10) of salvage WBRT >37.5 Gy showed superior OS. We proposed three RPA classes based on the control of both primary BC and extracranial metastasis and BED10 of salvage WBRT: class I, class II, and class III. In this model, patients with class I experienced the best OS (34.6 months; class II, 5.0 months; class III, 2.4 months; P < 0.001). CONCLUSIONS: In our RPA classification according to the control of both primary BC and extracranial metastasis and the dose of salvage WBRT, significant differences in OS were observed. The subsequent use of a systemic treatment showed better OS.

Favorable prognosis of patients who received adjuvant androgen deprivation therapy after radiotherapy achieving undetectable levels of prostate-specific antigen in high- or very high-risk prostate cancer.

INTRODUCTION: To determine the prognostic significance of long-term adjuvant androgen deprivation therapy (A-ADT) over 1 year in achieving undetectable levels of prostate-specific antigen (PSA) less than 0.001 ng/mL in prostate cancer patients with high- or very high-risk prostate cancer who underwent radiotherapy (RT). MATERIALS AND METHODS: A total of 197 patients with prostate cancer received RT, with a follow-up of ≥12 months. Biochemical failure was defined as PSA ≥nadir + 2 ng/mL after RT. We analyzed clinical outcomes, including survival, failure patterns, and prognostic factors affecting outcomes. RESULTS: Biochemical failure-free survival (BCFFS), clinical failure-free survival, distant metastasis-free survival, cancer-specific survival, and overall survival (OS) rates at 5 years were 91.1%, 95.4%, 96.9%, 99.5%, and 89.1%, respectively. Administration of long-term A-ADT significantly predicted favorable BCFFS (p = 0.027) and OS (p < 0.001) in multivariate analysis. Nadir PSA ≤0.001 ng/mL was an independent prognostic factor for BCFFS (p = 0.006) and OS (p = 0.021). The use of long-term A-ADT significantly affected nadir PSA ≤0.001 ng/mL (p < 0.001). The patients with A-ADT for 1 year or longer had better BCFFS or OS than those for less than 1 year or those without A-ADT (p < 0.001). The best prognosis was demonstrated in patients treated with long-term A-ADT and nadir PSA ≤0.001 ng/mL in BCFFS (p < 0.001). CONCLUSION: The addition of long-term A-ADT over 1 year to RT demonstrated good treatment outcomes in patients with locally advanced prostate cancer. Achieving a nadir PSA value ≤0.001 ng/mL using combination therapy with RT and A-ADT is a powerful clinical predictor of treatment outcomes.

New brain metastases after whole-brain radiotherapy of initial brain metastases in breast cancer patients: the significance of molecular subtypes (KROG 16-12).

PURPOSE: To identify the risk factors leading to new brain metastases (BM) following brain-directed treatment for initial BM resulting from breast cancer (BC). METHODS: In this multi-institutional study, 538 BC patients with available follow-up imaging after brain-directed treatment for initial BM were analyzed. Tumor molecular subtypes were classified as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-, n = 136), HER2-positive (HER2+, n = 253), or triple-negative BC (TNBC, n = 149). RESULTS: In 37.4% of patients, new BM emerged at a median of 10.5 months after brain-directed treatment for initial BM. The 1-year actuarial rate of new BM for HR+/HER2-, HER2+, and TNBC were 51.9%, 44.0%, and 69.6%, respectively (p = 0.008). Initial whole-brain radiotherapy (WBRT) reduced new BM rates (22.5% reduction at 1 year, p < 0.001) according to molecular subtype (HR+/HER2-, 42% reduction at 1 year, p < 0.001; HER2+, 18.5%, p = 0.004; TNBC, 16.9%, p = 0.071). Multivariate analysis revealed an increased risk of new BM for the following factors: shorter intervals between primary BC diagnoses and BM (p = 0.031); TNBC (relative to HR+/HER2-) (p = 0.016); presence of extracranial metastases (p = 0.019); number of BM (>4) (p < 0.001); and BM in both tentorial regions (p = 0.045). Anti-HER2 therapy in HER2+ patients (p = 0.013) and initial use of WBRT (p < 0.001) significantly lowered new BM development. CONCLUSIONS: Tumor molecular subtypes were associated with both rates of new BM development and the effectiveness of initial WBRT. Anti-HER2 therapy in HER2+ patients significantly lowered new BM occurrence.

