Evidence-based clinical recommendations for hypofractionated radiotherapy: exploring efficacy and safety - Part 2. Lung (non-small cell lung cancer).

Several recent studies have investigated the use of hypofractionated radiotherapy (HFRT) for various cancers. However, HFRT for non-small cell lung cancer (NSCLC) with or without concurrent chemotherapy is not yet widely used because of concerns about serious side effects and the lack of evidence for improved treatment results. Investigations of HFRT with concurrent chemotherapy in NSCLC have usually been performed in single-arm studies and with a small number of patients, so there are not yet sufficient data. Therefore, the Korean Society for Radiation Oncology Practice Guidelines Committee planned this review article to summarize the evidence on HFRT so far and provide it to radiation oncology clinicians. In summary, HFRT has demonstrated promising results, and the reviewed data support its feasibility and comparable efficacy for the treatment of locally advanced NSCLC. The incidence and severity of esophageal toxicity have been identified as major concerns, particularly when treating large fraction sizes. Strategies, such as esophagus-sparing techniques, image guidance, and dose constraints, may help mitigate this problem and improve treatment tolerability. Continued research and clinical trials are essential to refine treatment strategies, identify optimal patient selection criteria, and enhance therapeutic outcomes.

Correction: Sung et al. Linear Tumor Regression of Rectal Cancer in Daily MRI during Preoperative Chemoradiotherapy: An Insight of Tumor Regression Velocity for Personalized Cancer Therapy. Cancers 2022, 14, 3749.

In the original publication [...].

The impact of boost radiation therapy after hysterectomy on cervical cancer patients with close or positive resection margins

Purpose We investigated the effect of boost radiation therapy (RT) in addition to whole pelvis RT (WPRT) on treatment outcome and safety of cervical cancer patients following hysterectomy with close/positive resection margins (RM). Methods We retrospectively analyzed 51 patients with cervical cancer who received WPRT with or without boost-RT as adjuvant treatment between July 2006 and June 2022. Twenty patients (39.2%) were treated with WPRT-alone, and 31 (60.8%) received boost-RT after WPRT using brachytherapy or intensity-modulated RT. Results The median follow-up period was 41 months. According to RT modality, the 4-year local control (LC) and locoregional control (LRC) rates of patients treated with WPRT-alone were 61% and 61%, respectively, whereas those in LC and LRC rates in patients who underwent WPRT with boost-RT were 93.2% and 75.3%, with p-values equal to 0.005 and 0.090, respectively. Seven patients (35.0%) had local recurrence in the WPRT-treated group compared to only two out of the 31 patients (6.5%) in the WPRT with boost-RT-treated counterparts (p = 0.025). Boost-RT was a significantly good prognostic factor for LC (p = 0.013) and LRC (p = 0.013). Boost-RT did not result in statistically-significant improvements in progression-free survival or overall survival. The acute and late toxicity rates were not significantly different between groups. Conclusion Boost RT following WPRT is a safe and effective treatment strategy to improve LC without increasing toxicity in patients with cervical cancer with close/positive RM after hysterectomy (AU)

Evidence-based clinical recommendations for hypofractionated radiotherapy: exploring efficacy and safety - Part 1. Brain and head and neck.

Advances in radiotherapy (RT) techniques, including intensity-modulated RT and image-guided RT, have allowed hypofractionation, increasing the fraction size over the conventional dose of 1.8-2.0 Gy. Hypofractionation offers advantages such as shorter treatment times, improved compliance, and under specific conditions, particularly in tumors with a low α/ß ratio, higher efficacy. It was initially explored for use in RT for prostate cancer and adjuvant RT for breast cancer, and its application has been extended to various other malignancies. Hypofractionated RT (HFRT) may also be effective in patients who are unable to undergo conventional treatment owing to poor performance status, comorbidities, or old age. The treatment of brain tumors with HFRT is relatively common because brain stereotactic radiosurgery has been performed for over two decades. However, re-irradiation of recurrent lesions and treatment of elderly or frail patients are areas under investigation. HFRT for head and neck cancer has not been widely used because of concerns regarding late toxicity. Thus, we aimed to provide a comprehensive summary of the current evidence for HFRT for brain tumors and head and neck cancer and to offer practical recommendations to clinicians faced with the challenge of choosing new treatment options.

