Dosimetric Analysis of a Phase I Study of PSMA-Targeting Radiopharmaceutical Therapy With 177 LuLudotadipep in Patients With Metastatic Castration-Resistant Prostate Cancer

Objective@#177 Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [ 177 Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC). @*Materials and Methods@#Data from 25 patients (median age, 73 years; range, 60–90) with mCRPC from a phase I study with activity escalation design of single administration of [ 177 Lu]Ludotadipep (1.85, 2.78, 3.70, 4.63, and 5.55 GBq) were assessed. Activity in the salivary glands, lungs, liver, kidneys, and spleen was estimated from whole-body scan and abdominal SPECT/CT images acquired at 2, 24, 48, 72, and 168 h after administration of [ 177 Lu]Ludotadipep. Red marrow activity was calculated from blood samples obtained at 3, 10, 30, 60, and 180 min, and at 24, 48, and 72 h after administration. Organand tumor-based absorbed dose calculations were performed using IDAC-Dose 2.1. @*Results@#Absorbed dose coefficient (mean ± standard deviation) of normal organs was 1.17 ± 0.81 Gy/GBq for salivary glands, 0.05 ± 0.02 Gy/GBq for lungs, 0.14 ± 0.06 Gy/GBq for liver, 0.77 ± 0.28 Gy/GBq for kidneys, 0.12 ± 0.06 Gy/GBq for spleen, and 0.07 ± 0.02 Gy/GBq for red marrow. The absorbed dose coefficient of the tumors was 10.43 ± 7.77 Gy/GBq. @*Conclusion@#[ 177 Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical trial with kidneys and bone marrow being the critical organs, and shows a high tumor absorbed dose.

One Versus Up‑to‑5 Lesion Measurements for Response Assessment by PERCIST in Patients with Lung Cancer / 대한핵의학회잡지

Purpose@#The optimal number of lesions to measure for response assessment from fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) is not validated for lung cancer. We compared 1 lesion and up-to-5 lesion measurements for response assessment in lung cancer per PET Response Criteria in Solid Tumors (PERCIST). @*Methods@#Patients with lung cancer with pre- and post-treatment PET/CT images were included. The standard uptake value corrected for lean body mass (SULpeak) of up-to-5 hottest target lesions was measured at each time point. The percent changes of ­SULpeak of the single hottest lesion and the sum of up-to-5 hottest lesions were computed. Pearson correlation coefficient evaluated the strength of association between the percent changes of ­SUL peak values from the 1 lesion and up-to-5 lesion analyses. Response categories were complete metabolic response (CMR) with no perceptible lesion; partial metabolic response (PMR), stable metabolic disease (SMD), or progressive metabolic disease (PMD) using the threshold of 30% and 0.8 unit change in ­SULpeak ; and unequivocal new lesion meant PMD. The concordance for response categorization was assessed by kappa statistics. @*Results@#A total of 40 patients (25 non-small cell lung cancer; 15 small cell lung cancer) were analyzed, all with 18F-FDGavid lung cancer. Average of 3 target lesions were measured for up-to-5 lesion analysis. Pearson’s r was 0.74 (P < 0.001) and increased to 0.96 (P < 0.001) when two outliers were excluded. Response categorization with 1 lesion and up-to-5 lesion analyses was concordant in 37 patients (92.5%, weighted kappa = 0.89). @*Conclusion@#Analyzing 1 lesion and up-to-5 lesions for response assessment by PERCIST showed high concordance in patients with lung cancer.

Bone SPECT/CT of the Foot and Ankle: Potential Clinical Application for Chronic Foot Pain / 대한핵의학회잡지

Diseases of the foot and ankle are common but relatively difficult to diagnose because of the complexity of the anatomy and the frequent occurrence of multiple diseases at the same time. For these reasons, management of chronic foot pain is often clinically challenging. MRI is the imaging modality of choice in many types of diseases causing chronic foot pain, due to high resolution and excellent soft tissue contrast. However, in the postoperative state, the use of MRI can be limited by artifact from metallic devices, and it may be difficult to confirm whether the pathology detected on the MRI is the actual cause of the pain. As bone scintigraphy provides metabolic information, it can help to find the origin of pain, and SPECT/CT can further improve the specificity by adding anatomical information. In daily clinical practice for management of foot and ankle pathologies, the use of bone SPECT/CT is gradually increasing. However, there has been limited evidence of usefulness of SPECT/CT in evaluating chronic foot pain. In this review article, the potential application of bone SPECT/CT for chronic foot pain is illustrated, and the role of SPECT/CT in the management of the foot and ankle diseases in clinical practice is described.

