Radiotherapy Data Research Articles

Hyaluronic Acid Spacer in Prostate Cancer Radiotherapy: Dosimetric Effects, Spacer Stability and Long-Term GI Toxicity and PRO in a Phase II-Study

<h3>Purpose/Objective(s)</h3> Rectal side effects are common after radiotherapy (RT) to the prostate. To reduce side effects, perirectal spacers to separate the prostate from the rectum, thereby reducing the rectal dose, may be beneficial. This study presents the impact of a hyaluronic acid (HA) perirectal spacer on the rectal dose, MRI evaluation of spacer thickness during RT and a five-year follow-up of patient-reported outcome (PRO) and gastrointestinal (GI) toxicity. <h3>Materials/Methods</h3> 81 patients (<75 years) with low- (T1c-T2 and Gleason ≤ 6 and PSA < 10) and intermediate-risk prostate cancer (PC) (T1c-T3a with 1 or 2 of the risk factors T2c-T3a or Gleason ≥ 7 or PSA ≥ 10) received transrectal injections with HA (Macrolane VRF 30, Q-Med/Galderma, Uppsala, Sweden) as a perirectal spacer in this phase II-study between 2010-2016. External beam RT, 78 Gy in 39 fractions, were given with 3DCRT or IMRT using fiducial markers as image guidance. MRI was performed before (MR0) and after HA injection (MR1), at the middle (MR2) and at the end of RT (MR3). GI toxicity was assessed up to five years according to the RTOG scale. PRO GI side effects were collected using The Swedish national prostate cancer registry (NPCR) and PCSS questionnaires. <h3>Results</h3> HA thickness was measured at the prostate base, middle and apex for 52 of 81 patients. Exclusion due to failed HA-injections (6), missing MRT or RT data (17), larger PTV margins (5) and other treatment (1). HA thickness and CTV-Rectum spaces in apex- and middle- position was decreasing from MR1 to MR2/MR3. No significant differences were found between MR2 and MR3. Overall, HA thickness in the middle position had the strongest significant correlation (Spearman's rho ρ= 0.70) to CTV-Rectum spacing. There was a significant decrease in the relative rectum volume that received 70.2 Gy (V90%) from MR0 (8.6 ±5.7 %) to MR1 (2.7± 4.1 %). There was a significant increase from MR1 to MR2 (6.0±9.0%) and no significant difference between MR2 and MR3 (5.7±7.9 %) in rectum V90%. All with significance p<0.05. At the end of RT 17 patients (25.8%) experienced grade 1 GI toxicity, and four patients (6.1%) grade 2. At six months the proportion of grade 2 and 3 GI toxicity was 3.2%, and 1.6%. After 18 months no grade ≥ 2 GI toxicity was observed. The estimated cumulative late grade ≥ 2 GI toxicity rate at 5 years was 4.8 %. PRO moderate or severe overall bowel problems at start RT, end of RT and 5 years were 0%, 17.6% and 12.2% with a mean score of 14.6 (scale 0–100; higher value refers to more symptoms/worse function) at 5 years. <h3>Conclusion</h3> After HA-spacer, the relative rectum volumes receiving 70.2 Gy (V90%) were significantly lower. V90% increased significantly from MR1 to MR2/MR3, but still a significant reduction from MR0. The 5-year cumulative risk of late GI toxicity grade >1 was low whereas 12 % reported moderate/severe GI-bothers in the PRO at 5 years.

Overall survival with or without adjuvant radiotherapy among different molecular subtypes of endometrial cancer (211)

Overall survival with or without adjuvant radiotherapy among different molecular subtypes of endometrial cancer (211)

PDCP: A Set of Tools for Extracting, Transforming, and Loading Radiotherapy Data from the Orthanc Research PACS

The Orthanc server is a light-weight open-source picture imaging and archiving system (PACS) used to store digital imaging and communications in medicine (DICOM) data. It is widely used in research environments as it is free, open-source and scalable. To enable the use of Orthanc stored radiotherapy (RT) data in data mining and machine learning tasks, the records need to be extracted, validated, linked, and presented in a usable format. This paper reports patient data collection and processing (PDCP), a set of tools created using python for extracting, transforming, and loading RT data from Orthanc PACs. PDCP enables querying, retrieving, and validating patient imaging summaries; analysing associations between patient DICOM data; retrieving patient imaging data into a local directory; preparing the records for use in various research questions; tracking the patient’s data collection process and identifying reasons behind excluding patient’s data. PDCP targeted simplifying the data preparation process in such applications, and it was made expandable to facilitate additional data preparation tasks.

Head and Neck Radiation Therapy Patterns of Practice Variability Identified as a Challenge to Real-World Big Data: Results From the Learning from Analysis of Multicentre Big Data Aggregation (LAMBDA) Consortium

