Radiotherapy Fractionation Research Articles

Facing problems in radiotherapy for breast cancer patients in Yogyakarta, Indonesia: A cohort retrospective study.

The aim of this study is to explore problems in radiotherapy for breast cancer patients in Yogyakarta, Indonesia, focusing on overall treatment time (OTT) and completion rate. A retrospective cohort study was conducted based on data from the Insurance Unit at a tertiary hospital in Yogyakarta, Indonesia. The study included all female outpatients with breast cancer who were treated with radiotherapy from January to December 2017 and met the inclusion criteria. The primary outcomes were OTT and completion rate. The secondary outcomes included the number of radiotherapy fractions, radiotherapy doses, number of radiotherapy interruption days, and reasons for radiotherapy interruption. The chi-squared and Mann-Whitney U tests were used to assess the differences in outcomes between two insurance schemes (JKN-PBI (Beneficiaries of Health Insurance Contribution Assistance) and JKN-NON-PBI (Non-Beneficiaries of Health Insurance Contribution Assistance)). The sample included 285 breast cancer patients (mean age: 53 years). The median OTT was 38 days (IQR: 17-48 days), with 123 (43.2%) patients having prolonged OTT. The completion rate was 57.9%. No significant differences in OTT (44.4% vs. 35.7%, p= 0.445) and completion rate (57.2% vs. 61.9%, p= 0.569) were found between the JKN-NON-PBI and JKN-PBI groups, respectively. In all, the data reported 3,022 interrupted days of radiotherapy across a total of 227 patients. The most common reason for radiotherapy interruption was unknown. There are problems in timely delivery and low completion rate of radiotherapy among breast cancer patients in Indonesia. There are no significant differences in OTT and completion rate between the insurance schemes.

Autoeczematization during radiation therapy – An unforeseen crumble

Radiotherapy induced acute skin reactions are common and an expected effect of radiotherapy. Radiation induced Eczematous eruptions, however, are rarely reported, with subsequent distant site eczema being infrequently seen and likely under recognized. The mechanism of autosensitization is poorly understood but seems to involve a cell-mediated immune response. Recognition is important to prevent excessive and inappropriate investigation and treatment. To the best of our knowledge and search, there are not many cases of such an autoimmune reaction to the radiation therapy. We present a unique case of eczematous reaction following 13 fractions of external beam radiotherapy in a case of non small cell carcinoma lung.

A COMPARATIVE PROSPECTIVE STUDY BETWEEN STANDARD AND ALTEREDFRACTIONATED RADIOTHERAPY FOR LOCALLY ADVANCED HEAD AND NECKSQUAMOUS CELL CARCINOMA

Background and Purpose: To compare conventionally fractionated chemoradiotherapy (CF-CRT) with two variants of altered fractionated radiotherapy (AFRT) in patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC). 64 patients diagnosed with LAHNSCC were randomized Material and Methods: either to receive CF-CRT (70 Gy/35 fractions) in Arm-I or hyper-fractionation radiotherapy (HFRT 81.6 Gy/68 fractions 1.2 Gy BID) in Arm-II or concomitant boost radiotherapy (CBT 71.6 Gy/28 fractions with last 16 fractions BID as concomitant boost) in Arm-III. 35mg/m2 cisplatin weekly was given as concurrent chemotherapy regimen in Arm-I. The primary objective was to assess acute toxicity, and the secondary endpoint was the radiotherapeutic response between CF-CRT and AFRT. Radiation Therapy Oncology Group (RTOG) criteria were used for evaluating acute toxicity. Response Evaluation Criteria In Solid Tumor 1.1 (RECIST 1.1) was used to assess response. Twenty-two, 21, and 21 Results: patients were randomly assigned to Arm-I, II, and III. The treatment was completed by 22, 17, and 18 patients in Arm-I, II, and III. The acute Grade-II skin toxicity was higher in Arm-II (58.8%) and III (50.0%) compared to Arm-I (36.3 %), but the correlation was insignicant (p- .17). Acute Grade-III mucosal toxicity was higher in Arm-II (35.2%) and III (38.8%), and it shows a trend towards signicance (p- .059). Arm-II had higher complete responder (52.9%) compared to Arm-I (27.2%), and the correlation was insignicant (p- .23). The AFRT Conclusion: arms II and III showed similar radiotherapeutic response as CF-CRT arm. Comparable acute toxicities were seen in all arms except for the mucosal toxicity, which was higher in Arm-II and III

Thoracic Radiotherapy in Extensive Disease Small Cell Lung Cancer: Multicenter Prospective Observational TRENDS Study.

