RT Treatment Research Articles

TRIBBLES1 (TRIB1) Pseudokinase Induces Treatment Resistance in GBM by Promoting Survival of Tumor Cells through the Akt Pathway

<h3>Purpose/Objective(s)</h3> Glioblastoma (GBM; WHO grade IV) is the most aggressive form of glioma with a dismal 5-year survival rate. The current therapies are largely ineffective and therapy resistance is commonly encountered. Therefore, there is an urgent need to identify druggable therapeutic targets in GBM. In this study we identified TRIB1, a Ser/Thr pseudokinase that functions as a scaffold to initiate Ubiquitin Proteasome System-mediated degradation of target proteins in the cell. It has also been shown to activate the MAPK and Akt signaling cascades in various cell types. Reports also suggest that TRIB1 contributes to chemotherapy resistance in various cancers. Therefore, we evaluated the role of TRIB1 in GBM cell proliferation/ survival and its contribution to therapy resistance. <h3>Materials/Methods</h3> We utilized patient-centered reverse translational approach to identify novel therapeutic targets. To this end, TRIB1 was identified by statistical association (Cox regression analysis) of the patient-derived mRNA profiling data publicly available from TCGA GBM cohort. TRIB1 was functionally validated <i>in vitro</i> by generating stable overexpression cell lines by antibiotic selection. TRIB1 was conditionally knocked down by doxycycline induction. Co-immunoprecipitation was performed to evaluate protein-protein interactions. Protein levels were detected by western blotting. Site-directed mutagenesis was performed to mutate specific amino acid. Patient derived primary cell lines overexpressing the wild type and mutant (W337A) Trib1 transgenes were injected intracranially to create tumors in nude mice. Changes in tumor volume and overall survival (OS) were determined. <h3>Results</h3> The mRNA profiling of TCGA GBM cohort revealed that increased <i>TRIB1</i> gene expression was associated with worse OS of GBM patients (HR=1.3 (1.0-1.5); P=0.019). Mice bearing TRIB1 transgene overexpressing tumors had highest tumor volume and lowest OS whereas mice bearing TRIB1-W337A tumors had the highest OS and lower tumor volume when measured. We also observed that overexpression of TRIB1 caused a decrease in apoptosis of primary GBM cell lines after RT and TMZ treatments <i>in vitro</i>. Overexpression of TRIB1 also increased the phosphorylation/activation of Akt in patient derived primary cell lines. Akt activation was similarly decreased after TRIB1 knockdown. TRIB1 bound directly to Akt in these cells. Following PI3K inhibition, Akt phosphorylation was detected to a greater level in TRIB1 overexpressing cells. <h3>Conclusion</h3> Our data suggest that heightened expression of TRIB1 in GBM cells contributes to RT/TMZ resistance by activating the prosurvival Akt signaling cascades. Therefore, targeting TRIB1 mediated Akt activation could provide a therapeutic benefit over targeting Akt directly, which may reduce Akt's oncogenic signal without risking the toxicity associated with available Akt- specific inhibitors.

Left Anterior Descending Coronary Artery Radiation Dose Association with All-Cause Mortality in NRG Oncology Trial RTOG 0617

Left Anterior Descending Coronary Artery Radiation Dose Association with All-Cause Mortality in NRG Oncology Trial RTOG 0617

Changes Over Time for Radiation Oncology Reimbursement for Specific Treatment Courses

<h3>Purpose/Objective(s)</h3> Radiation oncology (RO) has seen declines in Medicare reimbursement (MCR) and will see an additional $300 million projected decline if the RO Alternative Payment Model (RO-APM) is implemented. To our knowledge there are no contemporary studies analyzing changes in MCR over time for common RO treatment courses. Understanding how reimbursement for RO courses has changed over time will provide a baseline comparison for the RO-APM, as MCR under RO-APM is episode-based. Our study aims to quantify changes in MCR for common photon RT treatment courses from 2010 to 2020. We hypothesize that the declines will be highest for IMRT treatment courses. <h3>Materials/Methods</h3> CMS Physician/Supplier Procedure Summary databases were used to obtain reimbursement for all RO procedures in 2010, 2015, and 2020 for free-standing facilities. Average reimbursement (AR) per billing instance was calculated for each Healthcare Common Procedure Coding System code using 2020-adjusted dollars. For each RT course, a RO billing expert selected the codes associated with that course along with the billing frequency of each code. For each year, the billing frequency of each code for a given treatment was multiplied by the AR per code and the results summed. AR for 15 common RO courses were analyzed: head and neck (HN), breast (B), prostate (P), lung (L), and palliative (Pa)(Table). <h3>Results</h3> AR decreased for all 15 courses from 2010 to 2020. From 2015 to 2020, the only course that increased in AR was palliative 2D 30 Gy/10 (0.4% increase). IMRT courses saw the largest AR decline from 2010 to 2020. The AR for a 37-fx prostate bed IMRT plan averaged $32.1K in 2010, $23K in 2015 (-28%), and $19.7K in 2020 (-39%). The AR for a 5-fx IMRT accelerated partial breast irradiation (APBI) averaged $6.9K in 2010, $5.2K in 2015 (-25%) and $4.2K in 2020 (-39%). <h3>Conclusion</h3> We report significant declines in MCR from 2010 – 2020 for common RO courses with the largest declines for IMRT. Hypofractionated regimens were not spared severe cuts, discouraging its broader adoption. Policymakers should consider the significant cuts to MCR that have already occurred when considering further cuts, and the negative impact of such cuts on quality and access to care.

