Chan Woo Wee

Locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy plus concurrent weekly cisplatin with or without neoadjuvant chemotherapy

Purpose The outcomes of locoregionally advanced nasopharyngeal carcinoma patients treated with concurrent chemoradiation (CCRT) using intensity-modulated radiotherapy (IMRT) with/without neoadjuvant chemotherapy (NCT) were evaluated. Materials and Methods Eighty-three patients who underwent NCT followed by CCRT (49%) or CCRT with/without adjuvant chemotherapy (51%) were reviewed. To the gross tumor, 67.5 Gy was prescribed. Weekly cisplatin was used as concurrent chemotherapy. Results With a median follow-up of 49.4 months, the 5-year local control, regional control, distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival rates were 94.7%, 89.3%, 77.8%, 68.0%, and 81.8%, respectively. In multivariate analysis, the American Joint Committee on Cancer stage (p = 0.016) and N stage (p = 0.001) were negative factors for DMFS and DFS, respectively. Overall, NCT demonstrated no benefit and an increased risk of severe hematologic toxicity. However, compared to patients treated with CCRT alone, NCT showed potential of improving DMFS in stage IV patients. Conclusion CCRT using IMRT resulted in excellent local control and survival outcome. Without evidence of survival benefit from phase III randomized trials, NCT should be carefully administered in locoregionally advanced nasopharyngeal carcinoma patients who are at high-risk of developing distant metastasis and radiotherapy-related mucositis. The results of ongoing trials are awaited.

Novel recursive partitioning analysis classification for newly diagnosed glioblastoma: A multi-institutional study highlighting the MGMT promoter methylation and IDH1 gene mutation status

BACKGROUND AND PURPOSE To refine the recursive partitioning analysis (RPA) classification for glioblastoma incorporating the MGMT methylation and IDH1 mutation status. METHODS AND MATERIALS Three-hundred forty patients were treated with radiotherapy plus concurrent and adjuvant temozolomide in three tertiary-referral hospitals. MGMT methylation and IDH1 mutation status were available in all patients. Methylation of the MGMT (MGMTmeth) and mutation of IDH1 (IDH1mut) were observed in 42.4% and 6.2% of the patients, respectively. RESULTS The median follow-up for survivors and all patients was 33.2 and 20.5months, respectively. The median survival (MS) was 23.6months. RPA was performed on behalf of the results of the Cox proportional hazards model. MGMT methylation generated the initial partition (MGMTmeth vs. MGMTunmeth) in the RPA. Three final RPA classes were identified; class I=MGMTmeth/IDH1mut or MGMTmeth/IDH1wt/GTR/KPS≥90 (MS, 67.2months); class II=MGMTmeth/IDH1wt/GTR/KPS<90, MGMTmeth/IDH1wt/residual disease, MGMTunmeth/age<50, or MGMTunmeth/age≥50/GTR (MS, 24.0months); class III=MGMTunmeth/age≥50/residual disease (MS, 15.2months). CONCLUSIONS A novel RPA classification for glioblastoma was formulated highlighting the impact of MGMTmeth and IDH1mut in the temozolomide era. This model integrating pertinent molecular information can be used effectively for the patient stratification in future clinical trials. An external validation is ongoing.

Intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy in rectal cancer treated with neoadjuvant concurrent chemoradiation: a meta-analysis and pooled-analysis of acute toxicity

