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.

How rapid advances in imaging are defining the future of precision radiation oncology.

Imaging has an essential role in the planning and delivery of radiotherapy. Recent advances in imaging have led to the development of advanced radiotherapy techniques-including image-guided radiotherapy, intensity-modulated radiotherapy, stereotactic body radiotherapy and proton beam therapy. The optimal use of imaging might enable higher doses of radiation to be delivered to the tumour, while sparing normal surrounding tissues. In this article, we review how the integration of existing and novel forms of computed tomography, magnetic resonance imaging and positron emission tomography have transformed tumour delineation in the radiotherapy planning process, and how these advances have the potential to allow a more individualised approach to the cancer therapy. Recent data suggest that imaging biomarkers that assess underlying tumour heterogeneity can identify areas within a tumour that are at higher risk of radio-resistance, and therefore potentially allow for biologically focussed dose escalation. The rapidly evolving concept of adaptive radiotherapy, including artificial intelligence, requires imaging during treatment to be used to modify radiotherapy on a daily basis. These advances have the potential to improve clinical outcomes and reduce radiation-related long-term toxicities. We outline how recent technological advances in both imaging and radiotherapy delivery can be combined to shape the future of precision radiation oncology.

Quality of life outcomes after low dose-rate brachytherapy for localized prostate cancer: Current status and future perspectives.

The present review summarizes data from studies reporting on health-related quality of life after brachytherapy and competing modalities. There are various therapeutic modalities for localized prostate cancer, including radical surgery, external beam radiotherapy and active surveillance. Advances in surgical and radiation treatment have entered clinical practice in the form of robot-assisted surgery or intensity-modulated radiotherapy. Brachytherapy remains the main treatment option for patients with localized prostate cancer, with 10-year survival data showing favorable outcomes. Because each treatment modality has achieved favorable survival outcomes, focus in determining appropriate treatment has shifted toward health-related quality of life, where each treatment has a different profile and/or adverse symptoms. The development of health-related quality of life assessment tools has allowed the creation of a pool of specific health-related quality of life data across many studies. The present article reviews the impact of brachytherapy and other modalities on quality of life, as well as future directions.

Current status of intensity-modulated radiation therapy for prostate cancer: History, clinical results and future directions.

External beam radiotherapy has changed dramatically over several decades with the improvement of computer hardware and software, and machinery developments. Intensity-modulated radiation therapy is the most sophisticated technique for all cancer treatment with radiation therapy, and is widely disseminated and available for daily use in many countries. Several retrospective and prospective studies have shown that intensity-modulated radiation therapy reduces the radiation dose in the organs at risk with diminished rates of acute and late toxicity, even with higher doses (>74 Gy). An important technique for the clinical use of intensity-modulated radiation therapy is image-guided radiation therapy. The clinical benefit for prostate image-guided radiation therapy has been assessed by comparing the outcomes of patients with either the image-guided radiation therapy or non-image-guided radiation therapy technique. These studies have shown that image-guided radiation therapy significantly decreases acute and late rectal and bladder toxicities. Randomized trials and meta-analysis have shown that higher doses result in better biochemical control. More recently, hypofractionated radiation therapy comparing hypofractionated radiation therapy versus conventional fractionated radiation therapy have shown that hypofractionated radiation therapy produces biochemical control and toxicity rated similar to those produced by conventional fractionated radiation therapy. The clinical use of ultrahypofractionated radiation therapy and simultaneous integrated boost technique is necessary to evaluate its further safety and benefits. Intensity-modulated radiation therapy is also widely accepted in the field of salvage therapy and for the patients with distant oligometastases. The purpose of the present review is to summarize the history of intensity-modulated radiation therapy, new techniques for intensity-modulated radiation therapy, hypofractionation and future directions for prostate cancer.

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.

Local Therapy Improves Overall Survival in Patients With Newly Diagnosed Metastatic Prostate Cancer.