(1) Introduction: Small cell lung cancer (SCLC) is an aggressive tumor type, accounting for about 15% of all lung cancers. Radiotherapy (RT) plays a fundamental role in both early and advanced stages. Currently, in advanced disease, the use of consolidative chest RT should be recommended for patients with good response to platinum-based first-line chemotherapy, but its use has not yet been standardized. The present prospective study aims to evaluate the pattern of care of consolidative chest RT in patients with advanced stage SCLC, and its effectiveness in terms of disease control and tolerability. (2) Materials and methods: This study was a multicenter prospective observational trial, proposed and conducted within the AIRO lung study group to evaluate the pattern of care of consolidative chest RT after first-line chemotherapy in patients with advanced SCLC. The patient and tumor characteristics, doses, fractionation and volumes of thoracic RT and prophylactic cranial irradiation (PCI), as well as the thoracic and extrathoracic response to the treatment, toxicity and clinical outcomes, were collected and analyzed. (3) Results: From January 2017 to December 2019, sixty-four patients were enrolled. Median follow-up was 33 months. The median age was 68 years (range 42-81); 38 patients (59%) were male and 26 (41%) female. Carboplatin + etoposide for 6 cycles was the most commonly used first-line therapeutic scheme (42%). With regard to consolidative chest RT, 56% of patients (35) received 30 Gy in 10 factions and 16 patients (26%) received 45 Gy in 15 sessions. The modulated intensity technique was used in 84.5% of cases, and post-chemotherapy macroscopic residual disease was the target volume in 87.5% of patients. Forty-four patients (69%) also underwent PCI. At the last follow-up, over 60% of patients did not experience chest disease progression, while 67% showed extrathoracic progression. At the first radiological evaluation after RT, complete response and stable disease were recorded in 6% and 46% of the cases, respectively. Two patients had a long-term complete response to the combined treatment. The brain was the first site of extrathoracic progression in 28%. 1y and 2y OS and PFS were 67%, 19%, 28% and 6%, respectively. Consolidative chest RT was well-tolerated in the majority of patients; it was interrupted in three cases (due to G2 pulmonary toxicity, disease progression and clinical decay, respectively). Only 1 patient developed G3 asthenia. (4) Conclusions: Consolidative chest RT has been shown to be useful in reducing the risk of thoracic disease progression and is absolutely well-tolerated in patients with advanced stage SCLC with good response after first-line chemotherapy. Among the Italian centers that participated in this study, there is still variability in the choice of fractionation and target volumes, although the guidelines contain clear recommendations. The aim of future research should be to clarify the role and modalities of chest RT in the era of immunotherapy in advanced-stage SCLC.

Palliative appropriateness criteria: external validation of a new method to evaluate the suitability of palliative radiotherapy fractionation

BackgroundRecently, the palliative appropriateness criteria (PAC) score, a novel metric to aid clinical decision-making between different palliative radiotherapy fractionation regimens, has been developed. It includes baseline parameters including but not limited to performance status. The researchers behind the PAC score analyzed the percent of remaining life (PRL) on treatment. The latter was accomplished by calculating the time between start and finish of palliative radiotherapy (minimum 1 day in case of a single-fraction regimen) and dividing it by overall survival in days from start of radiotherapy. The purpose of the present study was to validate this novel metric.Patients and methodsThe retrospective validation study included 219 patients (287 courses of palliative radiotherapy). The methods were identical to those employed in the score development study. The score was calculated by assigning 1 point each to several factors identified in the original study and using the online calculator provided by the PAC developers.ResultsMedian survival was 6 months and death within 30 days from start of radiotherapy was recorded in 13% of courses. PRL on treatment ranged from 1 to 23%, median 8%. Significant associations were confirmed between online-calculated PAC score, observed survival, and risk of death within 30 days from the start of radiotherapy. Patients with score 0 had distinctly better survival than all other groups. The score-predicted median risk of death within 30 days from start of radiotherapy was 22% in our cohort. A statistically significant correlation was found between predicted and observed risk (p < 0.001). The original and present study were not perfectly concordant regarding number and type of baseline parameters that should be included when calculating the PAC score.ConclusionThis study supports the dual strategy of PRL and risk of early death calculation, with results stratified for fractionation regimen, in line with the original PAC score study. When considering multifraction regimens, the PAC score identifies patients who may benefit from shorter courses. Additional work is needed to answer open questions surrounding the underlying components of the score, because the original and validation study were only partially aligned.