Background To compare the acute gastrointestinal (GI) and genitourinary (GU) toxicity profiles between intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) in rectal cancer patients treated with neoadjuvant chemoradiation (NCRT) using meta-analysis and pooled-analysis from published articles. Methods Literature search was performed in PubMed and EMBASE from inception to March 2017. The odd ratios (ORs) were calculated and random effects model was used for meta-analysis. Chi-square or Fishers exact test was performed for the pooled-analysis. Results Six studies including a total of 859 patients met the inclusion criteria. Most patients (98.7%) received NCRT. In the meta-analysis, IMRT reduced grade ≥ 2 acute overall GI toxicity, diarrhea and proctitis with ORs of 0.38, 0.32 and 0.60, respectively (all P < 0.05), compared to 3DCRT. IMRT also reduced acute grade ≥ 3 proctitis compared to 3D-CRT (OR, 0.24; P = 0.03). No significant heterogeneity or publication bias was detected. In the pooled-analysis, IMRT reduced the incidence of grade ≥ 2 acute overall GI toxicity, diarrhea, proctitis and GU toxicity (all P < 0.05). Moreover, lower incidence of grade ≥ 3 acute overall GI toxicity, diarrhea and proctitis were observed in the patients treated with IMRT (all P < 0.05). Conclusions IMRT significantly reduced acute toxicity in locally advanced rectal cancer patients treated with NCRT compared to 3DCRT.

Impact of interim progression during the surgery-to-radiotherapy interval and its predictors in glioblastoma treated with temozolomide-based radiochemotherapy

This study was designed to investigate the impact of interim progression of disease (PD) during the surgery-to-radiotherapy interval (SRI) and its predictors in glioblastoma based on MRIs. A total of 222 patients were planned for radiotherapy (RT) and 166 of them were evaluable for the presence of interim PD by 2 separate MRIs. The size criteria from the updated Response Assessment in Neuro-Oncology criteria was adopted to determine interim PD. 32 (19.3%) patients experienced interim PD, and their median survival (MS) was shorter than patients without PD in univariate (11.3 vs. 19.6 months, p < 0.001) and multivariate analysis (HR 2.237, 95% CI 1.367–3.660, p = 0.002). The volume of residual enhancing tumor (p = 0.003) and prolongation of the SRI (p = 0.004) were significant predictors of interim PD. Every 1-cc increase in residual enhancing tumor and every 1-day prolongation of the SRI significantly increased the risk of interim PD by 3.9% (p = 0.003) and 8.1% (p = 0.004), respectively. A significant portion of patients demonstrate interim PD during SRI and these patients have poor prognosis. The presence of interim PD should be concerned as a significant confounding factor for stratification in future clinical trials. A baseline pre-RT MRI is essential for accurate disease evaluation and RT-target delineation, especially in patients with larger residual disease after surgery and prolonged SRI due to the high risk of interim PD.

Prognostic stratification and nomogram for survival prediction in hepatocellular carcinoma patients treated with radiotherapy for lymph node metastasis.

OBJECTIVE To establish a prognostic model for overall survival prediction in patients with hepatocellular carcinoma (HCC) treated with external beam radiotherapy (RT) for lymph node (LN) metastasis. METHODS 105 patients with HCC underwent RT for LN metastasis. The median age, biologically effective RT dose and follow-up period were 60 years, 59 Gy10 and 5.7 months, respectively. 51 patients had symptoms related to LN metastasis. RESULTS The median survival (MS) was 5.8 months for all patients. For patients with LN-related symptoms, MS was 3.8 months compared with 10.7 months for those without LN-related symptoms. On multivariate analysis of pre-RT factors, symptoms related to LN metastasis [hazard ratio (HR) 2.93], Child-Pugh Class B-C (HR 2.77), uncontrolled intrahepatic disease (HR 2.74) and non-nodal distant metastasis (HR 1.62) were significantly poor prognostic factors for survival (all p < 0.05). Prognostic grouping into three groups by the number of risk factors also had a significant predictive value for survival, with patients having 0, 1, 2 and 3-4 risk factors demonstrating MS of 18.0, 11.7, 5.7 and 3.0 months, respectively (p < 0.001). A clinical nomogram based on the four prognostic factors was formulated and demonstrated good accuracy for predicting 6-month survival with a concordance index of 0.77. CONCLUSION In a heterogeneous group of patients with HCC treated with RT for LN metastasis, the presence of LN-related symptoms was highly associated with poor survival. The prognostic grouping and nomogram developed by the present study can be effectively used for the prediction of survival. ADVANCES IN KNOWLEDGE Patients treated with RT for LN metastases harbour various clinical features. Prognostic model and nomogram can help in predicting survival in these patients.

