Advances in personalized radiotherapy.

Radiotherapy is a mainstay of cancer treatment. The clinical response to radiotherapy is heterogeneous, from a complete response to early progression. Recent studies have explored the importance of patient characteristics in response to radiotherapy. In this editorial, we invite contributions for a BMC Cancer collection of articles titled 'Advances in personalized radiotherapy' towards the improvement of treatment response.

A Review of the Evolving Role of Radiotherapy in the Treatment of Neuroendocrine Neoplasms.

BACKGROUND: Neuroendocrine neoplasms (NENs) are rare tumours that develop from neuroendocrine cells in various parts of the body. The management of this disease poses a significant challenge because of the heterogeneous clinical presentation and varying degrees of aggressiveness. A multidisciplinary approach is often required in complex clinical situations. Radiotherapy (RT) plays a key role in managing NETs in both curative and palliative settings. SUMMARY: In this review, we summarize and discuss recent developments in the field of advanced RT in early-stage, locally advanced, and metastatic NENs. We highlight limitations in current approaches and discuss future potential treatment strategies for patients with NENs.

Contemporary radiotherapy: present and future.

Oncology care is increasingly a multidisciplinary endeavour, and radiation therapy continues to have a key role across the disease spectrum in nearly every cancer. However, the field of radiation oncology is still one of the most poorly understood of the cancer disciplines. In this Review, we attempt to summarise and contextualise developments within the field of radiation oncology for the non-radiation oncologist. We discuss advancements in treatment technologies and imaging, followed by an overview of the interplay with advancements in systemic therapy and surgical techniques. Finally, we review new frontiers in radiation oncology, including advances within the metastatic disease continuum, reirradiation, and emerging types of radiation therapy.

A Century of Fractionated Radiotherapy: How Mathematical Oncology Can Break the Rules.

Radiotherapy is involved in 50% of all cancer treatments and 40% of cancer cures. Most of these treatments are delivered in fractions of equal doses of radiation (Fractional Equivalent Dosing (FED)) in days to weeks. This treatment paradigm has remained unchanged in the past century and does not account for the development of radioresistance during treatment. Even if under-optimized, deviating from a century of successful therapy delivered in FED can be difficult. One way of exploring the infinite space of fraction size and scheduling to identify optimal fractionation schedules is through mathematical oncology simulations that allow for in silico evaluation. This review article explores the evidence that current fractionation promotes the development of radioresistance, summarizes mathematical solutions to account for radioresistance, both in the curative and non-curative setting, and reviews current clinical data investigating non-FED fractionated radiotherapy.

Radiotherapy resources in Africa: an International Atomic Energy Agency update and analysis of projected needs.

The number of patients with cancer in Africa has been predicted to increase from 844 279 in 2012 to more than 1·5 million in 2030. However, many countries in Africa still lack access to radiotherapy as a part of comprehensive cancer care. The objective of this analysis is to present an updated overview of radiotherapy resources in Africa and to analyse the gaps and needs of the continent for 2030 in the context of the UN Sustainable Development Goals. Data from 54 African countries on teletherapy megavoltage units and brachytherapy afterloaders were extracted from the Directory for Radiotherapy Centres, an electronic, centralised, and continuously updated database of radiotherapy centres. Cancer incidence and future predictions were taken from the GLOBOCAN 2018 database of the International Agency for Research on Cancer. Radiotherapy need was estimated using a 64% radiotherapy utilisation rate, while assuming a machine throughput of 500 patients per year. As of March, 2020, 28 (52%) of 54 countries had access to external beam radiotherapy, 21 (39%) had brachytherapy capacity, and no country had a capacity that matched the estimated treatment need. Median income was an important predictor of the availability of megavoltage machines: US$1883 (IQR 914-3269) in countries without any machines versus $4485 (3079-12480) in countries with at least one megavoltage machine (p=0·0003). If radiotherapy expansion continues at the rate observed over the past 7 years, it is unlikely that the continent will meet its radiotherapy needs. This access gap might impact the ability to achieve the Sustainable Development Goals, particularly the target to reduce preventable, premature mortality by a third, and meet the target of the cervical cancer elimination strategy of 90% with access to treatment. Urgent, novel initiatives in financing and human capacity building are needed to change the trajectory and provide comprehensive cancer care to patients in Africa in the next decade.

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.

Anal Squamous Cell Carcinoma: Radiation Therapy Alone Must Be Avoided.

