Jae-Soo Koh

Prediction Model of Chemotherapy Response in Osteosarcoma by 18F-FDG PET and MRI

Response to neoadjuvant chemotherapy is a significant prognostic factor for osteosarcoma; however, this information can be determined only after surgical resection. If we could predict histologic response before surgery, it might be helpful for the planning of surgeries and tailoring of treatment. We evaluated the usefulness of 18F-FDG PET for this purpose. Methods: A total of 70 consecutive patients with a high-grade osteosarcoma treated at our institute were prospectively enrolled. All patients underwent 18F-FDG PET and MRI before and after neoadjuvant chemotherapy. We analyzed the predictive values of 5 parameters, namely, maximum standardized uptake values (SUVs), before and after (SUV2) chemotherapy, SUV change ratio, tumor volume change ratio, and metabolic volume change ratio (MVCR) in terms of their abilities to discriminate responders from nonresponders. Results: Patients with an SUV2 of less than or equal to 2 showed a good histologic response, and patients with an SUV2 of greater than 5 showed a poor histologic response. The histologic response of a patient with an intermediate SUV2 (2 < SUV2 ≤ 5) was found to be predictable using MVCR. A patient with an MVCR of less than 0.65 is likely to be a good responder, whereas a patient with an MVCR of greater than or equal to 0.65 is likely to be a poor responder. According to our model, the predictive values for good responders and poor responders were 97% (31/32) and 95% (36/38), respectively. Conclusion: We found that combined information on 18F-FDG PET and MRI scans, acquired before and after chemotherapy, could be used to predict histologic response to neoadjuvant chemotherapy in osteosarcoma.

RANKL expression is related to treatment outcome of patients with localized, high-grade osteosarcoma.

The receptor activator of nuclear factor κB ligand (RANKL/TNFSF11) is expressed in metastatic bone cancer cells and has been suggested to play a key role in cell migration and metastatic behavior. We determined whether RANKL expression is correlated to clinical behavior of localized, high‐grade osteosarcoma.

Combination of 18F-FDG PET/CT and Diffusion-Weighted MR Imaging as a Predictor of Histologic Response to Neoadjuvant Chemotherapy: Preliminary Results in Osteosarcoma

We evaluated the potential of 18F-FDG PET/CT and diffusion-weighted imaging (DWI) to monitor the histologic response in patients with extremity osteosarcoma receiving neoadjuvant chemotherapy, using sequential PET/CT and MR imaging. Methods: We prospectively registered 28 patients with high-grade osteosarcoma treated with 2 cycles of neoadjuvant chemotherapy and surgery. All patients underwent sequential 18F-FDG PET/CT and MR imaging before (PET/MR1) and after neoadjuvant chemotherapy (PET/MR2). Maximum standardized uptake value (SUV), tumor volume based on MR imaging (MRV), and the mean apparent diffusion coefficient (ADC) values were measured on PET/MR1 (SUV1, MRV1, and ADC1) and PET/MR2 (SUV2, MRV2, and ADC2). The percentage changes in maximum SUV (ΔSUV), MRV (ΔMRV), and ADC (ΔADC) were calculated, and the correlations among these parameters were evaluated. After surgery, the effects of neoadjuvant chemotherapy were graded histopathologically: grades III and IV (necrosis of ≥ 90%) indicated a good response, and grades I and II (necrosis of < 90%) indicated a poor response. The optimum cutoff values of ΔSUV, ΔMRV, ΔADC, and their combination for predicting histologic response were assessed by single- and multi-receiver-operating-characteristic curve analysis. Results: Twenty-seven patients were enrolled in the present study after 1 patient with inadequate acquisition of MR imaging was excluded. ΔSUV and ΔADC negatively correlated with each other (ρ = −0.593, P = 0.001), and ΔMRV did not correlate with ΔSUV or ΔADC. The cutoff value, sensitivity, specificity, and accuracy for predicting good histologic response were ≤ −52%, 67%, 87%, and 78%, respectively, for ΔSUV and > 13%, 83%, 73%, and 78%, respectively, for ΔADC. However, ΔMRV did not predict histologic response. Sensitivity, specificity, and accuracy were 83%, 87%, and 85%, respectively, using the combined criterion of ΔSUV ≤ −31% and ΔADC > 13%. Conclusion: In the current preliminary study, both PET/CT and DWI are useful for predicting histologic response after neoadjuvant chemotherapy in osteosarcoma. Combining PET/CT and DWI may be an effective method to predict the histologic response of patients to neoadjuvant chemotherapy.

