Hyun-Cheol Kang

The safety and efficacy of EGF-based cream for the prevention of radiotherapy-induced skin injury: results from a multicenter observational study

Purpose This study was designed to evaluate the efficacy and safety of topically applied recombinant human epidermal growth factor (rhEGF) for the prevention of radiation-induced dermatitis in cancer patients. Materials and Methods From December 2010 to April 2012, a total of 1,172 cancer patients who received radiotherapy (RT) of more than 50 Gy were prospectively enrolled and treated with EGF-based cream. An acute skin reaction classified according to the Radiation Therapy Oncology Group 6-point rating scale was the primary end point and we also assessed the occurrence of edema, dry skin, or pruritus. Results The percentage of radiation dermatitis with maximum grade 0 and grade 1 was 19% and 58% at the time of 50 Gy, and it became 29% and 47% after completion of planned RT. This increment was observed only in breast cancer patients (from 18%/62% to 32%/49%). Adverse events related to the EGF-based cream developed in 49 patients (4%) with mild erythema the most common. Skin toxicity grade >2 was observed in 5% of the patients. Edema, dry skin, and pruritus grade ≥3 developed in 9%, 9%, and 1% of the patients, respectively. Conclusion Prophylactic use of an EGF-based cream is effective in preventing radiation dermatitis with tolerable toxicity. Further studies comparing EGF cream with other topical agents may be necessary.

Immunohistochemical analysis of cyclooxygenase-2 and brain fatty acid binding protein expression in grades I-II meningiomas: correlation with tumor grade and clinical outcome after radiotherapy.

This study was done to evaluate the association of cyclooxygenase 2 (COX‐2) and brain fatty acid binding protein (BFABP) with tumor grade and outcome of grades I‐II meningiomas treated with radiotherapy. From 1996 to 2008, 40 patients with intracranial grades I‐II meningiomas were treated with radiotherapy. Immunohistochemical staining for COX‐2 and BFABP were performed on formalin‐fixed paraffin‐embedded tissues. COX‐2 expression was significantly associated with BFABP status and both COX‐2 (P < 0.01) and BFABP (P = 0.01) expression were stronger in the grade II meningiomas than in grade I tumors. Among the clinicopathologic factors, age and COX‐2 status were prognostic in progression‐free survival. Patients with moderate or strong COX‐2 expression had worse outcome than those with negative or weak COX‐2 expression (P = 0.03) after controlling for potential confounders. Our results suggest that the molecular biomarker COX‐2 has prognostic significance in intracranial grades I‐II meningiomas following radiotherapy.

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.

The Role of Radiotherapy in the Treatment of Newly Diagnosed Supratentorial Low-grade Oligodendrogliomas: Comparative Analysis with Immediate Radiotherapy versus Surgery Alone

PURPOSE The purpose of this study was to evaluate the role of immediate postoperative radiotherapy (RT) in adult patients with a low-grade oligodendroglioma (LODG). MATERIALS AND METHODS A total of 74 patients, older than 15 years, were treated in our institution between April 1990 and March 2006 for newly diagnosed LODGs. After surgery, 43 patients were treated with immediate RT with a total dose of 54~55.8 Gy with 1.8 Gy fractions (RT group) and 31 patients were followed with no adjuvant RT (OP group). All patients were closely observed until tumor progression or death with frequent work-ups including neurological examinations and MRI. Primary endpoints were overall survival and progression-free survival. The median follow-up duration of survivors was 6.2 years in the RT group and 5.8 years in the OP group. RESULTS Median progression-free survival was 13.2 years in the RT group and 4.6 years in the OP group; multivariate analysis confirmed improved outcome with the use of immediate RT (hazard ratio, 0.22; 95% confidence interval-CI, 0.09~0.55; p<0.001). Median overall survival was 14.9 years in the RT group and 9.8 years in the OP group; the use of adjuvant RT was also associated with a trend toward better overall survival after immediate RT based on multivariate analysis (hazard ratio, 0.3; 95% CI, 0.08~1.17; p=0.082). No severe RT related complications were observed. CONCLUSION Immediate RT following surgery appears to be an effective treatment modality for supratentorial LODGs. However, the potential benefit of adjuvant RT for overall survival needs to be tested prospectively in the future.

