Radiotherapy Dose Research Articles

Habitat escalated adaptive therapy (HEAT): a phase 2 trial utilizing radiomic habitat-directed and genomic-adjusted radiation dose (GARD) optimization for high-grade soft tissue sarcoma

BackgroundSoft tissue sarcomas (STS), have significant inter- and intra-tumoral heterogeneity, with poor response to standard neoadjuvant radiotherapy (RT). Achieving a favorable pathologic response (FPR ≥ 95%) from RT is associated with improved patient outcome. Genomic adjusted radiation dose (GARD), a radiation-specific metric that quantifies the expected RT treatment effect as a function of tumor dose and genomics, proposed that STS is significantly underdosed. STS have significant radiomic heterogeneity, where radiomic habitats can delineate regions of intra-tumoral hypoxia and radioresistance. We designed a novel clinical trial, Habitat Escalated Adaptive Therapy (HEAT), utilizing radiomic habitats to identify areas of radioresistance within the tumor and targeting them with GARD-optimized doses, to improve FPR in high-grade STS.MethodsPhase 2 non-randomized single-arm clinical trial includes non-metastatic, resectable high-grade STS patients. Pre-treatment multiparametric MRIs (mpMRI) delineate three distinct intra-tumoral habitats based on apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) sequences. GARD estimates that simultaneous integrated boost (SIB) doses of 70 and 60 Gy in 25 fractions to the highest and intermediate radioresistant habitats, while the remaining volume receives standard 50 Gy, would lead to a > 3 fold FPR increase to 24%. Pre-treatment CT guided biopsies of each habitat along with clip placement will be performed for pathologic evaluation, future genomic studies, and response assessment. An mpMRI taken between weeks two and three of treatment will be used for biological plan adaptation to account for tumor response, in addition to an mpMRI after the completion of radiotherapy in addition to pathologic response, toxicity, radiomic response, disease control, and survival will be evaluated as secondary endpoints. Furthermore, liquid biopsy will be performed with mpMRI for future ancillary studies.DiscussionThis is the first clinical trial to test a novel genomic-based RT dose optimization (GARD) and to utilize radiomic habitats to identify and target radioresistance regions, as a strategy to improve the outcome of RT-treated STS patients. Its success could usher in a new phase in radiation oncology, integrating genomic and radiomic insights into clinical practice and trial designs, and may reveal new radiomic and genomic biomarkers, refining personalized treatment strategies for STS.Trial registrationNCT05301283.Trial statusThe trial started recruitment on March 17, 2022.

Osteoradionecrosis incidence in pre-radiation teeth extractions: A prospective study.

To evaluate osteoradionecrosis (ORN) incidence in a cohort of patients undergoing tooth extraction (TE) before radiotherapy (RT) for head and neck cancers. The study protocol was approved by the Ethics Committee of Università Cattolica del Sacro Cuore (ID-2132) and registered at clinicaltrials.gov (ID: NCT04009161). TE was performed in case of signs of pericoronitis, periapical lesions, restorative impossibility, severe periodontitis. ORN was defined as exposed bone at an unhealed post-extraction socket in the absence of oncological recurrence. The RT plans were reviewed, and each post-extractive socket was contoured to calculate the received radiation dose. In total, 156 patients with 610 TE were enrolled. The mean follow-up was 567 days. ORN was diagnosed in four patients (2.6% of patients and 0.7% of TE). Need for osteotomy and radiation dose at the extraction site were associated with ORN (OR for osteotomy: 21.9, 95% CI: 2.17-222.2, p = 0.009; OR for RT dose: 1.1, 95% CI: 1-1.15, p = 0.05). TE appears to be a significant risk factor for ORN, particularly when osteotomy is required, and post-extraction sockets receive a high RT dosage. This study proposes a decision-making algorithm for TE and outlines a straightforward surgical protocol.