Tumor Necrosis Rate Adjusted by Tumor Volume Change Is a Better Predictor of Survival of Localized Osteosarcoma Patients

BackgroundWe assessed whether new parameter that considers both tumor volume change and necrosis rate predicts metastasis-free survival of localized osteosarcoma patients. We also evaluated relationship between tumor volume change and necrosis rate or metastasis-free survival.MethodsWe retrospectively reviewed 151 patients with stage II osteosarcoma who were treated with surgery and neoadjuvant chemotherapy. The tumor volume change was measured and calculated based on pre- and postchemotherapy magnetic resonance images. The mean metastasis-free interval was 83.1xa0months. We calculated adjusted tumor necrosis rate as following formula: 100–(100–necrosis rate)xa0×xa0postchemotherapy/prechemotherapy tumor volume. Survival and logistic regression analyses were used to evaluate the correlation among size parameters, tumor necrosis rate and survival.ResultsThe 5-year metastasis-free survival rate of 151 patients was 71.4% (95% CI, 67.7–75.1%). American Joint Committee on Cancer (AJCC) stage IIB (RR 2.27; 95% CI, 1.11–4.62; Pxa0=xa00.025) and poor adjusted tumor necrosis rate (RR 2.02; 95% CI, 1.05–3.89; Pxa0=xa00.035) independently correlated with metastasis-free survival period. Further, tumor volume change independently correlated with necrosis rate. Decreased tumor volume could predict good response, with sensitivity of 80.2%, specificity of 68.6%, and positive predictive value (PPV) of 74.7%. Increased or stable tumor volume could predict poor response, with sensitivity of 68.6%, specificity of 80.2%, and PPV of 75.0 %.ConclusionThe necrosis rate adjusted by the tumor volume change is an independent prognostic factor in osteosarcoma. This adjusted tumor necrosis rate may serve as a basis for risk-adapted therapy in combination with other prognostic factors.

Initial Metabolic Tumor Volume Measured by 18F-FDG PET/CT Can Predict the Outcome of Osteosarcoma of the Extremities

We evaluated the ability of metabolic and volumetric parameters measured by pretreatment 18F-FDG PET/CT to predict the survival of patients with osteosarcoma of the extremities. Methods: The records of 83 patients with American Joint Committee on Cancer stage II extremity osteosarcoma treated with surgery and chemotherapy were retrospectively reviewed. Imaging parameters (maximum standardized uptake value, metabolic tumor volume [MTV], total lesion glycolysis, and tumor volume based on MR images) were measured before treatment, and histologic responses to neoadjuvant chemotherapy were assessed by examination of postsurgical specimens. Receiver-operating-characteristic curve analyses and the Cox proportional hazards model were used to analyze whether imaging and clinicopathologic parameters could predict metastasis-free survival. Results: Of the imaging parameters, MTV at the fixed standardized uptake value threshold of 2.0 (MTV(2.0)) most accurately predicted metastasis by receiver-operating-characteristic curve analysis (area under the curve = 0.679, P = 0.011). By multivariate analysis, MTV(2.0) > 105 mL (relative risk, 3.93; 95% confidence interval, 1.55–9.92) and poor response to neoadjuvant chemotherapy (relative risk, 4.83; 95% confidence interval, 1.64–14.21) independently shortened metastasis-free survival (P = 0.004 for both parameters). The stratification of patients by the combined criteria of MTV(2.0) and histologic response predicted outcome in more detail. Conclusion: MTV is an independent predictor of metastasis in patients with osteosarcoma of the extremities. The combination of MTV and histologic response predicts survival more accurately than the chemotherapeutic response alone.

18F-FDG PET SUVmax as an indicator of histopathologic response after neoadjuvant chemotherapy in extremity osteosarcoma

PurposeThis study evaluated the usefulness of the maximum standardized uptake value (SUVmax) as a measure of histologic response to neoadjuvant chemotherapy in patients with extremity osteosarcoma. The correlation between [18u2009F]FDG PET SUVmax values and histologic response to preoperative chemotherapy was also assessed prospectively using PET/MRI.MethodsA total of 26 consecutive patients with high-grade osteosarcoma were prospectively enrolled. All patients underwent parallel PET and MRI scans before and after neoadjuvant chemotherapy. Using the PET and MRI images and pathologic mapping, we assessed the percentage necrosis by histology at the highest metabolic activity point in the tumors. This was defined as the minimum histologic response. The predictive values of SUVmax before (SUV1) and after (SUV2) chemotherapy and the SUV change ratio were determined. Correlations were also investigated among SUV2, minimum histologic response and histologic response.ResultsHistologically, 13 patients were classified as good responders and 13 as poor responders. Patients with an SUV2 of >5 showed a poor histologic response. A significant correlation was found between SUV2 and histologic response (Spearman’s rho −0.642; Pu2009<u20090.001), and SUV2 and histologic response were both found to be significantly correlated with minimum histologic response (Spearman’s rho −0.515 and 0.911; Pu2009=u20090.007 and Pu2009<u20090.001, respectively).ConclusionA SUVmax of more than 5 after neoadjuvant chemotherapy identified the majority of histologic nonresponders (sensitivity 61.3xa0%, PPV 88.9xa0%). Tumor necrosis at the point of maximum metabolic activity was found to be significantly correlated with the histologic response of entire resected specimen.