Comparison of long-term treatment outcomes of T2N0M0 laryngeal squamous cell carcinoma using different treatment methods.

Early [stage I and II (T2N0M0)] laryngeal cancer types are currently recommended to be treated with a single modality, consisting of definitive radiation therapy or larynx-preserving surgery. Although the treatment outcomes of stage I are good, the frequency of successful outcomes decreases with T2N0M0. Therefore, the present study investigated the treatment outcomes of different treatment methods in T2N0M0 laryngeal cancer. In total, 83 patients with previously untreated T2N0M0 laryngeal squamous cell carcinoma were enrolled. Patients were grouped by treatment method: Radiation therapy (RT; 27 patients); chemoradiotherapy (CRT; 46 patients) with cisplatin base; and surgery-based therapy (SBT; ten patients). The recurrence rates of the RT, CRT and SBT groups were 44.4, 19.6 and 50%, respectively. Moreover, the local control rates of the RT, CRT and SBT groups were 55.6, 87.0 and 80%, respectively. The CRT group had a significantly lower recurrence rate and higher local control rate compared with the RT group (P<0.05). In the survival analysis, overall and disease-specific survival rate did not differ significantly among the treatment groups. However, 3- and 5-year disease-free survival rates (DFS) of the RT group were both 55%, those of the SBT group were both 50% and those of the CRT group were both 80%. Furthermore, the DFS was significantly higher in CRT group compared with the other groups (P=0.02). Using multivariate analysis with Cox regression, it was found that the treatment method was the most important factor for DFS and had a significant impact in the CRT group. In addition, in patients with glottic cancer with anterior commissure and subglottic invasion, the CRT group had significantly improved DFS compared with the RT group, whereas there was no significant difference between the two groups in patients without subglottic invasion. According to National Cancer Institution Common Toxicity Criteria (version 5.0), more patients had toxicity in the CRT group compared with the RT group. However, in the RT and CRT groups, no patients demonstrated mortality due to toxicity, and treatment-related toxicities were manageable. Collectively, although definitive conclusions could not be established, due to the limitations of this retrospective study, the results suggest that CRT had a positive impact on the local control and DFS rates with manageable toxicity in patients with T2N0M0 laryngeal cancer.

Postoperative radiotherapy for WHO grade II-III intracranial ependymoma in adults: An intergroup collaborative study (KROG 18-06/KNOG 18-01).

BACKGROUND AND PURPOSE: To evaluate the impact of adjuvant postoperative radiotherapy (PORT) in adult WHO grade II-III intracranial ependymoma (IEPN). MATERIALS AND METHODS: A total of 172 pathologically confirmed adult grade II-III IEPN patients from 12 institutions were eligible. Of them, 106 (61.6%) and 66 (38.4%) patients were grade II and III, respectively. For grade II and III IEPNs, 51 (48.1%) and 59 (89.4%) patients received PORT, respectively. The median dose to the primary tumor bed was 54.0 Gy and 59.4 Gy for grade II and III patients, respectively. The prognostic impact of sex, age, performance, WHO grade, location, size, surgical extent, and PORT on local control (LC), progression-free survival (PFS), and overall survival (OS) were evaluated by univariate and multivariate analysis. RESULTS: The median follow-up period for survivors was 88.1 months. The 5-/10-year LC, PFS, and OS rates were 64.8%/54.0%, 56.4%/44.8%, and 76.6%/71.0%, respectively. On multivariate analysis, adjuvant PORT significantly improved LC (P = 0.002), PFS (P = 0.002), and OS (P = 0.043). Older age (P < 0.001), WHO grade III (P < 0.001), larger tumor size (P = 0.004), and lesser surgical extent (P < 0.001) were also negative factors for OS. Adjuvant PORT also improved LC (P = 0.010), PFS (P = 0.007), and OS (P = 0.069) on multivariate analysis for grade II IEPNs. CONCLUSION: This multicenter retrospective study supports the role of adjuvant PORT in terms of disease control and survival in adult grade II-III IEPNs. Prospective randomized trials focused on individualized treatment based on molecular subtypes is warranted.