The impact of boost radiation therapy after hysterectomy on cervical cancer patients with close or positive resection margins.

PURPOSE: We investigated the effect of boost radiation therapy (RT) in addition to whole pelvis RT (WPRT) on treatment outcome and safety of cervical cancer patients following hysterectomy with close/positive resection margins (RM). METHODS: We retrospectively analyzed 51 patients with cervical cancer who received WPRT with or without boost-RT as adjuvant treatment between July 2006 and June 2022. Twenty patients (39.2%) were treated with WPRT-alone, and 31 (60.8%) received boost-RT after WPRT using brachytherapy or intensity-modulated RT. RESULTS: The median follow-up period was 41 months. According to RT modality, the 4-year local control (LC) and locoregional control (LRC) rates of patients treated with WPRT-alone were 61% and 61%, respectively, whereas those in LC and LRC rates in patients who underwent WPRT with boost-RT were 93.2% and 75.3%, with p-values equal to 0.005 and 0.090, respectively. Seven patients (35.0%) had local recurrence in the WPRT-treated group compared to only two out of the 31 patients (6.5%) in the WPRT with boost-RT-treated counterparts (p = 0.025). Boost-RT was a significantly good prognostic factor for LC (p = 0.013) and LRC (p = 0.013). Boost-RT did not result in statistically-significant improvements in progression-free survival or overall survival. The acute and late toxicity rates were not significantly different between groups. CONCLUSION: Boost RT following WPRT is a safe and effective treatment strategy to improve LC without increasing toxicity in patients with cervical cancer with close/positive RM after hysterectomy.

Is reduced-dose whole-brain radiotherapy also feasible in primary CNS lymphoma for curative or salvage purpose?

PURPOSE: Recently, reduced-dose whole-brain radiotherapy (WBRT) has been used to treat primary central nervous system lymphoma (PCNSL). However, whether reduced-dose WBRT is also an acceptable option for curative or salvage purposes has not yet been reported. We analyzed the clinical outcomes of patients with PCNSL who received radiotherapy for curative or salvage purposes and compared the clinical outcomes according to the WBRT dose. METHODS: A total of 66 patients were divided into two groups: those treated with 30 Gy (2 Gy per fraction) or less WBRT (low-dose WBRT, n = 34) and those treated with more than 30 Gy WBRT (high-dose WBRT, n = 32). The median WBRT dose was 25.2 and 49.6 Gy in low-dose and high-dose WBRT groups, respectively. The median total radiotherapy dose, including the boost dose, was 50 Gy (range, 36.0-55.8 Gy). RESULTS: The 3-year overall survival and progression-free survival were 77.8% and 29.8%, respectively. Intracranial relapse occurred in 31 patients (47.0%) at a median of 27 months after RT. Overall survival and progression-free survival did not differ between the two groups. The 3-year intracranial disease control rate did not differ between the two groups (35.2% vs. 41.6%, p = 0.300). Grade 3 or higher neurological toxicities were observed in six patients, of whom five were in the high-dose WBRT group. CONCLUSION: Reduced-dose WBRT in curative and salvage treatments for PCNSL had no significant negative effect on the intracranial disease control rate or survival. Therefore, without impaired efficacy, use of reduced-dose WBRT appears promising for reduction of neurotoxicity.

Reduced volume intensity-modulated radiotherapy with simultaneous integrated boost for patients with high-grade glioma: A retrospective observational study.