Comparison of (18)F-FDG PET/CT and (99 m)Tc-MDP bone scintigraphy for detection of bone metastasis in osteosarcoma

ObjectiveWe compared the diagnostic performance of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and (99xa0m)Tc-methylene diphosphonate bone scintigraphy (BS) for the detection of bone metastasis in osteosarcoma.Materials and methodsWe retrospectively reviewed 206 patients with stage II–IV osteosarcoma treated with surgery and chemotherapy as well as at least one paired PET/CT and BS scan (defined as an examination). PET/CT and BS images were interpreted separately. When analyzing the diagnostic yield of a combination of PET/CT and BS (PET/CT+BS), an examination was considered positive if either PET/CT or BS scored positive. The final diagnosis was obtained from histological findings or clinical follow-up with imaging studies for at least 6xa0months. Diagnostic performances of PET/CT, BS, and their combinations were calculated.ResultsOut of 833 examinations in 206 patients, 55 with 101 lesions in 38 patients were confirmed as bone metastases. The sensitivity, specificity, and diagnostic accuracy were 95, 98, and 98xa0%, respectively, for PET/CT; 76, 97, and 96xa0%, respectively, for BS; and 100, 96, and 97xa0%, respectively, for PET/CT+BS in an examination-based analysis. Lesion-based analysis demonstrated that the sensitivity of PET/CT+BS (100xa0%) was significantly higher than that of PET/CT (92xa0%) or BS (74xa0%) alone. BS detected significantly less bone metastases in the growth plate region than outside the growth plate region (22 vs. 77xa0%).ConclusionsPET/CT is more sensitive and accurate than BS for diagnosing bone metastases in osteosarcoma. The combined use of PET/CT and BS improves sensitivity.

Initial tumor size predicts histologic response and survival in localized osteosarcoma patients.

To evaluate the correlation between histologic response and size parameters, and to analyze the prognostic importance of size parameters on metastasis‐free survival in localized osteosarcoma patients.

Early response monitoring to neoadjuvant chemotherapy in osteosarcoma using sequential 18 F-FDG PET/CT and MRI

PurposeWe evaluated the potential of sequential fluorine-18 fluorodeoxyglucose (18u2009F-FDG) positron emission tomography (PET)/computed tomography (CT) and MRI (PET/MRI) after onexa0cycle of neoadjuvant chemotherapy to predict a poor histologic response in osteosarcoma.MethodsA prospective study was conducted on 30 patients with osteosarcoma treated with twoxa0cycles of neoadjuvant chemotherapy and surgery. All patients underwent PET/MRI before, after onexa0cycle, and after the completion of neoadjuvant chemotherapy, respectively. Imaging parameters [maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor volume based on magnetic resonance (MR) images (MRV)] and their % changes were calculated on each PET/MRI data set, and histological responses were evaluated on the postsurgical specimen.ResultsA total of 17 patients (57xa0%) exhibited a poor histologic response after twoxa0cycles of chemotherapy. Unlike the little volumetric change in MRI, PET parameters significantly decreased after one and twoxa0cycles of chemotherapy, respectively. After onexa0cycle of chemotherapy, SUVmax, MTV, and TLG predicted the poor responders. Among these parameters, either MTV ≥ 47xa0mL or TLG ≥ 190xa0g after onexa0cycle of chemotherapy was significantly associated with a poor histologic response on multivariate logistic regression analysis (OR 8.98, pu2009=u20090.039). The sensitivity, specificity, and accuracy of these parameters were 71xa0%, 85xa0% and 77xa0%; and 71xa0%, 85xa0% and 77xa0%, respectively.ConclusionThe histologic response to neoadjuvant chemotherapy in osteosarcoma can be predicted accurately by FDG PET after one course of chemotherapy. Among PET parameters, MTV and TLG were independent predictors of the histologic response.

Prognostic effects of doctor-associated diagnostic delays in osteosarcoma

IntroductionIn this retrospective study, we evaluated to what extent diagnostic delays impact prognosis in osteosarcoma.Materials and methodsThe authors identified 26 osteosarcoma patients who had undergone inappropriate procedure-associated diagnostic delays of more than 45xa0days after surgery, calculated overall survival rates, and analyzed clinicopathologic characteristics.ResultsInitial clinical impressions were of a benign bone tumor in 15 patients, fracture in 8, and infection in 3. After initial inappropriate procedures, primary surgeons failed to send a tissue sample to a pathologist for definite diagnosis in 12 cases, and pathologists made incorrect diagnoses in the other 14. The average doctor-associated diagnostic delay after inappropriate surgery for these 26 patients was 10.5xa0months. Following referral to our institute, 22 underwent both surgery and chemotherapy and the remaining 4 patients underwent chemotherapy only. Four of the 26 patients were alive at last follow-ups. Estimated 5- and 10-year overall survival rates were 26 and 10%, respectively.ConclusionsThe present study shows that doctor-associated diagnostic delay superimposed on an inappropriate primary procedure has a significant detrimental effect on overall survival in osteosarcoma. This study demonstrates that surgeons and pathologists should spare no effort to minimize diagnostic errors and delays.