Clinical utility of texture analysis of 18F-FDG PET/CT in patients with Stage I lung cancer treated with stereotactic body radiotherapy.

We evaluated the reproducibility and predictive value of texture parameters and existing parameters of 18F-FDG PET/CT images in Stage I non-small-cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT). Twenty-six patients with Stage I NSCLC (T1-2N0M0) were retrospectively analyzed. All of the patients underwent an 18F-FDG PET/CT scan before treatment and were treated with SBRT. Each tumor was delineated using PET Edge (MIM Software Inc., Cleveland, OH), and texture parameters were calculated using open-source code CGITA. From 18F-FDG PET/CT images, three conventional parameters, including maximum standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), and four texture parameters, including entropy and dissimilarity (derived from a co-occurrence matrix) and high-intensity large-area emphasis (HILAE) and zone percentage (derived from a size-zone matrix) were analyzed. Reproducibility was evaluated using two independent delineations conducted by two observers. The ability to predict local control (LC), progression-free survival (PFS) and overall survival (OS) was tested for each parameter. All of the seven parameters except zone percentage showed good reproducibility, with intraclass correlation coefficient values >0.8. In univariate analysis, only HILAE was a significant predictor for LC. Histology, dose fractionation, and maximum SUV were associated with PFS, and histology and dose fractionation were associated with OS. We showed that texture parameters derived from 18F-FDG PET/CT were reproducible and potentially beneficial for predicting LC in Stage I lung cancer patients treated with SBRT.

Formula corrected maximal standardized uptake value in FDG-PET for partial volume effect and motion artifact is not a prognostic factor in stage I non-small cell lung cancer treated with stereotactic body radiotherapy.

OBJECTIVE: It is known that the partial volume effect and respiratory motion blur affect quantitative parameters such as the maximum standardized uptake value (SUVmax) in FDG-PET, especially in small lesions. The purpose of this study was to assess the prognostic value of corrected SUVmax, which was corrected SUVmax for the partial volume effect and respiratory motion blur, in patients with stage I non-small cell lung cancer (NSCLC) after treatment with stereotactic body radiotherapy (SBRT). METHODS: Fifty-one patients who were treated with SBRT between 2005 and 2011 in our institute were enrolled. The median tumor diameter was 2.2 cm (range 0.9-3.9 cm). The prescribed dose was typically 48 Gy in 4 fractions, 60 Gy in 8 fractions or 60 Gy in 15 fractions to the isocenter of irradiation fields. Each raw SUVmax was corrected using the recently proposed formula, and the correlations of raw SUVmax and corrected SUVmax with local control rate (LCR) were analyzed retrospectively. RESULTS: Median raw SUVmax before SBRT was 6.4 (range 0.6-22.8). Median corrected SUVmax was 8.0 (range 0.8-22.8), which was significantly increased (p < 0.01). The median follow-up period for survivors was 45.3 months (range 18.5-82.0 months). The 3-year LCR and overall survival rates were 81.8 and 65.2 %, respectively. In univariate analysis, raw SUVmax [per 1 increase; p = 0.02, hazard ratio (HR) 1.20, 95 % confidence interval (CI) 1.03-1.42] was significantly correlated with LCR, but corrected SUVmax did not show a significant correlation with LCR (per 1 increase; p = 0.15, HR 1.07, 95 % CI 0.96-1.19). Other factors significantly correlated with LCR were diagnosis (pathological diagnosis vs. clinical diagnosis; p = 0.04, HR 6.17, 95 % CI 1.08-116) and tumor diameter (per 1 mm increase; p < 0.01, HR 1.33, 95 % CI 1.15-1.61). CONCLUSIONS: Tumor diameter was the most significant predictor of LCR after SBRT. Correction for the partial volume effect and respiratory motion blur may weaken the prognostic value of SUVmax.

Impact of tumor attachment to the pleura measured by a pretreatment CT image on outcome of stage I NSCLC treated with stereotactic body radiotherapy.

BACKGROUND: Pleural invasion status is known to be a predictor of survival after pulmonary resection for non-small cell lung cancer. Our goal was to determine whether the length of tumor attachment to the pleura on a pretreatment CT image has prognostic value as an alternative to pleural invasion status for stage I non-small cell lung cancer treated with stereotactic body radiotherapy (SBRT). METHODS: A total of 90 tumors in 87 patients (males: 68, females: 19) who received SBRT between March 2005 and September 2011 in our institution were reviewed. The median age of the patients was 78 years (range, 48-90 years). The median tumor diameter was 2.2 cm (range, 0.9-4.2 cm). The prescribed dose was typically 48 Gy in 4 fractions, 60 Gy in 8 fractions or 60 Gy in 15 fractions to the isocenter with 6 MV X-ray using 4 non-coplanar and 3 coplanar static beams. The lengths of attachment were measured using pretreatment CT images at the lung window. Cumulative incidence rates were calculated using Kaplan-Meier curves, and univariate and multivariate analyses for in-field tumor control, locoregional control (LRC), freedom from distant metastasis and freedom from progression (FFP) were performed using a Cox proportional hazards model. RESULTS: Of the 90 tumors, 42 tumors were attached to the pleura (median, 14.7 mm; range, 4.3-36.0 mm), 21 tumors had pleural indentation and 27 tumors had no attachment. The median follow-up period for survivors was 46.1 months. The 3-year in-field control, LRC, FFP and overall survival rates were 91.2%, 75.3%, 63.8% and 68.6%, respectively. SBRT dose and tumor diameter were independently significant predictors of in-field control (p = 0.02 and p = 0.04, respectively). Broad attachment to the pleura, the length being more than 14.7 mm, was a negative independent predictor of LRC and FFP (p = 0.02 and p = 0.01, respectively). CONCLUSIONS: Pleural attachment status on a pretreatment CT image might be an important predictor of LRC and FFP.