BACKGROUND: The role of local therapy, in the form of radiation therapy (RT) or radical prostatectomy(RP), and its association on outcomes is not well established in patients with metastatic prostate cancer. METHODS: Using the National Cancer Database (NCDB), we evaluated patterns of care and outcomes among patients diagnosed with metastatic prostate cancer from 2004 to 2013 treated with local therapy (RP, intensity-modulated radiation therapy [IMRT], or 2D/3D-conformal radiation therapy [CRT]). The association between local therapy, co-variates, and outcomes was assessed in a multivariable Cox proportional hazards model and Propensity score (PS) matching was performed to balance confounding factors. Survival was estimated using the Kaplan-Meier method. RESULTS: Among the 1,208,180 patients in the NCDB with prostate cancer, 6,051 patients met the inclusion criteria. No local therapy was used in 5,224 patients, while 622 (10.3%), 52 (0.9%), 153 (2.5%) patients received RP, IMRT, and 2D/3D-CRT, respectively. Use of local therapy was associated with younger age (≤70), lower co-morbidity score, lower T-stage, Gleason score <8, node-negative status, private, and Medicare insurance, higher income quartile, and treatment at comprehensive or academic/research programs (P < 0.05). Five-year overall survival for patients receiving local therapy was 45.7% versus 17.1% for those not receiving local therapy (P < 0.01). In multivariate analysis, RP (HR = 0.51; 95%CI, 0.45-0.59, P < 0.01) and IMRT (HR = 0.47; 95%CI, 0.31-0.72, P < 0.01) were independently associated with superior overall survival. After PS-matching, the use of local therapy (RP or IMRT) remained significantly associated with overall survival (HR = 0.35; 95%CI, 0.30-0.41, P < 0.01). CONCLUSIONS: The use of RP and IMRT, to treat the primary disease, was associated with improvements in overall survival for patients with metastatic prostate cancer. We have identified patient-specific variations in the use of local therapy that may be tested in subsequent prospective clinical trials to improve patient outcomes in this setting. Prostate 77: 559-572, 2017. © 2017 Wiley Periodicals, Inc.

Patterns of care of IMRT usage in postoperative management of uterine cancer.

OBJECTIVE: To analyze the patterns of care regarding intensity modulated radiation therapy (IMRT) usage in the postoperative management of uterine cancer. METHODS: The National Cancer Database was queried to identify women with endometrial adenocarcinoma who underwent hysterectomy followed by external beam radiation between 2004-2012. Descriptive statistics were used to analyze IMRT usage with comparison via the Chi Square test. Overall survival was also compared between IMRT and three dimensional conformal radiation therapy. Multivariable logistic regression and multivariable Cox Regression were used to identify covariables that impact IMRT usage and improved survival respectively. RESULTS: 7839 women were included in this study. IMRT utilization increased from 1.9% in 2004 to 32.4% in 2012 (p<0.001). The adjusted odds ratio (OR) for IMRT in 2012 compared with 2004 was 24.90, 95% CI 15.24-40.67 (p<0.001). Aside from year, other predictors of IMRT usage on multivariate analysis were positive nodes, higher dose, private insurance and higher income. Black race was associated with lower IMRT usage compared to Whites with an OR of 0.60, 95% CI 0.44-0.81 (p=0.001). IMRT was not associated with significantly increased survival (HR 0.86, 95% CI 0.73-1.01, p=0.06). Black race and positive nodes were associated with decreased survival within the group studied whereas private insurance and higher income were associated with improved survival. CONCLUSIONS: In this hospital-based registry, IMRT has significantly increased in utilization for postoperative radiation in uterine cancer between 2004-2012 although not resulting in significantly improved survival. Socioeconomic and racial disparities exist in the allocation of IMRT usage.

Impact of changing rectal dose volume parameters over time on late rectal and urinary toxicity after high-dose intensity-modulated radiotherapy for prostate cancer: A 10-years single centre experience.