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.

Predictive Value of Interim and End-of-Therapy 18F-FDG PET/CT in Patients with Follicular Lymphoma / 대한핵의학회잡지

PURPOSE@#¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is the standard imaging modality for response evaluation in FDG-avid lymphoma, but the prognostic value is not established in follicular lymphoma (FL). This study investigated the prognostic value of Deauville 5-point scale (D5PS) from paired interim PET/CT (PET(Interim)) and end-of-induction therapy PET/CT (PET(EOI)) in patients with FL.@*METHODS@#FL staging and response assessment PET/CT images from 2013 to 2015 were retrospectively reviewed. PET(Interim) was performed 3 or 4 cycles after chemotherapy and PET(EOI) after 6 or 8 cycles. D5PS scores of 1, 2, and 3 were considered as negative (−), and scores 4 and 5 were considered as positive (+). Statistical analysis was done using Cox regression analysis, Kaplan-Meier survival analysis, and the log-rank test.@*RESULTS@#Thirty-three patients with set of baseline, interim, and end-of-induction therapy PET/CTstudies were included. Ten patients (30.3%) had progression. The median progression-free survival (PFS) was 38.8 months (range 3.5–72.7 months). On PET(Interim), 23 patients were negative and 10 were positive. On PET(EOI) scans, 29 patients were negative, and 4 were positive. On multivariate analysis, PET(EOI)(−) was associated with longer PFS. PET(Interim)(+) and PET(EOI)(+) patients had a significantly shorter PFS than PET(Interim)(−) patients (39.9 months, 95%confidence interval [CI] 23.0–56.9, versus 55.5months, 95%CI 49.7–61.2, p=0.005) and PET(EOI)(−) patients (14.2 months, 95% CI 8.5–19.8, versus 60.5 months, 95% CI 52.1–69.0, p<0.001).@*CONCLUSION@#For patients with FL, PET(Interim) and PET(EOI) response is predictive of PFS, and PET(EOI)(+) is an independent prognostic factor for progression of FL.

Predictive Value of Interim and End-of-Therapy 18F-FDG PET/CT in Patients with Follicular Lymphoma / 대한핵의학회잡지

PURPOSE: ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is the standard imaging modality for response evaluation in FDG-avid lymphoma, but the prognostic value is not established in follicular lymphoma (FL). This study investigated the prognostic value of Deauville 5-point scale (D5PS) from paired interim PET/CT (PET(Interim)) and end-of-induction therapy PET/CT (PET(EOI)) in patients with FL.METHODS: FL staging and response assessment PET/CT images from 2013 to 2015 were retrospectively reviewed. PET(Interim) was performed 3 or 4 cycles after chemotherapy and PET(EOI) after 6 or 8 cycles. D5PS scores of 1, 2, and 3 were considered as negative (−), and scores 4 and 5 were considered as positive (+). Statistical analysis was done using Cox regression analysis, Kaplan-Meier survival analysis, and the log-rank test.RESULTS: Thirty-three patients with set of baseline, interim, and end-of-induction therapy PET/CTstudies were included. Ten patients (30.3%) had progression. The median progression-free survival (PFS) was 38.8 months (range 3.5–72.7 months). On PET(Interim), 23 patients were negative and 10 were positive. On PET(EOI) scans, 29 patients were negative, and 4 were positive. On multivariate analysis, PET(EOI)(−) was associated with longer PFS. PET(Interim)(+) and PET(EOI)(+) patients had a significantly shorter PFS than PET(Interim)(−) patients (39.9 months, 95%confidence interval [CI] 23.0–56.9, versus 55.5months, 95%CI 49.7–61.2, p=0.005) and PET(EOI)(−) patients (14.2 months, 95% CI 8.5–19.8, versus 60.5 months, 95% CI 52.1–69.0, p<0.001).CONCLUSION: For patients with FL, PET(Interim) and PET(EOI) response is predictive of PFS, and PET(EOI)(+) is an independent prognostic factor for progression of FL.