Post radiation mucosal ulcer risk after a hypofractionated stereotactic boost and conventional fractionated radiotherapy for oropharyngeal carcinoma

Background/purpose Post radiation mucosal ulcers (PRMU) after treatment for oropharyngeal squamous cell carcinoma (OPSCC) can have a huge negative impact on patients’ quality of life, but little is known concerning risk factors and the impact of fraction size. Therefore, the goal of this study was to determine the pattern of PRMU development and to identify risk factors after a hypofractionated stereotactic body radiotherapy boost (SBRT) compared to conventionally fractionated radiotherapy for OPSCC. Material and methods We performed a retrospective cohort study (N = 332) of OPSCC patients with ≥ 1-year disease-free survival, treated with 46 Gy Intensity Modulated Radiotherapy (IMRT) (2 Gy fractions) followed by either an SBRT boost of 16.5 Gy (5.5 Gy fractions) (N = 180), or 24 Gy IMRT (2 Gy fractions) (N = 152). PRMU (grade ≥ 2) was scored when observed > three months after the last radiotherapy (RT) fraction (CTCAE v5.0). Potential risk factors were analyzed with Cox regression models using death as competing risk. Dose at the PRMU site was calculated by projecting delineated PRMU on the planning CT. Results All cases of PRMU (N = 64) occurred within 24 months; all were grade 2. The cumulative incidence at 2 years in the SBRT boost group was 26% (N = 46) vs. 12% (N = 18) for conventional fractionation (p = 0.003). Most PRMU developed within nine months (N = 48). PRMU occurring > nine months (N = 16) were mainly observed in the SBRT boost group (N = 15). Sex (p = 0.048), acute tube feeding (p = < 0.001), tumor subsite tonsil (p = 0.001), and N stage (p = 0.017) were associated with PRMU risk at multivariable regression in the hypofractionated SBRT boost group. All 25 delineated PRMU were located within the high dose regions. Conclusion The risk of PRMU should be included in the cost benefit analysis when considering future research using a hypofractionated SBRT boost for OPSCC patients.

On Plasma Fractionation Treatment and Its Implications in Cells

Here, we present a novel plasma treatment regime—plasma fractionation, analogous to the concept of dose fractionation in radiotherapy, which could see the application in plasma-based cancer treatment. In plasma fractionation, a single acute dose of plasma is divided into multiple small dosages (fractionated dosages) and administered to the cells in vitro at 24-h intervals. We utilized a helium plasma jet and studied the effects of plasma fractionation in an immortalized keratinocyte line (HaCaT) and a squamous cell carcinoma line (A431). The effects were assessed over three cell seeding densities—8000, 3500, and 1000 cells/well. Our results show that at all seeding densities, plasma fractionation produced lower levels of cell death in both cell types compared to the same dose administered as a single plasma treatment. This highlights the potential of plasma fractionation as a potentially safer method to conduct plasma treatments in the future. We also show that A431 cells were more sensitive to a single acute plasma treatment than HaCaT cells, at cell densities that are subconfluent (1000 cells/well). A similar difference in sensitivity between HaCaT cells and A431 cells was not observed on exogenous treatment with hydrogen peroxide, pointing to the importance of other shorter lived plasma components.

Radiotherapy Fraction in Limited-Stage Small Cell Lung Cancer in the Modern Era: A Systematic Review and Meta-Analysis of 8006 Reconstructed Individual Patient Data.