BACKGROUND: Anal squamous cell carcinoma (ASCC) is the most common histological subtype of anal cancer. Rates have been observed to increase in recent years. Combined chemoradiotherapy (CCRT) is currently the gold standard of treatment. The aim of this study is to assess ASCC prevalence, treatment trends, and overall survival (OS) in the United States. METHODS: Patients diagnosed with stage I-IV ASCC were identified from the National Cancer Database from 2004 to 2015. The primary outcome was 5-year OS, which was analyzed using Kaplan-Meier survival curves, log-rank test, and Cox proportional hazards models. RESULTS: 34,613 cases were included (stage I: 21.45%; II: 41.00%; III: 31.62%; IV: 5.94%), with an increasing trend in prevalence. CCRT was the most used treatment. Multimodal treatment, combining surgery with CCRT, offered the best OS rates for stage I, II, and IV cancers (I: 84.87%; II: 75.12%; IV: 33.08%), comparable with survival of stage III patients treated with CCRT (III: 61.14%). Radiation alone had the worse OS rates, and on adjusted analysis, radiation treatment alone had the greatest risk of mortality (I: hazard ratio, 2.01; 95% confidence interval, 1.14-3.54; P = 0.016; II: 2.05, 1.44-2.93, P < 0.001; IV: 1.99, 0.99-4.02, P = 0.054). CONCLUSIONS: ASCC has increased in prevalence, notably in stage III and IV disease. Although CCRT is the most commonly used treatment type for all stages of ASCC, multimodal treatment offers better OS in stages I, II, and IV. Treatment with radiation alone offers the worst OS no matter the stage and should no longer be used as a solitary treatment modality.

FLASH Radiotherapy: Current Knowledge and Future Insights Using Proton-Beam Therapy.

FLASH radiotherapy is the delivery of ultra-high dose rate radiation several orders of magnitude higher than what is currently used in conventional clinical radiotherapy, and has the potential to revolutionize the future of cancer treatment. FLASH radiotherapy induces a phenomenon known as the FLASH effect, whereby the ultra-high dose rate radiation reduces the normal tissue toxicities commonly associated with conventional radiotherapy, while still maintaining local tumor control. The underlying mechanism(s) responsible for the FLASH effect are yet to be fully elucidated, but a prominent role for oxygen tension and reactive oxygen species production is the most current valid hypothesis. The FLASH effect has been confirmed in many studies in recent years, both in vitro and in vivo, with even the first patient with T-cell cutaneous lymphoma being treated using FLASH radiotherapy. However, most of the studies into FLASH radiotherapy have used electron beams that have low tissue penetration, which presents a limitation for translation into clinical practice. A promising alternate FLASH delivery method is via proton beam therapy, as the dose can be deposited deeper within the tissue. However, studies into FLASH protons are currently sparse. This review will summarize FLASH radiotherapy research conducted to date and the current theories explaining the FLASH effect, with an emphasis on the future potential for FLASH proton beam therapy.

[Application and Development Trend of Medical Image Automatic Segmentation Technology in Radiation Therapy].

The development of medical image segmentation technology has been briefly reviewed. The applications of auto-segmentation of organs at risk and target volumes based on Atlas and deep learning in the field of radiotherapy have been introduced in detail, respectively. Then the development direction and product model for general automatic sketching tools or systems based on solid clinical data are discussed.

Definitive external-beam radiotherapy versus radical prostatectomy in clinically localized high-risk prostate cancer: a retrospective study.

BACKGROUND: Optimal treatment of high-risk prostate cancer remains controversial. We aimed to compare treatment outcomes of prostate cancer patients treated with definitive external-beam radiotherapy (ExRT) or radical prostatectomy (RP). METHODS: The records of 120 high-risk clinical stage T2b-T4 N0 M0 prostate cancer patients treated with definitive ExRT or RP were reviewed. Patients with pretreatment prostate-specific antigen (PSA) levels ≥20 ng/mL or clinical ≥T3 stage or Gleason score (GS) ≥8 were included in the study. Biochemical failure free survival (BFFS), distant metastasis free survival (DMFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed. Cox regression analysis was performed to determine predictors of BF. RESULTS: Seventy-two patients received definitive ExRT with androgen-deprivation therapy in 95.8% and 48 patients underwent RP with pelvic lymph node dissection. Mean age (67.7 ± 6.6 vs 64.5 ± 7.6 year, p = 0.017) and the rate of patients with PSA levels ≥20 ng/mL (69.4% vs 47.9%, p = 0.022) were higher in the definitive ExRT group than the RP group. Distributions of GS and clinical T stage were similar. Mean follow-up was 60.2 ± 30.3 months in the definitive ExRT group and 41.3 ± 21.5 months in the RP group (p <  0.001). Twenty-five % of the RP group received adjuvant ExRT and 41.7% received salvage ExRT. Biochemical failure was significantly higher (52.1% vs 21.4%, p <  0.001) and the mean BFFS was significantly lesser (34.4 ± 3.9 vs 97.8 ± 5.9 months, p < 0.001) in the RP group than the definitive ExRT group. However, DMFS, CSS and OS were similar in both groups. In multivariate analysis, being in the RP group significantly increased the risk of BF (p < 0.001). Furthermore, not receiving pelvic lymphatic irradiation in the definitive ExRT group (p = 0.048) and having positive surgical margin in the RP group (p = 0.050) increased the risk of BF. CONCLUSIONS: BF was significantly higher and the mean BFFS was significantly lesser in high-risk prostate cancer patients undergoing RP than definitive ExRT while DMFS, CSS and OS were similar in both treatment groups.