Radiation nephritis: (99m)Tc hydroxydiphosphonate bone scan, (99m)Tc dimercaptosuccinic acid renal scan, and ¹⁸F-FDG PET/CT findings

No abstract available.

Prognostic Value of Pre- and Post-Treatment FDG PET/CT Parameters in Small Cell Lung Cancer Patients / 대한핵의학회잡지

PURPOSE: To evaluate the prognostic value of PET parameters obtained from pre- and post-treatment FDG PET/CT examinations in patients with SCLC.METHODS: Fifty-nine patients with initially diagnosed SCLC from 2009 to 2014 were included and had chemotherapy and/or concurrent chemoradiotherapy. FDG PET/CT examinations were performed before (PET1) and after (PET2) treatment to evaluate treatment response. A region of interest was placed over the primary lesion and metastatic lymph nodes within the thoracic cavity. PET parameters including change from PET1 to PET2 (Δ in %) were acquired: SUVmax, SUVpeak, MTV2.5, TLG, ΔSUVmax, ΔSUVpeak, ΔMTV and ΔTLG. Patient characteristics including staging, age, sex, LDH and response evaluation by RECIST were surveyed. Statistical analysis was done using Kaplan-Meier method and Cox regression analysis with respect to OS and PFS.RESULTS: The median follow-up was 9.6 months (2.5–80.5 months). 27 patients were LD and 32 were ED. Fortysix patients (78.0%) had died, and median OS was 8.6 months; 51 patients (86%) showed disease progression, and median PFS was 2.5 months. On univariate analysis, patients with ED, high interval change (ΔSUVmax and ΔSUVpeak) and low PET2 parameters showed longer OS and PFS. Multivariate analyses demonstrated that ΔSUVpeak (HR 2.6, P = 0.002) was an independent prognostic factors for OS, and MTV2.5 of PET2 (HR 2.8, P = 0.001), disease stage (HR 2.7, P = 0.003) and RECIST (HR 2.0, P = 0.023) were independent prognostic factors for PFS.CONCLUSIONS: Metabolic and volumetric PET parameters obtained from pre- and post-treatment FDG PET/CT examinations in patients with SCLC have significant prognostic information.

Prognostic Value of Pre- and Post-Treatment FDG PET/CT Parameters in Small Cell Lung Cancer Patients / 대한핵의학회잡지

PURPOSE@#To evaluate the prognostic value of PET parameters obtained from pre- and post-treatment FDG PET/CT examinations in patients with SCLC.@*METHODS@#Fifty-nine patients with initially diagnosed SCLC from 2009 to 2014 were included and had chemotherapy and/or concurrent chemoradiotherapy. FDG PET/CT examinations were performed before (PET1) and after (PET2) treatment to evaluate treatment response. A region of interest was placed over the primary lesion and metastatic lymph nodes within the thoracic cavity. PET parameters including change from PET1 to PET2 (Δ in %) were acquired: SUVmax, SUVpeak, MTV2.5, TLG, ΔSUVmax, ΔSUVpeak, ΔMTV and ΔTLG. Patient characteristics including staging, age, sex, LDH and response evaluation by RECIST were surveyed. Statistical analysis was done using Kaplan-Meier method and Cox regression analysis with respect to OS and PFS.@*RESULTS@#The median follow-up was 9.6 months (2.5–80.5 months). 27 patients were LD and 32 were ED. Fortysix patients (78.0%) had died, and median OS was 8.6 months; 51 patients (86%) showed disease progression, and median PFS was 2.5 months. On univariate analysis, patients with ED, high interval change (ΔSUVmax and ΔSUVpeak) and low PET2 parameters showed longer OS and PFS. Multivariate analyses demonstrated that ΔSUVpeak (HR 2.6, P = 0.002) was an independent prognostic factors for OS, and MTV2.5 of PET2 (HR 2.8, P = 0.001), disease stage (HR 2.7, P = 0.003) and RECIST (HR 2.0, P = 0.023) were independent prognostic factors for PFS.@*CONCLUSIONS@#Metabolic and volumetric PET parameters obtained from pre- and post-treatment FDG PET/CT examinations in patients with SCLC have significant prognostic information.