The optimal thoracic radiotherapy (TRT) dose and fractionation for limited-stage small cell lung cancer (LS-SCLC) using modern techniques remain unclear. We conducted systematic review and meta-analyses of the efficacy and safety differences between definitive hypofractionated TRT (HypoTRT), conventional TRT (ConvTRT) and hyperfractionated TRT (HyperTRT), especially in the modern era. Eligible randomized controlled trials (RCTs), real-world cohorts, and single-arm trials published between 1990 and 2021 were identified. Two meta-analyses of overall survival (OS) were conducted: (i) a random-effects meta-analysis based on reconstructed individual-patient data (IPD) of all studies; and (ii) a Bayesian network meta-analysis based on study-level aggregated data (AD) of RCTs. The incidences of severe radiation-related toxicities were compared using the random-effects meta-regression model. Overall, 53 of the 30,031 publications met the inclusion criteria, and a total of 8006 IPD were reconstructed. After adjusting for key treatment variables and stratification by study type, there were no significant differences in the OS rates between the altered fractionation regimens (HypoTRT vs. HyperTRT, aHR [adjusted HR] = 1.05, 95% CI 0.93-1.19; ConvTRT vs. HyperTRT, aHR = 1.00, 95% CI 0·90-1.11; HypoTRT vs. ConvTRT, aHR = 1.05, 95% CI 0.91-1.20). In the modern era, the survival outcomes of all three schedules, while remaining comparable, have improved significantly. Results of the AD-based network meta-analysis were consistent with those of IPD analysis, and HypoTRT was ranked as the best regimen (SUCRA = 81%). There were no significant differences in toxicities between groups when using modern radiation techniques. In the modern era, no significant differences in OS or severe radiation-related toxicities were observed between altered schedules in LS-SCLC. HypoTRT may be associated with moderate and non-significant OS improvements, which should be further confirmed in prospective randomized phase III trials.

Current Trends and Challenges in Real-World Breast Cancer Adjuvant Radiotherapy: A Practical Review.

Background: The treatment of breast cancer (BC) remains a constant and rapidly evolving issue for multidisciplinary breast cancer teams. Considering the emerging understanding and advances in the biological course of this disease, new trends in radiotherapy fractionation, systemic therapies, and oncoplastic surgical techniques are revolutionizing adjuvant treatment approaches to BC. Novel challenges are questioning the integration of adjuvant radiotherapy (ART) into the real-world clinical setting. Methods: PubMed literature search was conducted in order to extract data supporting the role of new trends in breast cancer adjuvant approach according to rising issues in the multidisciplinary team discussion such as sequencing with chemotherapy (CT) plus whole breast hypofractionated radiotherapy (HF-WBRT); the role of ART after neoadjuvant CT (NACT) followed by breast conservative surgery (BCS) in early BC achieving pathological complete remission (pCR); and the integration of ART in immediate autologous breast oncoplastic reconstruction after mastectomy (a-IBR). Furthermore, there are still several concerns about toxicity with adjuvant trastuzumab emtansine (T-DM1) or breast re-irradiation after BCS relapse in long-term survivors refusing mastectomy. Results: Among 40 hits, only 12 studies answered to these issues. Many of them were retrospective studies. Less than 500 patients met the criteria for these issues and several conclusions were found exhaustive. Conclusion: Few issues seem to have literature solutions, while there are still open questions in regard to these new trends. Novel strategies through prospective or randomized studies and new consensus guidelines are required.

Advancing the treatment of localized prostate cancer with MR-guided radiotherapy.

External beam radiotherapy (EBRT) is an important cornerstone in the treatment of localized prostate cancer. Current image-guided radiotherapy (IGRT) techniques allow for more accurate and precise delivery of radiation treatment by the use of imaging before each fraction. Magnetic resonance guided radiotherapy (MRgRT) is the next step in IGRT with hybrid systems combining linear accelerators with MRI-scanners. With MRgRT, it is possible to visualize pelvic anatomy in great detail and subsequently perform replanning of the radiation dose distribution before each radiotherapy fraction. This technique has the potential to increase the therapeutic window of EBRT, by improved normal tissue sparing due to margin reduction and more accurate target dose delivery. This is particularly promising for prostate cancer, with its biology lending itself to ultra-hypofractionation, reducing radiotherapy treatment to as little as five fractions. Also, recent studies have shown that focal dose escalation to the intraprostatic tumor to high ablative doses can substantially increase disease-free survival. In this article, we discuss these unique opportunities as well as the potential future benefits of MRgRT in prostate cancer treatment.