The use of derma-fat grafts to eliminate defects during operations on the parotid glands

Introduction. The effectiveness of surgical treatment of parotid gland tumors is determined by the frequency of local relapse and functional and aesthetic results, which are determined not only by the anatomical and functional safety of the facial nerve. It is also very important to level aesthetic deformities of the parotid region and reduce the severity of frey’s syndrome. Aim. To retrospectively analyze the use of dermal fat grafts to correct defects during operations on the parotid glands. Materials and methods. Our study included 7 patients (2 men and 5 women) who were treated at the Leningrad Regional Clinical Oncology Dispensary named after L. D. Roman from 2021 to 2022. The average age of the patients was 49.7 years (42–64 years), the average follow-up period was 20.4 months (19–22 months). All patients underwent total / subtotal resection of the parotid gland; we used an abdominal dermal fat graft to close the defect. Histological examination of the surgical material revealed a pleomorphic adenoma of the parotid gland in 5 cases; in 2 cases, a ma-lignant tumor (adenocystic carcinoma and basal cell carcinoma of the salivary glands), which required adjuvant radiation therapy in radical doses. To assess aesthetic and functional results in the recipient and donor areas, we developed and used a questionnaire. Results. 6–8 months after the end of treatment, 5 patients completed questionnaires. 4 people indicated complete symmetry of the face, one patient indicated an average depression. 3 patients did not note any pain in the parotid area, 2 patients had minor discomfort that did not cause any problems. Only one respondent noted redness of the face when eating, which did not cause him any problems; the rest of the survey participants did not find these changes. None of the survey participants noted the appearance of sweat on their face when eating. Conclusion. The use of dermal fat grafts can improve the aesthetic and functional results of treatment in patients undergoing operations on the parotid glands. This technique is quite easy to use and does not significantly increase the time of surgical intervention. A derma-fat graft does not make it difficult to monitor disease relapses.

Quality of Life and Depression Symptoms After Therapy De-Escalation in HPV+ Oropharyngeal Squamous Cell Carcinoma

Despite interest in therapy de-escalation for survivors of human papillomavirus-mediated oropharyngeal squamous cell carcinoma (HPV-positive OPSCC), the association of de-escalated therapy with patient-reported quality of life (QoL) outcomes and burden of depressive symptoms remains unclear. To identify associations between clinicopathologic and therapeutic variables with patient-reported QoL outcomes and depression symptom burden in patients with HPV-positive OPSCC, who were enrolled in a therapy de-escalation trial. In this nonrandomized controlled, open-label, curative-intent therapy de-escalation clinical trial in adults with stage I, II, and III HPV-positive OPSCC, patients were recruited from a high-volume head and neck oncology practice. The main outcomes of this study included quantitative, patient-reported QoL and depression symptoms per well-validated inventories. Patient-reported QoL was based on Functional Assessment of Cancer Therapy-Head & Neck (FACT-HN) scores (range, 0-148; lower score indicates inferior QoL). Patient-reported depression-related symptom burden was based on Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) scores (range, 0-27; a higher score indicates a higher burden of depression symptoms). Baseline clinicopathologic and treatment variables were paired with FACT-HN and QIDS-SR scores at baseline, 3, 6, 12, 24, and 36 months. Linear mixed-effect models with a random intercept were used for each participant and fixed effects for other measures. Regression coefficients are reported with 95% CIs. A total of 95 patients were followed up for a median (IQR) of 2.2 (1.6-3.2) years. Of these, 93 patients (98%) were male with a mean (SD) age of 60.5 (8.2) years. Overall, 54 participants (57%) had a history of current or former smoking, 47 (50%) underwent curative-intent surgery (with or without adjuvant therapy), and 48 (50%) underwent primary radiotherapy (with or without chemotherapy). The median (IQR) radiotherapy dose was 60 (60-70) Gy. Five deaths and 2 recurrence events were observed (mean [SD] recurrence interval, 1.4 [1.5] years). A higher radiotherapy dose was the only modifiable factor associated with inferior patient-reported QoL (lower FACT-HN) (coefficient, -0.66 [95% CI, -1.09 to -0.23]) and greater burden of depression-related symptoms (higher QIDS-SR) (coefficient, 0.11 [95% CI, 0.04-0.19]). With the 70-Gy dose as reference, improvements in FACT-HN and QIDS-SR scores were identified when patients received 51 to 60 Gy (coefficient, 12.75 [95% CI, 4.58-20.92] and -2.17 [-3.49 to -0.85], respectively) and 50 Gy or lower (coefficient, 15.03 [4.36-25.69] and -2.80 [-4.55 to -1.04]). In this nonrandomized controlled, open-label, curative-intent therapy de-escalation trial, a higher radiotherapy dose was associated with inferior patient-reported QoL and a greater burden of depression-related symptoms. This suggests opportunities for improved QoL outcomes and reduced depression symptom burden with a reduction in radiotherapy dose. ClinicalTrials.gov Identifier: NCT04638465.