Prognostic Value of Baseline ¹⁸F-Fluorodeoxyglucose PET/CT in Patients with Multiple Myeloma: A Multicenter Cohort Study

OBJECTIVE: We investigated the prognostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with multiple myeloma (MM). MATERIALS AND METHODS: Subjects were 76 patients with newly diagnosed myeloma and pretreatment with 18F-FDG PET/CT from four hospitals. The PET/CT features were evaluated and the clinical characteristics were reviewed. Prognostic factors related to poor progression-free survival (PFS) and overall survival (OS) were identified using a Cox proportional hazards regression model and a prediction scale was developed based on the identified factors. RESULTS: Multivariate analysis showed that the presence of 18F-FDG-avid focal bone lesions (≥ 3) was a significant and independent predictor of PFS (hazard ratio [HR] = 3.28, p = 0.007) and OS (HR = 11.78, p = 0.001). The presence of extramedullary disease on PET/CT scan was also a significant predictor of poor PFS (HR = 2.79, p = 0.006) and OS (HR = 3.89, p = 0.003). A prognostic scale was developed using these two predictors. An increase in score on the scale corresponded to a significantly increased risk of poor OS (p = 0.005). In addition, Kaplan-Meier analysis demonstrated that patient survival varied significantly according to the scale (p < 0.001 for OS and p = 0.001 for PFS). CONCLUSION: 18F-FDG-avid focal lesions and the presence of extramedullary disease on PET/CT scan are significantly associated with poor OS in MM patients. The scale developed according to these predictors represents a potential prognostic tool for evaluation of patients with MM.

F-18 FDG PET Findings for Vogt-Koyanagi-Harada Disease / 대한핵의학회잡지

Vogt-Koyanagi-Harada disease is a rare multisystemic granulomatous autoimmune disorder affecting pigmented tissues such as the choroid, meninges, inner ear, and the skin. Neurologic symptoms are usually mild. Clinical manifestations include generalized muscle weakness, headache, meningismus, vertigo, decreased visual acuity, hearing loss and mental changes ranging from mild confusion to psychosis, hemiparesis, dysarthria, and aphasia. Seizures are very rare. We describe a case of ¹⁸F-fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET) and software-fused PET-magnetic resonance imaging (MRI) in Vogt-Koyanagi-Harada disease with seizure.

The Role of F-18 FDG PET/CT in Intrahepatic Cholangiocarcinoma / 대한핵의학회잡지

PURPOSE: The aim of this study was to evaluate the diagnostic and prognostic role of metabolic parameters of FDG PET/CT in patients with intrahepatic cholangiocarcinoma (ICC).METHODS: From December 2008 to December 2013, 76 FDG PET/CT scans performed for initial staging of ICC in a single institution (57 male and 19 female; mean age 68 ± 9 years) were retrospectively reviewed. Patients with history of other known malignancy were excluded. Detection rates of regional lymph node and distant metastasis by FDG PET/CT were analyzed in comparison with conventional imaging modalities such as CT or MRI. Metabolic parameters including maximum, peak and mean standardized uptake values (SUVmax, SUVpeak, SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), glucose corrected SUV (SUVgluc), and glucose corrected TLG (TLGgluc) were measured for the primary tumor. Cut-off values for the metabolic parameters were calculated by ROC curve analysis, and used to dichotomize the patient groups. The overall survival time (OS) was calculated and compared using the Cox proportional hazard regression analysis.RESULTS: The median duration of follow-up period was 5.4 months (interquartile range: 1.45~15.45). FDG PET/CT showed higher sensitivity than conventional imagingmodalities in detection of regional node involvement (74.5 % vs. 61.8 %, p = 0.013). In six patients, distant metastasis was identified only by FDG PET/CT. The mean SUVmax, SUVpeak, SUVmean, MTV, and TLG for the primary tumor were 8.2 ± 3.1, 6.8 ± 2.5, 4.0 ± 0.8, 192.7 ± 360.5 cm3, and 823.7 ± 1615.4, respectively. Patients with higher (≥7.3, HR: 4.280, p = 0.001), higher SUVpeak (≥6.5, HR: 2.333, p = 0.020), higher SUVmean (≥3.9, HR: 2.799, p = 0.004), higher SUVgluc (≥8.1, HR: 2.648, p = 0.012), and higher TLGgluc (≥431.6, HR: 2.186, p = 0.030) showed significantly shorter survival time. By multivariate study, operability was an independent prognostic factor for longer survival (HR: 4.113, p= 0.005).CONCLUSION: FDG PET/CT is an important diagnostic imaging tool in the nodal staging and detection of distant metastasis in ICC patients. Metabolic parameters may have a significant role as prognostic factors in patients with ICC.

