Differential Perspectives by Specialty on Oligometastatic Colorectal Cancer: A Korean Oligometastasis Working Group’s Comparative Survey Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Despite numerous studies on the optimal treatments for oligometastatic disease (OMD), there is no established interdisciplinary consensus on its diagnosis or classification. This survey-based study aimed to analyze the differential opinions of colorectal surgeons and radiation oncologists regarding the definition and treatment of OMD from the colorectal primary. @*Materials and Methods@#A total of 141 participants were included in this study, consisting of 63 radiation oncologists (44.7%) and 78 colorectal surgeons (55.3%). The survey consisted of 19 questions related to OMD, and the responses were analyzed using the chi-square test to determine statistical differences between the specialties. @*Results@#The radiation oncologists chose “bone” more frequently compared to the colorectal surgeons (19.2% vs. 36.5%, p=0.022), while colorectal surgeons favored “peritoneal seeding” (26.9% vs. 9.5%, p=0.009). Regarding the number of metastatic tumors, 48.3% of colorectal surgeons responded that “irrelevant, if all metastatic lesions are amendable to local therapy”, while only 21.8% of radiation oncologist chose same answer. When asked about molecular diagnosis, most surgeons (74.8%) said it was important, but only 35.8% of radiation oncologists agreed. @*Conclusion@#This study demonstrates that although radiation oncologists and colorectal surgeons agreed on a majority of aspects such as diagnostic imaging, biomarker, systemic therapy, and optimal timing of OMD, they also had quite different perspectives on several aspects of OMD. Understanding these differences is crucial to achieving multidisciplinary consensus on the definition and optimal management of OMD.

Metastasis-Directed Local Therapy of Hepatic Oligometastasis from Colorectal Cancer and Future Perspective in Radiation Therapy / Journal of the Korean Cancer Association, 대한암학회지

Introduction of the concept for oligometastasis led to wide application of metastasis-directed local ablative therapies for metastatic colorectal cancer (CRC). By application of the metastasis-directed local ablative therapies including surgical resection, radiofrequency ablation (RFA), and stereotactic ablative body radiotherapy (SABR), the survival outcomes of patients with metastatic CRC have improved. The liver is the most common distant metastatic site in CRC patients, and recently various metastasis-directed local therapies for hepatic oligometastasis from CRC (HOCRC) are widely used. Surgical resection is the first line of metastatic-directed local therapy for HOCRC, but its eligibility is very limited. Alternatively, RFA can be applied to patients who are ineligible for surgical resection of liver metastasis. However, there are some limitations such as inferior local control (LC) compared with surgical resection and technical feasibility based on location, size, and visibility on ultrasonography of the liver metastasis. Recent advances in radiation therapy technology have led to an increase in the use of SABR for liver tumors. SABR is considered complementary to RFA for patients with HOCRC who are ineligible for RFA. Furthermore, SABR can potentially result in better LC for liver metastases > 2-3 cm compared with RFA. In this article, the previous studies regarding curative metastasis-directed local therapies for HOCRC based on the radiation oncologist’s and surgeon’s perspective are reviewed and discussed. In addition, future perspectives regarding SABR in the treatment of HOCRC are suggested.

Effect of isoflavone supplementation on menopausal symptoms:a systematic review and meta-analysis of randomized controlled trials

BACKGROUND/OBJECTIVES@#Complementary and alternative medicines can be used to alleviate climacteric symptoms that significantly affect the quality of life of postmenopausal women. Isoflavones are the most common plant-based therapies for postmenopausal changes, but the results of previous studies have been controversial.MATERIALS/METHODS: To investigate whether isoflavones would affect menopausal symptoms as well as ovarian hormones, we performed a systematic review and metaanalysis. The PubMed and EMBASE databases were used to perform the systematic search.Included studies were limited to randomized controlled trials (RCTs) assessing the impact of isoflavone supplementation on menopausal symptoms. @*RESULTS@#Eleven studies were included for the final quantitative assessment. Isoflavone intervention was varied between 49.3 and 135 mg of isoflavones per day for 12 wk–2 yrs.The meta-analysis showed that supplementation of isoflavones significantly increased the estradiol levels (standardized mean difference [SMD] = 0.615, P = 0.035) and Kupperman index (SMD = 3.121, P = 0.003) but had no significant effect on hot flashes, folliclestimulating hormone, and luteinizing hormone. However, both estradiol and the Kupperman index showed significant heterogeneity among studies (I2 = 94.7%, P < 0.001 and I2 = 98.1%, P < 0.001, respectively). @*CONCLUSIONS@#Although the results showed a significant SMD in estradiol and the Kupperman index, the results should be interpreted with caution due to the high heterogeneity. Further validation with a larger RCT will be necessary. Overall, isoflavone supplementation has distinct effects on the climacteric symptoms and hormonal changes in postmenopausal women.