BACKGROUND: External beam radiotherapy is an excellent treatment for patients with prostate cancer (PC). Assessing long-term radiotherapy-induced toxicity is important. We evaluated the impact of implementing different rectal dose volume constraints (DVC) on late rectal and urinary toxicity. MATERIAL AND METHODS: Six hundred and thirty-seven PC patients were treated with high-dose intensity-modulated radiotherapy (IMRT) in the primary (median dose of 78 Gy to the prostate) or postoperative setting [median dose of 74 (adjuvant) and 76 Gy (salvage) to the prostatic bed]. Three groups were defined according to different DVC applied over time. The incidence of late rectal and urinary toxicity was evaluated. Three-year actuarial risk estimations of grade 2-3 rectal and urinary toxicity were calculated (Kaplan-Meier statistics). RESULTS: Median follow-up was five years. Overall, the incidence of late grade 3 and 2 rectal toxicity was 1% and 11%. The calculated three-year actuarial risk of developing late grade≥2 rectal toxicity decreased from 16% to 7% and 5% for patients in Group 1, Group 2 and Group 3, respectively (p<0.001). Respectively, 17 (4%) and 98 (24%) patients developed grade 3 and 2 late urinary toxicity in the primary setting. In the postoperative setting, 15 (6%) and 62 (26%) patients developed grade 3 and 2 urinary toxicity, respectively. The three-year actuarial risk of developing late≥grade 2 urinary toxicity in primary- and postoperative-treated patients was 22% and 23%, respectively. This was not significantly different between the three groups. CONCLUSION: The majority of patients developed no or only moderate rectal toxicity after high-dose IMRT for PC. Implementing different rectal DVC resulted in a significant decrease of late rectal toxicity without affecting urinary toxicity.

[Advanced radiation therapy project for cancer treatment--from Hokkaido to the world, the world access to Hokkaido].

Cancer is the most major cause of death in Japan recently. In this symposium, we explained advanced treatment technology for cancer treatment, now used and that will be used in near future at the Hokkaido University Hospital. Intensity Moderated Radiation Therapy (IMRT) and Proton Beam Therapy (PBT) are considered to be the most promising and advanced technologies for cancer treatment. Various kinds of radiation treatment equipment and methods have been developed and constructed at the Hokkaido University. One of the most worlds wide famous one is the real time tumor tracking radiotherapy system. The FIRST (Funding for World-Leading Innovative R&D on Science and Technology) Program has been supporting us to produce cutting-edge technology. We hope that this symposium would help the audience to understand the latest technology for cancer treatment especially in the field of radiation therapy and also we wish the audience would recognize the importance of the research aspect that have been performed at Hokkaido University and its Hospital.

Changing trends in radiation therapy technologies in the last year of life for patients diagnosed with metastatic cancer in the United States.

BACKGROUND: Our goal was to investigate utilization trends for advanced radiation therapy (RT) technologies, such as intensity-modulated radiation therapy (IMRT) and stereotactic radiosurgery (SRS), in the last year of life among patients diagnosed with metastatic cancer. METHODS: We used the Surveillance, Epidemiology and End Results (SEER)-Medicare linked databases to analyze claims data in the last 12 months of life for 64,525 patients diagnosed with metastatic breast, colorectal, lung, pancreas, and prostate cancers from 2000 to 2007. Logistic regression modeling was conducted to analyze potential demographic, health services, and treatment-related variables' influences on receipt of advanced RT. RESULTS: Among the 19,161 (29.7%) patients who received radiation therapy, there was a significant decrease in the proportion of patients who received the simplest radiation technique (ie, 2D-radiation therapy) (P < .0001), and significant increases in the proportions of patients receiving more advanced radiation techniques (ie, IMRT, and SRS; P < .0001 for all curves); although the rates for use of IMRT and SRS in 2007 remained under 5%. On multivariate analyses, receipt of RT varied significantly by non-clinical characteristics such as race, marital status, neighborhood income, and SEER region. Patients who received hospice care in the last year of life were more likely to receive radiation therapy (OR = 1.35, 95% CI = 1.30-1.40) but less likely to be treated with IMRT (OR = 0.76, 95% CI = 0.62-0.92). CONCLUSIONS: Although the proportion of patients receiving RT in the last year of life for metastatic cancer did not change for most of the past decade, we observed significant trends toward more advanced radiation techniques.