Giant Cell Tumor of the Rib: Two Cases of F-18 FDG PET/CT Findings / 대한핵의학회잡지

We report two cases of giant cell tumor arising from the rib and their F-18 FDG PET/CT findings. The two patients complained of chest wall pain, and large lobulated soft tissue masses with intense FDG uptake were seen on F-18 FDG PET/CT. A malignant tumor such as osteosarcoma or chondrosarcoma was suspected due to the large size of the mass, bony destruction, and intense FDG uptake. En bloc resection was performed and final pathologic results revealed giant cell tumor of the rib. Giant cell tumor of the rib is very rare, and larger lesions with high FDG uptake can be misdiagnosed as an intrathoracic malignancy arising from the rib, pleura, or chest wall.

Multiple endocrine neoplasia type 1 with anterior mediastinal parathyroid adenoma: successful localization using Tc-99m sestamibi SPECT/CT

The most common manifestation of multiple endocrine neoplasia type 1 (MEN1) is hyperparathyroidism. Treatment of hyperparathyroidism in MEN patients is surgical removal of the parathyroid glands, however ectopic parathyroid gland is challenging for treatment. A 51-year-old female, the eldest of 3 MEN1 sisters, had hyperparathyroidism with ectopic parathyroid adenoma in the mediastinal para-aortic region, which was detected by technetium-99m (Tc-99m) sestamibi scintigraphy and single-photon emission computed tomography/computed tomography (SPECT/CT). She underwent total parathyroidectomy with video-assisted thoracoscopic surgery on an anterior mediastinal mass. Anterior mediastinal parathyroid adenoma in MEN1 patients is rare. Precise localization of an ectopic parathyroid gland with Tc-99m sestamibi SPECT/CT can lead to successful treatment of hyperparathyroidism. This is the first reported case in the literature of mediastinal parathyroid adenoma in MEN1 patient visualized by Tc-99m sestamibi SPECT/CT.

Predictors of Distant Metastasis after Radical Surgery Followed by Postoperative Radiotherapy with or without Chemotherapy for Oropharyngeal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We investigated the prognostic factors for distant metastasis (DM) in patients with locally advanced oropharyngeal cancer (OPC) treated with surgery and adjuvant radiotherapy with or without concurrent chemotherapy. MATERIALS AND METHODS: Eighty-five patients treated between January 1995 and August 2014 were evaluated retrospectively. Data regarding the pathological tumour and nodal status, human papillomavirus (HPV) status, treatment characteristics, and pretreatment maximum standardized uptake value (SUVmax) of 18-fluoro-2-deoxyglucose positron emission tomography–computed tomography scan (¹⁸F-FDG PET-CT) were evaluated, and their influence on DM and survival outcomes were analyzed. RESULTS: Median follow-up period was 48.0 months. Recurrence was observed in 20 patients, including locoregional recurrence and DM. DM was observed in 13 patients. A multivariate analysis confirmed that the presence of lymphovascular invasion (p=0.031), lower neck lymph node (LN) involvement (p=0.006), SUVmax ≥ 9.7 (p=0.014), and tumour size ≥ 3 cm (p=0.037) significantly affected DM. HPV status was not associated with DM. Perineural invasion (p=0.048), lower neck LNinvolvement (p=0.008), SUVmax ≥ 9.7 (p=0.019), and tumour size ≥ 3 cm (p=0.033) were also significant factors for the DM-free survival rate. CONCLUSION: Lower neck LN involvement, high SUVmax in pretreatment ¹⁸F-FDG PET-CT, and large tumour size were predictive factors for DM in patients of OPC.