Dosimetric comparison of fixed field dynamic IMRT and VMAT techniques in simultaneous integrated boost radiotherapy of prostate cancer

High-risk prostate cancer can take advantage of the combination of hypofractionated radiotherapy and pelvic conventional fraction radiotherapy. The comparison between fixed field dynamic IMRT and VMAT techniques can provide suggestions for clinical treatment. We selected 10 high-risk prostate cancer patients who received radiotherapy at the cancer center of Sun Yat-sen University from January 2016 to December 2019. The targets contained in prostate, seminal vesicles and pelvic lymph nodes. With the same prescription and optimized parameters, 9F, single-arc (1ARC) and double-arc (2ARC) treatment plans were developed. The dose distribution of the targets, OAR, MU, treatment time and gamma pass ratios of dose verification was compared. The D2% (69.37 ± 0.89) Gy, D50% (66.92 ± 0.63) Gy, HI (0.09 ± 0.02), and CI (0.83 ± 0.05) of PTV1 in 9F were slightly better than those of 1ARC which were (71.13 ± 1.21) Gy, (68.50 ± 0.76) Gy, (0.12 ± 0.02), (0.74 ± 0.07), except D98%, the difference was significant (P < .05). All dosimetry indices of PTV1 in 9F and 2ARC were close and have no significant differences (P > .05). The V95% (99.45 ± 0.78)% of PTV2 in 9F was slightly better than that in 1ARC (99.35 ± 1.28)%. The difference was significant (P < .05). All dosimetry indices of PTV2 in 9F and 2ARC were close and the difference was not significant (P > .05). The Dmean of the bladder and the V67.5 Gy of rectum between all three plans were similar. The Dmean of left and right femoral in 1ARC and 2ARC were lower than that in 9F, and the difference was significant (P < .05). Other dosimetry indices of OARs in 9F were lower than those in 1ARC and 2ARC, and much lower than 1ARC. The difference was significant (P < .05). Mean monitor units in 1ARC and 2ARC were fewer by 70.0% and 67.2% in comparison with 9F. The treatment mean time in 1ARC and 2ARC was shorter by 81.7% and 61% in comparison with 9F. Verification pass ratios of γ (3%/3 mm) were 97.8% (9F), 98.9% (1ARC) and 99.4% (2ARC) respectively. The difference was significant (P < .05). Compared with IMRT, VMAT improved delivery efficiency noticeably. Two arcs provided comparable tumor dosimetry coverage, but performed worse in dose sparing for bladder, rectum and small bowel. The IMRT plan was preferable to VMAT in prostate cancer simultaneous integrated boost radiotherapy.

Combination of immune checkpoint inhibitors with radiation therapy in cancer: A hammer breaking the wall of resistance.

Immuno-oncology is an emerging field in the treatment of oncological diseases, that is based on recruitment of the host immune system to attack the tumor. Radiation exposure may help to unlock the potential of the immune activating agents by enhancing the antigen release and presentation, attraction of immunocompetent cells to the inflammation site, and eliminating the tumor cells by phagocytosis, thereby leading to an overall enhancement of the immune response. Numerous preclinical studies in mouse models of glioma, murine melanoma, extracranial cancer, or colorectal cancer have contributed to determination of the optimal radiotherapy fractionation, as well as the radio- and immunotherapy sequencing strategies for maximizing the antitumor activity of the treatment regimen. At the same time, efficacy of combined radio- and immunotherapy has been actively investigated in clinical trials of metastatic melanoma, non-small-cell lung cancer and renal cell carcinoma. The present review summarizes the current advancements and challenges related to the aforementioned treatment approach.

P53 Modulates Radiosensitivity in Head and Neck Cancers-From Classic to Future Horizons.

p53, initially considered a tumor suppressor, has been the subject of research related to cancer treatment resistance in the last 30 years. The unfavorable response to multimodal therapy and the higher recurrence rate, despite an aggressive approach, make HNSCC a research topic of interest for improving therapeutic outcomes, even if it is only the sixth most common malignancy worldwide. New advances in molecular biology and genetics include the involvement of miRNA in the control of the p53 pathway, the understanding of mechanisms such as gain/loss of function, and the development of different methods to restore p53 function, especially for HPV-negative cases. The different ratio between mutant p53 status in the primary tumor and distant metastasis originating HNSCC may serve to select the best therapeutic target for activating an abscopal effect by radiotherapy as a "booster" of the immune system. P53 may also be a key player in choosing radiotherapy fractionation regimens. Targeting any pathway involving p53, including tumor metabolism, in particular the Warburg effect, could modulate the radiosensitivity and chemo-sensitivity of head and neck cancers.

