Risk Factors for Distant Metastasis in Extrahepatic Bile Duct Cancer after Curative Resection (KROG 1814).

PURPOSE: Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated. MATERIALS AND METHODS: Medical records of 1,418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated. RESULTS: After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥ 3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs. 27.7%; p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors. CONCLUSION: Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.

The aryl hydrocarbon receptor controls mesenchymal stromal cell-mediated immunomodulation via ubiquitination of eukaryotic elongation factor-2 kinase.

Mesenchymal stem cells (MSCs) have great therapeutic advantages due to their immunosuppressive properties. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor whose signaling plays an important role in the immune system. AHR may be involved in the regulation of MSC-associated immunomodulatory functions. However, the mechanisms by which AHR controls the immunosuppressive functions of MSCs are not well understood. Here, we report that Ahr-deficient MSCs show decreased therapeutic efficacy against graft-versus-host disease (GVHD) compared to wild-type (WT)-MSCs. This was probably due to decreased iNOS protein expression, which is a key regulatory enzyme in MSC immunomodulation. The expression of eukaryotic elongation factor 2 kinase (eEF2K), which inhibits the elongation stage of protein synthesis, is significantly increased in the Ahr-deficient MSCs. Inhibition of eEF2K restored iNOS protein expression. AHR is known to act as an E3 ligase together with CUL4B. We observed constitutive binding of AHR to eEF2K. Consequently, ubiquitination and degradation of eEF2K were inhibited in Ahr-deficient MSCs and by the AHR antagonist CH223191 in WT-MSCs. In summary, AHR regulates the immunomodulatory functions of MSCs through ubiquitination of eEF2K, thereby controlling iNOS protein synthesis and its product, nitric oxide levels.

Evaluating the Necessity of Adaptive RT and the Role of Deformable Image Registration in Lung Cancer with Different Pathologic Classifications.

BACKGROUND: This study aimed to analyze differential radiotherapy (RT) responses according to the pathological type of lung cancer to see the possibility of applying adaptive radiotherapy (ART). METHODS: ART planning with resampled-computed tomography was conducted for a total of 30 patients (20 non-small-cell lung cancer patients and 10 small-cell lung cancer patients) using a deformable image registration technique to reveal gross tumor volume (GTV) changes according to the duration of RT. RESULTS: The small-cell lung cancer group demonstrated an average GTV reduction of 20.95% after the first week of initial treatment (p = 0.001), whereas the adenocarcinoma and squamous cell carcinoma groups showed an average volume reduction of 20.47% (p = 0.015) and 12.68% in the second week. The application of ART according to the timing of GTV reduction has been shown to affect changes in radiation dose irradiated to normal tissues. This suggests that ART applications may have to be different depending on pathological differences in lung cancer. CONCLUSION: Through these results, the present study proposes the possibility of personalized treatment options for individual patients by individualizing ART based on specific radiation responses by pathologic types of lung cancer.

CyberKnife based fractionated stereotactic radiotherapy as an upfront treatment for cerebral arteriovenous malformation.

BACKGROUND: To explore the therapeutic outcomes of CyberKnife based fractionated stereotactic radiotherapy (CKFRT) for patients with cerebral arteriovenous malformations (AVM). METHODS: Between January 2008 and October 2020, 45 patients underwent CKFRT for cerebral AVMs as a first treatment. The delineation of AVM targets included AVM nidus. The mean target volume was 4.07 cm3, and 9 lesions (20%) were larger than 10.0 cm3. The mean marginal dose was 24 Gy (range, 20-35 Gy). CKFRT was delivered in median 3 fractions (range, 2 âˆ¼ 5 fractions). AVM obliteration following CKFRT was confirmed by magnetic resonance imaging or angiography. RESULTS: During a median follow-up of 47 (5-148) months, complete obliteration and partial obliteration of AVM after CKFRT were obtained in 23 (51%) and 13 (29%) patients, respectively. Median time to complete obliteration was 39 (15-63) months. The cumulative probability of complete obliteration rate at 3 years was 47%. Complete obliteration rate of AVM was associated with Radiosurgery-based AVM score, which was consisted of AVM volume, patients age, and AVM location. One (2%) patient had hemorrhage during the follow-up period. CONCLUSIONS: CKFRT is an effective primary treatment for patients with cerebral AVMs with a low hemorrhage risk.