PurposeOutside of randomized clinical trials, it is difficult to develop clinically relevant evidence-based recommendations for radiation therapy (RT) practice guidelines owing to lack of comprehensive real-world data. To address this knowledge gap, we formed the Learning from Analysis of Multicenter Big Data Aggregation consortium to cooperatively implement RT data standardization, develop software solutions for data analysis, and recommend clinical practice change based on real-world data analyzed. The first phase of this “Big Data” study aimed at characterizing variability in clinical practice patterns of dosimetric data for organs at risk (OARs) that would undermine subsequent use of large-scale, electronically aggregated data to characterize associations with outcomes. Evidence from this study was used as the basis for practical recommendations to improve data quality. Methods and MaterialsDosimetric details of patients with head and neck cancer treated with radiation therapy between 2014 and 2019 were analyzed. Institutional patterns of practice were characterized, including structure nomenclature, volumes, and frequency of contouring. Dose volume histogram (DVH) distributions were characterized and compared with institutional constraints and literature values. ResultsPlans for 4664 patients treated to a mean plan dose of 64.4 ± 13.2 Gy in 32 ± 4 fractions were aggregated. Before implementation of TG-263 guidelines in each institution, there was variability in OAR nomenclature across institutions and structures. With evidence from this study, we identified a targeted and practical set of recommendations aimed at improving the quality of real-world data. ConclusionsQuantifying similarities and differences among institutions for OAR structures and DVH metrics is the launching point for next steps to investigate potential relationships between DVH parameters and patient outcomes.

Abstract P3-19-01: CANTO RT: The largest prospective multicenter cohort of early breast cancer patients treated with radiotherapy including full DICOM RT data

Abstract Purpose: In this paper, we describe the methodology used, and provide a first characterization of the study population and radiotherapy (RT) data in CANTO-RT (CANcer TOxicities Radiotherapy), the largest available multicenter prospective cohort of early breast cancer (BC) patients treated with RT that aims to identify predictors of development, and persistence of long-term toxicities. Methods: CANTO (NCT01993498) is a French prospective clinical cohort study of 10 150 patients with stage I-III BC from 26 cancer centers. Patients matching all CANTO inclusion and exclusion criteria, who received RT and were still in follow up, in the 10 top recruiting CANTO centers, with a minimum follow up of 3 years, were selected for CANTO-RT. Eligible patients had breast/chest wall +/- lymph node RT with curative intent. Individual full DICOM RT files (CT, RT Structure, RT Dose, RT Plan) were collected, anonymized, structured and analyzed on the CANTO-RT/UNITRAD web platform using AQUILAB Share Place™ and Analytics Dose module. Characteristics of the patients and tumors (including TNM, histology, HER2, estrogen and progesterone receptor) were recorded at baseline. Characteristics of the treatments, skin, lung, cardiovascular, neurological, musculoskeletal toxicities (CTCAE v4.0), QOL (BR23, QLQC30), cosmetic, and oncological outcomes were assessed at diagnosis (baseline), 3-6 (M0), 12 (M12), 36 (M36) and 60 (M60) months after completion of primary surgery, chemotherapy or radiotherapy whichever came last together, with blood, plasma and serum tests. Results: CANTO-RT enrolled 3875 BC patients between June 2012 and February 2017 with a median follow-up of 64 months :1947 (50.2%) left side, 1850 (47.8%) right side and 78 (2%) bilateral BC. The vast majority of patients had hormone receptor-positive tumors 3321 (85.7%) and 553 (14.3%) had human epidermal growth factor 2 (HER2) positive tumors; 2586 (66.7%) had stage pT1 and 2525 (65.2%) pN0 disease; 2087 (53.8%) neoadjuvant or adjuvant chemotherapy, 477 (12.3%) adjuvant trastuzumab and 3138 (81%) adjuvant endocrine therapy. Among 3797 patients with unilateral RT, 3065 (80.4%) had breast conserving surgery, 747 (19.6%) total mastectomy; 2712 (71.5%) sentinel node and 1080 (28.5%) axillary dissection. Tumor bed boost was delivered in 2658 patients (68.5%) and lymph node RT in 1356 patients (35%) including internal mammary chain in 844 patients (21.8%). Most patients 3691 (95.3%) were treated with 3D conformal RT and 184 (4.7%) with intensity-modulated RT. Normofractionated RT (2Gy/fraction) was mostly used (69.9%). Clinical target (breast, chest wall, lymph nodes) and contoured organs at risk (heart, left anterior descending coronary, lung, spinal cord, esophagus, thyroid, brachial plexus, contralateral breast, humeral head) contours and dose/volume histograms were automatically extracted after quality control procedure excluding corrupted files and inconsistencies 36 (1%) (Table 1). Conclusion: CANTO-RT is the largest early breast cancer prospective cohort with full individual clinical and DICOM RT data available. CANTO-RT is a valuable resource, open for collaborative projects, for identification and validation of clinical and dosimetric predictive factors of RT related toxicities. Further long term follow up is ongoing. Table 1.Baseline characteristics of the CANTO RT breast cancer patients.CharacteristicsBreast Cancer Patients [N(%) or Mean (range)]Age at enrolmentMean (range), years56.5 (23.3-85.8)Tumour size (pT)T037 (1)T12586 (66.7)T21058 (27.3)T3177 (4.6)Missing17 (0.4)Nodal status (pN)02525 (65.2)11035 (26.7)2223 (5.8)379 (2)Missing13 (0.3)Tumour histologyInfiltrating Ductal3011 (77.7)Lobular473 (12.2)Others (including mixed)381 (9.8)Missing10 (0.3)Hormone Receptors positiveNegative541 (14)Positive3321 (85.7)Missing13 (0.3)HER2Negative3305 (85.3)Positive553 (14.3)Missing17 (0.4)Type of chemotherapyNo chemotherapy1788 (46.1)Neoadjuvant chemotherapy450 (11.6)Adjuvant chemotherapy1629 (42)Peri-adjuvant chemotherapy (neo + adjuvant)8 (0.2)Hormonal therapyNo730 (18.8)Yes3138 (81)Missing7 (0.2)Herceptin treatmentNo or Not applicable3378 (87.2)Yes477 (12.3)Missing20 (0.5)Type of breast surgerylumpectomy3113 (80.3)Mastectomy734 (18.9)Right lumpectomy and Left mastectomy13 (0.3)Right mastectomy and Left lumpectomy9 (0.2)None6 (0.2)Type of lymph node surgerySentinel node2746 (70.9)Axillary dissection1086 (28)Right sentinel node, Left axillary dissection20 (0.5)Right axillary dissection, left sentinel node12 (0.3)None11 (0.3)Radiation therapyRight Side1850 (47.8)Left Side1947 (50.2)Bilateral78 (2.0)Patients with boostNo or Not applicable1217 (31.4)Yes2658 (68.6)Lymph node levels treatedNone2519 (65)Yes1356 (35)Level 1284 (20.9)Level 2340 (25.1)Level 31072 (79.1)Level 41348 (99.4)Internal mammary chain844 (62.2)Irradiation techniques3D3691 (95.3)IMRT184 (4.7)Fractionation regimensNormofractionation 25-fractions2707 (69.9)Hypofractionation 15-16 fractions166 (4.3)Hypofractionation and Partial breast irradiation51 (1.3)Unspecified fractionation - CTV breast or chest wall not delineated951 (24.5) Citation Format: Thomas Sarrade, Rodrigue Allodji, Youssef Ghannam, Guillaume Auzac, Sibille Everhard, Ophélie Querel, Youlia Kirova, Karine Peignaux, Philippe Guilbert, Claire Charra-Brunaud, Julien Blanchecotte, Rezart Belshi, David Pasquier, Séverine Racadot, Céline Bourgier, Sandrine Ducornet, David Gibon, Fabrice André, Florent De Vathaire, Sofia Rivera. CANTO RT: The largest prospective multicenter cohort of early breast cancer patients treated with radiotherapy including full DICOM RT data [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-01.