Postmastectomy Radiation Therapy (PMRT) before and after 2-Stage Expander-Implant Breast Reconstruction: A Systematic Review.

Background: In those undergoing treatment for breast cancer, evidence has demonstrated a significant improvement in survival, and a reduction in the risk of local recurrence in patients who undergo postmastectomy radiation therapy (PMRT). There is uncertainty about the optimal timing of PMRT, whether it should be before or after tissue expander or permanent implant placement. This study aimed to summarize the data reported in the literature on the effect of the timing of PMRT, both preceding and following 2-stage expander-implant breast reconstruction (IBR), and to statistically analyze the impact of timing on infection rates and the need for explantation. Methods: A comprehensive systematic review of the literature was conducted using the PubMed/Medline, Ovid, and Cochrane databases without timeframe limitations. Articles included in the analysis were those reporting outcomes data of PMRT in IBR published from 2009 to 2017. Chi-square statistical analysis was performed to compare infection and explantation rates between the two subgroups at p < 0.05. Results: A total of 11 studies met the inclusion criteria for this study. These studies reported outcomes data for 1565 total 2-stage expander-IBR procedures, where PMRT was used (1145 before, and 420 after, implant placement). There was a statistically significant higher likelihood of infection following pre-implant placement PMRT (21.03%, p = 0.000079), compared to PMRT after implant placement (9.69%). There was no difference in the rate of explantation between pre-implant placement PMRT (12.93%) and postimplant placement PMRT (11.43%). Conclusion: This study suggests that patients receiving PMRT before implant placement in 2-stage expander-implant based reconstruction may have a higher risk of developing an infection.

Quantitative survival impact of composite treatment delays in head and neck cancer.

BACKGROUND: Multidisciplinary management of head and neck cancer (HNC) must reconcile increasingly sophisticated subspecialty care with timeliness of care. Prior studies examined the individual effects of delays in diagnosis-to-treatment interval, postoperative interval, and radiation interval but did not consider them collectively. The objective of the current study was to investigate the combined impact of these interwoven intervals on patients with HNC. METHODS: Patients with HNC who underwent curative-intent surgery with radiation were identified in the National Cancer Database between 2004 and 2013. Multivariable models were constructed using restricted cubic splines to determine nonlinear relations with overall survival. RESULTS: Overall, 15,064 patients were evaluated. After adjustment for covariates, only prolonged postoperative interval (P < .001) and radiation interval (P < .001) independently predicted for worse outcomes, whereas the association of diagnosis-to-treatment interval with survival disappeared. By using multivariable restricted cubic spline functions, increasing postoperative interval did not affect mortality until 40 days after surgery, and each day of delay beyond this increased the risk of mortality until 70 days after surgery (hazard ratio, 1.14; 95% confidence interval, 1.01-1.28; P = .029). For radiation interval, mortality escalated continuously with each additional day of delay, plateauing at 55 days (hazard ratio, 1.25; 95% confidence interval, 1.11-1.41; P < .001). Delays beyond these change points were not associated with further survival decrements. CONCLUSIONS: Increasing delays in postoperative and radiation intervals are associated independently with an escalating risk of mortality that plateaus beyond certain thresholds. Delays in initiating therapy, conversely, are eclipsed in importance when appraised in conjunction with the entire treatment course. Such findings may redirect focus to streamlining those intervals that are most sensitive to delays when considering survival burden. Cancer 2018. © 2018 American Cancer Society.

ÖGRO survey on radiotherapy capacity in Austria : Status quo and estimation of future demands.

BACKGROUND: A comprehensive evaluation of the current national and regional radiotherapy capacity in Austria with an estimation of demands for 2020 and 2030 was performed by the Austrian Society for Radiation Oncology, Radiobiology and Medical Radiophysics (ÖGRO). MATERIALS AND METHODS: All Austrian centers provided data on the number of megavoltage (MV) units, treatment series, fractions, percentage of retreatments and complex treatment techniques as well as the daily operating hours for the year 2014. In addition, waiting times until the beginning of radiotherapy were prospectively recorded over the first quarter of 2015. National and international epidemiological prediction data were used to estimate future demands. RESULTS: For a population of 8.51 million, 43 MV units were at disposal. In 14 radiooncological centers, a total of 19,940 series with a mean number of 464 patients per MV unit/year and a mean fraction number of 20 (range 16-24) per case were recorded. The average re-irradiation ratio was 14%. The survey on waiting times until start of treatment showed provision shortages in 40% of centers with a mean waiting time of 13.6 days (range 0.5-29.3 days) and a mean maximum waiting time of 98.2 days. Of all centers, 21% had no or only a limited ability to deliver complex treatment techniques. Predictions for 2020 and 2030 indicate an increased need in the overall number of MV units to a total of 63 and 71, respectively. CONCLUSION: This ÖGRO survey revealed major regional differences in radiooncological capacity. Considering epidemiological developments, an aggravation of the situation can be expected shortly. This analysis serves as a basis for improved public regional health care planning.