Variability of Gross Tumor Volume Delineation for Stereotactic Body Radiotherapy of the Lung With Tri-60Co Magnetic Resonance Image-Guided Radiotherapy System (ViewRay): A Comparative Study With Magnetic Resonance- and Computed Tomography-Based Target Delineation

Introduction: To evaluate the intra-/interobserver variability of gross target volumes between delineation based on magnetic resonance imaging and computed tomography in patients simulated for stereotactic body radiotherapy for primary lung cancer and lung metastasis. Materials and Methods: Twenty-five patients (27 lesions) who underwent computed tomography and magnetic resonance simulation with the MR-60Co system (ViewRay) were included in the study. Gross target volumes were delineated on the magnetic resonance imaging (GTVMR) and computed tomography (GTVCT) images by 2 radiation oncologists (RO1 and RO2). Volumes of all contours were measured. Levels of intraobserver (GTVMR_RO vs GTVCT_RO) and interobserver (GTVMR_RO1 vs GTVMR_RO2; GTVCT_RO1 vs GTVCT_RO2) agreement were evaluated using the generalized κ statistics and the paired t test. Results: No significant volumetric difference was observed between all 4 comparisons (GTVMR_RO1 vs GTVCT_RO1, GTVMR_RO2 vs GTVCT_RO2, GTVMR_RO1 vs GTVMR_RO2, and GTVCT_RO1 vs GTVCT_RO2; P > .05), with mean volumes of GTVs ranging 5 to 6 cm3. The levels of agreement between those 4 comparisons were all substantial with mean κ values of 0.64, 0.66, 0.74, and 0.63, respectively. However, the interobserver agreement level was significantly higher for GTVCT compared to GTVMR (P <.001). The mean κ values significantly increased in all 4 comparisons for tumors >5 cm3 compared to tumors ≤5 cm3 (all P < .05). Conclusion: No significant differences in volumes between magnetic resonance- and computed tomograpghy-based Gross target volumes were found among 2 ROs. Magnetic resonance-based GTV delineation for lung stereotactic body radiotherapy also demonstrated acceptable interobserver agreement. Tumors >5 cm3 show higher intra-/interobserver agreement compared to tumors <5 cm3. More experience should be accumulated to reduce variability in magnetic resonance-based Gross target volumes delineation in lung stereotactic body radiotherapy.

Validation of a novel molecular RPA classification in glioblastoma (GBM-molRPA) treated with chemoradiation: A multi-institutional collaborative study

BACKGROUND AND PURPOSE A novel molecular recursive partitioning analysis classification has recently been reported integrating the MGMT promoter methylation (MGMTmeth) and IDH1 mutation (IDH1mut) status for glioblastoma (GBM-molRPA) patients treated with temozolomide-based chemoradiation. The current study was initiated to validate the model in a multi-institutional study. MATERIALS AND METHODS Four-hundred seventy-one newly diagnosed GBM patients (validation cohort) were allocated to classes I-III of the previously reported GBM-molRPA model. Of the patients, 15.7%, 56.1%, and 28.2% patients were GBM-molRPA class I, II, and III, respectively. MGMTmeth and IDH1mut were observed in 32.3 and 8.8% of patients, respectively. In the training plus validation cohort of 692 patients, 16.2%, 60.8%, and 23.0% patients were class I, II, and III, respectively. RESULTS The median follow-up for survivors and the median survival (MS) of patients was 23.3 and 18.4 months, respectively. The MS for GBM-molRPA class I, II, and III was 49.7 (95% CI, 22.8-76.6), 19.2 (95% CI, 16.2-22.1), and 13.8 months (95% CI, 11.8-15.4) (P < .001 for all comparisons) in the validation cohort. In the training plus validation cohort, the MS was 58.5 (95% CI, 40.7-76.3), 21. (95% CI, 18.6-23.3), and 14.3 months (95% CI, 12.5-16.1) (P < .001 for all comparisons) for class I, II, and III, respectively. CONCLUSION The GBM-molRPA is a valid model. This GBM-molRPA classification can be useful in clinics and guiding patient stratification in future clinical trials.