Provincial variations in radiotherapy utilization as a measure of access: A pan-Canadian study

Background and purposeAccess to radiotherapy (RT) is a key component of a cancer control strategy. However, radiotherapy utilization (RTU) rates fall short of desired benchmarks in certain Canadian provinces. We aimed to describe provincial variations in RTU across Canada. Materials and methodsWe calculated radiotherapy utilization ratios (RTUR) for each Canadian province from 2016 (RT case counts divided by incidence counts), by cancer type (all cancers, lung, breast, rectal, prostate) and treatment intent (curative, palliative) where data were available. Data were extracted from each provincial RT data repository, cancer registry and/or RT department. We compared RTURs descriptively across provinces and to Ontario benchmarks, and calculated an estimated national RTUR. In provinces with capacity for data linkage, RTURs were compared to a linked (patient-specific) method of calculating utilization, by linking each incident case to whether RT was received within 1 year of diagnosis (RTU-1 yr). ResultsExcluding three provinces that included re-treatments, all-cancer RTURs ranged from 0.31 in Manitoba to 0.40 in Nova Scotia. The national all-cancer RTUR was 0.35, which was comparable to Ontario benchmarks (0.34). Larger variations were seen by cancer type, with an absolute difference in RTURs of 28% for lung cancers, 27% for breast cancers, 21% for rectal cancers, and 18% for prostate cancers. RTURs for nearly all provinces were below established Ontario benchmarks for each cancer type, except prostate cancer. RTURs over-estimated RTU-1 yr by at most 5%, except for prostate cancers where they over-estimated RTU-1 yr by up to 15%. ConclusionsRTU varies by province in Canada, and most notably by cancer subsite. More granular data at the regional level and by healthcare facility is required to further tailor strategies aimed at improving RT access. RTURs also serve as a reasonable surrogate for linked RTU, and both methods can contribute meaningfully to measure RTU depending on the context and data availability.

Radiation Oncology-Specific Surveillance After Palliative Radiation Treatment for Spine and Non-Spine Bone Metastases

Palliative radiation therapy (RT) can be an effective tool for bone metastases. NCCN guidelines recommend imaging every 3 months after RT for spine metastases (SM), yet no standard surveillance guidelines exist after RT for non-spine bone metastases (NSBM). We sought to evaluate factors associated with radiation oncology-specific follow-up after palliative RT.In a large single-institution retrospective cohort analysis, we identified all patients receiving RT for bone metastases by ICD-10 codes and RT prescription from 2017-2019. Demographic, clinical, and RT data were collected. Overall survival (OS) was calculated using Kaplan-Meier analysis. Factors associated with urgent care (UC) evaluation and radiation oncology follow-up were evaluated with multivariable logistic regression among patients surviving or followed to 3 months post-RT.Overall, 3082 patients (39% NSBM, 61% SM) received RT for bone metastases. Within 3 months of RT, 49% had radiation oncology follow-up, 79% underwent imaging, and 27% were seen in the UC. For patients with NSBM, follow-up CT was most common (55%) while for SM, MRI and CT were common (both 54%). Median OS was 10.0 months for SM (95% CI 8.9-11.0) and 13.5 months for NSBM (95% CI 11.5-15.5), with 1343 (71%) SM patients and 923 (77%) NSBM patients surviving to > = 3 months post-RT. Of the 2266 3-month survivors (41% NSBM, 59% SM), 1619 (71%) had radiation oncology follow-up, with higher performance status (OR 2.1, 95% CI 1.44-3.05) and younger patients (< 65yo; OR 1.2 95% CI 1.04-1.50) more likely to have follow-up. Median time-to-visit was 59 days (IQR 38-77), with follow-up time distributions significantly different between SM and NSBM (U = 333075, P = 0.01). Of the 3-month survivors, 553 (24%) patients were seen in the UC, with older and white patients less likely to visit the UC (P < 0.05). Median OS for NSBM was longer than the OS for SM patients (22.1 v 17.5 months; HR 0.87 [95% CI 0.78-0.98]). A minority of patients (397, 18%) underwent a subsequent RT course, occurring within 3 months for 183 patients and at a median time of 95 days [IQR 61-130]. Younger age and race were associated with a subsequent RT course (P < 0.05), while performance status and gender were not associated.After RT for bone metastases, most patients had radiation oncology-specific surveillance, which was associated with younger age and improved performance status. Most patients survived to 3 months post-RT, with a substantial minority receiving a second RT course. Patients with NSBM had longer survival and different time-to-follow-up compared to SM, highlighting the need for further clarification on what the optimal follow-up should be for NSBM. Race was a predictor of UC visits, likely reflecting health disparities that require further investigation. These data support radiation oncology specific follow-up after RT, particularly among younger patients and those with higher performance status with specific attention to racial disparities.