A comparison of treatment plan quality between Tri-Co-60 intensity modulated radiation therapy and volumetric modulated arc therapy for cervical cancer

PURPOSE To investigate the plan quality of tri-Co-60 intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) for cervical cancer. METHODS A total of 20 patients who received postoperative radiotherapy for cervical cancer were selected. For each patient, a tri-Co-60 IMRT plan for which the target volume was the planning target volume (PTV) generated by adding 1mm isotropic margins from the clinical target volume (CTV) and a VMAT plan for which the target volume was the PTV generated by adding 7mm and 10mm margins from the CTV were generated. The tri-Co-60 IMRT plans were generated with the ViewRay™ system while the VMAT plans were generated with 15-MV photon beams from a linear accelerator (prescription dose=50.4Gy in 28 fractions). RESULTS The average volumes of the PTVs and CTVs were 704.9cc±87.8cc and 271.6cc±51.6cc, respectively. No noticeable differences in the dose-volumetric parameters for the target volumes were observed between the tri-Co-60 IMRT and VMAT plans. The values of V40Gy for the small bowel and rectal wall, V45Gy of the bladder, and V35Gy of the femoral heads for the VMAT plans were 14.6%±7.8%, 54.4%±4.2%, 30.0%±4.7%, and 8.9%±3.3%, respectively. Those of the tri-Co-60 IMRT plans were 2.8%±2.1%, 23.0%±8.9%, 17.1%±6.1%, and 0.3%±0.4%, respectively. CONCLUSIONS Owing to the target margin reduction capability, the tri-Co-60 IMRT plans were more favorable than the VMAT plans for cervical cancer.

Development of patient‐controlled respiratory gating system based on visual guidance for magnetic‐resonance image‐guided radiation therapy

Purpose The aim of this study is to develop a visual guidance patient‐controlled (VG‐PC) respiratory gating system for respiratory‐gated magnetic‐resonance image‐guided radiation therapy (MR‐IGRT) and to evaluate the performance of the developed system. Methods The near‐real‐time cine planar MR image of a patient acquired during treatment was transmitted to a beam projector in the treatment room through an optical fiber cable. The beam projector projected the cine MR images inside the bore of the ViewRay system in order to be visible to a patient during treatment. With this visual information, patients voluntarily controlled their respiration to put the target volume into the gating boundary (gating window). The effect of the presence of the beam projector in the treatment room on the image quality of the MRI was investigated by evaluating the signal‐to‐noise ratio (SNR), uniformity, low‐contrast detectability, high‐contrast spatial resolution, and spatial integrity with the VG‐PC gating system. To evaluate the performance of the developed system, we applied the VG‐PC gating system to a total of seven patients; six patients received stereotactic ablative radiotherapy (SABR) and one patient received conventional fractionated radiation therapy. Results The projected cine MR images were visible even when the room light was on. No image data loss or additional time delay during delivery of image data were observed. Every indicator representing MRI quality, including SNR, uniformity, low‐contrast detectability, high‐contrast spatial resolution, and spatial integrity exhibited values higher than the tolerance levels of the manufacturer with the VG‐PC gating system; therefore, the presence of the VG‐PC gating system in the treatment room did not degrade the MR image quality. The average beam‐off times due to respiratory gating with and without the VG‐PC gating system were 830.3 ± 278.2 s and 1264.2 ± 302.1 s respectively (P = 0.005). Consequently, the total treatment times excluding the time for patient setup with and without the VG‐PC gating system were 1453.3 ± 297.3 s and 1887.2 ± 469.6 s, respectively, on average (P = 0.005). The average number of beam‐off events during whole treatment session was reduced from 457 ± 154 times to 195 ± 90 times by using the VG‐PC gating system (P < 0.001). Conclusions The developed system could improve treatment efficiency when performing respiratory‐gated MR‐IGRT. The VG‐PC gating system could be applied to any kind of bore‐type radiotherapy machine.