Differences in radiotherapy application according to regional disease characteristics of hepatocellular carcinoma

There are differences in opinion regarding the application of external beam radiotherapy in the treatment of hepatocellular carcinoma. Some major guidelines state that external beam radiotherapy is yet to attain a sufficient level of evidence. However, caution should be exercised when attempting to understand the clinical need for external beam radiotherapy solely based on the level of evidence. Previously, external beam radiotherapy had low applicability in the treatment of hepatocellular carcinoma before computed tomography-based planning was popularized. Modern external beam radiotherapy can selectively target tumor cells while sparing normal liver tissues. Recent technologies such as stereotactic body radiotherapy have enabled more precise treatment. The characteristics of hepatocellular carcinoma differ significantly according to the regional etiology. The main cause of hepatocellular carcinoma is the hepatitis B virus. It is commonly diagnosed as a locally advanced tumor but with relatively preserved hepatic function. The majority of these hepatocellular carcinoma cases are found in the East Asian population. Hepatocellular carcinoma caused by hepatitis C virus or other benign hepatitis tends to be diagnosed as a less locally aggressive tumor but with deteriorated liver function. The Western world and Japan tend to have patients with such causes. External beam radiotherapy has been more commonly performed for the former, although the use of external beam radiotherapy in the latter might have more concerns with regard to hepatic toxicity. This review discusses the above subjects along with perspectives regarding external beam radiotherapy in recent guidelines.

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.

Differences in radiotherapy application according to regional disease characteristics of hepatocellular carcinoma

There are differences in opinion regarding the application of external beam radiotherapy in the treatment of hepatocellular carcinoma. Some major guidelines state that external beam radiotherapy is yet to attain a sufficient level of evidence. However, caution should be exercised when attempting to understand the clinical need for external beam radiotherapy solely based on the level of evidence. Previously, external beam radiotherapy had low applicability in the treatment of hepatocellular carcinoma before computed tomography-based planning was popularized. Modern external beam radiotherapy can selectively target tumor cells while sparing normal liver tissues. Recent technologies such as stereotactic body radiotherapy have enabled more precise treatment. The characteristics of hepatocellular carcinoma differ significantly according to the regional etiology. The main cause of hepatocellular carcinoma is the hepatitis B virus. It is commonly diagnosed as a locally advanced tumor but with relatively preserved hepatic function. The majority of these hepatocellular carcinoma cases are found in the East Asian population. Hepatocellular carcinoma caused by hepatitis C virus or other benign hepatitis tends to be diagnosed as a less locally aggressive tumor but with deteriorated liver function. The Western world and Japan tend to have patients with such causes. External beam radiotherapy has been more commonly performed for the former, although the use of external beam radiotherapy in the latter might have more concerns with regard to hepatic toxicity. This review discusses the above subjects along with perspectives regarding external beam radiotherapy in recent guidelines.

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.

Practical Advice for South Korean Medical Researchers Regarding Open-Access and Predatory Journals / Journal of the Korean Cancer Association, 대한암학회지

In recent decades, the volume of scholarly literature worldwide has increased significantly, and open-access publishing has become commonplace. These changes are even more dominant in South Korea. Comparing the periods of 1981-2000 and 2001-2020, the number of medical articles produced in Korea increased by 16.8 times on the Web of Science platform (13,223 to 222,771 papers). Before 1990, almost no open-access articles were produced in South Korea, but in the last 10 years open-access publications came to account for almost 40% of all South Korean publications on Web of Science. Along with the expansion of literature and the development of open-access publishing, predatory journals that seek profit without conducting quality assurance have appeared and undermined the academic corpus. In this rapidly changing environment, medical researchers have begun contemplating publication standards. In this article, recent trends in academic publishing are examined from international and South Korean perspectives, and the significance of open-access publishing and recent changes are discussed. Practical methods that can be used to select legitimate publishers, including open-access journals, and identify predatory journals are also discussed.