Radiotherapy (RT) is an essential treatment for patients with high-grade gliomas. however, a consensus on the target area of RT has not yet been achieved. In this study, we aimed to analyze progression-free survival (PFS), recurrence patterns, and toxicity in patients who received reduced volume intensity-modulated radiotherapy with simultaneous integrated boost (rvSIB-IMRT). In addition, we attempted to identify prognostic factors for recurrence. Twenty patients with high-grade gliomas who received rvSIB-IMRT between July 2011 and December 2021 were retrospectively analyzed. For rvSIB-IMRT, clinical target volume 1/2 was set at a 5 to 10 mm margin on each gross tumor volume (GTV) 1 (resection cavity and enhanced lesion) and GTV2 (high-signal lesion of T2/fluid-attenuated inversion recovery). RT doses were prescribed to 60 Gy/30 fractions (fxs) for planning target volume (PTV)1 and 51 to 54 Gy/30 fxs for PTV2. The median PFS and overall survival of the total cohorts were 10.6 and 13.6 months, respectively. Among the 12 relapsed patients, central, in-field, and marginal recurrences were identified in 8 (66.7%), 2 (16.7%), and 1 patient (8.3%), respectively. Distant recurrence was identified in 3 patients. Gross total resection (GTR) and high Ki-67 index (>27.4%), and subventricular involvement (SVI) were identified as significant factors for PFS in the multivariate analysis. During the follow up, 4 patients showed pseudoprogression and 1 patient showed radiation necrosis. The rvSIB-IMRT for high-grade gliomas resulted in comparable PFS and tolerable toxicity. Most recurrences were central/in-field (10 cases of 12, 83.4%). GTR, high Ki-67 index (>27.4%), and SVI were significant factors for recurrence.

Re-Irradiation with Intensity-Modulated Radiation Therapy for the Treatment of Recurrent Cervical Cancer in the Pelvis: An Analysis of Outcomes and Toxicity.

Background and Objectives: Treatment options for most patients with recurrent cervical cancer within the previously irradiated field are limited. This study aimed to investigate the feasibility and safety of re-irradiation using intensity-modulated radiation therapy (IMRT) for patients with cervical cancer who experienced intrapelvic recurrence. Materials and Methods: We retrospectively analyzed 22 patients with recurrent cervical cancer who were treated with re-irradiation for intrapelvic recurrence using IMRT between July 2006 and July 2020. The irradiation dose and volume were determined based on the range considered safe for the tumor size, location, and previous irradiation dose. Results: The median follow-up period was 15 months (range: 3-120) and the overall response rate was 63.6%. Of the symptomatic patients, 90% experienced symptom relief after treatment. The 1- and 2-year local progression-free survival (LPFS) rates were 36.8% and 30.7%, respectively, whereas the 1- and 2-year overall survival (OS) rates were 68.2% and 25.0%, respectively. Multivariate analysis revealed that the interval between irradiations and gross tumor volume (GTV) were significant prognostic factors for LPFS. The response to re-irradiation showed borderline statistical significance for LPFS. The GTV and response to re-irradiation were also independent prognostic factors for OS. Grade 3 late toxicities were observed in 4 (18.2%) of the 22 patients. Recto- or vesico-vaginal fistula occurred in four patients. The irradiation dose was associated with fistula formation with borderline significance. Conclusions: Re-irradiation using IMRT is a safe and effective treatment strategy for patients with recurrent cervical cancer who previously received RT. Interval between irradiations, tumor size, response to re-irradiation, and radiation dose were the main factors affecting efficacy and safety.

Non-endometrioid endometrial cancer: analysis of recurrence pattern and identification of prognostic and treatment factors affecting recurrence and survival.