Regional lymph node recurrence after stereotactic body radiation therapy for lung cancer: Patterns of recurrence, treatment approaches, and clinical outcomes (KROG 21-09).

PURPOSE: To present the multi-institutional data on patterns of recurrence, treatment approaches, and clinical outcomes for regional lymph node (LN) recurrence after stereotactic body radiation therapy (SBRT) for primary lung cancer. MATERIALS AND METHODS: The medical records of 114 patients who experienced regional LN recurrence as the first recurrence after lung SBRT were retrospectively reviewed. Patterns of recurrence were classified as local recurrence, regional recurrence, and distant metastasis. Clinical outcomes including progression-free survival (PFS) and overall survival (OS) were analyzed. RESULTS: Half of the patients had regional LN recurrence only. The most common simultaneous recurrence was distant metastasis (38.6 %). Common sites of regional recurrence were ipsilateral hilar (47.2 %), ipsilateral upper mediastinal (40.6 %), and subcarinal (42.5 %) LN stations. 24 (21.1 %) patients underwent salvage radiation therapy (RT), and 44 (38.6 %) patients underwent palliative treatment. Better OS was observed in the salvage RT group (p = 0.025). The 1-year PFS and OS rates were 27.7 % and 55.2 %, respectively, with salvage RT, 14.0 % and 39.9 %, respectively, with palliative treatment, and 22.8 % and 26.8 %, respectively, with no additional treatment. Multivariate analysis showed that salvage RT (PFS, HR 0.463, p = 0.050; OS, HR 0.312, p = 0.002), palliative treatment (PFS, HR 0.436, p = 0.013; OS, HR 0.553, p = 0.050), and simultaneous distant metastasis (PFS, HR 2.335, p = 0.005; OS, HR 1.726, p = 0.054) affected clinical outcomes. CONCLUSION: Many cases of regional LN recurrence are confined to the locoregional area of patients, and appropriate treatment can improve the prognosis of these patients.

CyberKnife-based stereotactic radiosurgery or fractionated stereotactic radiotherapy in older patients with brain metastases from non-small cell lung cancer.

PURPOSE: We analyzed clinical results of CyberKnife (CK)-based stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) in older patients (age ≥65 years) affected by brain metastases (BM) from non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Forty-three older patients with 92 BM were treated with CK-based SRS/FSRT at our institution between 2009 and 2019. The end-point was overall survival (OS). Univariate and multivariate analyses were performed to identify the prognostic factors influencing OS. The in-field local control (IFLC) within the SRS/FSRT field was also assessed. RESULTS: During a median follow-up period of 18 months, the median OS was 32 months. NSCLC-specific graded prognostic assessment (GPA) (p = 0.027) was an independent significant factor affecting OS in the multivariate analysis. The median IFLC period was 31 months, and the total BM volume (p = 0.025) appeared to be a significant feature of IFLC. No adverse events >grade 2 were reported after SRS/FSRT. CONCLUSION: CK-based SRS/FSRT is a safe and efficient option for older patients with BM arising from NSCLC, showing good OS without severe side effects. GPA, which was consisted in age, performance status, extra-cerebral metastasis, and number of BM, seemed to be predictive factors for OS.

Effects of Tumor-Rib Distance and Dose-Dependent Rib Volume on Radiation-Induced Rib Fractures in Patients with Breast Cancer.

This study aimed to investigate the effects of tumor-rib distance and dose-dependent rib volume on radiation-induced rib fractures (RIRFs) in patients with breast cancer. We retrospectively included 510 women with breast cancer who underwent surgical resection with adjuvant radiotherapy. The tumor-rib distance was measured using preoperative computed tomography (CT) images. Postoperative chest wall thickness and dose-dependent rib volumes, which are absolute rib volumes receiving >20 Gy (V20), 30 Gy (V30), 40 Gy (V40), 45 Gy (V45), and 50 Gy (V50), were measured from the stimulation CT images for radiation treatment planning. We assessed the relationship of RIRF with tumor-rib distance, postoperative chest wall thickness, and dose-dependent rib volumes. Patients with high values of tumor-rib distance and postoperative chest wall thickness had significantly lower risks of RIRF than those with low values. Patients with high values of V20, V30, V40, V45, and V50 had significantly higher risks of RIRF than those with low values. In a multivariate analysis, tumor-rib distance and all five dose-dependent rib volumes, as well as osteoporosis and radiation field, were independent risk factors for RIRF. Tumor-rib distance and dose-dependent rib volume were independent risk factors for RIRF in patients with breast cancer.