Development of the anti-cancer food scoring system 2.0: Validation and nutritional analyses of quantitative anti-cancer food scoring model

Long-term Disease-free Survival after Trimodality Treatment of Recurrent Hepatocellular Carcinoma Involving the Inferior Vena Cava and Right Atrium

Hepatocellular carcinoma (HCC) involving the inferior vena cava (IVC) and/or right atrium (RA) is a rare and intractable disease. A standard treatment has not been established yet, owing to the rarity of disease and difficulties in the therapeutic treatment. Herein, we report the case of a patient who had recurrent HCC (after a prior lobectomy) involving both IVC and RA and underwent multimodality treatments including external beam radiotherapy and transarterial chemotherapy, followed by sorafenib treatment. The disease was well controlled with local treatments and sustained for 7 years until last follow-up after the systemic treatments. Our case shows a possibility of long-term survival for patients affected by HCC involving IVC and/or RA, after a rigorous multimodality treatment strategy.

Plasma Cell-Free DNA as a Predictive Marker after Radiotherapy for Hepatocellular Carcinoma

PURPOSE: Cell-free DNA (cfDNA) is gaining attention as a novel biomarker for oncologic outcomes. We investigated the clinical significance of cfDNA in hepatocellular carcinoma (HCC) patients treated with radiotherapy (RT). MATERIALS AND METHODS: Fifty-five patients with HCC who received RT were recruited from two prospective study cohorts: one cohort of 34 patients who underwent conventionally fractionated RT and a second of 21 patients treated with stereotactic body radiation therapy. cfDNA was extracted and quantified. RESULTS: In total, 30% of the patients had multiple tumors, 77% had tumors >2 cm, and 32% had portal vein tumor thrombus. Optimal cut-off values for cfDNA levels (33.65 ng/mL and 37.25 ng/mL, before and after RT) were used to divide patients into low-DNA (LDNA) and high-DNA (HDNA) groups. The pre-RT HDNA group tended to have more advanced disease and larger tumors (p=0.049 and p=0.017, respectively). Tumor response, intrahepatic failure-free rates, and local control (LC) rates were significantly better in the post-RT LDNA group (p=0.017, p=0.035, and p=0.006, respectively). CONCLUSION: Quantitative analysis of cfDNA was feasible in our cohorts. Post-RT cfDNA levels were negatively correlated with treatment outcomes, indicating the potential for the use of post-RT cfDNA levels as an early predictor of treatment responses and LC after RT for HCC patients.

A Case of Complete Response with Biliary Stenosis after Hepatic Arterial Injection and Stereotactic Body Radiotherapy to Hepatoecllular Carcinoma with Portal Vein Thrombosis

Curative treatment of hepatocellular carcinoma (HCC) with portal vein invasion is difficult to achieve, and the prognosis is dismal. Combining external beam radiotherapy (EBRT) with hepatic arterial infusion chemotherapy (HAIC) has shown favorable local therapeutic effects for patients with HCC exhibiting portal vein invasion. Stereotactic body radiotherapy (SBRT) is a recently developed EBRT modality that shows excellent tumor control. The combination of SBRT and HAIC for HCC with portal vein invasion has not been well-studied. We report a patient with HCC and portal vein invasion who achieved 15 months of survival with complete response status after combination SBRT and HAIC. The patient later experienced grade 3 biliary stricture and died of liver abscesses of unknown etiologies that subsequently appeared.

A Survey of Radiation Therapy Utilization in Korea from 2010 to 2016: Focusing on Use of Intensity-Modulated Radiation Therapy