Study design and early result of a phase I study of SABR for early-stage glottic cancer: SABR for Early Glottic Cancer

Avoidance of organs at risk has become possible with advances in image‐guided volumetric‐modulated arc therapy (VMAT) techniques. This study was designed to evaluate the safety and feasibility of stereotactic ablative radiotherapy (SABR) for early stage glottic cancer. This report presents the preliminary result of the first and second dose level.

Prognostic impact of elective supraclavicular nodal irradiation for patients with N1 breast cancer after lumpectomy and anthracycline plus taxane-based chemotherapy (KROG 1418): A multicenter case-controlled study

Purpose This study was conducted to evaluate the impact of supraclavicular lymph node radiotherapy (SCNRT) on N1 breast cancer patients receiving post-lumpectomy whole-breast irradiation (WBI) and anthracycline plus taxane-based (AT) chemotherapy. Materials and Methods We performed a case-control analysis to compare the outcomes of WBI and WBI plus SCNRT (WBI+SCNRT). Among 1,147 patients with N1 breast cancer who received post-lumpectomy radiotherapy and AT-based chemotherapy in 12 hospitals, 542 were selected after propensity score matching. Patterns of failure, disease-free survival (DFS), distant metastasis-free survival (DMFS), and treatment-related toxicity were compared between groups. Results A total of 41 patients (7.6%) were found to have recurrence. Supraclavicular lymph node (SCN) failure was detected in three patients, two in WBI and one in WBI+SCNRT. All SCN failures were found simultaneously with distant metastasis. There was no significant difference in patterns of failure or survival between groups. The 5-year DFS and DMFS for patients with WBI and WBI+SCNRT were 94.4% versus 92.6% (p=0.50) and 95.1% versus 94.5% (p=0.99), respectively. The rates of lymphedema and radiation pneumonitis were significantly higher in the WBI+SCNRT than in the WBI. Conclusion We did not find a benefit of SCNRT for N1 breast cancer patients receiving AT-based chemotherapy.

Postmastectomy Radiotherapy in Patients with pT1-2N1 Breast Cancer Treated with Taxane-Based Chemotherapy: A Retrospective Multicenter Analysis (KROG 1418)

Purpose The purpose of this study was to evaluate the impact of postmastectomy radiotherapy (PMRT) on loco-regional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival (OS) in pT1-2N1 patients treated with taxane-based chemotherapy. Materials and Methods We retrospectively reviewed the medical data of pathological N1 patients who were treated with modified radical mastectomy and adjuvant taxane-based chemotherapy in 12 hospitals between January 2006 and December 2010. Results We identified 714 consecutive patients. The median follow-up duration was 69 months (range, 1 to 114 months) and the 5-year LRRFS, DFS, and OS rates were 97%, 94%, and 98%, respectively, in patients who received PMRT (PMRT [+]). The corresponding figures were 96%, 90%, and 96%, respectively, in patients who did not receive PMRT (PMRT [–]). PMRT had no significant impact on survival. Upon multivariable analysis, only the histological grade (HG) was statistically significant as a prognostic factor for LRRFS and DFS. In a subgroup analysis of HG 3 patients, PMRT (+) showed better DFS (p=0.081). Conclusion PMRT had no significant impact on LRRFS, DFS, or OS in pT1-2N1 patients treated with taxane-based chemotherapy. PMRT showed a marginal benefit for DFS in HG 3 patients. Randomized studies are needed to confirm the benefit of PMRT in high risk patients, such as those with HG 3.