Outcomes after stereotactic body radiotherapy for lung tumors, with emphasis on comparison of primary lung cancer and metastatic lung tumors.

BACKGROUND: The goal of this study was to determine the prognostic factors associated with an improved overall outcome after stereotactic body radiotherapy (SBRT) for primary lung cancer and metastatic lung tumors. METHODS: A total of 229 lung tumors in 201 patients were included in the study. SBRT of 45 Gy in 3 fractions, 48 Gy in 4 fractions, 60 Gy in 8 fractions or 60 Gy in 15 fractions was typically used to treat 172 primary lungs cancer in 164 patients and 57 metastatic lung tumors in 37 patients between January 2001 and December 2011. Prognostic factors for local control (LC) and overall survival (OS) were analyzed using a Cox proportional hazards model. RESULTS: The median biologically effective dose was 105.6 Gy based on alpha/beta = 10 (BED10). The median follow-up period was 41.9 months. The 3-year LC and OS rates were 72.5% and 60.9%, and the 5-year LC and OS rates were 67.8% and 38.1%, respectively. Radiation pneumonitis of grades 2, 3 and 5 occurred in 22 patients, 6 patients and 1 patient, respectively. Multivariate analyses revealed that tumor origin (primary lung cancer or metastatic lung tumor, p < 0.001), tumor diameter (p = 0.005), BED10 (p = 0.029) and date of treatment (p = 0.011) were significant independent predictors for LC and that gender (p = 0.012), tumor origin (p = 0.001) and tumor diameter (p < 0.001) were significant independent predictors for OS. CONCLUSIONS: SBRT resulted in good LC and tolerable treatment-related toxicities. Tumor origin and tumor diameter are significant independent predictors for both overall survival and local control.

Long-term results of radiotherapy combined with nedaplatin and 5-fluorouracil for postoperative loco-regional recurrent esophageal cancer: update on a phase II study.

BACKGROUND: In 2006, we reported the effectiveness of chemoradiotherapy for postoperative recurrent esophageal cancer with a median observation period of 18 months. The purpose of the present study was to update the results of radiotherapy combined with nedaplatin and 5-fluorouracil (5-FU) for postoperative loco-regional recurrent esophageal cancer. METHODS: Between 2000 and 2004, we performed a phase II study on treatment of postoperative loco-regional recurrent esophageal cancer with radiotherapy (60 Gy/30 fractions/6 weeks) combined with chemotherapy consisting of two cycles of nedaplatin (70 mg/m2/2 h) and 5-FU (500 mg/m2/24 h for 5 days).The primary endpoint was overall survival rate, and the secondary endpoints were progression-free survival rate, irradiated-field control rate and chronic toxicity. RESULTS: A total of 30 patients were enrolled in this study. The regimen was completed in 76.7% of the patients. The median observation period for survivors was 72.0 months. The 5-year overall survival rate was 27.0% with a median survival period of 21.0 months. The 5-year progression-free survival rate and irradiated-field control rate were 25.1% and 71.5%, respectively. Grade 3 or higher late toxicity was observed in only one patient. Two long-term survivors had gastric tube cancer more than 5 years after chemoradiotherapy.Pretreatment performance status, pattern of recurrence (worse for patients with anastomotic recurrence) and number of recurrent lesions (worse for patients with multiple recurrent lesions) were statistically significant prognostic factors for overall survival. CONCLUSIONS: Radiotherapy combined with nedaplatin and 5-FU is a safe and effective salvage treatment for postoperative loco-regional recurrent esophageal cancer. However, the prognosis of patients with multiple regional recurrence or anastomotic recurrence is very poor.

Prognostic factors for local control of stage I non-small cell lung cancer in stereotactic radiotherapy: a retrospective analysis.