PURPOSE: We investigated the characteristics of recurrence pattern and survival of patients with non-endometrioid endometrial cancer (NEEC) and attempted to identify prognostic and treatment factors affecting disease-free survival (DFS) and overall survival (OS) of these patients. METHODS: Fifty-seven patients with histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stage IA-IVA NEEC from February 2003 to December 2021 were retrospectively analyzed. RESULTS: The 5­year DFS and OS rates of the total cohort were 50.6% and 56.1%, respectively. Recurrence occurred in 28 patients (49.1%) during follow-up, and the most common recurrence pattern was distant metastasis (DM; 78.6% of total recurrences). The occurrence of relapse significantly reduced 5­year OS (recurrence group vs. non-recurrence group: 12.5% vs. 100%; p < 0.001). In univariate analysis, adjuvant radiotherapy (RT) group showed significantly higher 5­year DFS (56.7% vs. 37.9%; p = 0.04), local recurrence-free survival (91.6% vs. 50.5%; p = 0.01), and regional recurrence-free survival (88.2% vs. 56.5%; p < 0.01) than the non-RT group. In multivariate analysis, advanced FIGO stage was identified as a negative prognostic factor for DFS and OS. Lymphovascular space invasion (LVSI) and adjuvant RT were independent prognostic factors for DFS. CONCLUSION: The most common recurrence pattern observed in patients with NEEC was DM. FIGO stage and LVSI were identified as prognostic factors for survival, and RT was identified as a therapeutic modality that could increase DFS. To improve the OS of patients with NEEC, the addition of effective chemotherapy that can reduce DM may be important.

Current Evidence of a Deintensification Strategy for Patients with HPV-Related Oropharyngeal Cancer.

Human papillomavirus (HPV)-related oropharyngeal cancer differs from HPV-negative oropharyngeal cancer in terms of etiology, epidemiology, and prognosis. Younger and lower comorbidity patient demographics and favorable prognosis allow HPV-related oropharyngeal cancer patients to anticipate longer life expectancy. Reducing long-term toxicities has become an increasingly important issue. Treatment deintensification to reduce toxicities has been investigated in terms of many aspects, and the reduction of radiotherapy (RT) dose in definitive treatment, replacement of platinum-based chemotherapy with cetuximab, response-tailored dose prescription after induction chemotherapy, and reduction of adjuvant RT dose after transoral surgery have been evaluated. We performed a literature review of prospective trials of deintensification for HPV-related oropharyngeal cancer. In phase II trials, reduction of RT dose in definitive treatment showed comparable survival outcomes to historical results. Two phase III randomized trials reported inferior survival outcomes for cetuximab-based chemoradiation compared with cisplatin-based chemoradiation. In a randomized phase III trial investigating adjuvant RT, deintensified RT showed noninferior survival outcomes in patients without extranodal extension but worse survival in patients with extranodal extension. Optimal RT dosage and patient selection require confirmation in future studies. Although many phase II trials have reported promising outcomes, the results of phase III trials are needed to change the standard treatment. Since high-level evidence has not been established, current deintensification should only be performed as part of a clinical study with caution. Implementation in clinical practice should not be undertaken until evidence from phase III randomized trials is available.

Linear Tumor Regression of Rectal Cancer in Daily MRI during Preoperative Chemoradiotherapy: An Insight of Tumor Regression Velocity for Personalized Cancer Therapy.