Chemoradiation in elderly patients with glioblastoma from the multi-institutional GBM-molRPA cohort: is short-course radiotherapy enough or is it a matter of selection?

BACKGROUND: The optimal radiotherapy regimen in elderly patients with glioblastoma treated by chemoradiation needs to be addressed. We provide the results of a comparison between conventionally fractionated standard radiotherapy (CRT) and short-course radiotherapy (SRT) in those patients treated by temozolomide-based chemoradiation. METHODS: Patients aged 65 years or older from the GBM-molRPA cohort were included. Patients who were planned for a ≥ 6-week or ≤ 4-week radiotherapy were regarded as being treated by CRT or SRT, respectively. The median RT dose in the CRT and SRT group was 60 Gy in 30 fractions and 45 Gy in 15 fractions, respectively. RESULTS: A total of 260 and 134 patients aged older than 65 and 70 years were identified, respectively. CRT- and SRT-based chemoradiation was applied for 192 (73.8%) and 68 (26.2%) patients, respectively. Compared to SRT, CRT significantly improved MS from 13.2 to 17.6 months and 13.3 to 16.4 months in patients older than 65 years (P < 0.001) and 70 years (P = 0.002), respectively. Statistical significance remained after adjusting for age, performance status, surgical extent, and MGMT promoter methylation in both age groups. The benefit was clear in all subgroup analyses for patients with Karnofsky performance score 70-100, Karnofsky performance score ≤ 60, gross total resection, biopsy, methylated MGMT promoter, and unmethylated MGMT promoter (all P < 0.05). CONCLUSION: CRT significantly improved survival compared to SRT in elderly glioblastoma patients treated with chemoradiation in selected patients amenable for chemoradiation. This study is hypothesis-generating and a prospective randomized trial is urgently warranted.

Correction to: Chemoradiation in elderly patients with glioblastoma from the multi­institutional GBM­molRPA cohort: is short­course radiotherapy enough or is it a matter of selection?

The name of author Do Hoon Lim was incorrect in the initial online publication. The original article has been corrected.

Treatment time to the end of thoracic radiotherapy has more predictive power for survival than radiation dose intensity in patients with limited-stage small-cell lung cancer receiving concurrent chemoradiation of more than 45 Gy.

The optimal protocol for thoracic radiotherapy (TRT) in combination with chemotherapy in patients with limited-stage small-cell lung cancer (LS-SCLC) remains elusive. The present study aimed to evaluate radiation parameters in association with survival outcomes. A total of 101 patients with LS-SCLC who completed TRT at ≥45 Gy and concurrent chemotherapy were retrospectively reviewed. The median dose and duration of TRT were 50 Gy and 38 days, respectively. The median duration from the start of either therapy to the end of TRT (SER) was 60 days. The median survival for all patients was 26.9 months. The 3-year local control (LC), progression-free survival (PFS) and overall survival (OS) rates were 52.0, 29.5 and 37.6%, respectively, and the 5-year LC, PFS and OS rates were 50.1, 28.3 and 26.7%, respectively. Univariate analysis revealed that patient age, tumor stage, timing and dose of TRT, SER, prophylactic cranial irradiation (PCI), and tumor response were significantly associated with treatment outcomes. Multivariate analysis revealed that stage was the only significant prognostic factor for LC (P=0.011), PFS (P<0.001) and OS (P<0.001). Tumor response (P=0.014), PCI (P=0.007) and SER (P=0.005) were significant predictors of OS. OS was improved in patients who achieved complete response, and their SER was ≤70 days (P<0.001). Short treatment duration (SER ≤70 days) was a significant predictor of OS in patients with LS-SCLC who completed planned TRT at ≥45 Gy with concurrent chemoradiotherapy.