Trends in the incidence of thyroid cancer in Incheon Province, South Korea, from 2004 to 2013: A representative sample study from Incheon cancer registry.

AIM: This study aimed to assess the trends in the incidence of thyroid cancer in Incheon Province, South Korea, from 2004 to 2013 and to identify its association with thyroid cancer screening. METHODS: We evaluated randomly sampled data of 10% of thyroid cancer patients collected between 2004 and 2013 from the Incheon Cancer Registry, Incheon, South Korea. The expected annual incidence rates of thyroid cancer from 2004 to 2013 were calculated, and the trends in annual incidence change were assessed using a Poisson regression model. In addition, the annual proportion change in the thyroid cancer population according to the detection method and tumor size was also calculated by evaluating the linear-by-linear association. RESULTS: The average expected prevalence of thyroid cancer was 30 per 100,000 individuals from 2004 to 2013. The expected annual incidence of thyroid cancer per 100,000 individuals increased from 7 in 2004 to 49 in 2013, with an annual 1.25-fold difference (p < 0.001). Screening helped improve the detection of thyroid cancer annually, with the proportion increasing by screening detection (p < 0.001). Majority (54%) of the tumors were small (< 10 mm) and their detection rate increased from 2004 to 2013 (p < 0.001). CONCLUSIONS: The incidence of thyroid cancer has increased from 2004 to 2013 in Incheon Province, South Korea, with the increase being most significant for small tumors. These findings indicate that the increased incidence is primarily due to the widespread use of screening and not an actual increase in clinically significant thyroid cancer.

Role of adjuvant chemoradiotherapy and chemotherapy in patients with resected gallbladder carcinoma: a multi-institutional analysis (KROG 19-04).

OBJECTIVE: The effectiveness of adjuvant treatments for resected gallbladder carcinoma (GBC) has remained unclear due to lack of randomized controlled trials; thus, the aim of present study was to evaluate the role of adjuvant treatments, including chemoradiotherapy (CRT) and/or chemotherapy (CTx), in patients with resected GBC. METHODS: A total of 733 GBC patients who received curative-intent surgical resection were identified in a multi-institutional database. Of 733 patients, 372 (50.8%) did not receive adjuvant treatment, whereas 215 (29.3%) and 146 (19.9%) received adjuvant CTx and CRT, respectively. The locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), and overall survival (OS) of the adjuvant treatment groups were compared according to tumor stage (stage II vs. stage III-IV). RESULTS: In stage II disease (n = 381), the 5-year LRFS, RFS, and OS were not significantly different among the no-adjuvant therapy, CTx, and CRT groups, and positive resection margin, presence of perineural invasion, and Nx classification were consistently associated with worse LRFS, RFS, and OS in the multivariate analysis (P < 0.05). For stage III-IV (n = 352), the CRT group had significantly higher 5-year LRFS, RFS, and OS than the no-adjuvant therapy and CTx groups (67.8%, 45.2%, and 56.9%; 37.9%, 28.8%, and 35.4%; and 45.0%, 30.0%, and 45.7%, respectively) (P < 0.05). CONCLUSIONS: CRT has value as adjuvant treatment for resected GBC with stage III-IV disease. Further study is needed for stage II disease with high-risk features.

Current usage of stereotactic body radiotherapy for oligometastatic prostate cancer in Korea: patterns of care survey (KROG 19-08).