A comparative and prospective study of two different radiation fractionation schedules with concurrent chemotherapy in locally advanced head-and-neck squamous cell carcinoma

Background: Accelerated fractionation radiotherapy has radiobiological advantage of preventing accelerated tumor repopulation and logistic advantage of treating more patients than conventionally fractionated radiotherapy because of its relatively shorter treatment duration. Aims and Objectives: In this study, we compared accelerated fractionation with conventionally fractionated radiotherapy in terms of tumor response and acute toxicities for the treatment of locally advanced head-and-neck carcinomas. Materials and Methods: Patients with Stage III and IVA carcinoma of head-and-neck region were randomized into two groups. The study group patients received accelerated radiotherapy to a total dose of 66Gy in 33 fractions, 2Gy/fraction, 6 fractions/week over a time period of 5.5 weeks. Control group received conventionally fractionated radiotherapy to same total dose and fraction size but 5 fractions/week, over a time period of 6.5 weeks. Both groups received concurrent weekly Cisplatin. All patients were followed up weekly for treatment related acute toxicity during the treatment and then at every month for 6 months after completion of treatment. Results: About 26.6% patients of study arm achieved complete response in comparison to 25.6% of control arm, but the difference was not statistically significant (P=0.957). Although statistically not significant, higher grade of skin toxicity (60%vs.35%, P=0.179) and xerostomia (46% vs. 29%, P=0.155) was also numerically higher in accelerated fractionation. Conclusion: For locally advanced head-and-neck carcinoma, accelerated fractionation radiotherapy with concurrent chemotherapy can be considered as an acceptable and effective alternative of conventionally fractionated concurrent chemoradiotherapy in terms of treatment response and acute toxicity profile.

Optimization of antitumor radiotherapy fractionation via mathematical modeling with account of 4 R’s of radiobiology

A spatially-distributed continuous mathematical model of solid tumor growth and treatment by fractionated radiotherapy is presented. The model explicitly accounts for the factors, widely referred to as 4 R’s of radiobiology, which influence the efficacy of radiotherapy fractionation protocols: tumor cell repopulation, their redistribution in cell cycle, reoxygenation and repair of sublethal damage of both tumor and normal tissues. With the use of special algorithm the fractionation protocols that provide increased tumor control probability, compared to standard clinical protocol, are found for various physiologically-based values of model parameters under the constraints of fixed overall normal tissue damage and maximum admissible fractional dose. In particular, it is shown that significant gain in treatment efficacy can be achieved for tumors of low malignancy by the use of protracted hyperfractionated protocols. The optimized non-uniform protocols are characterized by gradual escalation of fractional doses in their last parts, which start after the levels of oxygen and nutrients significantly elevate throughout the tumor and accelerated tumor proliferation manifests itself, which is a well-known experimental phenomenon.

The Impact of COVID-19 on Radiotherapy Services in Scotland, UK: A Population-based Study

AimsThe effect of the COVID-19 pandemic on cancer radiotherapy services is largely unknown. The aim of the present study was to investigate the impact of the resultant contingency plans on radiotherapy cancer services in Scotland. Materials and methodsDetailed data of radiotherapy activity at our centre were collected from 1 April 2019 to 31 March 2021. Differences in mean weekly radiotherapy courses, dose and fractionation patterns and treatment intent were compared with corresponding pre-pandemic months for all treatment sites. Qualitative data were collected for a subgroup of radical radiotherapy patients. ResultsTotal radiotherapy courses decreased from 6968 to 6240 (–10%) compared with the previous year, prior to the pandemic. Average weekly radiotherapy courses delivered were 134 (standard deviation ±13), decreasing by 10% to 120 (standard deviation 15) (Welch's t-test, P < 0.001). The greatest decrease in new start treatment courses was observed from May to August 2020 (–7.7%, –24.0%, –16.7% and –18.7%) compared with the corresponding months in 2019. A significant reduction was seen for female patients <70 years (–16%) compared with females >70 years (–8%) or their male counterparts (–7% and –6%, respectively). By diagnosis, the largest reductions between pre- and post-pandemic levels were for anal (–26%), breast (–18%) and prostate (–14%) cancer. Contrarily, a significant increase was found for bladder (28%) and oesophageal (11%) cancers. ConclusionsOver the first 12 months of the COVID-19 pandemic, radiotherapy activity significantly decreased compared with the 12 months prior. Due to issued guidance, the use of hypofractionated regimens increased, contributing to the reduction in treatments for some tumour sites. An increase in other tumour sites can probably be attributed to the reduction or cancellation of surgical interventions. These results will inform our understanding of the indirect consequences of the pandemic on radiotherapy services.