Funding UK cancer care: time for a level playing field?

Improving cancer survival rates is a UK priority and equity of access to high quality cancer irrespective of geography is a key principle. Surgery, radiation therapy and systemic therapy remain the cornerstone of the multidisciplinary management of cancer. However, costs of cancer care continue to escalate. A recent review (1) estimated the global costs of cancer care caused by death and disability as US $895 billion (excluding indirect medical costs and based on 2008 figures). Approximately 49% of patients are cured by surgery, 40% by radiotherapy alone or in combination with other treatments and 11% by systemic therapy. With > 90,000 patients per annum treated with curative intent by radiotherapy in the UK, one would anticipate that access to modern radiotherapy techniques would have a high priority. However, there are substantial differences in the NHS uptake of new anti-cancer agents and advanced radiation technologies. In this article, these differences are explored and recommendations made for addressing them.

Trends in Radiation Therapy for Bone Metastases, 2015 to 2017: Choosing Wisely in the Era of Complex Radiation.

PURPOSE: Guidelines recommend short-course (≤10 fractions) external-beam radiation therapy (EBRT) for bone metastases. Stereotactic body radiation therapy (SBRT) may also improve outcomes; however, routine use is not recommended outside clinical trials. We assessed national radiation therapy trends in complex techniques for bone metastases and associated expenditures. METHODS AND MATERIALS: Using a claims-based Medicare data set covering 84% of beneficiaries, we assessed the relative proportion of all radiation episodes represented by bone metastases. We then evaluated use of short-course and long-course (>10 fractions) EBRT, intensity modulated radiation therapy (IMRT), and SBRT for bone metastases in hospital-affiliated outpatient (OPD) or freestanding (FREE) facilities. We assessed differences using χ2d or Wilcoxon rank sum tests for categorical and continuous variables, respectively. We identified associations with modality, fractionation, and expenditures using multivariable logistic/linear regression. RESULTS: Among 467,781 radiation episodes for 17 cancer diagnoses, the overall proportion of episodes dedicated to bone metastases (9.4%) was stable from 2015 to 2017, although treatments were increasing in the hospital-affiliated outpatient setting (P < .005). We identified 40,993 episodes for bone metastases, of which 63% were short-course EBRT, 24% were long-course EBRT, 7% were SBRT, and 6% were IMRT. Techniques more common in the hospital-affiliated outpatient setting included short-course EBRT (OPD, 69%, vs FREE, 56%) and SBRT (OPD, 9%, vs FREE, 5%). Techniques more common among free-standing centers included long-course EBRT (OPD, 19%, vs FREE, 31%) and IMRT (OPD, 4%, vs FREE, 9%). From 2015 to 2017, long-course EBRT decreased by an absolute 8%; short-course EBRT, SBRT, and IMRT increased by 4%, 2.5%, and 1%, respectively. The SBRT/IMRT uptake did not differ by setting (P = .4). Differences in expenditures between SBRT and short-course EBRT decreased by a relative 8% in professional and 12% in technical fees. CONCLUSIONS: Approximately 1 in 4 patients received long-course EBRT, with small reductions in use largely replaced by complex treatment modalities. However, expenditures for complex modalities also decreased over time. As alternative payment models take effect, quality metrics are needed to ensure appropriate, effective, and safe delivery of complex technologies.

Deep inspiration breath hold reduces the mean heart dose in left breast cancer radiotherapy.