Objective: Neoadjuvant chemoradiotherapy (CCRT) is current standards of care for locally advanced rectal cancer. The precise and thorough investigation of a tumor during the full course of CCRT by means of daily MRI can provide an idea on real-time treatment sensitivity in addition to tumor biology. Tumor volumetry from daily MRI during CCRT may allow patient-driven treatment decisions. Material and Methods: Patients diagnosed with cT3-4 and/or cN+ rectal adenocarcinoma undergoing preoperative CCRT with capecitabine on the pelvis up to 50 Gy in 25 daily fractions from November 2018 to June 2019 were consecutively included. Rectal tumor volume was uniformly measured by a single physician (YKK) in daily 0.35T MRI obtained with MR-guided linear accelerator. Primary endpoint was to assess the pattern of tumor volume regression throughout the full course of CCRT using daily registration MRI. Secondary endpoint was to assess the effect of tumor regression velocity on disease-free survival (DFS). Tumor regression velocity (cc) per fraction of each patient was calculated using the simple regression analysis of tumor volumes from fraction 1 to fraction 25. Results: Twenty patients were included. Daily tumor volumetry demonstrated linear tumor regression during CCRT. The tumor regression velocity of all 20 patients was 2.40 cc per fraction (R2 = 0.93; p < 0.001). The median tumor regression velocity was 1.52 cc per fraction. Patients with tumor regression velocity ≥ 1.52 cc per fraction were grouped as rapid regressors (N = 9), and those with tumor regression velocity < 1.52 cc per fraction were grouped as slow regressors (N = 11). Rapid regressors had greater tumor regression velocity (4.58 cc per fraction) compared to that of slow regressors (0.78 cc per fraction) with statistical significance (p < 0.001). The mean DFS of rapid regressors was 36.8 months, numerically longer than the 31.9 months of slow regressors (p = 0.400) without statistical significance. Rapid regressors had numerically superior DFS rate compared to slow regressors without statistical significance. The 2-year DFS was 88.9% for rapid regressors and 72.7% for slow regressors, respectively (p = 0.400). Conclusion: This study is the first observation of linear tumor regression in daily MRI during the preoperative CCRT of locally advanced rectal cancer. Daily tumor regression velocity discriminated DFS, although without statistical significance. This study with a phenomenal approach is hypothesis-generating. Nevertheless, the potential of CCRT from therapeutics to a newer level, the "theranostics", has been inceptively suggested. Further validation studies for the value of daily tumor volumetry on treatment decisions are warranted.

Application of real-time MRI-guided linear accelerator in stereotactic ablative body radiotherapy for non-small cell lung cancer: one step forward to precise targeting.

PURPOSE: Tumor motion is a major challenge in stereotactic ablative body radiotherapy (SABR) for non-small cell lung cancer (NSCLC), causing excessive irradiation to compensate for this motion. Real-time tumor tracking with a magnetic resonance imaging-guided linear accelerator (MR-Linac) could address this problem. This study aimed to assess the effects and advantages of MR-Linac in SABR for the treatment of lung tumors. METHODS: Overall, 41 patients with NSCLC treated with SABR using MR-Linac between March 2019 and December 2021 were included. For comparison, 40 patients treated with SABR using computed tomography-based modalities were also enrolled. The SABR dose ranged from 48 to 60 Gy in 3-5 fractions. The primary endpoint was a lower radiation volume compared to CT-based SABR. The secondary endpoint was the local control rate of SABR using the MR-Linac. RESULTS: The median follow-up time was 19 months (range: 3-105 months). There was no significant difference in the gross tumor volume between the MR and CT groups (7.1 ± 9.3 cm3 vs 8.0 ± 6.8 cm3, p = 0.643), but the planning target volume was significantly smaller in the MR group (20.8 ± 18.8 cm3 vs 34.1 ± 22.9 cm3, p = 0.005). The 1-year local control rates for the MR and CT groups were 92.1 and 75.4%, respectively (p = 0.07), and the 1-year overall survival rates were 87.4 and 87.0%, respectively (p = 0.30). CONCLUSION: Lung SABR with MR-Linac can reduce the radiation field without compromising the local control rate. Further follow-up is needed to assess the long-term effects.

Rosmarinic Acid, as an NHE1 Activator, Decreases Skin Surface pH and Improves the Skin Barrier Function.