The initial experience of MRI-guided precision prone breast irradiation with daily adaptive planning in treating early stage breast cancer patients.

A major challenge in breast radiotherapy is accurately targeting the surgical cavity volume. Application of the emerging MRI-guided radiotherapy (MRgRT) technique in breast radiotherapy may enable more accurate targeting and potentially reduce side effects associated with treatment. To study the feasibility of delivering MRI-guided partial breast radiotherapy or Precision Prone Irradiation (PPI) to treat DCIS and early stage breast cancer patients. Eleven patients with diagnosed DCIS or early stage breast cancer treated with lumpectomy underwent CT-based and MRI-based simulations and treatment planning in the prone position. MRI-guided radiotherapy was utilized to deliver partial breast irradiation. A customized adaptive plan was created for each delivered radiotherapy fraction and the cumulative doses to the target volumes and nearby organs at risk were determined. The CT-based and the MRI-guided radiotherapy plans were compared with respect to target volumes, target volume coverage, and dose to nearby organs. All patients receiving PPI successfully completed their treatments as planned. Clinical target volume (CTV) and planning target volume (PTV) dose coverage and organs-at-risk (OAR) dose constraints were met in all fractions planned and delivered and the MRI-guided clinical target volumes were smaller when compared to those of the CT-based partial breast radiotherapy plans for these eleven patients. MRI-guided partial breast radiotherapy as a breast radiotherapy technology is feasible and is a potential high clinical impact application of MRgRT. PPI has the potential to improve the therapeutic index of breast radiotherapy by more accurately delivering radiation dose to the cavity target and decreasing toxicities associated with radiation to the surrounding normal tissues. Prospective clinical data and further technical refinements of this novel technology may broaden its clinical implementation.

Cost-effectiveness of 5 fraction and partial breast radiotherapy for early breast cancer in the UK: model-based multi-trial analysis

PurposeWe estimated the cost-effectiveness of 4 radiotherapy modalities to treat early breast cancer in the UK. In a subgroup of patients eligible for all modalities, we compared whole-breast (WB) and partial breast (PB) radiotherapy delivered in either 15 (WB15F, PB15F) or 5 fractions (WB5F, PB5F). In a subgroup ineligible for PB radiotherapy, we compared WB15F to WB5F.MethodsWe developed a Markov cohort model to simulate lifetime healthcare costs and quality-adjusted life years (QALYs) for each modality. This was informed by the clinical analysis of two non-inferiority trials (FAST Forward and IMPORT LOW) and supplemented with external literature. The primary analysis assumed that radiotherapy modality influences health only through its impact on locoregional recurrence and radiotherapy-related adverse events.ResultsIn the primary analysis, PB5F had the least cost and greatest expected QALYs. WB5F had the least cost and the greatest expected QALYs in those only eligible for WB radiotherapy. Applying a cost-effectiveness threshold of £15,000/QALY, there was a 62% chance that PB5F was the cost-effective alternative in the PB eligible group, and there was a 100% chance that WB5F was cost-effective in the subgroup ineligible for PB radiotherapy.ConclusionsHypofractionation to 5 fractions and partial breast radiotherapy modalities offer potentially important benefits to the UK health system.

Circulating levels of IL-6 and TGF-β1 in patients with prostate cancer undergoing radiotherapy: associations with acute radiotoxicity and fatigue symptoms