Evaluation of Prognostic Factors for the Parotid Cancer Treated With Surgery and Postoperative Radiotherapy.

OBJECTIVES: To investigate the prognostic factors and treatment outcomes of primary parotid carcinoma treated with surgery and postoperative radiotherapy (PORT). METHODS: We reviewed retrospectively 57 patients with primary parotid carcinoma who were treated with surgery and PORT between 2005 and 2014. Superficial parotidectomy was performed in 19 patients, total parotidectomy in 10 patients, and total parotidectomy with lymph node dissection in 28 patients PORT on the tumor bed was performed in 41 patients, while PORT on tumor bed and ipsilateral cervical lymph nodes was performed in 16 patients. RESULTS: With a median follow-up of 66 months, the 5-year overall survival, disease-free survival, locoregional control, and distant control rates were 77.0%, 60.2%, 77.6%, and 72.8%, respectively. The 5-year overall survival by stage was 100%, 100%, 80.0%, and 46.4% in stage I, II, III, and IV, respectively. Recurrences at primary lesions were found in seven patients, while at cervical nodes in six patients. Distant recurrences were developed in 12 patients. No patient with the low and intermediate histologic grade developed distant failure. As prognostic factors, the histologic grade for overall survival (P=0.005), pathological T-stage (P=0.009) and differentiation grade (P=0.009) for disease-free survival, pathological T-stage for locoregional control (P=0.007), and lympho-vascular invasion (P=0.023) for distant recurrence were significant on multivariate analysis. CONCLUSION: This study revealed that differentiation grade, histologic grade, pathological T-stage, and lympho-vascular invasion were significant independent prognostic factors on clinical outcomes.

Survival outcomes of breast cancer patients with brain metastases: A multicenter retrospective study in Korea (KROG 16-12).

PURPOSE: This study evaluated the influence of prognostic factors and whole brain radiotherapy (WBRT) on overall survival (OS) of breast cancer (BC) patients with brain metastases (BM). METHODS AND MATERIALS: Medical records of 730 BC patients diagnosed with BM from 2000 to 2014 at 17 institutions were retrospectively reviewed. OS was calculated from BM diagnosis. Median follow-up duration was 11.9 months (range, 0.1-126.2). RESULTS: Median OS was 15.0 months (95% CI: 14.0-16.9). Patients with different BC-specific graded prognostic assessment (GPA) scores showed significant differences (p < 0.001) in OS. In multivariate analysis, histologic grade 3 (p = 0.014), presence of extracranial metastasis (p < 0.001), the number of BM (>4; p = 0.002), hormone receptor negativity (p = 0.005), HER2-negativity (p = 0.003), and shorter time interval (<30 months) between BC and BM diagnosis (p = 0.007) were associated with inferior OS. By summing the ß-coefficients of variables that were prognostic in multivariate analyses, we developed a prognostic model that stratified patients into low-risk (≤0.673) and high-risk (>0.673) subgroups; the high-risk subgroup had poorer median OS (10.1 months, 95% CI: 7.9-11.9 vs. 21.9 months, 95% CI: 19.5-27.1, p < 0.001). Univariate and multivariate analyses of propensity score-matched patients diagnosed with BM ≥ 30 months after BC diagnosis (n = 389, "late BM") revealed that WBRT-treated patients showed superior OS compared to non-WBRT-treated patients (p = 0.070 and 0.030, respectively). CONCLUSION: Our prognostic model identified high-risk BC patients with BM who might benefit from increased surveillance; if validated, our model could guide treatment selection for such patients. Patients with late BM might benefit from WBRT as initial local treatment.

Prognostic significance of lymphovascular invasion in patients with prostate cancer treated with postoperative radiotherapy.

