Local control correlates with overall survival in radiotherapy for early-stage non-small cell lung cancer: A systematic review.

PURPOSE: Local control (LC) is an important outcome of local cancer therapy, besides overall survival (OS). We conducted a comprehensive literature search to investigate whether a high LC rate contributes to good OS in radiotherapy for early-stage non-small cell lung cancer (ES-NSCLC). MATERIALS AND METHODS: Studies in patients receiving radiotherapy for peripheral ES-NSCLC, mainly staged as T1-2N0M0 were included for a systematic review. Relevant information was collected including, dose fractionation, T stage, median age, 3-year LC, cancer-specific survival (CSS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and OS. Correlations between outcomes and clinical variables were evaluated. RESULTS: After screening, 101 data points from 87 studies including 13,435 patients were selected for the quantitative synthesis. Univariate meta-regression analysis revealed that the coefficients between the 3-year LC and 3-year DFS, DMFS, CSS, and OS were 0.753 (95% confidence interval (CI): 0.307-1.199; p < 0.001), 0.360 (95% CI: 0.128-0.593; p = 0.002), 0.766 (95% CI: 0.489-1.044; p < 0.001), and 0.574 (95% CI: 0.275-0.822; p < 0.001), respectively. Multivariate analysis revealed that the 3-year LC (coefficient, 0.561; 95% CI: 0.254-0.830; p < 0.001) and T1 proportion (coefficient, 0.207; 95% CI: 0.030-0.385; p = 0.012) were significantly associated with the 3-year OS and CSS (coefficient for 3-year LC, 0.720; 95% CI: 0.468-0.972; p < 0.001 and T1 proportion, 0.002; 95% CI: 0.000-0.003; p = 0.012). Toxicities ≥ grade 3 were low (3.4%). CONCLUSIONS: Three-year LC was correlated with three-year OS in patients receiving radiotherapy for ES-NSCLC. A 5% increase in 3-year LC is expected to improve the 3-year CSS and OS rates by 3.8% and 2.8%, respectively.

Relationship between Dose Prescription Methods and Local Control Rate in Stereotactic Body Radiotherapy for Early Stage Non-Small-Cell Lung Cancer: Systematic Review and Meta-Analysis.

Variations in dose prescription methods in stereotactic body radiotherapy (SBRT) for early stage non-small-cell lung cancer (ES-NSCLC) make it difficult to properly compare the outcomes of published studies. We conducted a comprehensive search of the published literature to summarize the outcomes by discerning the relationship between local control (LC) and dose prescription sites. We systematically searched PubMed to identify observational studies reporting LC after SBRT for peripheral ES-NSCLC. The correlations between LC and four types of biologically effective doses (BED) were evaluated, which were calculated from nominal, central, and peripheral prescription points and, from those, the average BED. To evaluate information on SBRT for peripheral ES-NSCLC, 188 studies were analyzed. The number of relevant articles increased over time. The use of an inhomogeneity correction was mentioned in less than half of the articles, even among the most recent. To evaluate the relationship between the four BEDs and LC, 33 studies were analyzed. Univariate meta-regression revealed that only the central BED significantly correlated with the 3-year LC of SBRT for ES-NSCLC (p = 0.03). As a limitation, tumor volume, which might affect the results of this study, could not be considered due to a lack of data. In conclusion, the central dose prescription is appropriate for evaluating the correlation between the dose and LC of SBRT for ES-NSCLC. The standardization of SBRT dose prescriptions is desirable.

Feasibility of marker-less stereotactic body radiotherapy for hepatocellular carcinoma.