Equivalent uniform aerobic dose in radiotherapy for hypoxic tumors

Objective. Equivalent uniform aerobic dose (EUAD) is proposed for comparison of integrated cell survival in tumors with different distributions of hypoxia and radiation dose. Approach. The EUAD assumes that for any non-uniform distributions of radiation dose and oxygen enhancement ratio (OER) within a tumor, there is a uniform distribution of radiation dose under hypothetical aerobic conditions with OER = 1 that produces equal integrated survival of clonogenic cells. This definition of EUAD has several advantages. First, the EUAD allows one to compare survival of clonogenic cells in tumors with intra-tumor and inter-tumor variation of radio sensitivity due to hypoxia because the cell survival is recomputed under the same benchmark oxygen level (OER = 1). Second, the EUAD for homogeneously oxygenated tumors is equal to the concept of equivalent uniform dose. Main results. We computed the EUAD using radiotherapy dose and the OER derived from the 18F-Fluoromisonidazole PET (18F-FMISO PET) images of hypoxia in patients with glioblastoma, the most common and aggressive type of primary malignant brain tumor. The 18F-FMISO PET images include a distribution of SUV (Standardized Uptake Value); therefore, the SUV is converted to partial oxygen pressure (pO2) and then to the OER. The prognostic value of EUAD in radiotherapy for hypoxic tumors is demonstrated using correlation between EUAD and overall survival (OS) in radiotherapy for glioblastoma. The correction to the EUAD for the absolute hypoxic volume that traceable to the tumor control probability improves the correlation with OS. Significance. While the analysis proposed in this research is based on the 18F-FMISO PET images for glioblastoma, the EUAD is a universal radiobiological concept and is not associated with any specific cancer or any specific PET or MRI biomarker of hypoxia. Therefore, this research can be generalized to other cancers, for example stage III lung cancer, and to other hypoxia biomarkers.

Incidence and Factors Associated With the Development of Calvarial Osteoradionecrosis in Patients Treated for Cutaneous Malignancies

Study Design Retrospective cohort study. Objective Calvarial osteoradionecrosis (ORN) is a rare but devastating complication of radiotherapy. The aim of this study was to describe the cumulative incidence of Calvarial ORN in patients in patients treated for cutaneous malignancy of the scalp. Methods Data was compiled from patient records of a large tertiary hospital Plastic Surgery department and radiotherapy records of an affiliated cancer Center. We included all patients that were treated for cutaneous malignancies of the scalp that received radiotherapy. Patient demographics, cancer stage, treatment modalities, intraoperative details, and patient outcome data were recorded. Patients with incomplete radiotherapy data were excluded. Results We analyzed 105 radiotherapy treatments to the scalp administered to 84 patients and recorded 7 cases of calvarial ORN resulting in a gross incidence of 6.67% per radiotherapy treatment. The parietal bone was the most frequently targeted site of radiotherapy and accordingly the most common site of ORN (85.7%). Median time from radiotherapy dose to the development of ORN was 846 days. Higher number of radiotherapy fractionation ( P = .038), cumulative radiotherapy dose ( P = .035), prolonged radiotherapy duration ( P = .022) and skin grafting ( P = .003) were associated with the development of ORN. Conclusions Our findings suggest radiotherapy variables, such as prolonged radiotherapy duration, increased cumulative dose and higher radiotherapy fractions were strongly associated with the development of ORN. In addition, skin grafting following surgical resection was associated with the development of ORN. Further studies with larger sample sizes are required to further explore this relationship.