PURPOSE: To determine prognostic significance of lymphovascular invasion (LVI) in prostate cancer patients who underwent adjuvant or salvage postoperative radiotherapy (PORT) after radical prostatectomy (RP). MATERIALS AND METHODS: A total of 168 patients with prostate cancer received PORT after RP, with a follow-up of ≥12 months. Biochemical failure after PORT was defined as prostate-specific antigen (PSA) ≥0.2 ng/mL after PORT or initiation of androgen deprivation therapy (ADT) for increasing PSA levels regardless of the value. We analyzed the clinical outcomes including survivals, failure patterns, and prognostic factors affecting the outcomes. RESULTS: In total, 120 patients (71.4%) received salvage PORT after PSA levels were >0.2 ng/mL or owing to clinical failure. The 5-year biochemical failure-free survival (BCFFS), clinical failure-free survival (CFFS), distant metastasis-free survival (DMFS), overall survival, and cause-specific survival rates were 78.3%, 94.3%, 95.0%, 95.8%, and 97.3%, respectively, during a follow-up range of 12-157 months (median: 64 months) after PORT. On multivariate analysis, PSA level of ≤1.0 ng/mL at the time of receiving PORT predicted favorable BCFFS, CFFS, and DMFS. LVI predicted worse CFFS (p = 0.004) and DMFS (p = 0.015). Concurrent and/or adjuvant ADT resulted in favorable prognosis for BCFFS (p < 0.001) and CFFS (p = 0.017). CONCLUSION: For patients with adverse pathologic findings, PORT should be initiated as early as possible after continence recovery after RP. Even after administering PORT, LVI was an unfavorable predictive factor, and further intensive adjuvant therapy should be considered for these patients.

Radiation hardness of cadmium telluride solar cells in proton therapy beam mode.

We evaluated the durability of cadmium telluride (CdTe) solar cells upon proton beam irradiation as well as the possibility of achieving a dosimeter usable in proton beam therapy by applying 100 MeV of pencil beam scanning (PBS) irradiation. Specifically, a 100 MeV proton PBS beam was applied at irradiation doses of 0, 1012, 1013, 1014, and 1015 cm-2. According to the results, the remaining factors (defined as the ratio of the degraded value to the initial value) of open-circuit voltage (Voc), short-circuit current (Jsc), fill-factor (FF), and efficiency (ƞ) which are solar cell performance parameters, were approximately 89%, 44%, 69%, and 30%, respectively, compared to those of the reference cell (without irradiation) at the highest dose of 1×1015 cm-2. In particular, the conversion efficiency, which is the main factor, was approximately 70% of that of the reference cell even at a high fluence of 1×1014 cm-2. In addition, we observed the projected range of the hydrogen atoms based on the PBS beam energy using the Tool for Particle Simulation software and assessed the amount of fluence accumulated in a CdTe cell. As the energy increased, the fluence accumulated inside the cell tended to decrease owing to the characteristics of the Bragg peak of the proton. Thus, the radiation damage to the cell induced by the proton beam was reduced. The results of this study are expected to provide valuable reference information for research on dosimetry sensors composed of thin-film solar cells, serving as the basis for future application in proton beam therapy with CdTe solar cells.

Intensity-modulated radiotherapy for stage I glottic cancer: a short-term outcomes compared with three-dimensional conformal radiotherapy.

PURPOSE: To investigate the differences in treatment outcomes between two radiation techniques, intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT). MATERIALS AND METHODS: We retrospectively analyzed 160 (IMRT = 23, 3DCRT = 137) patients with stage I glottic cancer treated from January 2005 through December 2016. The IMRT was performed with TomoTherapy (16 patients), volumetric-modulated arc therapy (6 patients), and step-and-shoot technique (1 patient), respectively. The 3DCRT was performed with bilateral parallel opposing fields. The median follow-up duration was 30 months (range, 31 to 42 months) in the IMRT group and 65 months (range, 20 to 143 months) in the 3DCRT group. RESULTS: The 5-year overall survival and 3-year local control rates of the 160 patients were 95.7% and 91.4%, respectively. There was no significant difference in 3-year local control rates between the IMRT and 3DCRT groups (94.4% vs. 91.0%; p = 0.587). Thirteen of 137 patients in the 3DCRT group had recurrences. In the IMRT group, one patient had a recurrence at the true vocal cord. Patients treated with IMRT had less grade 2 skin reaction than the 3DCRT group, but this had no statistical significance (4.3% vs. 21.2%; p = 0.080). CONCLUSION: IMRT had comparable outcomes with 3DCRT, and a trend of less acute skin reaction in stage I glottic cancer patients.