Exploring Correlation Between CT Number and ADC Value for Understanding Radiation Response

Radiation induced changes in CT number (CTN) have been observed during/after radiation therapy (RT) in various tumors and healthy tissues and have been shown to correlate with radiation response. As CTN is related to the combined radiation attenuations of the intracellular volume (ICV) and the extracellular volume (ECV), the observed CTN changes may be contributed by the radiation induced variations in ICV and ECV, e.g., the ratio of ICV and ECV, in the tumor/tissue. The apparent diffusion coefficient (ADC), derived from diffusion-weighted MRI (DWI) is known to represent cellularity, i.e., the IVC/ECV ratio. The ADC or its change during/after RT has been shown to predict radiation response. CT and ADC images are commonly used in RT, offering necessary and complimentary data, one for anatomic and another for functional information. Based on these observations, we hypothesize that CTN correlates with ADC and this correlation can help understand radiation response in RT. The purpose of this study is to verify this hypothesis by analyzing selected CT and ADC data collected in our clinic.Spleen and kidney were selected as the target organs for this study as they have no fat tissue that can interfere with and add complexity to the analysis. Data for a total of 20 and 15 patients with abdominal/pelvic cancers were used for the spleen and kidney analyses, respectively. The image data included the CT acquired during the standard CT simulation using the same CT scanner at 120 kVp and the ADC maps derived from the DWI acquired immediately before the first fraction using a 1.5T MR-Linac. The time gap between the CT and ADC acquisitions were approximately 3 weeks. Spleen and kidneys (left and right) were contoured on both the ADC and the CT images. The mean values of the ADC and CTN from the voxels within the contours were analyzed using a linear regression method.The CTNs over the patient cohort have a median of 44.7 HU (range 31.5 ∼ 56.9 HU) for spleen, and 29.7 HU (range 23.0 ∼ 38.2 HU) for kidney. Both spleen and kidney data show a strong correlation between CTN and ADC (r = -0.80 for spleen and -0.83 for kidney, P < 0.001 for both). The linear regression lines were ADC = -0.0212 x CTN + 1.86 for the spleen and ADC = -0.0220 x CTN + 2.64 for the kidney. The difference between the y-intercepts may be interpreted as the additional water flow related to the renal filtration. With such an adjustment the data for the two organs can be fitted into one regression line same as that for the spleen.There is a strong correlation between CTN and ADC in kidneys and spleen, suggesting that CTN is related to the ICV/ECV ratio (measured by ADC) and the radiation-induced changes in CTN during RT is related to the ADC changes. Further studies are needed to confirm the CTN and ADC correlation and to use the correlation for understanding radiation response.

Radiotherapy Bridging in Patients With R/R High-Grade Lymphoma Receiving CD19 CAR-T in the UK

Radiotherapy Bridging in Patients With R/R High-Grade Lymphoma Receiving CD19 CAR-T in the UK

Variability in Proton Craniospinal Irradiation Practices in the United States: A Pediatric Proton Consortium Registry (PPCR) Study