Safety and Feasibility of Simultaneous Integrated Boost in Extreme 1-Week Hypofractionated Radiotherapy for Early Breast Cancer

<h3>Purpose/Objective(s)</h3> The phase 3 FAST-Forward trial reported that 26 Gy in 5 fractions (fx) over 1 week for early-breast cancer patients after breast conserving surgery was non-inferior to the standard 40 Gy in 15fx over 3 weeks for local tumor control and normal tissue effects. In this study, a sequential tumor bed boost was allowed (10 or 16 Gy in 2 Gy/fx) if required. The aim of our study is to evaluate the safety and feasibility of a simultaneous integrated boost (SIB) up to 29/30 Gy over 5fx in order to avoid treatment lengthening when a boost is indicated. <h3>Materials/Methods</h3> From March 2020 to December 2021, 126 patients eligible for 5fx-RT schedule were referred to our institution and selected for the analysis. A SIB to the tumor bed up to 29 Gy in 5fx of 5,8 Gy was indicated when any of the following criteria appeared: Age < 60 years, high-grade tumors and lymphovascular or perineural invasion. When positive margins were observed in the histological exam, a SIB up to 30 Gy in 5fx of 6 Gy was prescribed. Patient´s toxicity was assessed at 4 different points: During RT and at 1-, 6- and 12-months follow-up. Toxicity was evaluated using CTCAE 5.0 criteria. <h3>Results</h3> Mean follow-up was 6.25 months and mean age was 56 years (32-83). During RT course, no toxicities were observed. G1-2 dermatitis was observed in 9 patients at first month assessment, but all of them had disappeared at 6 months after RT. According to skin-color changes, 11% of the patients presented skin hyperpigmentation at first month assessment but in most cases was not observed in subsequent evaluations. Only 4% of the patients presented G1 fatigue and skin induration in the first medical visit after RT. No severe toxicities were found in any patient at any time during follow-up. Complete details are shown in table 1. In addition, one patient developed mastitis during the first month after RT but was easily solved with oral antibiotics. <h3>Conclusion</h3> According to our data, administration of SIB up to 29/30 Gy in 5fx is safe and feasible for early-breast cancer patients requiring adjuvant RT after breast conserving surgery. SIB could replace sequential boost in these patients shortening the RT treatment and improving patients' compliance and comfort. Further follow-up is needed in order to assess chronic toxicity.

P18.05.A Bevacizumab in atypical and anaplastic meningiomas: the BEMEN study

Abstract Background meningiomas are the most frequent primary brain tumours. The current standard treatment for atypical and anaplastic meningioma can include surgical resection and radiotherapy. Despite the high rate of relapse no systemic treatment is indicated. Few data are available regarding the effectiveness of bevacizumab (BEV) in this setting. We performed a retrospective analysis investigating the efficacy and safety of BEV in meningioma patients relapsed after receiving surgery and radiotherapy. Gene mutations were also collected Material and Methods we retrospectively analyzed patients treated with off-label BEV at the Veneto Institute of Oncology from July 2019 to February 2022. Major inclusion criteria were histologically-confirmed diagnosis of grade 2-3 meningioma (according to WHO 2016 classification), previous treatment with surgery and radiotherapy, no indication to further surgical reintervention or reirradiation, absence of major contraindications to the use of BEV. Data were estrapolated from local clinical records. Bevacizumab was administered at 10 or 5mg/Kg every 2 weeks (at physician’s discretion) until progressive disease/death or unacceptable toxicity. Kaplan-Meier curves were used to estimate the survival rate; CTCAE v 5.0 was used to estimate treatment-related toxicities; RANO criteria were used for radiological assessment; NGS Foundation One panel was used to examine molecular data Results the median follow up was 13 months (3-30 range). 26 patients were enrolled. Median age was 68 ys (29-84); male pts were 16 (61%); 61% (16 pts) with atypical meningioma, 38.5% (10 pts) with anaplastic meningioma; 27% (7 pts) had underwent 2 or more surgeries; 58% had had 2 or more RT treatments; 96.1% (25 pts) received &amp;lt;2 previous lines of systemic treatment. 77% (20 pts) and 23% (6) received BEV 10 and 5mg/Kg every 2 weeks, respectively. For 61% of patients (16 pts), NGS analyses were available; 62% (10 pts) harboured NF2 mutations (1 patient had a confirmed diagnosis of neurofibromatosis type 2), 23% (6 pts) CDKN2A/2B deletion, 11% (3 pts) PTEN mutation, 8% (2 pts) FGFR mutation, 8% (2 pts) JAK alteration. Overall survival (OS) rate was 82% and 62% at 6 and 12 months respectively; 6 months PFS rate was 83%. 4 patients showed PR, 11 SD, 6 PD, no patient had CR; 5 patients were not evaluable for response. Among evaluable patients the disease control rate (stability+response) was 71% and the objective response rate was 19%. Median PFS and OS were not reached19% (5 pts) experienced CTCAE grade 1 or 2 toxicity, mainly hypertension (4 pts); 1 patient experienced grade 3 hypertension. Conclusion BEV showed very promising activity in recurrent grade 2-3 meningioma. The treatment was well tolerated. BEV should be considered an optimal therapeutic option in this setting of meningioma patients. The NGS results might be useful in identifying targetable mutations in case of further recurrence