Validation of a novel molecular RPA classification in glioblastoma (GBM-molRPA) treated with chemoradiation: A multi-institutional collaborative study.

BACKGROUND AND PURPOSE: A novel molecular recursive partitioning analysis classification has recently been reported integrating the MGMT promoter methylation (MGMTmeth) and IDH1 mutation (IDH1mut) status for glioblastoma (GBM-molRPA) patients treated with temozolomide-based chemoradiation. The current study was initiated to validate the model in a multi-institutional study. MATERIALS AND METHODS: Four-hundred seventy-one newly diagnosed GBM patients (validation cohort) were allocated to classes I-III of the previously reported GBM-molRPA model. Of the patients, 15.7%, 56.1%, and 28.2% patients were GBM-molRPA class I, II, and III, respectively. MGMTmeth and IDH1mut were observed in 32.3 and 8.8% of patients, respectively. In the training plus validation cohort of 692 patients, 16.2%, 60.8%, and 23.0% patients were class I, II, and III, respectively. RESULTS: The median follow-up for survivors and the median survival (MS) of patients was 23.3 and 18.4 months, respectively. The MS for GBM-molRPA class I, II, and III was 49.7 (95% CI, 22.8-76.6), 19.2 (95% CI, 16.2-22.1), and 13.8 months (95% CI, 11.8-15.4) (P < .001 for all comparisons) in the validation cohort. In the training plus validation cohort, the MS was 58.5 (95% CI, 40.7-76.3), 21. (95% CI, 18.6-23.3), and 14.3 months (95% CI, 12.5-16.1) (P < .001 for all comparisons) for class I, II, and III, respectively. CONCLUSION: The GBM-molRPA is a valid model. This GBM-molRPA classification can be useful in clinics and guiding patient stratification in future clinical trials.

p16 as a prognostic factor for the response to induction chemotherapy in advanced hypopharyngeal squamous cell carcinoma.

The present study was conducted to investigate the prognostic significance of p16 (also known as cyclin-dependent kinase inhibitor 2A) in the treatment of induction chemoradiotherapy for advanced hypopharyngeal squamous cell carcinoma (HPSCC). Patients who were treated with at least two cycles of induction chemotherapy followed by concurrent chemoradiotherapy for locally advanced HPSCC were reviewed in the study. The staining results were analyzed to examine the association between the chemotherapy response and the survival outcome. A total of 45 patients were enrolled for the present study; the majority had received induction chemotherapy with docetaxel, cisplatin, and 5-FU. Following induction chemotherapy, 17 patients (37.8%) exhibited a complete response and 28 patients (62.2%) exhibited a partial response. There were 11 patients (24.4%) with p16-positive immunohistochemical stains and 30 patients (66.7%) with p53-positive immunohistochemical stains. There was no significant difference in chemotherapy response, overall survival, or progression-free survival time between groups with p16-positive and p16-negative stains. Low p53 expression and chemotherapy response were not associated with each other. High p16 expression did not correlate with low p53 expression. In this study, p16 was not determined to predict the chemotherapy response for HPSCC. High p16 expression did not correlate with survival incidence for patients with HPSCC.

Effect of irradiation-induced intercellular adhesion molecule-1 expression on natural killer cell-mediated cytotoxicity toward human cancer cells.