BACKGROUND: This study aimed to assess the recent changes of radiation therapy (RT) modalities in Korea. In particular, we focused on intensity-modulated radiation therapy (IMRT) utilization as the main index, presenting the application status of advanced RT. METHODS: We collected information from the Korean Health and Insurance Review and Assessment Service data based on the National Health Insurance Service claims and reimbursements records by using treatment codes from 2010 to 2016. We classified locating region of each institution as capital vs. non-capital areas and metropolitan vs. non-metropolitan areas to assess the regional difference in IMRT utilization in Korea. RESULTS: IMRT use has been steadily increased in Korea, with an annual increase estimate (AIE) of 37.9% from 2011 to 2016 (P < 0.001) resulting in IMRT being the second most common RT modality following three-dimensional conformal radiotherapy. In general, an increasing trend of IMRT utilization was observed, regardless of the region. The rate of AIE in the capital areas or metropolitan areas was higher than that in non-capital areas or non-metropolitan areas (40.7% vs. 31.9%; P < 0.001 and 39.7% vs. 29.4%; P < 0.001, respectively). DISCUSSION: The result of our survey showed that IMRT has become one of the most common RT modalities. IMRT is becoming popular in both metropolitan and non-metropolitan areas, while metropolitan area has faster AIE possibly due to concentration of medical resources and movement of advanced patients.

Development of quantitative index evaluating anticancer or carcinogenic potential of diet: the anti-cancer food scoring system 1.0

BACKGROUND/OBJECTIVE: Cancer is closely related to diet. One of the most reliable reports of the subject is the expert report from the World Cancer Research Fund & American Institute of Cancer Research (WCRF&AICR). However, majority of the studies including above were written with academic terms and in English. The aim of this study is to create a model, named Anti-Cancer Food Scoring System (ACFS), to provide a simple index of the anticancer potential of food. SUBJECTS/METHODS: We created ACFS codes of various food groups. The evidence of the ACFS codes was provided by the literature at a level comparable to that suggested in the WCRF&AICR report or from the WCRF&AICR report. The ACFS grade was calculated considering food group, cooking, and normalization. Application was performed for Koreans' 20 common meals, which encompass multinational recipes. RESULT: We calculated the ACFS grades of Koreans' 20 common meals. The results were not significantly different from the WCRF&AICR guidelines or information from the National Cancer Information Center of Korea. The grades were briefly interpreted as follows: grade S. ideal for cancer prevention; grade A. good for cancer prevention; grade B, might have anticancer potential; grade C, difficult to be regarded as preventive or carcinogenic; grade D, might against cancer prevention; grade E, probably against cancer prevention. CONCLUSIONS: The ACFS provides a simple index of anticancer potential of diets. This indicator can be useful for the people without expertise, and is effective in evaluating the diets including Asian foods. The ACFS can help design of future clinical or nutritional studies of cancer prevention.

Establishment of a Disease-Specific Graded Prognostic Assessment for Hepatocellular Carcinoma Patients with Spinal Metastasis

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) patients with spinal metastasis (SM) show heterogeneous lengths of survival. In this study, we develop and propose a graded prognostic assessment for HCC patients with SM (HCC-SM GPA). METHODS: We previously reported the outcomes of 192 HCC patients with SM who received radiotherapy from April 1992 to February 2012. Prognostic factors that significantly affected survival in that study were used to establish the HCC-SM GPA. Validation was performed using an independent cohort of 63 patients recruited from September 2011 to March 2016. RESULTS: We developed the HCC-SM GPA using the following factors: Eastern Cooperative Oncology Group performance status (0–2, 0 point; 3–4, 1 point), controlled primary HCC (yes, 0 point; no, 2 points), and extrahepatic metastases other than bone (no, 0 point; yes, 1 point). Patients were stratified into low (GPA=0), intermediate (GPA=1 to 2), and high risk (GPA=3 to 4). When applied to the validation cohort, the HCC-SM GPA determined median survival durations of 13.6, 4.8, and 2.6 months and 1-year overall survival rates of 58.3%, 17.8%, and 7.3% for the low-, intermediate-, and high-risk patient groups, respectively (p<0.001). CONCLUSIONS: Our newly proposed HCC-SM GPA successfully predicted survival outcomes.

Application of radiotherapy for hepatocellular carcinoma in current clinical practice guidelines

In oncologic practice, treatment guidelines provide appropriate treatment strategies based on evidence. Currently, many guidelines are used, including those of the European Association for the Study of the Liver and European Organization for Research and Treatment of Cancer (EASL-EORTC), National Comprehensive Cancer Network (NCCN), Asia-Pacific Primary Liver Cancer Expert (APPLE), and Korean Liver Cancer Study Group and National Cancer Centre (KLCSG-NCC). Although radiotherapy is commonly used in clinical practice, some guidelines do not accept it as a standard treatment modality. In this review, we will investigate the clinical practice guidelines currently used, and discuss the application of radiotherapy.