BACKGROUND: The feasibility of marker-less stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) has not yet been established, and, thus, was examined in the present study. MATERIAL AND METHODS: We retrospectively investigated patients who received marker-less SBRT for locally untreated HCC tumors between July 2005 and December 2018. Radiotherapy planning CT was performed under fixation with vacuum cushions and abdominal compression. The clinical target volume (CTV) was equivalent to the gross tumor volume (GTV). The internal target volume (ITV) margin to CTV was determined from calculations based on the motion of the diaphragm. The planning target volume (PTV) margin to ITV was 5-6 mm. In the set-up, radiotherapy planning CT and linac-integrated cone-beam CT performed in the same imaging and fixation settings were merged by referring to the anatomical components surrounding target tumors. The primary endpoint was the 3-year cumulative local tumor progression rate. The upper limit of the 95% confidence interval for the 3-year cumulative local tumor progression rate was less than 7.0%, which was interpreted as favorable local control and feasible for marker-less SBRT. Local tumor progression was assessed by mRECIST. RESULTS: We reviewed 180 patients treated with 35-40 Gy/5 fractions. The median follow-up time for the local tumor progression of censored tumors was 32.3 months (range, 0.3-104). The 3-year cumulative local tumor progression rate was 3.0% (95% CI, 1.1-6.5%). The 3-year overall survival rate was 71.6% (95% CI, 63.5-78.2%). Regarding acute hematologic toxicities, grade 3 hypoalbuminemia and thrombocytopenia were detected in 1 (0.6%) and 5 (2.9%) patients, respectively. Treatment-related death from SBRT was not observed. SBRT was initiated within 7 days after radiotherapy planning CT for 84% (152/180) of patients. CONCLUSIONS: Marker-less SBRT for HCC achieved favorable local control that fulfilled the threshold. This result suggests that marker-less SBRT with appropriate settings is a feasible treatment strategy.

Stereotactic Body Radiation Therapy With a High Maximum Dose Improves Local Control, Cancer-Specific Death, and Overall Survival in Peripheral Early-Stage Non-Small Cell Lung Cancer.

PURPOSE: We investigated whether delivery of a high biologically effective dose (BED) to primary tumors affects systemic outcomes of cancer-specific death (CSD) and overall survival (OS) rates after stereotactic body radiation therapy (SBRT) in patients with early-stage non-small cell lung cancer (ES-NSCLC). METHODS AND MATERIALS: Among consecutive ES-NSCLC patients treated with SBRT between 2005 and 2019, we retrospectively identified patients who received a prescription of 50 to 60 Gy in 5 fractions with maximum doses of 62.5 to 100 Gy. Patients were categorized by maximum BED within the planning target volume with a threshold dose of 200 Gy. Outcomes were analyzed in all and matched patients. RESULTS: Overall, 433 patients were eligible, and 262 and 171 patients were categorized into HighBED and LowBED groups, respectively. After propensity score matching, pairs of 154 patients were selected. Median follow-up times for the HighBED and LowBED groups were 52.3 months (range, 0.8-107.2 months) and 121.6 months (range, 3.0-162.8 months), respectively. The local recurrence rate in the HighBED group was significantly lower than that in the LowBED group (5-year rate, 1.3% and 7.2%; hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.03-0.65; P = .011). Rates of any recurrence and CSD in the HighBED group were significantly lower (5-year any recurrence: 18.1% and 32.1%; HR, 0.52; 95% CI, 0.33-0.83; P = .0058; 5-year CSD: 9.5% and 21.8%; HR, 0.38; 95% CI, 0.20-0.70; P = .002), and OS in the HighBED group was significantly better compared with the LowBED group (5-year rate: 61.7% and 51.8%; HR, 0.71; 95% CI, 0.50-1.00; P = .047). CONCLUSION: In patients with peripheral ES-NSCLC, SBRT with a high maximum dose may improve not only local control, but also any recurrence, CSD, and OS rates without increased toxicity. Further trials designed to evaluate whether higher intensity SBRT increases local control rates and contributes to improved CSD and OS outcomes are anticipated.

Local control by salvage stereotactic body radiotherapy for recurrent/residual hepatocellular carcinoma after other local therapies.