Investigation of skin dose of post-mastectomy radiation therapy for the halcyon and tomotherapy treatment machine: Comparison of calculation and in vivo measurements

In treatments such as post-mastectomy radiation therapy (PMRT) for breast cancer patients, skin doses are of great importance in terms of tumor control and side effects. This dosimetric study aimed to measure the skin dose on the chest wall surface for post-mastectomy radiotherapy with Tomotherapy and Halcyon devices using thermoluminescence dosimetry (TLD) and to evaluate the accuracy of the skin dose calculated by treatment planning systems (TPS). Computed tomography (CT) images of the Alderson Rando phantom were obtained. Treatment plans were created with Tomotherapy and Halycon devices for a total of 50 Gy with a fraction dose of 2 Gy to the target volume. The left chest wall was divided into 9 regions for detailed surface dose assessment. 88 dose measurement points were determined on the left chest wall. The phantom was irradiated separately in Halycon and Tomotherapy devices. In vivo, dose measurements were performed with TLD in both devices. TPS and TLD doses were compared for the left chest wall surface. For skin dose, TLD measurements were lower than the dose estimate by Tomotherapy TPS and higher than the dose estimate by Halycon TPS. In addition, the skin dose measurements showed that the skin dose of the Tomotherapy device was higher than that of the Halycon. It is recommended to consider the distance of the treatment device and the accuracy of the TPS dose calculation in skin dose assessment in PMRT.

DIBH reduces right coronary artery and lung radiation dose in right breast cancer loco-regional radiotherapy

To determine whether deep inspiratory breath-hold (DIBH) reduces dose to organs-at-risk (OAR), in particular the right coronary artery (RCA), in women with breast cancer requiring right-sided post-mastectomy radiotherapy (PMRT) including internal mammary chain (+IMC) radiotherapy (RT). Fourteen consecutive women requiring right-sided PMRT + IMC were retrospectively identified. Nodal delineation was in accordance with European Society for Radiology and Oncology (ESTRO) guidelines and tangential chest wall fields marked. Patients were planned with Anisotropic Analytical Algorithm using free-breathing (FB) and DIBH datasets. Dose was calculated using Acuros External Beam algorithm. FB and DIBH dose comparisons were analyzed for heart, RCA and right lung, as were chest wall and IMC planning target volumes (PTVs). DIBH vs FB resulted in median decreases of: the RCA mean dose by 0.6Gray (Gy) (interquartile range (IQR) 0.1, 1.9) (p = 0.002), RCA max dose by 1.8Gy (IQR 0.8, 6.1) (p = 0.002), and V5Gy by 2.9% (IQR 0.0, 37.2) (p = 0.016). RCA data indicated no statistically significant dosimetric reduction ≥10Gy. A median reduction of 1.7Gy (c -0.0, 7.1) (p = 0.019) in maximum heart dose was recorded with DIBH vs FB; no significant difference was observed in other heart and left anterior descending coronary artery parameters. The median reduction in right lung mean dose was 2.8Gy for DIBH vs FB plans (IQR 1.6, 3.6) (p = 0.001); significant median reductions of V5Gy, V20Gy, and V30Gy were all achieved with DIBH. Chest wall PTV coverage did not significantly differ between DIBH and FB plans; IMC dosimetric coverage improved with use of DIBH (V47.5Gy, V45Gy, V42Gy). DIBH reduced OAR dose in right-sided PMRT + IMC patients. A novel finding was that DIBH decreased RCA dose. Heart and right lung dose were also decreased with DIBH, whilst optimally dosed PTVs were maintained.

A Comparative Study of Clinical Outcomes in Locally Advanced Cervical Cancer: External Beam Radiotherapy (EBRT) and Sequential High Dose Rate Intracavitary Brachytherapy (HDRICBT) with or without Concurrent Cisplatin on the Day of ICBT Insertion - A Tertiary Care Center Randomized Controlled Trial in India.