BackgroundThe goal of research was to investigate the possible relations between serum concentrations of IL-6 and TGF-β1, individual and clinical characteristics, and adverse effects of radiotherapy in patients with prostate cancer: acute and late genitourinary and gastrointestinal toxicity, and fatigue.MethodsThirty-nine patients with localized or locally advanced prostate cancer who were treated with radiotherapy were enrolled in this study. The acute radiotoxicity grades and fatigue levels were assessed during the radiotherapy and 1 month after the radiotherapy. Estimation of the late radiotoxicity was performed every three months in the first year, every four months in the second year, and then every six months. Serum levels of IL-6 and TGF-β1 were determined before radiotherapy and after the 25th radiotherapy fraction by ELISA.ResultsThe significant positive association between diabetes mellitus and changes in acute genitourinary toxicity grades during the radiotherapy was observed in prostate cancer patients. In addition, patients who were smokers had significantly higher maximum fatigue levels in comparison with patients who were non-smokers. The circulating IL-6 levels were significantly higher after the 25th radiotherapy fraction in comparison with levels determined before radiotherapy. The significant positive correlations between pretreatment TGF-β1 levels and maximum genitourinary toxicity grades and between TGF-β1 levels after the 25th fraction and genitourinary toxicity grades after the 25th fraction, were found. The pretreatment IL-6 concentrations and TGF-β1 concentrations after the 25th fraction were positively correlated with maximum genitourinary toxicity grades. The IL-6 levels after the 25th fraction were positively associated with genitourinary toxicity grades after this fraction. The pretreatment IL-6 concentrations were significantly positively correlated with maximum fatigue scores. The significant positive correlation between IL-6 concentrations and fatigue scores after the 25th fraction was determined. The positive correlations between IL-6 and TGF-β1 concentrations measured after the 25th fraction and maximum fatigue scores were observed.ConclusionsOur results suggest that serum levels of IL-6 and TGF-β1 might influence the severity of acute genitourinary radiotoxicity and fatigue in patients with prostate cancer. Combining clinical parameters and circulating cytokine levels might be useful for the prediction of adverse reactions to radiotherapy.

Tumor Outcomes for ROMAN: Phase 3 Trial of Avasopasem Manganese (GC4419) for Severe Oral Mucositis (SOM) in Patients Receiving Chemoradiotherapy (CRT) for Locally Advanced Head and Neck Cancer (LAHNC)

<h3>Purpose/Objective(s)</h3> Intensity-modulated radiotherapy (IMRT) plus cisplatin is an established treatment for LAHNC, but ∼70% of patients develop SOM (WHO grade [gr] 3 or 4), limiting their ability to eat solids (gr 3) or liquids (gr 4), and often requiring feeding tube nutrition. There are no US-approved drugs to reduce SOM in LAHNC. A radiotherapy (RT)-induced burst of superoxide initiates oral mucositis (OM) development (Sonis 2004). Avasopasem (GC4419, AVA) is an investigational selective small molecule dismutase mimetic designed to convert superoxide to hydrogen peroxide, which may protect normal cells from, and potentially sensitize cancer cells to, RT (Riley DP 2006, El-Mahdy 2020). In a randomized, double-blind phase 2b trial, AVA reduced duration and incidence of SOM due to CRT for LAHNC vs placebo (PBO) (Anderson 2019) and maintained 2-yr tumor outcomes. The present trial (NCT03689712) further assessed safety and efficacy of AVA to reduce SOM due to CRT for LAHNC of the oral cavity (OC) or oropharynx (OP). <h3>Materials/Methods</h3> Double-blind, PBO-controlled trial; patients receiving 60-72 Gy of IMRT (≥50 Gy to ≥2 OM sites) plus cisplatin (weekly or q3 weeks) were randomized 3:2 to IV AVA 90 mg vs PBO M-F before each RT fraction. OM by the WHO scale was assessed by trained evaluators biweekly during RT & weekly for 2 weeks thereafter. Primary endpoint: SOM (WHO gr 3 or 4) incidence through the end of IMRT. Secondary endpoints included SOM duration through 2 weeks post-IMRT, gr 4 OM incidence through the end of IMRT, and tumor outcomes. <h3>Results</h3> N=455 randomized, 407 (241 AVA/166 PBO) primary analysis population; med. age 61; 86% male; 82% OP. Statistically significant 16% relative reduction in SOM incidence (54% vs 64%; <i>p</i>=0.045) and 56% relative reduction in SOM duration (median, 8 vs 18 days; <i>p</i>=0.002) were observed. Gr 4 incidence was reduced 27% (<i>p</i>=0.052). Improvement was seen in multiple secondary and exploratory endpoints (table). Adverse event frequencies were comparable between treatment groups without clear AVA-specific toxicity or increase in cisplatin-attributable toxicity. Available tumor outcome data will be reported. <h3>Conclusion</h3> AVA produced statistically significant, clinically meaningful improvement of SOM vs PBO that was consistent across multiple measures of SOM, with an adverse event profile consistent with expectations for IMRT/cisplatin. Tumor outcomes will be reported. Funder Galera Therapeutics, Inc.