Stratum corneum (SC) pH regulates skin barrier functions and elevated SC pH is an important factor in various inflammatory skin diseases. Acidic topical formulas have emerged as treatments for impaired skin barriers. Sodium proton exchanger 1 (NHE1) is an important factor in SC acidification. We investigated whether topical applications containing an NHE1 activator could improve skin barrier functions. We screened plant extracts to identify NHE1 activators in vitro and found Melissa officinalis leaf extract. Rosmarinic acid, a component of Melissa officinalis leaf extract, significantly increased NHE1 mRNA expression levels and NHE1 production. Immunofluorescence staining of NHE1 in 3D-cultured skin revealed greater upregulation of NHE1 expression by NHE1 activator cream, compared to vehicle cream. Epidermal lipid analysis revealed that the ceramide level was significantly higher upon application of the NHE1 activator cream on 3D-cultured skin, compared to application of a vehicle cream. In a clinical study of 50-60-year-old adult females (n = 21), application of the NHE1 activator-containing cream significantly improved skin barrier functions by reducing skin surface pH and transepidermal water loss and increasing skin hydration, compared to patients who applied vehicle cream and those receiving no treatment. Thus, creams containing NHE1 activators, such as rosmarinic acid, could help maintain or recover skin barrier functions.

MRI-guided radiotherapy for PVTT in HCC patients: evaluation of the efficacy and safety.

PURPOSE: This study aims to evaluate the efficacy, feasibility, and safety of the magnetic resonance imaging (MRI)-guided tumor tracking hypofractionated radiotherapy (HFRT) and stereotactic body radiation therapy (SBRT) for portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) patients. METHODS: We retrospectively reviewed the twelve cases of unresectable HCC with tumor thrombus in the main trunk or first branch of the portal vein that were treated with MRI-guided tumor tracking HFRT or SBRT using the ViewRay Linac MRIdian system between June 2019 and January 2021. The HFRT was performed with a total of 50 Gy in 10 fractions, and SBRT performed in a range of 36-50 Gy with 4-5 fractions. The median biologic effective dose (BED) with an a/b ratio of 10 was 75 Gy10 (range 68.4-100 Gy10). RESULTS: The median follow-up duration was 5.0 months (range 1.9-12.8 months). Ten patients (83.3%) showed an objective response of PVTT. At the time of analysis, ten patients (83.3%) showed local control. The 1-year intrahepatic control rate was 48.9%. Three patients (25%) showed mild gastrointestinal symptoms, and there were no cases of grade 3 or higher toxicity. For hepatic toxicity, there were no cases in which the Child-Pugh score increased by more than two points after RT without disease progression. CONCLUSION: MRI-guided tumor tracking HFRT and SBRT was a feasible, effective, and safe treatment option in HCC patients with tumor thrombi in the main trunk or first branch of the portal vein.

A Lipid Mixture Enriched by Ceramide NP with Fatty Acids of Diverse Chain Lengths Contributes to Restore the Skin Barrier Function Impaired by Topical Corticosteroid.

INTRODUCTION: The stratum corneum (SC) is a skin barrier that consists of corneocytes, intercellular lipids, and corneodesmosomes. Ceramides are composed of sphingoid bases linked with various types of fatty acids (FAs), and they are an essential constituent of SC intercellular lipids. Among their subtypes, ceramide NP with a phytosphingosine base is especially important. Most of the previous studies on barrier recovery have focused on a specific ceramide with a single chain FA, not with diverse chain lengths. Skin barrier function is impaired by various factors, including topical corticosteroid. OBJECTIVE: We evaluated whether a lipid mixture enriched by ceramide NP with FAs of diverse chain lengths (CER [NP]*) can restore the skin barrier function impaired by topical corticosteroid. METHODS: Twenty-seven healthy adult male volunteers were recruited. Topical corticosteroid was applied on both volar forearms of volunteers. Then, the test cream containing a lipid mixture with CER (NP)* was applied on the left forearm, and a vehicle cream without a lipid mixture was applied on the right forearm of each subject. The functional parameters of the skin barrier were compared before and after the treatment. Epidermal differentiation markers, hyaluronic acid synthase 3 (HAS3), cytokine levels, and the lipid profiles in the SC were analyzed. RESULTS: The functional parameters of the skin barrier, such as barrier recovery rate, SC integrity, and SC hydration were significantly improved in the test cream-applied site compared to the vehicle cream-applied sites. Filaggrin and HAS3 levels were significantly higher in the sites applied with the test cream. Interleukin (IL)-1α levels were also significantly increased in these sites. IL-2, IL-6, IL-10, and IL-13 levels were significantly decreased in the test cream-applied sites. Lipid analyses showed that C18, C20, and total ceramide NP levels significantly increased in the sites where the test cream was applied. Also, C16, C18, C20, C24, and total ceramide NP levels were significantly elevated in the test cream-applied sites after acute barrier disruption. CONCLUSION: Our results demonstrate that a lipid mixture enriched by CER (NP)* could recover the barrier function impaired by topical corticosteroid.