BACKGROUND AIMS: Irradiation enhances the adhesion between natural killer (NK) cells and target cells by up-regulating intercellular adhesion molecule-1 (ICAM-1) on target cells. Therefore, we investigated the effect of irradiation-induced ICAM-1 expression on human cancer cells on NK cell-mediated cytotoxicity. METHODS: Expression levels of ICAM-1 on the target cell surface before and after irradiation of six human cancer cell lines (HL60, SKBR-3, T47D, HCT-116, U937 and U251) were analyzed by flow cytometry. Ex vivo expansion of NK cells from human peripheral blood mononuclear cells was performed by co-culture with irradiated K562 cells. The related adhesion molecule lymphocyte function-associated antigen 1 (LFA-1) on NK cells was analyzed by flow cytometry. An enzyme-linked immunosorbent assay was used to detect interferon-γ (IFN-γ), and WST-8 assays were performed to check NK cell cytotoxicity. Finally, blocking assays were performed using monoclonal antibodies against ICAM-1 or LFA-1. RESULTS: LFA-1 expression increased on NK cells after expansion (P <0.001). The expression of ICAM-1 was significantly upregulated by irradiation after 24 h in various cell lines, including HL60 (P <0.001), SKBR-3 (P <0.001), T47D (P <0.001) and U937 (P <0.001), although the level of expression depended on the cell line. ICAM-1 expression was extremely low before and after irradiation in U251 cells. NK cell-mediated cytotoxicity increased after irradiation of HL60 (P <0.001), SKBR-3 (P <0.001), T47D (P = 0.003), and U937 (P = 0.004) cells, in which ICAM-1 expression was significantly increased after irradiation. IFN-γ production by NK cells in response to HL60 (P <0.001) and T47D (P = 0.011) cells significantly increased after irradiation. NK cell-mediated cytotoxicity against irradiated SKBR-3 (P <0.001) and irradiated T47D cells (P = 0.035) significantly decreased after blocking of ICAM-1. Blocking of LFA-1 on NK cells resulted in reduced cytotoxicity against irradiated HL60 (P <0.001) and irradiated SKBR-3 (P <0.001). CONCLUSIONS: Irradiation upregulates ICAM-1 expression on the surface of human cancer cells and enhances activated NK cell-mediated cytotoxicity. Therefore, irradiation combined with NK cell therapy may improve the antitumor effects of NK cells.

Correlation of biologically effective dose and the tumor control in Stage I (<5 cm) non-small cell lung cancer with stereotactic ablative radiotherapy: a single institutional cohort study.

BACKGROUNDS: Stereotactic ablative radiotherapy (SABR) is one of the newly developed innovative radiotherapy and of which optimal dose prescription needs to be standardized. We aimed to investigate the dose-response relationship for patients with SABR. METHODS: Fifty-three patients with Stage I non-small cell lung cancer patients, who underwent SABR between November 2006 and January 2015, were evaluated retrospectively. Thirteen patients (24.5%), who refused the surgery were included and 40 patients (75.5%) were medically inoperable at diagnosis. The median age was 74 years. The median SABR dose was 50 Gy in 3-8 fractions and the median biologically effective dose (BED;α/ß = 10) was 105.6 Gy (range: 60-160.53 Gy). RESULTS: The median follow-up was 37.1 months. The 1 and 3 year local control rates were 91.7% and 85.1%. The 3 year overall and progression-free survival rate were 63.3% and 47.5%, respectively, and freedom from progression was 62.2%. Local control rate and 3-year overall survival according to tumor size was 100% and 79.4% in T1 tumors in a while 61.8% and 45% in T2a tumors. The 3-year local and regional control by BED10 was 79.4% and 69.4% in ≤100 Gy vs. 89.1% and 100% in >100 Gy (P = 0.526, 0.004). Dyspnea more than Grade 3 was reported in six (11.3%) patients and Grade 1 chest pain was shown in five (9.4%) patients. CONCLUSIONS: The excellent regional control was conferred with a prescription of more than BED10 of 100 Gy, which also might be needed to achieve better local tumor control in T2a patients with tolerable lung function.