BACKGROUND: Growing evidence suggests that metastasis-directed therapy and/or prostate-directed therapy may benefit patients with oligometastatic prostate cancer (OMPC). Stereotactic body radiotherapy (SBRT) is increasingly used to treat oligometastases in various cancers. The purpose of this study was to investigate the current patterns of curative-intent SBRT for OMPC in Korea. METHODS: A 20-item questionnaire was sent to 326 radiation oncologists in 93 institutions in Korea. Only 1 physician per institution was required to complete the survey. Subsequently, the second survey consisting of 3 clinical scenarios was sent to 64 physicians with clinical experience in SBRT: case 1, cT4N0M1 (direct invasion to two pelvic bones); case 2, cT2N0M1 (three bone metastases); and case 3, solitary spine metastasis after radical prostatectomy. RESULTS: Seventy-six physicians from 93 institutions (82%) answered the first survey. The multidisciplinary team approach was practiced in 16 institutions (21%). Most physicians (75%) agreed on the definition of oligometastases as limited lesions and/or organs ≤5: 25% agreed with low-volume disease according to CHAARTED trial. During the last year, 49 physicians (64%) treated OMPC patients with curative intent. Sixty four physicians (84%) had a clinical experience with SBRT: 48 (75%) stated that both dose and fraction number should be considered when defining SBRT, whereas others (25%) stated that only fraction size should be considered. Fifty-five faculties (86%) answered the second survey. Physicians agreed with oligometastases in 89% for case 1, in 80% for case 2, and in 100% for case 3. The rate of SBRT application was the highest in case 3 (70%). CONCLUSIONS: There was diversity in the patterns of SBRT for OMPC in Korea. Additional prospective studies are necessary to strengthen evidence regarding role of SBRT in OMPC.

Role of adjuvant radiotherapy in extrahepatic bile duct cancer: A multicenter retrospective study (Korean Radiation Oncology Group 18-14).

PURPOSE: To evaluate the role of adjuvant radiotherapy (RT) after curative resection in patients with extrahepatic bile duct (EHBD) cancer. METHODS: Between January 2000 and December 2015, 1475 patients with EHBD cancer who underwent curative resection were accrued from 14 institutions in Korea. Among these, 959 patients did not receive any adjuvant therapy (RT(-) group), while 516 underwent postoperative RT with or without chemotherapy (RT(+) group). RESULTS: The median age was 67 years. Nodal involvement was present in 482 patients (32.7%), and resection margin was involved in 293 patients (19.9%). RT(+) group had more patients with proximal tumours, advanced tumours, nodal involvement, perineural invasion, and involved resection margin than RT(-) group (all p < 0.001). With a median follow-up of 36 months, there were 211 locoregional recurrences, 307 distant metastases and 322 combined locoregional and distant failures. On multivariate analysis incorporating age, tumour location, differentiation, pT classification, pN classification, perineural invasion and resection margin, adjuvant RT was associated with improved overall survival (hazard ratio, 0.74; 95% confidence interval, 0.63-0.86; p < 0.001). When RT(+) group was separated into RT alone, concurrent chemoradiotherapy (CCRT) and CCRT followed by chemotherapy, the greatest benefit was observed in patients treated with CCRT followed by chemotherapy (hazard ratio, 0.52; 95% confidence interval, 0.41-0.68). CONCLUSIONS: Adjuvant RT combined with chemotherapy improved survival outcomes of resected EHBD cancer patients. Considering the greatest benefit observed in patients receiving CCRT followed by chemotherapy, a randomised controlled trial comparing chemotherapy alone and CCRT followed by chemotherapy is urgently needed.

Implications of Radiotherapy Utilization in Korea from 2010 to 2019.

BACKGROUND: This study was to assess the rate of radiotherapy (RT) utilization according to the modality in South Korea to identify the implications of contemporary RT patterns. METHODS: We collected information from claims and reimbursement records of the National Health Insurance Service from 2010 to 2019. We classified the location of each institution as capital (Seoul, Incheon, and Gyeonggi-do) and non-capital areas. RESULTS: The rate of RT utilization in total cancer patients nationwide was 24.5% in 2010, which consistently has increased to 36.1% in 2019 (annual increase estimate [AIE], 4.5%). There was an abrupt increase in patients receiving intensity-modulated RT (IMRT), with an AIE of 33.5%, and a steady decline in patients receiving three-dimensional conformal RT (3DCRT), with an AIE of -7.1%. The commonest RT modality was IMRT (44.5%), followed by 3DCRT and stereotactic RT (SRT) (37.2% and 13.5%) in 2019. An increasing trend of advanced RT (such as IMRT and SRT) utilization was observed regardless of the region, although the AIE in the capital areas was slightly higher than that in non-capital areas. CONCLUSION: The utilization of overall RT application and especially of advanced modalities remarkably increased from 2010 to 2019. We also found gaps in their AIEs between capital and non-capital areas. We should ensure that advanced RT is accessible to all cancer patients across South Korea.