The current study aimed to delve into the comparative clinical outcomes between external beam radiation therapy (EBRT) and sequential High Dose Rate Intracavitary Brachytherapy (HDRICBT) with or without concurrent cisplatin administration on the day of intracavitary brachytherapy (ICBT) insertion in women with locally advanced cervical cancer. In this study, conducted between January 2017 and July 2018 at a leading institute in India, diagnosed and untreated patients of locally advanced carcinoma cervix were randomized into two groups. Arm 1 received concurrent cisplatin before each course of brachytherapy, while Arm 2 underwent brachytherapy alone. The outcomes were compared in terms of acute and late toxicities, treatment response, and follow-up. Data analysis was performed using SPSS 16, with statistical significance set at p < 0.05. Both study arms showed similar complete response (CR) rates of 73.3%, with no significant advantage of concurrent cisplatin before brachytherapy. However, a noteworthy trend emerged during follow-up. In the concurrent cisplatin group, the CR rate increased from 73.3% post 1 month of brachytherapy to 86.7% at 3 months and 83.3% at 6 months. Contrastingly, the control group showed CR rates of 73.3% post 1 month, 80% at 3 months, and 76.6% at 6 months. While not statistically significant, this observation suggests a possible enhancement in response rates with concurrent cisplatin and ICBT. Future studies focusing on the optimal drug, dosage, scheduling, and combining cisplatin with other agents are recommended to further explore the potential benefits observed in this study.

Impact of Radiotherapy on Radiation-Induced Brain Injury in Patients with Nasopharyngeal Carcinoma Using Nano-Magnetic Resonance Imaging

This study investigate the changes of white matter injury induced by radiation after radiotherapy in patients with nasopharyngeal carcinoma (NPC) and its association with cognitive dysfunction using multiple MRI methods. A total of 42 patients with NPC who underwent radiotherapy at xxx Hospital between December 2018 and June 2021 were included. The patients were randomly divided into 4 groups based on the timing of radiotherapy. Superparamagnetic iron oxide nanoparticles were used as MRI contrast agents. DTI and MRS scans were conducted to measure FA, ADC, NAA/Cho, Cho/Cr, and NAA/Cr ratios in the hippocampus of both temporal lobes. A cognitive assessment was performed using the MoCA and MMSE scales. After radiotherapy, patients experienced a decline in cognitive scores, which stabilized after 6 months. White matter changes were observed in the hippocampus, with decreased FA and increased ADC values that gradually returned to normal levels. Cho value increased and NAA value decreased initially but eventually returned to pre-treatment levels. No significant changes occurred in the Cr value. Metabolite ratios decreased within 3 months post-radiotherapy but gradually increased thereafter, remaining lower than pre-treatment levels at 6 months. Higher radiation doses did not significantly affect FA and ADC values but decreased white matter metabolite ratios. In conclusion, we reveal that the dosage and duration of radiotherapy can influence the degree of brain injury in patients with NPC and highlights the cognitive decline, white matter changes, and changes in metabolite ratios after radiotherapy for NPC, providing insights into the effects of radiation on brain structure and function.

Role of external radiation in benign tumors: A clinical outcome and safety audit of 7 years from a tertiary care center in India.

Radiotherapy (RT) is a well-established modality for treating malignancies, but its role in treatment of benign lesions has not been well explored. Herein, we present a retrospective analysis of a 7-year data regarding the benefit and the safety profile of RT for treating benign tumors in our institute. Data of 23 patients who received RT for benign tumors from January 2015 to April 2022 were retrieved, and a retrospective analysis was conducted. All the pertinent demographic data, treatment and follow-up data were retrieved. The most common presentations were nasopharyngeal angiofibroma, vertebral hemangioma, paraganglioma, and others. The most common sites of occurrence were head and neck (43%) and paravertebral region (22%). Volumetric modulated arc therapy was the most commonly employed RT technique (39%), followed by three-dimensional conformal RT (34%) and two-dimensional conventional radiotherapy (26%). The median RT dose delivered was 36 Gy (range: 20-54 Gy). The median follow-up duration was 53 months (range: 3-120 months). Nine (39%) patients had progressive disease with a median time to progression of 8 months (range: 1-30 months). The median disease-free survival (DFS) was 70 months, while the 1-, 3-, and 5-year DFS rates were 97%, 88%, and 62%, respectively. Four patients (17%) died, all due to disease progression. The 1-, 3-, and 5-year overall survival rates was 97%, 85%, and 50%, respectively. The rate of radiation-induced cancer (RIC) was 0% as none of the patients had developed RIC secondary to radiation. RT is a safe and an effective option to manage benign tumors either in an adjuvant setting or in inoperable patients requiring definitive treatment, as well as in a setting to alleviate symptoms, providing excellent survival benefits. However, further prospective studies with much higher sample size are required to establish the absolute benefit and to estimate the risk of RIC, which will further direct for a better utilization of RT in treating benign tumors.