Frailty-the missing constraint in radiotherapy treatment planning for older adults.

Current demographic changes translate into an increased frequency of cancer in older adults. Available data show that about 45-55% of the new cancer patients will need RT treatments, with an expected increase of 20-30% in the future. To provide the best cancer care it is mandatory to assess frailty, offer appropriate curative treatments to patients and personalise them for the frail. Based on published data, the median prevalence of frailty in older population is about 42%. Recently, the free radical theory of frailty has been proposed stating that oxidative damage is more prevalent in frail patients. In parallel, RT is one of the most frequent cancer treatments offered to older adults and is a source of external free radicals. RT dose constraints correlate with toxicity rates, so we open the question whether frailty should be considered when defining these constraints. Thus, for this paper, we will highlight the importance of frailty evaluation for RT treatment decisions and outcomes.

Potential effect of acupuncture in xerostomia induced by radiotherapy in head and neck cancer patients: a randomized preliminary study

ObjectiveThe aim of the present exploratory work was to investigate if acupuncture objectively improves xerostomia and if results are sufficiently relevant to perform further studies. Material and methodsA preliminary clinical study, randomized, non-blinded and controlled with a waiting list was designed. The initial sample of the study consisted of 33 patients with malignant neoplasia in the head and neck area, submitted to RT treatment between October 2014 and May 2015 in the Radiotherapy Service of Centro Hospitalar do Porto at Oporto (Portugal). After applying inclusion/exclusion criteria the final patient's sample consisted of 18 patients randomized in two groups (experimental and control groups). The experimental group (EG) was submitted to 8 acupuncture sessions. The control group (CG) consisted of patients of the “waiting list”. All patients were subjected to the sialometry and modified Schimer tests. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core Module (QLQ-C30) and Head and Neck Module (QLQ-H&N35) were also used. ResultsThere was a statistically significant increase in the amount of saliva (p < 0.001) and an increase in salivary flow, without stimulation (p = 0.001) and with stimulation (p = 0.011), when comparing experimental and control group. There was also an improvement in the “dry mouth sensation” in EG (p = 0.03) and a tendency to improve symptoms associated with xerostomia in the EG. ConclusionsDespite the methodological limitations, our study suggests that the acupuncture treatment used can objectively increase salivary production (flow and quantity) and improve the quality of life of the patients. There were not detected side effects associated with acupuncture. These results are sufficiently relevant to perform further studies.

The dynamic changes of soil air‐filled porosity associated with soil shrinkage in a Vertisol