Craniospinal irradiation (CSI) is commonly used for pediatric brain tumors with propensity for spread in the CSF, principally medulloblastoma. Evolving technology has led to the use of highly conformal radiotherapy (RT) techniques for CSI, including proton therapy. Target delineation and plan coverage are therefore critical for CSI, but there is ongoing controversy and variability in these realms, with little available data on practice patterns. We sought to characterize proton CSI practice patterns in the US by examining CSI plans in the Pediatric Proton Consortium Registry (PPCR).We queried the PPCR for all proton CSI data from 2015-2020. Each plan was manually reviewed for: prescription dose; coverage of optic nerves, vertebral bodies, lateral spinal nerve roots, and sacral nerves; esophageal mean and max doses; and lens max doses. Coverage was assessed at the 95% prescription isodose line. We determined the rate of vertebral body sparing (VBS), as defined by SIOP guidelines, in skeletally immature patients (boys < 16y, girls < 14y).PPCR supplied data for 451 patients; 317 had complete RT data (208 males and 109 females). Medulloblastoma was the most common diagnosis (217), followed by germ cell (32). The median age was 8.8y (IQR 5.8 - 12.4). The median CSI dose was 23.4 Gy (range 10.8 - 45 Gy). Most patients were treated prone (95.6%). Optic nerves were covered completely in 152 cases (47.9%). The average max dose to lenses was 79.1% of prescription (22.6 Gy) vs. 38.2% (10.6 Gy) depending on optic coverage (P < 0.01). Four plans (1.3%) failed to cover the lateral spinal nerve roots. Thirty-nine cases (12.3%) did not completely cover sacral nerves. VBs were spared in 87 cases (27.4%), and covered fully in 138 (43.5%). The remaining 92 plans (29.0%) covered the anterior VBs to a lower dose or utilized anterior avoidance (intermediate sparing). Of 277 plans for skeletally immature patients, 52 (18.8%) were VBS. Both VBS and intermediate sparing significantly reduced mean and max esophageal doses compared to full coverage (P < 0.01). VBS rates by institution (n = 13) varied significantly, from 0 to 71.4%. Rates also increased over time (5.8% in 2015-16; 36.8% in 2017-20).There is significant variability in proton CSI practices nationally, with regard to optic nerve, sacral nerve, and VB coverage. VBS was associated with reduced esophageal doses, and this CSI technique has been correlated in clinical studies to reduced GI and hematologic toxicity. There is growing evidence that VBS may not result in clinically significant growth abnormality, and an ongoing phase II trial is studying this. As evidence evolves, the promulgation of clear guidelines is recommended to optimize and standardize target delineation and planning of CSI.

Concurrent use of nivolumab and radiotherapy for patients with metastatic non‑small cell lung cancer and renal cell carcinoma with oligometastatic disease progression on nivolumab

Checkpoint inhibitors (CPIs), such as nivolumab, have transformed the treatment paradigm for patients with metastatic non-small cell lung cancer (mNSCLC) and metastatic renal cell carcinoma (mRCC). The combination of CPIs and radiotherapy (RT) constitutes a multimodal treatment approach that may work synergistically and facilitate augmented systemic responses. The aim of the present retrospective study was to assess the efficacy and safety of continuation of nivolumab treatment with the addition of RT in patients with mNSCLC and mRCC who develop oligometastatic disease progression on single-agent nivolumab. All patients with mNSCLC and mRCC who received nivolumab at the Department of Oncology, Prince Sultan Military Medical City (Riyadh, Saudi Arabia) between November 2016 and April 2018 were identified. The records of patients who developed oligometastatic disease progression during nivolumab treatment and were subsequently treated with RT, with nivolumab continued beyond disease progression, were retrospectively reviewed. Details of RT, clinical outcomes and toxicity data were collected. Of the 96 patients who received nivolumab, 22 received multiple courses of RT. A total of 39 sites were irradiated: Bone (n=15), lung (n=9), brain (n=8), adrenal gland (n=2), renal bed (n=2), skin (n=1), ethmoid sinus (n=1) and scalp (n=1). Partial response and complete response were noted at 25 (64%) and 3 (8%) sites, respectively. Stable disease was noted at 6 sites (15%) and disease progression was noted at 5 sites (13%). The median time on nivolumab from the date of the first fraction of RT was 4.5 months (range, 1.5-29 months) for patients with mNSCLC and 5 months (range, 1-38.5 months) for patients with mRCC. No patients developed grade 3-4 toxicities. Grade 2 pneumonitis was noted in 3 patients receiving lung RT. The addition of RT appeared to initiate a response and prolong the duration of nivolumab treatment. Therefore, the combination of nivolumab and RT was found to be well tolerated, with response rates exceeding those in published studies of nivolumab monotherapy.

Predictive modeling of hypoxic head and neck cancers during fractionated radiotherapy with gold nanoparticle radiosensitization.

Intrinsic radioresistance and increased proliferation rates in head and neck cancers (HNCs) are associated with negative radiotherapy (RT) treatment responses. The use of gold nanoparticles (AuNPs) as radiosensitizers could enable total radiation dose reduction and lowered radiation toxicity. AuNP radiosensitization may overcome hypoxia-induced radioresistance and treatment-induced accelerated repopulation of cancer cells in HNCs, improving radiotherapy outcomes. Tumor control was determined by considering individual cancer cell responses in probabilistic computational simulations using HYP-RT software for clinical radiotherapy doses and fractionation schedules along with three different nanoparticle administration schedules. Antagonistic tumor hypoxia and rapid tumor regrowth due to accelerated repopulation of cancers cells were taken into consideration. Simulations indicate that tumors that are conventionally uncontrollable can be controlled with AuNP radiosensitization. In simulations where the absence of AuNPs required radiotherapy doses above standard clinical prescriptions, reoccurring AuNP administration allowed for radiation dose reductions below standard clinical dose prescriptions. For example, considering a 2Gy per fraction radiotherapy schedule, tumor control was achieved with 57.2±5.1Gy (P=<0.0001) for weekly AuNP administration and 53.0±4.0Gy (P=<0.0001) for biweekly AuNP administration compared to 69.9±5.8Gy with no radiosensitization. AuNPs decreased the predicted RT total doses required to achieve tumor control via total stem cell elimination, offering an optimistic prediction and method for which hypoxia-induced and rapidly growing radioresistant tumors are treated more effectively. Outcomes are also shown to be sensitive to the RT schedule with data for hyperfractionated RT indicating the greatest benefits from radiosensitization.

Dose measurements in a thorax phantom at 3DCRT breast radiation therapy.