Postoperative radiotherapy for WHO grade II-III intracranial ependymoma in adults: An intergroup collaborative study (KROG 18-06/KNOG 18-01).

BACKGROUND AND PURPOSE: To evaluate the impact of adjuvant postoperative radiotherapy (PORT) in adult WHO grade II-III intracranial ependymoma (IEPN). MATERIALS AND METHODS: A total of 172 pathologically confirmed adult grade II-III IEPN patients from 12 institutions were eligible. Of them, 106 (61.6%) and 66 (38.4%) patients were grade II and III, respectively. For grade II and III IEPNs, 51 (48.1%) and 59 (89.4%) patients received PORT, respectively. The median dose to the primary tumor bed was 54.0 Gy and 59.4 Gy for grade II and III patients, respectively. The prognostic impact of sex, age, performance, WHO grade, location, size, surgical extent, and PORT on local control (LC), progression-free survival (PFS), and overall survival (OS) were evaluated by univariate and multivariate analysis. RESULTS: The median follow-up period for survivors was 88.1 months. The 5-/10-year LC, PFS, and OS rates were 64.8%/54.0%, 56.4%/44.8%, and 76.6%/71.0%, respectively. On multivariate analysis, adjuvant PORT significantly improved LC (P = 0.002), PFS (P = 0.002), and OS (P = 0.043). Older age (P < 0.001), WHO grade III (P < 0.001), larger tumor size (P = 0.004), and lesser surgical extent (P < 0.001) were also negative factors for OS. Adjuvant PORT also improved LC (P = 0.010), PFS (P = 0.007), and OS (P = 0.069) on multivariate analysis for grade II IEPNs. CONCLUSION: This multicenter retrospective study supports the role of adjuvant PORT in terms of disease control and survival in adult grade II-III IEPNs. Prospective randomized trials focused on individualized treatment based on molecular subtypes is warranted.

Reirradiation with intensity-modulated radiation therapy for recurrent or secondary head and neck cancer: Meta-analysis and systematic review.

BACKGROUND: To summarize outcomes of reirradiation with intensity-modulated radiotherapy (IMRT) for recurrent or secondary head and neck cancer (HNC). METHODS: Primary endpoints were 2-year local control (LC) and overall survival (OS). Studies involving only recurrent nasopharyngeal patients with cancer were excluded. RESULTS: A total of 17 studies involving 1635 patients were included. Fourteen (82%) of those were retrospective, and 15 (88%) were from single institution. Reirradiation with IMRT produced pooled 2-year LC and OS rates of 52% (95% confidence interval [CI], 46%-57%) and 46% (95% CI, 41%-50%), respectively. In subgroup analyses, the rate of salvage surgery (<42% vs ≥42%) influenced the pooled 2-year LC rate (45.9% vs 58.5%, P = .011). The pooled rates of late grade ≥ 3 and grade 5 toxicities were 26% (95% CI, 20%-32%) and 3.1% (95% CI, 2%-5%), respectively. CONCLUSIONS: Reirradiation with IMRT was an effective modality compared to historical outcomes in the pre-IMRT era.

Reirradiation using stereotactic body radiotherapy in the management of recurrent or second primary head and neck cancer: A meta-analysis and systematic review.

OBJECTIVES: We conducted a meta-analysis and systematic review of stereotactic body radiotherapy (SBRT)-based reirradiation efficacy in patients with recurrent or second primary head and neck cancer (RSHNC). METHODS: We systematically reviewed PubMed/MEDLINE, Embase, and Cochrane Library. The primary endpoint was 2-year overall survival (OS); secondary endpoints were grade >3 complications and response rate. RESULTS: We included 10 studies involving 575 patients (only 12% of whom underwent salvage surgery post-recurrence) with RSHNC who underwent SBRT; median SBRT reirradiation doses ranged from 24 to 44 Gy (median, 30 Gy) delivered with 3-6 fractions (median, 5 fractions). Median target volume of SBRT reirradiation was measured from 19 to 103 cm3. The pooled event rate of 2-year OS following SBRT reirradiation for RSHNC was 30.0% (95% confidence interval [CI] 24.5-36.1). The pooled rates of late grade ≥3 and grade 5 toxicity were 9.6% (95% CI 5.0-17.6) and 4.6% (95% CI 2.4-8.6), respectively. Grade 5 toxicity was not observed in five studies (range: 0-10.7%). The pooled rates of clinical response and complete response were 61.7% (95% CI 51.1-71.3) and 31.3% (95% CI 23.3-40.5), respectively, and the 2-year local control rate was 47.3% (95% CI 3.1-62.1). CONCLUSIONS: SBRT with median 30 Gy in 5 fractions is a feasible therapy showing good responses for patients with RSHNC not suitable for salvage surgery. However, to improve OS, SBRT reirradiation strategy should be investigated in terms of dose escalation for sustained control and combined systemic therapy.