AbstractSoil aeration is critical for crop growth, which is generally assessed by air‐filled porosity (AFP). In non‐rigid soils with high shrinkage and swelling, the AFP is not only related to the total porosity and soil moisture, but also to the soil shrinkage behaviour. However, the relationship between AFP and soil shrinkage has not been clarified. The objectives of this study were to (1) establish a mathematical equation to describe the behaviours of AFP associated with soil shrinkage (AFPsh); and (2) to evaluate the influence of tillage practice on the AFPsh. Undisturbed soil core samples were collected from the 0–10 cm to 10–20 cm layers in a Vertisol under four tillage treatments (No tillage, NT; Rotary tillage, RT; Subsoiling, SS; Deep ploughing, DP) to measure the changes in the volumes of soil core, soil water and air at different soil matric potentials. Our results showed that an equation of AFPsh as a function of moisture ratio (ϑ) was well established based on the developed soil shrinkage model (R2 &gt; 0.990, RMSE &lt;0.012). Compared with the AFP under a constant pore assumption (AFPc), the AFPsh was significantly decreased by 10.6% to 60.3% as soil water matric potentials were at &lt;−33 kPa in the 0–10 cm layer or at &lt;−10 kPa in the 10–20 cm layer (p &lt; 0.05). According to the AFPsh curve of the Vertisol, soil moisture content (θ) was approximately 68%–80% of the field capacity when AFPsh reached non‐limiting status (0.10 cm3 cm−3), where the soil matric potential was close to the wilting point (−1500 kPa). Deep tillage treatment (SS and DP) increased AFPsh, showing good performance in decreasing the risk of soil aeration deficit relative to the NT and RT treatment. Our results demonstrate that neglecting the porosity variations during shrinkage may lead to a high bias in the AFP prediction.Highlights An equation of AFP associated with soil shrinkage was established. AFP was significantly decreased when soil shrinkage was considered for a Vertisol. The Vertisol was easily subjected to both water and air stress due to soil shrinkage. Deep tillage practises improved soil aeration in the Vertisol.

Dynamics of Soil Organic Carbon and CO2 Flux under Cover Crop and No-Till Management in Soybean Cropping Systems of the Mid-South (USA)

The transition of natural landscapes to agricultural uses has resulted in severe loss of soil organic carbon, significantly contributing to CO2 emissions and rising global temperatures. However, soil has the largest store of terrestrial carbon (C), a considerable sink and effective strategy for climate change mitigation if managed properly. Cover crops (CC) and no-till (NT) management are two management strategies that are known to increase percent organic carbon (%OC); however, adoption of these practices has been low in the mid-South due to lack of region-specific research and resistance to unproven practices. Therefore, the purpose of this study was to evaluate the impacts of CC-NT treatments in soybean cropping systems on soil percent organic carbon (%OC) and CO2 flux following long-term implementation. Results showed significantly greater %OC in NT (1.27% ± 0.03) than reduced till (RT; 1.10% ± 0.03; p &lt; 0.001) and greater in both CC (rye: 1.23% ± 0.03, rye + clover: 1.22% ± 0.03) than no cover (1.11% ± 0.03; p &lt; 0.001). Bacterial abundance (p = 0.005) and pH (p = 0.006) were significant predictors of %OC. There was no overall significant difference in CO2 flux between tillage or CC treatments; however, there were significant differences between NT and RT in July of 2020 when %RH increased (p &lt; 0.001). Bacterial abundance negatively impacted CO2 flux (p &lt; 0.05), which contradicts most studies. The rate of proportional change and pattern of variability in C pools suggested loss of %OC in RT treatments that were not apparent when considering %OC alone. The results of this study provide valuable insight into C turnover and the effectiveness of CC use in the Mid-South to increase soil C stocks.

Risk and prognosis of secondary bladder cancer after radiation therapy for pelvic cancer.

BackgroundRadiation therapy (RT) is a crucial modality for the local control of pelvic cancer (PC), but the effect of pelvic RT on the development of secondary malignancy is still unclear. This study aimed to identify the relationship between radiation therapy received for the treatment of primary PC and subsequent secondary bladder cancer (SBC).MethodsThe Surveillance, Epidemiology, and End Results (SEER) database (from 1975 to 2015) was queried for PC. Fine-gray competing risk regression and Cox regression analyses were employed to assess the cumulative incidence of SBC. Poisson regression and multiple primary standardized incidence ratios (SIR) were used to evaluate the radiotherapy-associated risk for patients receiving RT. Subgroup analyses of patients stratified by latency time since PC diagnosis, calendar year of PC diagnosis stage, and age at PC diagnosis were also performed. Overall survival (OS) was compared among different treatment groups with SBC by Kaplan–Meier analysis.ResultsA total of 318,165 observations showed that the primary cancers were located in pelvic cavity, 256,313 patients did not receive radiation therapy (NRT), 51,347 patients who underwent external beam radiation therapy (EBRT), and 10,505 patients receiving a combination of EBRT and brachytherapy (EBRT–BRT) who developed SBC. Receiving two types of radiotherapy was strongly consistent with a higher risk of developing SBC for PC patients in Fine-Gray competing risk regression (NRT vs. EBRT, adjusted HR= 1.71, 95% CI: 1.54-1.90, P<0.001; NRT vs. EBRT–BRT, adjusted HR= 2.16, 95% CI: 1.78-2.63, P<0.001). The results of the dynamic SIR and Poisson regression analysis for SBC revealed that a slightly increased risk of SBC was observed after RT in the early latency and was significantly related to the variations of age at PC diagnosis and decreased with time progress. For OS, the SBC after NRT, SBC after EBRT, and SBC after EBRT-BRT of 10-year survival rates were 37.9%, 29.2%, and 22.2%, respectively.ConclusionRadiotherapy for primary PC was associated with higher risks of developing SBC than patients unexposed to radiotherapy. Different pelvic RT treatment modalities had different effects on the risk of SBC.