The anthropomorphic and anthropometric phantom developed by the research group NRI (Núcleo de Radiações Ionizantes) can reproduce the effects of the interactions of radiation occurring in the human body. The whole internal radiation transport phenomena can be depicted by film dosimeters in breast RT. Our goal was to provide a dosimetric comparison of a radiation therapy (RT) plan in a 4MV 3D-conformal RT (4MV-3DCR T) and experimental data measured in a breast phantom. The RT modality was two parallel opposing fields for the left breast with a prescribed dose of 2.0 Gy in 25 fractions. The therapy planning system (TPS) was performed on CA T3D software. The dose readings at points of interest (POI) pre-established in TPS were recorded. An anthropometric thorax-phantom with removal breast was used. EBT2 radiochromic films were inserted into the ipisilateral breast, contralateral breast, lungs, heart and skin. The irradiation was carried out on 4/80 Varian linear accelerator at 4MV. The mean dose at the OAR's presented statistically significant differences (p < 0.001) of 34.24%, 37.96% and 63.47% for ipsilateral lung, contralateral lung, and heart, respectively. The films placed at the skin-surface interface in the ipsilateral breast also showed statistically significant differences (p < 0.001) of 16.43%, -10.16%, -14.79% and 15.67% in the four quadrants, respectively. In contrast, the PTV dosimeters, representative of the left breast volume, encompassed by the electronic equilibrium, presented a non-significant difference with TPS, p = 0.20 and p = 0.90. There was a non-significant difference of doses in PTV with electronic equilibrium; although no match is achieved outside electronic equilibrium.

Neurocognitive Effects and Necrosis in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review

A PENTEC review of childhood cancer survivors who received brain radiation therapy (RT) was performed to develop models that aid in developing dose constraints for RT-associated central nervous system (CNS) morbidities. A comprehensive literature search, through the PENTEC initiative, was performed to identify published data pertaining to 6 specific CNS toxicities in children treated with brain RT. Treatment and outcome data on survivors were extracted and used to generate normal tissue complication probability (NTCP) models. The search identified investigations pertaining to 2 of the 6 predefined CNS outcomes: neurocognition and brain necrosis. For neurocognition, models for 2 post-RT outcomes were developed to (1) calculate the risk for a below-average intelligence quotient (IQ) (IQ <85) and (2) estimate the expected IQ value. The models suggest that there is a 5% risk of a subsequent IQ <85 when 10%, 20%, 50%, or 100% of the brain is irradiated to 35.7, 29.1, 22.2, or 18.1 Gy, respectively (all at 2 Gy/fraction and without methotrexate). Methotrexate (MTX) increased the risk for an IQ <85 similar to a generalized uniform brain dose of 5.9 Gy. The model for predicting expected IQ also includes the effect of dose, age, and MTX. Each of these factors has an independent, but probably cumulative effect on IQ. The necrosis model estimates a 5% risk of necrosis for children after 59.8 Gy or 63.6 Gy (2 Gy/fraction) to any part of the brain if delivered as primary RT or reirradiation, respectively. This PENTEC comprehensive review establishes objective relationships between patient age, RT dose, RT volume, and MTX to subsequent risks of neurocognitive injury and necrosis. A lack of consistent RT data and outcome reporting in the published literature hindered investigation of the other predefined CNS morbidity endpoints.

Abstract PS1-12: Factors associated with chronic breast lymphedema after adjuvant radiation in women undergoing breast conservation therapy

Abstract Purpose/Objective(s):Unlike temporary breast edema caused by post-lumpectomy radiation therapy (RT), the edema that persists beyond one year is not well defined and difficult to treat. The aim of this study is to define the incidence and risk factors for the development of chronic breast lymphedema in women undergoing lumpectomy with RT at a large metropolitan cancer center. Materials/Methods:A retrospective chart review was performed on all patients who underwent lumpectomy from 2014 to 2018. Women who did not undergo RT at our institution and those with stage IV disease were excluded from the analysis. Patient demographics, comorbidities, operative data, RT data and postoperative complications were obtained. Chronic breast lymphedema (CBL) was defined as edema that persisted beyond one year post completion of radiation therapy. Breast volumes were determined by contoured breast volumes or, if unavailable, estimated by the 95% isodose volumes from the RT treatment planning system. Using a density curve, the distribution of breast volumes was plotted for patients with and patients without CBL. Univariate analysis was used to evaluate factors associated with CBL. Multivariate regression analysis was used to evaluate factors associated with the risk of CBL while accounting for potential confounding variables as defined by the univariate analysis. Results:A total of 1173 patients were included for analysis. Seventy-four (6.3%) patients developed breast lymphedema beyond one year. For the entire cohort, mean age was 63 years old (SD=11.17), mean BMI was 31.15 kg/m2 (SD=7.17), mean breast volume was 1198.54 cm3 (SD=645.82 cm3), mean total radiation was 59.18 Gy (SD=16.76), and 139 (11.8%) patients underwent ALND. Compared to the cohort that did not develop CBL (n=1099), the CBL cohort (n=74) had a higher median BMI (33.23 kg/m2 vs. 29.81 kg/m2, P&amp;lt;0.001), higher percentage of African Americans (56.8% vs. 37.9%, P=0.004), larger median breast volume (1502.33 cm3 vs. 1083.59 cm3, P&amp;lt;0.001), higher percentage that underwent ALND (23% vs. 11.1%, P=0.005), and larger median size of lumpectomy specimen (128.00 cm3 vs. 94.57 cm3, P=0.002). When accounting for potential confounding variables, multivariate regression analysis revealed when breast volume was evaluated as a continuous variable, for every 1 cm3 increase in breast volume, the risk of breast lymphedema increases by 0.1% (OR=1.001, P&amp;lt;0.001). When breast volume was analyzed as a categorical variable using 1300 cm3 as the optimal cutoff (based on density curve evaluations), patients whose breast volume was greater than 1300 cm3 had nearly 3 times the risk of developing CBL (OR=2.976, P&amp;lt;0.001) compared to those with less than 1300 cm3 breast volume. The multivariate regression also demonstrated that CBL was associated with total radiation dose (OR=1.02, P=0.015) and African American race (OR=1.705, P=0.037). Conclusion:Chronic breast lymphedema presents a clinical concern for women undergoing lumpectomy with postoperative radiation, particularly in women with larger breasts. Further studies should focus on preventative strategies, as well as the psychosocial and economic impact of this morbidity. Citation Format: Sanjay Rama, Cara Canella, Jenna Luker, Kelley Park, Renee Barry, Saheli Ghosh, Simeng Zhu, Yalei Chen, Jessica Bensenhaver, Eleanor Walker, Kenneth Levin, Dunya Atisha, Maristella Evangelista. Factors associated with chronic breast lymphedema after adjuvant radiation in women undergoing breast conservation therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-12.