Total Lesion Glycolysis Using 18F-FDG PET/CT as a Prognostic Factor for Locally Advanced Esophageal Cancer

Standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) have been considered prognostic factors for survival in many cancers. However, their prognostic value for radiotherapy-treated squamous esophageal cancer has not been evaluated. In this study, SUV, MTV, and TLG were measured to predict their prognostic role in overall survival (OS) in 38 esophageal cancer patients who had undergone 18F-FDG PET/CT before radiotherapy. TLG demonstrated higher sensitivity and specificity for predicting OS than MTV and SUV; and a better OS was observed in patients with low TLG compared to those with high TLG in locally advanced disease (OS, 46.9 months; 95% confidence interval [CI], 33.50-60.26 vs. 25.3 months; 95% CI, 8.37-42.28; P=0.003). Multivariate analyses in these patients determined that TLG and the use of combination chemotherapy were the independent prognostic factors for OS (hazard ratio [HR], 7.12; 95% CI, 2.038-24.857; P=0.002 and HR, 6.76; 95% CI, 2.149-21.248; P=0.001, respectively). These results suggest that TLG is an independent prognostic factor for OS and a better predictor of survival than MTV and SUV in patients with locally advanced esophageal cancer treated with radiotherapy.

Clinical Characteristics and Continued Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Administration in EGFR-mutated Non-Small Cell Lung Cancer with Skeletal Metastasis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study was to analyze clinical characteristics of skeletal metastasis in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) and treatment outcomes of continued EGFR tyrosine kinase inhibitor (TKI) therapy in patients presenting with skeletal metastasis progression. MATERIALS AND METHODS: Of the 216 patients treated with EGFR-TKI for management of stage III-IV NSCLC between 2006 and 2012 in Seoul St. Mary's Hospital, 76 patients with confirmed EGFR-mutated NSCLC with skeletal metastases during therapy were analyzed retrospectively. RESULTS: Of 76 patients with EGFR mutant lung cancer with skeletal metastasis, 37 patients developed first progressive disease (PD) in skeletal regions. EGFR-TKI was continued in these 37 patients after first PD in skeletal regions. Median time to first PD of skeletal regions was 8.9 months (95% confidence interval [CI], 4.8 to 13.0). Median time of continued EGFR-TKI after first PD of skeletal regions was 8.0 months (95% CI, 2.9 to 13.0) in patients with disease progression of preexisting regions, 5.6 months (95% CI, 4.5 to 6.7) in patients showing new localized regions, and 3.3 months (95% CI, 1.1 to 5.5) in patients with multiple new metastatic regions (p=0.006). Median time of postskeletal metastasis progression survival was 23.0 months (95% CI, 13.5 to 32.5), 15.0 months (95% CI, 3 to 34.7), and 7.0 months (95% CI, 6.0 to 8.0) (p=0.004) in the above described patient groups, respectively. Overall, seven patients (18.9%) had more than one episode of skeletal progression of disease without extraskeletal PD. CONCLUSION: Continued EGFR-TKI treatment with adequate local treatment after progression of skeletal metastasis may be considered for patients who show disease progression in preexisting regions or local progression.

Interstitial Lung Change in Pre-radiation Therapy Computed Tomography Is a Risk Factor for Severe Radiation Pneumonitis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We examined clinical and dosimetric factors as predictors of symptomatic radiation pneumonitis (RP) in lung cancer patients and evaluated the relationship between interstitial lung changes in the pre-radiotherapy (RT) computed tomography (CT) and symptomatic RP. MATERIALS AND METHODS: Medical records and dose volume histogram data of 60 lung cancer patients from August 2005 to July 2006 were analyzed. All patients were treated with three dimensional (3D) conformal RT of median 56.9 Gy. We assessed the association of symptomatic RP with clinical and dosimetric factors. RESULTS: With a median follow-up of 15.5 months (range, 6.1 to 40.9 months), Radiation Therapy Oncology Group grade > or = 2 RP was observed in 14 patients (23.3%). Five patients (8.3%) died from RP. The interstitial changes in the pre-RT chest CT, mean lung dose (MLD), and V30 significantly predicted RP in multivariable analysis (p=0.009, p or = 2, > or = 3, or > or = 4 was higher in the patients with interstitial lung change (grade 2, 15.6% to 46.7%, p=0.03; grade 3, 4.4% to 40%, p=0.002; grade 4, 4.4% to 33.3%, p=0.008). Four of the grade 5 RP patients had diffuse interstitial change in pre-RT CT and received chemoradiotherapy. CONCLUSION: Our study identified diffuse interstitial disease as a significant clinical risk for RP, particularly fatal RP. We showed the usefulness of MLD, V20, V30, and NTCP in predicting the incidence and severity of RP.