Background: To clarify local control by salvage stereotactic body radiotherapy (SBRT) for recurrent/residual hepatocellular carcinoma (HCC) compared with initial definitive SBRT for local treatment-naïve HCC.Material and methods: We retrospectively investigated HCC patients that received SBRT between July 2005 and December 2017. We classified HCC tumors as the initial definitive SBRT group (Arm-1; initial definitive SBRT, Arm-2; initial definitive planned SBRT following transarterial chemoembolization (TACE)) and salvage SBRT group (Arm-3; salvage SBRT for recurrent/residual tumors after TACE, Arm-4; salvage SBRT for recurrent/residual tumors after radiofrequency ablation (RFA), Arm-5; salvage SBRT for recurrent/residual other than Arm-3 or Arm-4). Local control was evaluated by mRECIST.Results: We reviewed 389 HCC tumors of 323 patients treated by 35-40 Gy/5 fr. The median follow-up time for local recurrence of tumors was 34.8 months (range, 6.5-99.2). The cumulative local recurrence rates at 3 years of Arm-1-5 were 1.4% (95% CI, 0.3-4.4%), 5.0% (95% CI, 1.6-11.5%), 12.4% (95% CI, 5.7-21.9%), 14.8% (95% CI, 3.3-34.3%) and 7.3% (95% CI, 1.9-18.0%), respectively. The cumulative local recurrence rates at 3 years of initial definitive treatment and salvage treatment groups were 2.8% (95% CI, 1.1-5.6%) and 11.1% (95% CI, 6.3-17.3%), respectively (p=.004). On multivariate analysis, salvage treatment and the tumor diameter were significant risk factors of local recurrence (p = .02, p < .001 respectively). Estimated overall survival at 3 years for all patients in initial definitive treatment and salvage treatment groups were 71.5% (95% CI, 63.4-78.1%) and 66.1% (95% CI, 56.4-74.2%), respectively (p = .20). No treatment-related death caused by SBRT was observed.Conclusions: This analysis showed local control of salvage SBRT for recurrent/residual HCC was significantly worse than that of initial definitive SBRT for local treatment-naïve HCC. However, local control of salvage SBRT was relatively good, and salvage SBRT is one of the favorable treatment options for recurrent/residual HCC.

Frequency and predictors of detecting early locoregional recurrence/disease progression of oral squamous cell carcinoma with high-risk factors on imaging tests before postoperative adjuvant radiotherapy.

BACKGROUND: To clarify the frequency and predictors of detecting early locoregional recurrence/disease progression (LR/DP) during the interval between surgery and postoperative adjuvant radiotherapy with/without chemotherapy in patients with oral squamous cell carcinoma. METHODS: Data on 65 patients who had undergone the initial radical surgery for previously untreated oral squamous cell carcinoma which were scheduled to receive adjuvant radiotherapy with/without chemotherapy were reviewed. RESULTS: Of the 65 patients, 63 (97%) were margin-positive/close and/or extracapsular extension-positive (hereinafter, high-risk factors). Eighteen (28%) patients had abnormal findings suggestive of LR/DP on postoperative imaging. Fifteen (23%) patients were diagnosed with LR/DP and treatment policy was changed. Univariate and multivariate analyses revealed higher frequencies of abnormal findings suggestive of LR/DP (univariate/multivariate analysis, p = 0.020/0.036), diagnosing of LR/DP, and changing the treatment policy (univariate/multivariate analysis, p = 0.042/0.046), among the patients who underwent postoperative diagnostic imaging tests or radiotherapy-planning contrast-enhanced (CE) CT without diagnostic imaging tests as compared with those who underwent radiotherapy-planning non-CECT without such tests. CONCLUSION: The frequency of detecting of early LR/DP before postoperative adjuvant treatment in oral squamous cell carcinoma patients with high-risk factors was high. Furthermore, postoperative diagnostic imaging tests and radiotherapy-planning CECT may be useful to detect early LR/DP in oral squamous cell carcinoma patients before postoperative adjuvant therapy.

Pleural contact decreases survival in clinical T1N0M0 lung cancer patients undergoing SBRT.

BACKGROUND: Clinical staging, as used for patients treated with stereotactic body radiotherapy (SBRT) for early-stage lung cancer, inadequately accounts for pleural invasion, which is a pathologic criteria. Considering the current situation, we analyzed effects of relationships between tumors and the pleura on treatment outcomes of SBRT for early-stage lung cancer. MATERIALS AND METHODS: Among consecutive patients treated with SBRT between 2006 and 2017, we retrospectively identified non-small cell lung cancer patients with primary tumor diameters ≤4 cm and N0M0. The relationships between tumors and the pleura were investigated. The effects of these findings on treatment outcomes were analyzed. RESULTS: We identified 386 patients which met the inclusion criteria. Among these patients, 323 patients were with tumors of 0.1-3.0 cm (T1-size), and 63 patients were with tumors of 3.1-4.0 cm (T2a-size). Among patients with T1-size tumors, 120, 134, and 23 had findings of pleural contact, pleural indentation, and pleural thickening, respectively. When we divided T1-size patients into 2 groups based on pleural contact (contact- or contact+), the 3-year cause-specific mortality and overall survival in patients with T1-size & contact+ were significantly worse than those in patients with T1-size & contact- (17.6% (95% confidence interval (CI), 10.7-25.9%) vs. 6.6% (95% CI, 3.5-11.1%), p < 0.01), and 58.2% (95% CI, 47.6-67.5%) vs. 77.6% (95% CI, 70.5-83.2%), p < 0.01). Local recurrence, regional recurrence, pleural cavity recurrence, and distant metastasis were associated with worse cause-specific mortality and overall survival. On multivariate analysis, pleural contact was associated with cause-specific mortality (hazard ratio (HR), 1.96; 95% CI, 1.09-3.52; p = 0.03) and overall survival (HR, 1.59; 95% CI, 1.08-2.34; p = 0.02). CONCLUSION: Pleural contact in clinical T1N0M0 lung cancer patients was associated with significantly worse survivals.