Retrospective Analysis of the Factors Affecting Recurrence, Survival, and Effect of Hippocampus Radiotherapy Doses on Neurocognitive Functions in Patients Diagnosed with Glioblastoma Multiforme

Retrospective Analysis of the Factors Affecting Recurrence, Survival, and Effect of Hippocampus Radiotherapy Doses on Neurocognitive Functions in Patients Diagnosed with Glioblastoma Multiforme

The effect of MATLAB-based metal artifact reduction software on radiotherapy dose distribution

The effect of MATLAB-based metal artifact reduction software on radiotherapy dose distribution

Lonidamine Induced Selective Acidification and De-Energization of Prostate Cancer Xenografts: Enhanced Tumor Response to Radiation Therapy.

Prostate cancer is a multi-focal disease that can be treated using surgery, radiation, androgen deprivation, and chemotherapy, depending on its presentation. Standard dose-escalated radiation therapy (RT) in the range of 70-80 Gray (GY) is a standard treatment option for prostate cancer. It could be used at different phases of the disease (e.g., as the only primary treatment when the cancer is confined to the prostate gland, combined with other therapies, or as an adjuvant treatment after surgery). Unfortunately, RT for prostate cancer is associated with gastro-intestinal and genitourinary toxicity. We have previously reported that the metabolic modulator lonidamine (LND) produces cancer sensitization through tumor acidification and de-energization in diverse neoplasms. We hypothesized that LND could allow lower RT doses by producing the same effect in prostate cancer, thus reducing the detrimental side effects associated with RT. Using the Seahorse XFe96 and YSI 2300 Stat Plus analyzers, we corroborated the expected LND-induced intracellular acidification and de-energization of isolated human prostate cancer cells using the PC3 cell line. These results were substantiated by non-invasive 31P magnetic resonance spectroscopy (MRS), studying PC3 prostate cancer xenografts treated with LND (100 mg/kg, i.p.). In addition, we found that LND significantly increased tumor lactate levels in the xenografts using 1H MRS non-invasively. Subsequently, LND was combined with radiation therapy in a growth delay experiment, where we found that 150 µM LND followed by 4 GY RT produced a significant growth delay in PC3 prostate cancer xenografts, compared to either control, LND, or RT alone. We conclude that the metabolic modulator LND radio-sensitizes experimental prostate cancer models, allowing the use of lower radiation doses and diminishing the potential side effects of RT. These results suggest the possible clinical translation of LND as a radio-sensitizer in patients with prostate cancer.

Focused ultrasound-mediated blood–brain barrier opening is safe and feasible with moderately hypofractionated radiotherapy for brainstem diffuse midline glioma