Use of a Tumor Bed Boost in the Radiotherapy after Oncoplastic Breast Conserving Surgery.

Use of a radiotherapy (RT) tumor bed boost in addition to whole breast irradiation (WBI) after oncoplastic breast conserving surgery (OBCS) can be very challenging due to the massive tissue displacements. The aim of our study is to present relevant RT data regarding the use of a boost RT in patients who underwent OBCS and received adjuvant RT at Neolife Medical Center Bucharest. Materials and Methods: 12 patients treated with intensity modulated radiotherapy (IMRT), after OBCS, using conventional or hypofractionated schedules, between 10/2018 and 12/2020 were included in the study. Pre- and postoperative CT images and surgical clips when available were used for tumor bed (TB) localization and definition of the boost volume. Results: One or more risk factors associated with local recurrence (age under 51 years, high grade tumors, associated ductal carcinoma in situ) were present in 10 patients. Boost RT was delivered in 3 patients. Conclusions: TB localization for the boost RT is difficult without an appropriate marking. Surgical clips and communication between the surgeon and the radiation oncologist are essential for treatment success.

Radical Cancer Treatment is Safe During COVID-19: The Real World Experience of a Large London-Based Comprehensive Cancer Centre During the First Wave

Background: At the start of the COVID pandemic in Feburary 2020, there was a paucity of data to support clinical decisions regarding initiation and continuation of anti-cancer treatments. We felt it imperative to evaluate the safety of radical cancer treatments which were delivered whilst mitigating the risks of concurrent COVID-19 infection and complications.Methods: Using descriptive statistics, we report on the patient/tumour characteristics as well as short-term clinical outcomes of those patients undergoing radical treatment (i.e. systemic anti-cancer treatment (SACT), surgery, or radiotherapy (RT)) for their cancer during the first wave of COVID-19 compared to a similar pre-pandemic period.Findings: There was a reduction in patients undergoing radical treatment from 2019 to 2020 of: 28% for surgery; 18% for SACT; and 10% for RT. Whilst surgery was performed on more male patients (58%), more women received SACT (75%) and RT (58%). Within SACT, 36% received combination therapy, 35% systemic chemotherapy, 23% targeted treatments, 5% immunotherapy, and 2% biological therapy. A similar proportion of RT courses were delivered with radical intent in both 2019 and 2020 (53% vs 52%). Oncological outcomes were similar to pre-COVID-19 times; with 6 deaths at 30 days (Interpretation: Whilst there were fewer patients receiving radical multi-modaility anti-cancer treatments, those who did receive treatment were treated in a safe COVID-19 managed environment. Our findings highlight that cancer patients should have the confidence to attend hospitals and be reassured of the safety measures implemented.Funding: No funding source to be declared.Declaration of Interest: None to declare. Ethical Approval: Two data sources were utilised for this study. For the SACT and RT data, Guy’s Cancer Cohort, a research ethics committee approved research database (Reference number: 18/NW/0297) of routinely collected clinical data of cancer patients at Guy’s and St Thomas’ NHS Foundation Trust (GSTT)

Early Cardiac Effects of Contemporary Radiation Therapy in Patients With Breast Cancer

To characterize the early changes in echocardiographically derived measures of cardiac function with contemporary radiation therapy (RT) in breast cancer and to determine the associations with radiation dose-volume metrics, including mean heart dose (MHD). In a prospective longitudinal cohort study of 86 patients with breast cancer treated with photon or proton thoracic RT, clinical and echocardiographic data were assessed at 3 time points: within 4 weeks before RT initiation (T0), within 3 days before 6 weeks after the end of RT (T1), and 5 to 9 months after RT completion (T2). Associations between MHD and echocardiographically derived measures of cardiac function were assessed using generalized estimating equations to define the acute (T0 to T1) and subacute (T0 to T2) changes in cardiac function. The median estimates of MHD were 139 cGy (interquartile range, 99-249 cGy). In evaluating the acute changes in left ventricular ejection fraction (LVEF) from T0 to T1, and accounting for the time from RT, age, race, preexisting cardiovascular disease, and an interaction term with anthracycline or trastuzumab exposure and MHD, there was a modest decrease in LVEF of borderline significance (0.22%; 95% confidence interval [CI], -0.44% to 0.01%; P = .06) per 30-day interval for every 100 cGy increase of MHD. Similarly, there was a modest worsening in longitudinal strain (0.19%; 95% CI, -0.01% to 0.39%; P = .06) per 30-day interval for each 100 cGy increase in MHD. We did not find significant associations between MHD and changes in circumferential strain or diastolic function. With modern radiation planning techniques, there are modest subclinical changes in measures of cardiac function in the short-term. Longer-term follow-up studies are needed to determine whether these early changes are associated with the development of overt cardiac disease.