Analysis of PET parameters predicting response to radiotherapy for myeloid sarcoma.

PURPOSE: Positron-emission tomography (PET)-CT has recently been used for diagnostic imaging and radiotherapy for myeloid sarcoma, but there is little research on predicting the response of radiotherapy. The aim of this study was to analyze the association between PET-CT variables and the response to radiotherapy in patients with myeloid sarcoma. MATERIALS AND METHODS: This study was conducted in myeloid sarcoma patients who received radiotherapy and PET-CT before and after radiotherapy. The response to radiotherapy was evaluated based on the European Organization for Research and Treatment of Cancer PET response criteria, and binary regression analysis was performed to assess the factors predicting reductions in the maximum standardized uptake value (SUVmax). RESULTS: Twenty-seven sites in 12 patients were included in the study. Complete metabolic responses were seen in 24 patients after radiotherapy, a partial metabolic response in one, and progressive metabolic disease in two patients. The prescribed dose of more than 3000 cGy10 was significantly greater in the treatment control group (P = 0.024). In binary logistic regression analysis predicting reductions in the SUVmax of more than 70% after radiotherapy, the pretreatment SUVmax (≥ 7.5) and further chemotherapy after radiotherapy showed significant differences in univariate and multivariate analyses. CONCLUSION: Good metabolic responses (complete or partial) to radiotherapy were achieved in 92.6% of the myeloid sarcoma patients. Radiation doses < 3000 cGy10 and increased SUVmax were related to treatment failure and high SUVmax before radiotherapy was a factor influencing SUVmax reduction. Further large-scale studies are needed.

Upfront radiosurgery plus targeted agents followed by active brain control using radiosurgery delays neurological death in non-small cell lung cancer with brain metastasis.

The role of radiosurgery has become further accentuated in the era of targeted agents (TA). Thus, the neurologic outcome of radiosurgery in brain metastasis (BM) of non-small cell lung cancer (NSCLC) was reviewed. We analyzed 135 patients with BM of NSCLC who were administered Cyberknife radiosurgery (CKRS) as either initial or salvage therapy. We evaluated local failure (LF), intracranial failure (IF), and neurological death (ND) due to BM. Primary outcome was neurological death-free survival (NDFS). Median follow-up was 16.2 months. Median CKRS dose of 22 Gy was administered to median 2 targets per patient. Among 99 deaths, 14 (14%) were ND. Upfront treatment for BM included CKRS alone in 85 patients (63%), CKRS + TA in 26 patients (19%), and WBRT in 24 patients (18%). No patients or tumor related factors were associated with ND. However, the type of upfront treatment for BM was significantly associated with ND [HR 0.07 (95% CI 0.01-0.57) for CKRS + TA, HR 0.56 (95% CI 0.19-1.68) for CKRS alone] compared with the WBRT group (P = 0.01). The 2-year NDFS rates for the CKRS + TA, CRKS alone, and WBRT groups were 94%, 87%, and 78%, respectively (P = 0.03). Upfront CKRS showed significantly higher 2-year LF-free survival rate (P < 0.01). IF rate was insignificantly lower in the WBRT group compared with CKRS group (P = 0.38). Upfront CKRS + TA was associated with the best neurological outcome with high NDFS. Active brain control by early delivery of radiosurgery could achieve better neurological outcome in NSCLC with BM.