Treatment of multiple adjacent RT 1 gingival recessions with the modified coronally advanced tunnel (MCAT) technique and a collagen matrix or palatal connective tissue graft: 9-year results of a split-mouth randomized clinical trial

ObjectivesTo evaluate the long-term outcomes following treatment of RT 1 multiple adjacent gingival recessions (MAGR) using the modified coronally advanced tunnel (MCAT) with either a collagen matrix CM or a connective tissue graft (CTG).Material and methodsSixteen of the original 22 subjects included in a randomized, controlled split-mouth clinical trial were available for the 9-year follow-up (114 sites). Recessions were randomly treated by means of MCAT + CM (test) or MCAT + CTG (control). Complete root coverage (CRC), mean root coverage (MRC), gingival recession depth (GRD), probing pocket depth (PD), keratinized tissue width (KTW), and thickness (KGT) were compared with baseline values and with the 12-month results.ResultsAfter 9 years, CRC was observed in 2 patients, one in each group. At 9 years, MRC was 23.0 ± 44.5% in the test and 39.7 ± 35.1% in the control group (p = 0.179). The MRC reduction compared to 12 months was − 50.1 ± 47.0% and − 48.3 ± 37.7%, respectively. The upper jaw obtained 31.92 ± 43.0% of MRC for the test and 51.1 ± 27.8% for the control group (p = 0.111) compared to the lower jaw with 8.3 ± 46.9% and 20.7 ± 40.3%. KTW and KGT increased for both CM and CTG together from 2.0 ± 0.7 to 3.1 ± 1.0 mm (< 0.0001). There were no statistically significant changes in PD.ConclusionThe present results indicate that (a) treatment of MAGR using MCAT in conjunction with either CM or CTG is likely to show a relapse over a period of 9 years, and (b) the outcomes obtained in maxillary areas seem to be more stable compared to the mandibular ones.Clinical relevanceThe mean root coverage at 12 months could not be fully maintained over 9 years. On a long-term basis, the results seem to be less stable in the mandible as compared to maxillary areas.

Chitosan-coated compound fertilizer application and crop rotation alleviate continuous cotton cropping obstacles by modulating root exudates

Crop rotation combined with chitosan-coated compound fertilizer (CCCF) application could effectively solve continuous cropping obstacles (CtO), but how it affect crop root exudates to solve CtO remains unclear. In this study, soils (0–20 cm in depth) subjected to 20-years continuous cotton cropping and 20-year cotton-maize-wheat rotation were collected and used for the four treatments including continuous cropping (Ct), continuous cropping combined with CCCF application (CtC), crop rotation (Rt), and crop rotation combined with CCCF application (RtC) in a pot experiment. The soil bacterial community structure was analyzed by sequencing technology, and the root exudates, soil nutrient contents, and enzyme activities were also measured. The results showed that soil nutrient availability and soil enzyme activities in the CtC, Rt, and RtC treatments significantly increased compared with those in the Ct treatment (p < 0.05). The root exudates except for proline, salicylic acid, and coumaric acid increased in the Ct treatment, while all root exudates reduced in the CtC, Rt, and RtC treatments. Specially, coumaric acid was only detected in the Rt and RtC treatments. The contents of proline and salicylic acid in the CtC treatment increased compared with those in Ct treatment. Further, the relative abundance of Actinobacteria (Actin-), Acidobacteria (Acido-), and Gemmatimonadetes (Gemma-) all decreased in the CtC, Rt, and RtC treatment, while that of Proteobacteria (Prote-), Chloroflexi (Chlor-), and Bacteroidetes (Bacte-) all increased compared with those in Ct treatment. Correlation analysis between root exudates and bacterial phyla showed that coumaric acid, proline, and salicylic acid were negatively correlated with Actin-, and Myxococcota (Myxoc-), Methylomirabilota (Methy-). This may be due to that coumaric acid, the root exudate of the previous crop (wheat), can inhibit the propagation of Actin-, Acido-, and Gemma-, there by improving soil nutrient availability and enzyme activity. Besides, CCCF can inhibit Actin-, Methyl-, and Others by increasing the contents of proline and salicylic acid and the relative abundances of Prote-, Chlor-, and Bacte- and regulating the relationship between root exudates and rhizosphere soil environment (nutrients, enzyme activity, and bacterial diversity), thus solving CtO. This study will help us better understand the mechanism by which crop rotation combined with CCCF application solves CtO.