Risks of Retinopathy and Optic Neuropathy after Radiotherapy for Childhood Cancer: A Report From the Pediatric Normal Tissue Effects in the Clinic (PENTEC) Initiative

Few reports describe the risks of late ocular toxicities following radiation therapy (RT) for childhood cancers despite their impact on the quality of life. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) ocular task force aims to quantify the radiation dose dependence of select late ocular adverse effects. Here, we report preliminary results concerning retinopathy and optic neuropathy in childhood cancer survivors who received cranial RT. A systematic literature search was performed using PubMed, Medline, and Cochrane Library databases for peer-reviewed studies published from 1980-2014 related to childhood cancer, radiotherapy, and ocular endpoints including dry eye, eye pain, keratitis/corneal injury, conjunctival injury, cataract, retinopathy, eye muscle damage, eyelid fibrosis/atrophy, and optic neuropathy. This initial search yielded abstracts for 2941 studies, 260 of which were selected as potentially having useful outcomes and RT data. The majority of studies reported on cataract development. We chose to focus on the more life-altering endpoints. Five studies reported on retinopathy following conventionally fractionated external beam RT for pediatric cancers (retinoblastoma, head and neck rhabdomyosarcoma/soft tissue sarcoma, esthesioneuroblastoma) and included radiation dose information that could be used to model risk of retinopathy. Five studies included information on radiation dose to optic nerves/chiasm in children (for craniopharyngioma, optic glioma, esthesioneuroblastoma) following conventionally fractionated external beam RT and were used to evaluate risk of optic neuropathy. RT in these studies was typically delivered in 1.8-2 Gy/fraction. Retinopathy among childhood cancer survivors who received cranial RT was reported in 21 cases, at doses ranging from 44-69 Gy with a latency of 11-72 months. Based on limited data, dose-response modeling suggests 5% and 50% probabilities of developing retinopathy at ∼42 Gy and 62 Gy, respectively. Optic neuropathy was reported in 2 of 103 children treated with external beam RT for craniopharyngioma, optic glioma, or esthesioneuroblastoma, at doses of 55 Gy (latency 27 months) and 61 Gy (latency unknown) to the optic nerve. The remaining 101 children who did not develop optic neuropathy received doses ranging from 34-63 Gy to the optic nerve. Radiation dose effects in the eye are poorly studied in the pediatric population, aside from cataract development. The risk of retinopathy increases above doses of 40-45 Gy at 1.8-2 Gy/fraction. The risk of optic neuropathy is low but has been reported at doses ≥55 Gy at 1.8-2 Gy/fraction in the pediatric population.

PyCuRT: An Automated Data Curation Workflow for Radiotherapy Big Data Analysis using Pythons’ NyPipe

Personalized medicine in Radiotherapy (RT) aims to increase tumor control probability and decrease normal tissue toxicity. Recently, Radiomics is widely used to infer tumor/tissue characteristics and link outcome to applied dose and underlying biology. The building of robust models requires high amounts of data, which are often only available from multiple centers/sites. Missing standardization of data (inconsistent naming schemes, differences in acquisition parameters) makes manual curation necessary, which can be extremely time-consuming. Here, we propose a fully automated general framework that can sort all relevant RT data with minimal human intervention - pyCuRT. Our method builds upon NyPipe, a Python package used to create complex analysis workflows. Any DICOM directory containing different radiological data e.g., batch exported from PACS systems without specific structure requirements, can be used as input for pyCuRT. It checks the integrity of files and sorts them based on DICOM attributes. For RT data, using information from the RT Plan, pyCuRT links together the DICOM-RT objects, i.e., the RT planning CT, Structure Set (SS), and Dose Distribution (DD). Furthermore, the structure within the SS showing the highest overlap with the DD can be automatically identified, allowing the extraction of inconsistently named structures. The final output has a subject/session/scan structure. Parallelization is implemented to speed up computation on multi-core machines. Successful curation has been achieved in retrospectively collected data cohorts of 3 different cancer entities (brain n = 621, rectal n = 127, and pancreatic n = 13 for a total of ∼50000 scans), from several various institutions across Germany. In the rectal cohort, e.g., from more than 2000 present images, 774 CT scans with 224 unique series descriptions were identified. From them, pyCuRT extracted the RT planning CTs, and linked them to the corresponding RT-DD and RT-SS automatically. Furthermore, all structures with any combination of GTV or PTV in the name were correctly extracted from the SSs and saved as NIFTI (the 35 RT-SS not containing those structures were identified correctly). The total processing time was around 2 hours and a half, which corresponds to less than 3 seconds per scan. We propose a new, fully automated method to curate radiotherapy data coming from different institutions and vendors. Its robustness and usability were demonstrated in three cohorts of tumor entities treated with RT. Future work will expand the workflow to automatically classify MR sequences.