SUVmax Predicts Disease Progression after Stereotactic Ablative Radiotherapy in Stage I Non-small Cell Lung Cancer.

PURPOSE: Fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) is gaining evidence as a predictive factor in non-small cell lung cancer (NSCLC). Stereotactic ablative radiotherapy (SABR) is the standard treatment in early-stage NSCLC when a patient is unsuitable for surgery. We performed a study to assess the prognostic clinical significance of PET-CT after SABR in early-stage NSCLC. MATERIALS AND METHODS: Seventy-six patients with stage I NSCLC treated with SABR were investigated. Total radiation dose ranged from 36 to 63 Gy in three to eight fractions depending on tumor location and size. Respiratory motion control was implemented at simulation and during treatment. PET-CT prior to SABR was performed in 66 patients (86.8%). RESULTS: Median follow-up time was 32 months (range, 5 to 142 months). Local control rate at 1, 2, and 5 years were 95.9%, 92.8%, and 86.7%, respectively. Overall survival (OS) at 1, 2, and 5 years were 91.0%, 71.3%, and 52.1% respectively. Cause-specific survival at 1, 2, and 5 years were 98.6%, 93.1%, and 84.3% respectively. Tumor size and pre-SABR maximal standardized uptake value (SUVmax) demonstrated statistical significance in the Kaplan-Meier survival analyses with log-rank test. In multivariate analyses pre-SABR SUVmax remained statistically significant in correlation to OS (p=0.024; hazard ratio [HR], 3.2; 95% confidence interval [CI], 1.2 to 8.8) and with marginal significance in regards to regional progression-free survival (p=0.059; HR, 32.5; 95% CI, 2.6 to 402.5). CONCLUSION: Pre-SABR SUVmax demonstrated a predictive power in statistical analyses. Tumors with SUVmax above 6 at diagnosis were associated with inferior outcomes.

SUVmax Predicts Disease Progression after Stereotactic Ablative Radiotherapy in Stage I Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Fluorodeoxyglucose positron emission tomography–computed tomography (PET-CT) is gaining evidence as a predictive factor in non-small cell lung cancer (NSCLC). Stereotactic ablative radiotherapy (SABR) is the standard treatment in early-stage NSCLC when a patient is unsuitable for surgery. We performed a study to assess the prognostic clinical significance of PET-CT after SABR in early-stage NSCLC. @*Materials and Methods@#Seventy-six patients with stage I NSCLC treated with SABR were investigated. Total radiation dose ranged from 36 to 63 Gy in three to eight fractions depending on tumor location and size. Respiratory motion control was implemented at simulation and during treatment. PET-CT prior to SABR was performed in 66 patients (86.8%). @*Results@#Median follow-up time was 32 months (range, 5 to 142 months). Local control rate at 1, 2, and 5 years were 95.9%, 92.8%, and 86.7%, respectively. Overall survival (OS) at 1, 2, and 5 years were 91.0%, 71.3%, and 52.1% respectively. Cause-specific survival at 1, 2, and 5 years were 98.6%, 93.1%, and 84.3% respectively. Tumor size and pre-SABR maximal standardized uptake value (SUVmax) demonstrated statistical significance in the Kaplan-Meier survival analyses with log-rank test. In multivariate analyses pre-SABR SUVmax remained statistically significant in correlation to OS (p=0.024; hazard ratio [HR], 3.2; 95% confidence interval [CI], 1.2 to 8.8) and with marginal significance in regards to regional progression-free survival (p=0.059; HR, 32.5; 95% CI, 2.6 to 402.5). @*Conclusion@#Pre-SABR SUVmax demonstrated a predictive power in statistical analyses. Tumors with SUVmax above 6 at diagnosis were associated with inferior outcomes.