A scientific approach to skin radiotherapy nursing Article 3 - The skin RT prescription and plan especially in relation to volume and dose

Nurses play an important role in the RT of skin and its diseases. This is the third of four articles that attempts to provide a scientific basis for nurses to better understand skin RT patients, skin and its diseases, and acute RT skin reactions and how to care for them to achieve the best outcomes from RT treatments. The first paper outlined the role of the nurse as an integral part of the radiation oncology team and how to conduct an effective patient assessment to ensure the patient’s optimal journey to treatment completion. The second article described the anatomy, physiology, pathology and radiobiology of skin and its diseases. This third article describes the skin RT prescription and plan, especially in relation to volume and dose. The fourth paper will show how the nurse, by applying the knowledge from the previous articles, can predict, explain and care for any side effects that may arise. This knowledge is important for establishing patient expectations, preparing the patient for side effects, and giving scientifically based reasons for complying with care protocols. Hopefully, these articles will help support the nurse to deliver best care to skin RT patients. More prospective research is needed to elucidate the many remaining facets of nursing care for skin RT patients.

Early Prediction of Planning Adaptation Requirement Indication Due to Volumetric Alterations in Head and Neck Cancer Radiotherapy: A Machine Learning Approach.

Simple SummaryEarly prediction of significant alterations of head and neck (HN) cancer volume due to radiation therapy (RT) could provide an indication for necessary planning adaptations of the RT dose, tumor and organs at risk anatomy. However, the irregularities of the underlying cancer tissue and the patient-specific responses to RT render the prognostics for the tumor’s behavior exceedingly complex. In this study, a data-driven machine learning approach is proposed that incorporates the radiomic features of the low-dosage cone beam CT (CBCT) images clinically used in image-guided radiotherapy treatments in a feature selection and classification framework. The proposed model achieved high prediction performance, while able to identify indicative image characteristics for early prediction, further investigated in terms of their implications in HN cancer treated with RT.Background: During RT cycles, the tumor response pattern could affect tumor coverage and may lead to organs at risk of overdose. As such, early prediction of significant volumetric changes could therefore reduce potential radiation-related adverse effects. Nevertheless, effective machine learning approaches based on the radiomic features of the clinically used CBCT images to determine the tumor volume variations due to RT not having been implemented so far. Methods: CBCT images from 40 HN cancer patients were collected weekly during RT treatment. From the obtained images, the Clinical Target Volume (CTV) and Parotid Glands (PG) regions of interest were utilized to calculate 104 delta-radiomics features. These features were fed on a feature selection and classification procedure for the early prediction of significant volumetric alterations. Results: The proposed framework was able to achieve 0.90 classification performance accuracy while detecting a small subset of discriminative characteristics from the 1st week of RT. The selected features were further analyzed regarding their effects on temporal changes in anatomy and tumor response modeling. Conclusion: The use of machine learning algorithms offers promising perspectives for fast and reliable early prediction of large volumetric deviations as a result of RT treatment, exploiting hidden patterns in the overall anatomical characteristics.

Long-Term Disease Control After locoregional Pelvic Chemoradiation in Patients with Advanced Anal Squamous Cell Carcinoma.

IntroductionThe incidence of metastatic squamous cell carcinoma of the anus (SCCA) is increasing. Even if systemic docetaxel, cisplatin, and 5-Fluorouracil (DCF) provide a high rate of long-term remission, the role of pelvic chemoradiation (CRT) is unknown in this setting. We reported the safety and efficacy of local CRT in patients with synchronous metastatic SCCA who achieved objective response after upfront DCF.MethodsPatients included in Epitopes HPV01 or Epitopes HPV02 or SCARCE trials and treated with DCF followed by pelvic CRT were included. Concurrent chemotherapy was based on mitomycin (MMC) (10 mg/m² for two cycles) and fluoropyrimidine (capecitabine 825 mg/m² twice a day at each RT treatment day or two cycles of intra-venous 5FU 1000 mg/m² from day 1 to day 4). Primary endpoints were safety, local complete response rate, and local progression-free survival (PFS). Secondary endpoints were PFS, overall survival (OS), and metastasis-free survival (MFS).ResultsFrom 2013 to 2018, 16 patients received DCF followed by a complementary pelvic CRT for advanced SCCA. Median follow-up was 42 months [range, 11-71]. All patients received the complete radiation dose. Compliance to concurrent CT was poor. Overall, 13/15 of the patients (87%) had at least one grade 1-2 acute toxicity and 11/15 of the patients (73%) had at least one grade 3-4 toxicity. There was no treatment-related death. The most frequent grade 3-4 adverse effects were neutropenia (36%), dermatitis (40%), and anitis (47%). Eleven patients (73%) had at least one chronic grade 1 or 2 toxicity. One patient had a grade 4 chronic rectitis (7%). Complete local response rate was 81% at first evaluation and 62.5% at the end of the follow-up. Median local PFS was not reached and the 3-year local PFS was 77% (95%CI 76.8-77).ConclusionsIn patients with metastatic SCCA who had a significant objective response after upfront DCF, local CRT was feasible with high complete local response rate. The good local control rate, despite interruptions due to toxicities and low CT compliance, underline the role of pelvic RT. The high rate of toxicity prompts the need to adapt CRT regimen in the metastatic setting.