BACKGROUND: Patients with left breast cancer who undergo radiotherapy have a non-negligible risk of developing radiation-induced cardiovascular disease (CVD). Cardioprotection can be achieved through better treatment planning protocols and through respiratory gating techniques, including deep inspiration breath hold (DIBH). Several dosimetric studies have shown that DIBH reduces the cardiac dose, but clinical data confirming this effect is limited. The aim of the study was to compare the mean heart dose (MHD) in patients with left breast cancer who underwent radiotherapy at our institution as we transitioned from non-gated free-breathing (FB) radiotherapy to gated radiotherapy (FB-GRT), and finally to DIBH. PATIENTS AND METHODS: Retrospective study involving 2022 breast cancer patients who underwent radiotherapy at West Pomeranian Oncology Center in Szczecin from January 1, 2014 through December 31, 2017. We compared the MHD in these patients according to year of treatment and technique. RESULTS: Overall, the MHD for patients with left breast cancer in our cohort was 3.37 Gy. MHD values in the patients treated with DIBH were significantly lower than in patients treated with non-gated FB (2.1 vs. 3.48 Gy, p < 0.0001) and gated FB (3.28 Gy, p < 0.0001). The lowest MHD values over the four-year period were observed in 2017, when nearly 85% of left breast cancer patients were treated with DIBH. The proportion of patients exposed to high (> 4 Gy) MHD values decreased every year, from 40% in 2014 to 7.9% in 2017, while the percentage of patients receiving DIBH increased. CONCLUSIONS: Compared to free-breathing techniques (both gated and non-gated), DIBH reduces the mean radiation dose to the heart in patients with left breast cancer. These findings support the use of DIBH in patients with left breast cancer treated with radiotherapy.

Under-recognized toxicities of cranial irradiation.

Cranial irradiation of primary or metastatic lesions is frequent, historically with 3D-conformal radiation therapy and now with stereotactic radiosurgery and intensity modulation. Evolution of radiotherapy technique is concomitant to systemic treatment evolution permitting long time survival. Thus, physicians have to face underestimated toxicities on long-survivor patients and unknown toxicities from combination of cranial radiotherapy to new therapeutics as targeted therapies and immunotherapies. This article proposes to develop these toxicities, without being exhaustive, to allow a better apprehension of cranial irradiation in current context.

Emerging radiotherapy technologies and trends in nasopharyngeal cancer.

Technology has always driven advances in radiotherapy treatment. In this review, we describe the main technological advances in radiotherapy over the past decades for the treatment of nasopharyngeal cancer (NPC) and highlight some of the pressing issues and challenges that remain. We aim to identify emerging trends in radiation medicine. These include advances in personalized medicine and advanced imaging modalities, standardization of planning and delineation, assessment of treatment response and adaptive re-planning, impact of particle therapy, and role of artificial intelligence or automation in clinical care. In conclusion, we expect significant improvement in the therapeutic ratio of radiotherapy treatment for NPC over the next decade.

Proton therapy for locally advanced non-small cell lung cancer.

Radiation therapy is an essential component of treatment for locally advanced non-small cell lung cancer (NSCLC) but can be technically challenging because of the proximity of lung tumors to nearby critical organs or structures. The most effective strategy for reducing radiation-induced toxicity is to reduce unnecessary exposure of normal tissues by using advanced technology; examples from photon (X-ray) therapy have included three-dimensional conformal radiation therapy versus its predecessor, two-dimensional radiation therapy, and intensity-modulated photon radiation therapy versus its predecessor, three-dimensional conformal therapy. Using particle-beam therapy rather than photons offers the potential for further advantages because of the unique depth-dose characteristics of the particles, which can be exploited to allow still higher dose escalation to tumors with greater sparing of normal tissues, with the ultimate goal of improving local tumor control and survival while preserving quality of life by reducing treatment-related toxicity. However, the costs associated with particle therapy with protons are considerably higher than the current state of the art in photon technology, and evidence of clinical benefit from protons is increasingly being demanded to justify the higher financial burden on the healthcare system. Some such evidence is available from preclinical studies, from retrospective, single-institution clinical series, from analyses of national databases, and from single-arm prospective studies in addition to several ongoing randomized comparative trials. This review summarizes the rationale for and challenges of using proton therapy to treat thoracic cancers, reviews the current clinical experience, and suggests topics for future research.