BACKGROUND: The purpose of this study is to investigate the prognostic factors of stereotactic radiotherapy for stage I NSCLC to improve outcomes. METHODS: Stage I non-small cell lung cancer patients who were treated with stereotactic radiotherapy between 2005 and 2009 at our hospital were enrolled in this study. The primary endpoint was local control rate. Survival estimates were calculated from the completion date of radiotherapy using the Kaplan-Meier method. The prognostic factors including patients' characteristics and dose-volume histogram parameters were evaluated using Cox's proportional hazard regression model. RESULTS: Eighty patients (81 lesions) treated with 3 dose levels, 48 Gy/4 fractions, 60 Gy/8 fractions and 60 Gy/15 fractions, were enrolled in this study. Median follow-up was 30.4 months (range, 0.3 - 78.5 months). A Cox regression model showed T factor (p = 0.013), biological effective dose calculated from prescribed dose (BED10) (p = 0.048), and minimum dose for PTV (p = 0.013) to be prognostic factors for local control. Three-year overall survival rate and local control rate were 89.9% (T1: 86.8%, T2: 100%) and 89.0% (T1: 97.9%; T2: 64.8%), respectively. When the 3-year local control rates were examined by prescribed doses, they were 100% for the dose per fraction of 48 Gy /4 fractions (105.6 Gy BED10), 82.1% for 60 Gy/8 fractions (105 Gy BED10), and 57.1% for 60 Gy/15 fractions (84 Gy BED10). The median value of the minimum dose for PTV (%) was 89.88 (%), and the 3-year local control rates were 100% in those with the minimum dose for PTV (%) ≥ 89.88% and 79.2% in those with the minimum dose for PTV (%) < 89.88%. CONCLUSIONS: Our results suggest that T factor, BED10, and minimum dose for PTV influence the local control rate. Local control rate can be improved by securing the minimum dose for PTV.

Treatment outcome of high-dose image-guided intensity-modulated radiotherapy using intra-prostate fiducial markers for localized prostate cancer at a single institute in Japan.

BACKGROUND: Several studies have confirmed the advantages of delivering high doses of external beam radiotherapy to achieve optimal tumor-control outcomes in patients with localized prostate cancer. We evaluated the medium-term treatment outcome after high-dose, image-guided intensity-modulated radiotherapy (IMRT) using intra-prostate fiducial markers for clinically localized prostate cancer. METHODS: In total, 141 patients with localized prostate cancer treated with image-guided IMRT (76 Gy in 13 patients and 80 Gy in 128 patients) between 2003 and 2008 were enrolled in this study. The patients were classified according to the National Comprehensive Cancer Network-defined risk groups. Thirty-six intermediate-risk patients and 105 high-risk patients were included. Androgen-deprivation therapy was performed in 124 patients (88%) for a median of 11 months (range: 2-88 months). Prostate-specific antigen (PSA) relapse was defined according to the Phoenix-definition (i.e., an absolute nadir plus 2 ng/ml dated at the call). The 5-year actuarial PSA relapse-free survival, the 5-year distant metastasis-free survival, the 5-year cause-specific survival (CSS), the 5-year overall survival (OS) outcomes and the acute and late toxicities were analyzed. The toxicity data were scored according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up was 60 months. RESULTS: The 5-year PSA relapse-free survival rates were 100% for the intermediate-risk patients and 82.2% for the high-risk patients; the 5-year actuarial distant metastasis-free survival rates were 100% and 95% for the intermediate- and high-risk patients, respectively; the 5-year CSS rates were 100% for both patient subsets; and the 5-year OS rates were 100% and 91.7% for the intermediate- and high-risk patients, respectively. The Gleason score (<8 vs. ≥ 8) was significant for the 5-year PSA relapse-free survival on multivariate analysis (p = 0.044). There was no grade 3 or 4 acute toxicity. The incidence of grade 2 acute gastrointestinal (GI) and genitourinary (GU) toxicities were 1.4% and 8.5%, respectively. The 5-year actuarial likelihood of late grade 2-3 GI and GU toxicities were 6% and 6.3%, respectively. No grade 4 GI or GU late toxicity was observed. CONCLUSIONS: These medium-term results demonstrate a good tolerance of high-dose image-guided IMRT. However, further follow-up is needed to confirm the long-term treatment outcomes.

Adult human parvovirus-B19 infection presenting with hearing difficulty and dizziness.

Human parvovirus B19 (HPV-B19), a small and non-enveloped DNA virus, causes erythema infectiosum (EI) in children. In adults, however, it is known to cause a variety of symptoms. A 39-year-old woman visited our hospital because of low-grade fever, diarrhea, bilateral leg edema, and numbness in the right arm, one and a half months after her daughter developed EI. We diagnosed her as HPV-B19 infection after her daughter's history and positive test for serum HPV-B19 IgM antibody, together with the continued observations. Two weeks later, she developed dizziness and left hearing difficulty. However, we did not give her any medication. HPV-B19 IgM antibody value (2.4) measured after one month of the onset was decreased to 1.7, 1.1, and 0.9 after two, three, and five months of the onset, respectively. Thus, it took 5 months for the IgM antibody value to become negative. Her symptoms gradually improved along with the decrease in HPV-B19 antibody without any medication. Hearing difficulty and dizziness are not categorized as manifestations of HPV-B19 infection, because these symptoms are very rare. The present report indicates that the symptoms related to inner ear dysfunctions should be added to those associated with adult HPV-B19 infection. In conclusion, we should consider HPV-B19 infection when we evaluate patients with causeless hearing difficulty and dizziness.