Radiographers’ perception on the provision of psychosocial support for cancer patients

Abstract Introduction: Therapeutic radiographers are the first point of contact for cancer patients undergoing radiotherapy treatment and therefore have an important role in providing both physical and psychosocial support to these patients. This study aimed to evaluate therapeutic radiographers’ perception about their role in identifying and providing psychosocial support for patients receiving RT treatment. Method: The study used a cross-sectional, prospective research design. A self-designed questionnaire was distributed to all therapeutic radiographers (n = 26) working at a radiotherapy department in Malta. Results: A total of 21 therapeutic radiographers completed the questionnaire. All participants felt that the provision of psychological care was an important part of their role as therapeutic radiographers. The majority of the participants reported having the most confidence in giving treatment-related symptoms advice rather than psychological support. The most common barrier to providing psychological support was lack of training (95·2%), followed by the lack of an appropriate screening tool (85·7%), availability of private space to talk to patients (76·2%) and a lack of knowledge (61·9%). Conclusion: While most therapeutic radiographers believed that providing psychosocial support was an important aspect of their role, several barriers prevented them from fulfilling this role. Training, the introduction of a psychosocial screening tool and clear referral processes are recommended to improve radiotherapy service.

Improved crop protection and biodiversity of the agroecosystem by reduced tillage in rice paddy fields in southern China

Agricultural sustainability has benefited from the broad adoption of conservation agriculture (CA) practices for decades, in which the reduction of mechanical disturbances to soil (also known as reduced tillage, RT) is one of the most essential principles for CA implementation. Many studies have recommended the advantages of CA practices in the promotion of biodiversity, but the integrated impacts on crop productivity and biodiversity remain unclear. Since CA has been applied in rice production in the subtropical area of southern China for several years, the effects of CA, particularly the RT methods, need to be evaluated for the local and long-term adoption. In this study, we established an integrated network to illustrate how the reduction of tillage intensity influenced organisms including invertebrates (such as rice pests and their predators), pathogens and weeds, and then led to an impact on rice yield. The two-year study demonstrated that major rice pests, such as rice planthoppers, stem borers and apple snails, were effectively controlled by RT practice. Similarly, the occurrence of common diseases declined with less tillage. Compared to the conventional tillage (CT) treatment, the density of weeds in paddy fields deceased significantly in the RT treatment. In addition, the diversity and richness of pest predators increased remarkably in paddy fields where either reduced or no tillage was applied, which highlighted the significance of a CA strategy for the promotion of biodiversity in the agroecosystem. More importantly, the rice yield gradually increased after the two-year reduction of tillage. Taken together, our results suggest that the reduction of tillage intensity is beneficial for the protection of rice crops from various pests, and facilitates the sustainability of the agroecosystem and rice yield, which provides a solid basis and novel insights for the establishment of sustainable agroecosystems by CA-related practices in rice production in southern China.

Abstract 2549: Immune microenvironment landscape shows treatment-specific differences in rectal cancer patients