Treatment outcome of conservative surgery plus postoperative radiotherapy for extremity soft tissue sarcoma

PURPOSE: To evaluate the treatment outcome and prognostic factor of postoperative radiotherapy for extremity soft tissue sarcoma (STS). MATERIALS AND METHODS: Forty three patients with extremity STS were treated with conservative surgery and postoperative radiotherapy from January 1981 to December 2010 at Korea University Medical Center. Median total 60 Gy (range, 50 to 74.4 Gy) of radiation was delivered and 7 patients were treated with chemotherapy. RESULTS: The median follow-up period was 70 months (range, 5 to 302 months). Twelve patients (27.9%) sustained relapse of their disease. Local recurrence occurred in 3 patients (7.0%) and distant metastases developed in 10 patients (23.3%). The 5-year overall survival (OS) was 69.2% and disease free survival was 67.9%. The 5-year local relapse-free survival was 90.7% and distant relapse-free survival was 73.3%. On univariate analysis, no significant prognostic factors were associated with development of local recurrence. Histologic grade (p = 0.005) and stage (p = 0.02) influenced the development of distant metastases. Histologic grade was unique significant prognostic factor for the OS on univariate and multivariate analysis. Severe acute treatment-related complications, Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or 4, developed in 6 patients (14.0%) and severe late complications in 2 patients (4.7%). CONCLUSION: Conservative surgery with postoperative radiotherapy achieved a satisfactory rate of local control with acceptable complication rate in extremity STS. Most failures were distant metastases that correlate with tumor grade and stage. The majority of local recurrences developed within the field. Selective dose escalation of radiotherapy or development of effective systemic treatment might be considered.

Radiotherapy for pituitary adenomas: long-term outcome and complications

PURPOSE: To evaluate long-term local control rate and toxicity in patients treated with external beam radiotherapy (EBRT) for pituitary adenomas. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 60 patients treated with EBRT for pituitary adenoma at Korea University Medical Center from 1996 and 2006. Thirty-five patients had hormone secreting tumors, 25 patients had non-secreting tumors. Fifty-seven patients had received postoperative radiotherapy (RT), and 3 had received RT alone. Median total dose was 54 Gy (range, 36 to 61.2 Gy). The definition of tumor progression were as follows: evidence of tumor progression on computed tomography or magnetic resonance imaging, worsening of clinical sign requiring additional operation or others, rising serum hormone level against a previously stable or falling value, and failure of controlling serum hormone level so that the hormone level had been far from optimal range until last follow-up. Age, sex, hormone secretion, tumor extension, tumor size, and radiation dose were analyzed for prognostic significance in tumor control. RESULTS: Median follow-up was 5.7 years (range, 2 to 14.4 years). The 10-year actuarial local control rates for non-secreting and secreting adenomas were 96% and 66%, respectively. In univariate analysis, hormone secretion was significant prognostic factor (p = 0.042) and cavernous sinus extension was marginally significant factor (p = 0.054) for adverse local control. All other factors were not significant. In multivariate analysis, hormone secretion and gender were significant. Fifty-three patients had mass-effect symptoms (headache, dizziness, visual disturbance, hypopituitarism, loss of consciousness, and cranial nerve palsy). A total of 17 of 23 patients with headache and 27 of 34 patients with visual impairment were improved. Twenty-seven patients experienced symptoms of endocrine hypersecretion (galactorrhea, amenorrhea, irregular menstruation, decreased libido, gynecomastia, acromegaly, and Cushing's disease). Amenorrhea was abated in 7 of 10 patients, galactorrhea in 8 of 8 patients, acromegaly in 7 of 11 patients, Cushing's disease in 4 of 4 patients. Long-term complication was observed in 4 patients; 3 patients with cerebrovascular accident, 1 patient developed dementia. Of these patients, 3 of 4 received more than 60 Gy of irradiation. CONCLUSION: EBRT is highly effective in preventing recurrence and reducing mass effect of non-secreting adenoma. Effort to improve tumor control of secreting adenoma is required. Careful long-term follow-up is required when relatively high dose is applied. Modern radiosurgery or proton RT may be options to decrease late complications.