Late radiological changes after passive scattering proton beam therapy for Stage I lung cancer.

This study aimed to examine late radiological changes after proton beam therapy (PBT) for early-stage non-small cell lung cancer (NSCLC) and to clarify correlations between mass-like radiological changes and patient characteristics. CT scans of patients who underwent passive scattering PBT for T1-2N0M0 NSCLC were analyzed retrospectively. Patients were considered eligible if follow-up CT was performed for at least 2 years, with no definite evidence of local recurrence. The following five periods were defined: (i) 6-12 months, (ii) 12-24 months, (iii) 24-36 months, (iv) 36-48 months and (v) 48-60 months after PBT. Late (≥6 months) radiological changes were scored by consensus of three radiation oncologists according to classifications set forth by Koenig (Radiation injury of the lung after three-dimensional conformal radiation therapy. AJR Am J Roentgenol 2002;178:1383-8.). CT scans of 113 patients (median follow-up, 36 months; range, 24-137 months) were evaluated. Late radiological changes during Periods (i), (ii), (iii), (iv) and (v) included modified conventional pattern (80%, 79%, 72%, 58% and 56%, respectively), mass-like changes (8%, 9%, 14%, 22% and 18%, respectively), scar-like changes (4%, 9%, 11%, 17% and 24%, respectively) and no increased density (8%, 3%, 3%, 2% and 2%, respectively). Mass-like changes were observed in 23 patients (20%). Among patients who developed mass-like changes, the median interval between the initiation of PBT and the onset of mass-like changes was 19 months (range, 6-62 months). In multivariate analysis, a peripheral location was found to be a significant factor (P = 0.035; odds ratio: 4.44; 95% confidence interval: 1.12-21.28). In conclusion, mass-like changes were observed in 20% of patients who underwent PBT. Patients with peripheral tumors showed a higher incidence of mass-like changes.

Post-mastectomy radiation therapy without usage of a bolus may be a reasonable option.

To clarify the efficacy and toxicity of post-mastectomy radiation therapy (PMRT) without usage of a bolus, we identified 129 consecutive patients who received PMRT at the National Cancer Center Hospital East between 2003 and 2012. Seven of the 129 patients who received breast reconstruction before PMRT were excluded. All patients received PMRT of 6 MV photons, without usage of a bolus. The median follow-up duration for all eligible patients was 47.7 months (range: 4.0-123.2). Local, locoregional and isolated locoregional recurrence was found in 12 (9.8%), 14 (11%) and 5 patients (4.1%), respectively. The 3- and 5-year cumulative incidence of local recurrence, locoregional recurrence and isolated locoregional recurrence was 9.2 and 10.7%, 10.8 and 12.4%, and 4.3 and 4.3%, respectively. Although Grade 2 dermatitis was found in 11 patients (9.0%), no Grade 3-4 dermatitis was found. On univariate analysis, only a non-luminal subtype was a significant predictor for local recurrence (P < 0.001). On multivariate analysis, a non-luminal subtype remained as an independent predictor for local recurrence (P = 0.003, odds ratio: 10.9, 95% confidence interval: 2.23-53.1). In conclusion, PMRT without usage of a bolus resulted in a low rate of severe acute dermatitis without an apparent increase in local recurrence. PMRT without usage of a bolus may be reasonable, especially for patients with a luminal subtype.