Dosimetric comparison of incidental axillary irradiation between three-dimensional conformal and volumetric modulated arc techniques for breast cancer.

Radiotherapy techniques for breast cancer have evolved with efforts to reduce treatment-related side effects. In the present study, we conducted dosimetric analysis of incidental axillary irradiation between volumetric modulated arc therapy (VMAT) and three-dimensional conformal radiotherapy (3D-CRT). A total of 20 patients with early stage left breast cancer who underwent breast-conserving surgery followed by postoperative radiotherapy were analyzed. For VMAT plans, dose-volume constraints were not imposed on the axilla, as with 3D-CRT. We compared the dosimetric parameters of the planning target volumes, organs at risk and axillary level I-III of the two plans. VMAT showed better target coverage and a normal organ-sparing effect compared with 3D-CRT. The incidental axillary irradiation of VMAT was lower; the mean dose and the V40Gy were significantly reduced at all axillary levels, with the exception of no difference in the maximum dose to axillary level I. In conclusion, VMAT decreased incidental axillary irradiation, even in the absence of a dose-volume constraint on the axilla, and can, therefore, decrease the risk of radiotherapy-related lymphedema. However, caution is also required because it is unclear whether this incidental axillary irradiation is beneficial for reducing recurrence on the axilla.

Relationship Between Changes in Myocardial F-18 Fluorodeoxyglucose Uptake and Radiation Dose After Adjuvant Three-Dimensional Conformal Radiotherapy in Patients with Breast Cancer.

This study aimed to assess the relationship between radiation dose and changes in the irradiated myocardial F-18 fluorodeoxyglucose (FDG) uptake after radiotherapy (RT) in breast cancer patients. The data of 55 patients with left and 48 patients with right breast cancer who underwent curative surgical resection and adjuvant three-dimensional conformal RT and staging (PET1), post-adjuvant chemotherapy (PET2), post-RT (PET3), and surveillance (PET4) FDG positron emission tomography/computed tomography (PET/CT) were retrospectively reviewed. The median interval between PET1 and curative surgical resection, between the end of adjuvant chemotherapy and PET2, between the end of RT and PET3, and between the end of RT and PET4 were five days, 13 days, 132 days, and 353 days, respectively. The myocardial-to-blood pool uptake ratio was measured in all patients. For patients with left breast cancer, the 30 Gy- (30 Gy) and 47.5 Gy-irradiated myocardium-to-low-irradiated myocardium (47.5 Gy) FDG uptake ratios were additionally measured. There were no differences in the myocardial-to-blood pool uptake ratios between left and right breast cancer on all PET scans. For left breast cancer, higher 30 Gy and 47.5 Gy uptake ratios were observed on PET3 than on PET1 and PET2. Both uptake ratios decreased on PET4 compared to PET3, but, were still higher compared to PET1. On PET3 and PET4, the 47.5 Gy were higher than the 30 Gy uptake ratios, while there were no differences between them on PET1 and PET2. Although the whole myocardium FDG uptake showed no significant change, the irradiated myocardium FDG uptake significantly increased after RT and was related to radiation dose to the myocardium in breast cancer patients. These results might be an imaging evidence that supports the increased risk of heart disease after RT in patients with left breast cancer.

Tumor volume and sphericity as predictors of local control after stereotactic radiosurgery for limited number (1-4) brain metastases from nonsmall cell lung cancer.