Interaction between Medical Treatment and Minimally Invasive Surgical Treatment for the Malignancies of the Digestive Tract.

Recently, endoscopic diagnosis and treatment methods for early cancer in the digestive tract have made rapid progress. As for surgery, laparoscopic and thoracoscopic techniques have achieved rapidly advancing development in the last 2 decades. Early detection of the malignant lesion and the evolution of endoscopic and surgical device enabled in performing the minimally invasive surgery. Collaboration of medical treatment and minimally invasive surgery for advanced cancer is ongoing in the case of some conditions and in a few institutes. In this review, the contents of the core symposia on "Interaction between medical treatment and minimally invasive surgical treatment for the malignancies of the digestive tract", held at the 11, 12 and 13th annual meeting of the Japanese Gastroenterological Association, are summarized. At each annual meeting, the core symposium focused primarily on gastric, colorectal, and esophageal cancer treatment. For gastric cancer, endoscopic resection and laparoscopic surgery were 2 important key words. For colorectal cancer, multidisciplinary therapy was a major key word. And for esophageal cancer, endoscopic resection, chemoradiotherapy, thoracoscopic surgery and salvage surgery were key words. Patients' survival and quality of life are expected to further advance as a result of the collaboration of such therapeutic modalities.

Returning to work after multimodal treatment in glioblastoma patients.

OBJECTIVE Although multimodal treatment for glioblastoma (GBM) has resulted in longer survival, uncertainties exist regarding health-related quality of life and functional performance. Employment represents a useful functional end point and an indicator of social reintegration. The authors evaluated the rate of patients resuming their employment and the factors related to work capacity. METHODS The authors performed a retrospective study of working-age patients treated with surgery and radiochemotherapy between 2012 and 2015. Data were collected before and after surgery and at 6, 12, 18, and 24 months. Employment was categorized according to the French Socio-Professional Groups and analyzed regarding demographic and clinical data, performance status, socio-professional category, radiological features, type, and quality of resection. RESULTS A total of 125 patients, mean age 48.2 years, were identified. The mean follow-up was 20.7 months with a median survival of 22.9 months. Overall, 21 patients (18.3%) went back to work, most on a part-time basis (61.9%). Of the patients who were alive at 6, 12, 18, and 24 months after diagnosis, 8.7%, 13.8%, 15.3%, and 28.2%, respectively, were working. Patients going back to work were younger (p = 0.03), had fewer comorbidities (p = 0.02), and had a different distribution of socio-professional groups, with more patients belonging to higher occupation categories (p = 0.02). Treatment-related symptoms (36.2%) represented one of the main factors that prevented the resumption of work. Employment was strongly associated with performance status (p = 0.002) as well as gross-total removal (p = 0.04). No statistically significant difference was found regarding radiological or molecular features and the occurrence of complications after surgery. CONCLUSIONS GBM diagnosis and treatment has a significant socio-professional impact with only a minority of patients resuming work, mostly on a part-time basis.

Survival trends of oligodendroglial tumor patients and associated clinical practice patterns: a SEER-based analysis.

There is limited information on the management strategies and survival trends for oligodendroglioma patients. Here we used the Surveillance, Epidemiology and End Results (SEER, 1999-2012) database to analyze the historical trends of oligodendroglioma patient survival and correlate these trends to evolving clinical practice of radiation therapy (RT) use and surgical practice of gross total resection (GTR). We identified 2689 World Health Organization (WHO) grade II oligodendroglioma (abbreviated as O2) and 1191 WHO grade III oligodendroglioma (abbreviated as O3). Time-trend analyses were performed for overall survival, radiation treatment (RT) use, and extent of surgical resection (EOR). In multivariable Cox models that accounted for age, race, sex, tumor size, tumor location, EOR, and RT status, the hazard of dying from O3 has significantly decreased over the study period (p  <  0.01), while the hazard of dying from O2 has remained largely unchanged. A search of the published literature revealed articles reporting results largely supportive of these observations. The pattern of surgical practice and RT for O3 patients remained unchanged throughout the study period, suggesting that the survival improvement may be related to evolving patterns of medical management. Results from the SEER database indicate significant gains have been made in survival for O3 patients between 1999 and 2012. Such gains were not observed for O2 patients during this study period.