Abstract Introduction: Neoadjuvant therapy is the backbone of modern rectal cancer treatment. More intensive therapy leads to higher complete responses, which means an organ-preservation approach can be used. Insights in the biology of tumor response are essential for a successful implementation of such strategies, as different treatments may lead to specific tumor responses. In this study we aim to explore treatment-specific responses of tumor microenvironment and how these are related to patient outcome. Methods: Patients with adenocarcinoma of the rectum who had received one of five different treatment regimens between 2015-2019 were included; no neo-adjuvant therapy (NT), neo-adjuvant chemotherapy (CT), neo-adjuvant radiochemotherapy (RCT), neo-adjuvant radiotherapy with a long interval (LRT) or short interval (SRT). In order to minimize heterogeneity we excluded cT1 tumors, cT4 tumors as well as stage IV rectal cancers. Consecutive slides were stained for HE, LC3-II (autophagy stain) and a multiplex immunofluorescence VECTRA panel for CD8, CD3, CD20, Foxp3, CD11c and pan-CK AE 1/3. Tumor response was scored by two independent investigators. Results: A total of 80 rectal cancer patients were included. Median age was slightly biased, with older patients in the SRT groups and younger patients in the CT group (p=0.03). Less regression and more lymph-node involvement was seen among the CT group, while higher angioinvasion and lymph node involvement was seen in the SRT group. A fragmented pattern of response was more prevalent in CT and RCT treated patients (&amp;gt;73% of cases), whereas a shrinkage pattern of response was predominant in RTL treated patients (64% of cases). Furthermore, autophagic activity in tumor cells was increased in RCT treated patients, especially compared to NT and CT. When analyzing the tumor immunophenotype, differences were found according to specific treatment regimens. RCT treated patients seemed to have lower stromal CD4+ cells, Foxp3+ cells and CD11c+ cells. The latter were found to be especially decreased in treatments will longer intervals (CT, RCT, LTR) compared to those with no treatment or immediate surgery (NT and SRT). The specific relations within the network of immune cells and how these relate to autophagy and the patterns of response are currently being evaluated. Thus, further results will follow shortly. Conclusions: We demonstrated treatment-specific differences in the immune microenvironment landscape of rectal cancer patients. We found higher autophagic activity in patients who received RT treatment, especially significant in the RCT group. Lower immune cell density was observed in longer wait intervals, stressing the importance of immune recovery. Understanding the immune landscape after a specific therapy will shed light on to future treatment decisions, as using immunotherapy in combination with established treatments is the future of personalized therapy. Citation Format: Cristina Graham Martinez, Yari F. H. C. Barella, Sonay Kus Öztürk, Mark A. Gorris, Corrie A. Marijnen, Iris D. Nagtegaal. Immune microenvironment landscape shows treatment-specific differences in rectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2549.

Risk Factors for Biochemical Recurrence After PSMA-PET-Guided Definitive Radiotherapy in Patients With De Novo Lymph Node-Positive Prostate Cancer.

IntroductionThe National Comprehensive Cancer Network recommends external beam radiotherapy (EBRT) combined with androgen deprivation therapy (ADT) as the preferred treatment option for newly diagnosed node-positive (cN1) prostate cancer (PCa) patients. However, implementation of positron emission tomography targeting prostate-specific membrane antigen (PSMA-PET) in the staging of primary PCa patients has a significant impact on RT treatment concepts. This study aims to evaluate outcomes and their respective risk factors on patients with PSMA-PET-based cN1 and/or cM1a PCa receiving primary RT and ADT.MethodsForty-eight patients with cN0 and/or cM1a PCa staged by [18F]PSMA-1007-PET (n = 19) or [68Ga]PSMA-11-PET (n = 29) were retrospectively included. All patients received EBRT to the pelvis ± boost to positive nodes, followed by boost to the prostate. The impact of different PET-derived characteristics such as maximum standard uptake value (SUVmax) and number of PET-positive lymph nodes on biochemical recurrence-free survival (BRFS) (Phoenix criteria) and metastasis-free survival (MFS) was determined using Kaplan–Meier and Cox proportional hazard regression analyses.ResultsMedian follow-up was 24 months. Median initial serum prostate-specific antigen was 20.2 ng/ml (IQR 10.2–54.2). Most patients had cT stage ≥ 3 (63%) and ISUP grade ≥ 3 (85%). Median dose to the prostate, elective nodes, and PET-positive nodes was 75 Gy, 45 Gy, and 55 Gy, respectively. Ninety percent of patients received ADT with a median duration of 9 months (IQR 6–18). In univariate analysis, cM1a stage (p = 0.03), number of >2 pelvic nodes (p = 0.01), number of >1 abdominal node (p = 0.02), and SUVmax values ≥ median (8.1 g/ml for 68Ga-PSMA-11 and 7.9 g/ml for 18F-PSMA-1007) extracted from lymph nodes were significantly associated with unfavorable BRFS, but classical clinicopathological features were not. Number of >2 pelvic nodes (n = 0.03), number of >1 abdominal node (p = 0.03), and SUVmax values ≥ median extracted from lymph nodes were associated with unfavorable MFS. In multivariate analysis, number of >2 pelvic lymph nodes was significantly associated with unfavorable BRFS (HR 5.2, p = 0.01) and SUVmax values ≥ median extracted from lymph nodes had unfavorable MFS (HR 6.3, p = 0.02).ConclusionMore than 2 PET-positive pelvic lymph nodes are associated with unfavorable BRFS, and high SUVmax values are associated with unfavorable MFS. Thus, the number of PET-positive lymph nodes and the SUVmax value might be relevant prognosticators to identify patients with favorable outcomes.

PO-1774 Oxygen distribution in the microenvironment and RT treatment outcome: a modeling study on metastasis

PO-1774 Oxygen distribution in the microenvironment and RT treatment outcome: a modeling study on metastasis