Evaluation of Neoadjuvant Chemotherapy Effect in Osteosarcoma / 대한골관절종양학회지

PURPOSE: Various diagnostic imaging modalities have been used to evaluate the effect of neoadjuvant chemotherapy for osteosarcoma early and noninvasively. We evaluated the effectiveness of imaging studies of plain radiographs and positron-emission tomography/computed tomography (PET/CT) in predicting neoadjuvant chemotherapy effect for osteosarcoma and tried to establish a general principle in interpretation of PET/CT parameters. MATERIALS AND METHODS: Eighteen patients who underwent two cycles of neoadjuvant chemotherapy and surgical excision for osteosarcoma were enrolled. There were 13 males and 5 females, with a median age of 19 (11-63) years. Fifteen patients of 18 had the American Joint Committe on Cancer (AJCC) stage IIB. They had plain radiographs and PET/CT before and after neoadjuvant chemotherapy. The resected tumor specimens were pathologically examined to determine histological response grade using a conventional mapping method. Statistical analysis was performed to evaluate the correlation between histopathological necrosis rate, and radiographic finding category, post-chemotherapy maximum standardized uptake value (SUVmax), average standardized uptake value and metabolic tumor volume (MTV) as well as reduction rates of them. RESULTS: Eight patients were good responders to neoadjuvant chemotherapy based on histological evaluation. Median SUVmax reduction rate was 73 (23-77) % in good responders and 42 (-32-76) % in poor responders. Median MTV reduction rate was 93.5 (62-99) % in good responders and 46 (-81-100) % in poor responders. While radiographic finding category was not different according to histological response (p=1.0), SUVmax reduction rate was significantly different (p=0.041). Difference in MTV reduction rates approached statistical significance as well (p=0.071). CONCLUSION: While radiographic finding category was not reliable to assess neoadjuvant chemotherapy effect for osteosarcoma, reduction rate of SUVmax was a useful indicator in this study. As parameters of PET/CT can be influenced by various factors of settings, different centers have to make an effort to establish their own standard of judgement with reference of previous studies.

Clinical Responses and Prognostic Indicators of Concurrent Chemoradiation for Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate treatment outcomes and prognostic factors in non-small cell lung cancer (NSCLC) patients treated with concurrent chemoradiation. MATERIALS AND METHODS: From January 2005 to June 2009, 51 patients were treated with concurrent chemoradiation for 3 different aims: locally advanced stage III, locally recurrent disease, and postoperative gross residual NSCLC. Median age was 63 years. Distribution of stages by the 6th edition of American Joint Committee on Cancer (AJCC) was as follows: IIIA (37.3%), IIIB (56.9%). Chemotherapy was administered every week concurrently with radiation using one of the following regimens: paclitaxel (60 mg/m2), docetaxel+cisplatin (20 mg/m2+20 mg/m2), cisplatin (30 mg/m2). Total radiation dose was 16-66.4 Gy (median, 59.4 Gy). RESULTS: Median follow-up duration was 40.8 months. The overall response rate was 84.3% with 23 complete responses. The median survival duration for the overall patient group was 17.6 months. The 3-year survival rate was 17.8%. A total of 21 patients had recurrent disease at the following sites: loco-regional sites (23.6%), distant organs (27.5%). In the multivariate analysis of the overall patient group, a clinical tumor response (p=0.002) was the only significant prognostic factor for overall survival (OS). In the multivariate analysis of the definitive chemoradiation arm, the use of consolidation chemotherapy (p=0.022), biologically equivalent dose (BED)10 (p=0.007), and a clinical tumor response (p=0.030) were the significant prognostic factors for OS.The median survival duration of the locally recurrent group and the postoperative gross residual group were 26.4 and 23.9 months, respectively. CONCLUSION: Our study demonstrated that clinical tumor response was significantly associated with OS in the overall patient group. Further investigations regarding the optimal radiation dose in the definitive chemoradiation and the optimal treatment scheme in locally recurrent NSCLC would be required.