AIM: This study aims to evaluate the usage of brain metastases (BM) tumor volume and sphericity as prognostic factors in local control (LC) after stereotactic radiosurgery (SRS) for limited number (1-4) BM from nonsmall cell lung cancer (NSCLC). METHODS: We retrospectively reviewed 80 patients, with 141 BM, who were treated with SRS from 2012 to 2017. Local failure was defined as an increase in lesion size after SRS. LC and overall survival (OS) were estimated using Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. RESULTS: The median clinical and radiographic follow-up was 11.2 and 9.0 months, respectively. The median BM tumor volume was 0.31 cm3 (0.01-21.64 cm3 ) and the median tumor sphericity was 0.76 (0.39-0.95). The median LC of the entire cohort was 28.8 months. LC rate at last follow-up was achieved in 84.4% of patients (35.5% CR, 35.5% PR, and 13.5% SD). LC was 83.8% at 1 year and 56.3% at 2 years. On multivariate analysis, only sphericity (P < .001) and volume (P = .004) were found to be a strong predictor for LC. The median OS of the entire cohort was 24.1 months. On multivariate analysis, only GPA score was found to be a predictor for OS. CONCLUSION: BM tumor sphericity and volume were found to be strong predictors for LC. Tumor sphericity and volume should be taken into consideration when treating patients with BM and when designing future prospective studies and developing prognostic indices.

The prognostic value of PET/CT evaluation with Deauville score on the recurrence and survival in diffuse large B-cell lymphoma: a multi-institutional study of KROG 17-02.

The Korean Radiation Oncology Group (KROG) assessed the value of Deauville score (DS) on 18F-fluorodeoxyglucose Positron emission tomography-computed tomography (FDG PET/CT) as a predictor of recurrence and survival after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in diffuse large B-cell lymphoma (DLBCL). A total of 512 patients with stage I-III DLBCL who received six cycles of R-CHOP with or without radiation therapy (RT) and obtained treatment responses according to PET-CT imagings after R-CHOP ± RT were included. Patients were sorted into two arms; DS 4-5 arm (n = 24) was matched at a 1:2 ratio with DS 1-3 arm (n = 48) using propensity score matching method. After a median follow-up time of 37.2 months, the recurrence-free survival rate (86.6% vs. 66.8%, P = 0.041) and overall survival rate (86.9% vs. 62.2%, P = 0.009) at 5 years were significantly different between the DS 1-3 and DS 4-5 arms. DS 4-5 arm showed higher 5-years locoregional recurrence-free survival (88.8% vs. 74.3%, P = 0.155) and distant failure-free survival (91.1% vs. 84.3%, P = 0.333) than DS 1-3 arm. In the multivariate analysis, DS was still a significant factor for recurrence-free survival [hazard ratio (HR), 3.840 and confidence interval (CI), 1.068-13.806; P = 0.039] and overall survival rates (HR 4.453 and CI 1.274-15.562; P = 0.019). This study showed and validated that Deauville score of 4-5 of PET-CT imaging taken after full-course of R-CHOP chemotherapy with or without RT could predict recurrence-free survival and overall survival in DLBCL patients.

A phase 2 multicenter study of stereotactic body radiotherapy for hepatocellular carcinoma: Safety and efficacy.

BACKGROUND: Although several prospective studies have reported the efficacy of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC), treatment-related toxicity varies and has not been determined. Therefore, the authors evaluated the safety and efficacy of SBRT for patients with HCC in a hepatitis B virus-endemic area. METHODS: This multicenter phase 2 trial enrolled patients with unresectable HCC. Patients received SBRT with 45 to 60 Gy in 3 fractions. To evaluate gastroduodenal toxicity, esophagogastroduodenoscopy (EGD) was performed before and 2 months after SBRT. The primary endpoint was treatment-related severe toxicity at 1 year after SBRT. The secondary endpoints were the 2-year local control, progression-free survival, and overall survival rates. RESULTS: In total, 74 patients were enrolled between January 2012 and April 2015, and 65 eligible patients were analyzed. One patient experienced radiation-induced liver disease with acute grade ≥3 toxicity 1 month after SBRT. In addition, 1 patient had a grade 3 esophageal ulcer with stenosis 5 months after SBRT. The actuarial rate of treatment-related severe toxicity at 1 year was 3%. The pre-SBRT and post-SBRT EGD findings were not significantly different among the 57 evaluable patients who underwent EGD. The 2-year and 3-year local control rates were 97% and 95%, respectively. The progression-free and overall survival rates were 48% and 84% at 2 years, respectively, and 36% and 76% at 3 years, respectively. CONCLUSIONS: With a median follow-up of 41 months, this prospective multicenter study demonstrated that SBRT for patients with HCC is well tolerated and is an effective treatment modality.