Fluorodeoxyglucose positron-emission tomography ratio in non-small cell lung cancer patients treated with definitive radiotherapy

Purpose To determine whether the maximum standardized uptake value (SUV) of [18F] fluorodeoxyglucose uptake by positron emission tomography (FDG PET) ratio of lymph node to primary tumor (mSUVR) could be a prognostic factor for node positive non-small cell lung cancer (NSCLC) patients treated with definitive radiotherapy (RT). Materials and Methods A total of 68 NSCLC T1-4, N1-3, M0 patients underwent FDG PET before RT. Optimal cutoff values of mSUVR were chosen based on overall survival (OS). Independent prognosticators were identified by Cox regression analysis. Results The most significant cutoff value for mSUVR was 0.9 with respect to OS. Two-year OS was 17% for patients with mSUVR > 0.9 and 49% for those with mSUVR ≤ 0.9 (p = 0.01). In a multivariate analysis, including age, performance status, stage, use of chemotherapy, and mSUVR, only performance status (p = 0.05) and mSUVR > 0.9 (p = 0.05) were significant predictors of OS. Two-year OS for patients with both good performance (Eastern Cooperative Oncology Group [ECOG] ≤ 1) and mSUVR ≤ 0.9 was significantly better than that for patients with either poor performance (ECOG > 1) or mSUVR > 0.9, 23% (71% vs. 23%, p = 0.04). Conclusion Our results suggested that the mSUVR was a strong prognostic factor among patients with lymph node positive NSCLC following RT. Addition of mSUVR to performance status identifies a subgroup at highest risk for death after RT.

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.

Clinical outcomes and prognostic factors in patients with mycosis fungoides who underwent radiation therapy in a single institution

Purpose We aimed to evaluate clinical outcomes including progression-free survival (PFS), overall survival (OS), partial response, and complete response in patients who underwent radiation therapy (RT) for mycosis fungoides (MF). Also, we sought to find prognostic factors for clinical outcomes. Materials and Methods Total 19 patients confirmed with MF between 1999–2015 were retrospectively reviewed. Clinical and treatment characteristics, clinical outcomes, and and toxicities were analyzed. Results Eleven patients were treated with total skin electron beam radiotherapy (TSEBT) and 8 patients with involved field radiation therapy (IFRT) with median dose of 30 Gy, respectively. The median time interval from diagnosis to RT was 2.6 months (range, 0.4 to 87.3 months). The overall response rate was 100%; 11 patients (57.9%) had a complete response and 8 patients (42.1%) a partial response. The presence of positive lymph node at the time of consultation of RT was associated with lower OS (p = 0.043). In multivariate analysis, PFS was significantly lower for patients with increased previous therapies experienced following RT (p = 0.019) and for patients showing PR during RT (p = 0.044). There were no reported grade 3 or more skin toxicities related with RT. Conclusion Both IFRT and TSEBT are effective treatment for MF patients. Patients with short disease course before RT or complete response during RT are expected to have longer PFS. Positive lymph node status at the initiation of RT was associated woth poor OS, suggesting other treatment modalities such as low-dose RT for patients with low life-expectancy.

Correction: Lung density change after SABR: A comparative study between tri-Co-60 magnetic resonance-guided system and linear accelerator

Radiation-induced lung damage is an important treatment-related toxicity after lung stereotactic ablative radiotherapy (SABR). After implementing a tri-60Co magnetic-resonance image guided system, ViewRayTM, we compared the associated early radiological lung density changes to those associated with a linear accelerator (LINAC). Eight patients treated with the tri-60Co system were matched 1:1 with patients treated with LINAC. Prescription doses were 52 Gy or 60 Gy in four fractions, and lung dose-volumetric parameters were calculated from each planning system. The first two follow-up computed tomography (CT) were co-registered with the planning CT through deformable registration software, and lung density was measured by isodose levels. Tumor size was matched between the two groups, but the planning target volume of LINAC was larger than that of the tri-60Co system (p = 0.036). With regard to clinically relevant dose-volumetric parameters in the lungs, the ipsilateral lung mean dose, V10Gy and V20Gy were significantly poorer in tri-60Co plans compared to LINAC plans (p = 0.012, 0.036, and 0.017, respectively). Increased lung density was not observed in the first follow-up scan compared to the planning scan. A significant change of lung density was shown in the second follow-up scan and there was no meaningful difference between the tri-60Co system and LINAC for all dose regions. In addition, no patient developed clinical radiation pneumonitis until the second follow-up scan. Therefore, there was no significant difference in the early radiological lung damage between the tri-60Co system and LINAC for lung SABR despite of the inferior plan quality of the tri-60Co system compared to that of LINAC. Further studies with a longer follow-up period are needed to confirm our findings.