BackgroundDiffuse midline glioma (DMG) is a pediatric tumor with dismal prognosis. Systemic strategies have been unsuccessful and radiotherapy (RT) remains the standard-of-care. A central impediment to treatment is the blood–brain barrier (BBB), which precludes drug delivery to the central nervous system (CNS). Focused ultrasound (FUS) with microbubbles can transiently and non-invasively disrupt the BBB to enhance drug delivery. This study aimed to determine the feasibility of brainstem FUS in combination with clinical doses of RT. We hypothesized that FUS-mediated BBB-opening (BBBO) is safe and feasible with 39 Gy RT.MethodsTo establish a safety timeline, we administered FUS to the brainstem of non-tumor bearing mice concurrent with or adjuvant to RT; our findings were validated in a syngeneic brainstem murine model of DMG receiving repeated sonication concurrent with RT. The brainstems of male B6 (Cg)-Tyrc-2J/J albino mice were intracranially injected with mouse DMG cells (PDGFB+, H3.3K27M, p53−/−). A clinical RT dose of 39 Gy in 13 fractions (39 Gy/13fx) was delivered using the Small Animal Radiation Research Platform (SARRP) or XRAD-320 irradiator. FUS was administered via a 0.5 MHz transducer, with BBBO and tumor volume monitored by magnetic resonance imaging (MRI).ResultsFUS-mediated BBBO did not affect cardiorespiratory rate, motor function, or tissue integrity in non-tumor bearing mice receiving RT. Tumor-bearing mice tolerated repeated brainstem BBBO concurrent with RT. 39 Gy/13fx offered local control, though disease progression occurred 3–4 weeks post-RT.ConclusionRepeated FUS-mediated BBBO is safe and feasible concurrent with RT. In our syngeneic DMG murine model, progression occurs, serving as an ideal model for future combination testing with RT and FUS-mediated drug delivery.

Epidemiological, diagnostic and therapeutic profile of cerebral tumors in the radiotherapy department of Dalal Jamm hospital

Introduction: Brain tumors, whether benign or malignant, primary or secondary, raise public health concerns due to their relative rarity and high mortality and morbidity rates. They account for 1.6% of all cancer cases, with types predominating according to patient age and gender. Brain metastases are more frequent than primary malignant brain tumors. Advances in imaging have improved diagnosis and management, but the constraints of the African context limit access to care. Materials and Methods: This retrospective study included 105 patients with brain tumors treated between June 2018 and October 2022 at the Dalal Jamm Hospital in Guediawaye. Sociodemographic, clinical, radiological, therapeutic and evolutionary data were analyzed. Statistical analysis was performed with SPSS. Results: Of 1,740 patients treated with radiotherapy, 105 had brain tumors. Women were more numerous, with a mean age of 43.17 years. The most common symptoms were related to intracranial hypertension. The majority of patients were in good general condition on admission. The mean time from diagnosis of the primary lesion to the appearance of brain metastases was 48.37 weeks. Magnetic resonance imaging was underused. Secondary brain tumors were frequent, mainly of mammary origin. Radiotherapy was the main treatment, but limited access to radiotherapy centers led to delays. Radiotherapy doses varied according to tumor type. Concomitant chemotherapy was given for high-grade gliomas, but its use was limited due to cost and drug shortages. Palliative chemotherapy was rarely used. Median survival was 3 months.

Risk-Tailoring Radiotherapy for Endometrial Cancer: A Narrative Review.

Endometrial cancer is the most common gynecologic cancer in the United States and it contributes to the second most gynecologic cancer-related deaths. With upfront surgery, the specific characteristics of both the patient and tumor allow for risk-tailored treatment algorithms including adjuvant radiotherapy and systemic therapy. In this narrative review, we discuss the current radiation treatment paradigm for endometrial cancer with an emphasis on various radiotherapy modalities, techniques, and dosing regimens. We then elaborate on how to tailor radiotherapy treatment courses in combination with other cancer-directed treatments, including chemotherapy and immunotherapy. In conclusion, this review summarizes ongoing research that aims to further individualize radiotherapy regimens for individuals in an attempt to improve patient outcomes.

Deep-Learning for Rapid Estimation of the Out-of-Field Dose in External Beam Photon Radiation Therapy – A Proof of Concept

Background and purpose: The dose deposited outside of the treatment field during external photon beam radiotherapy treatment, also known as out-of-field dose, is the subject of extensive study as it may be associated with a higher risk of developing a second cancer, and could have deleterious effects on the immune system which compromise the efficiency of combined radio-immunotherapy treatments. Out-of-field dose estimation tools developed today in research, including Monte Carlo simulations and analytical methods, are not suited to the requirements of clinical implementation because of their lack of versatility and their cumbersome application. We propose a proof of concept based on deep learning for out-of-field dose map estimation that addresses the above limitations.Materials and methods: For this purpose, a 3D U-Net, considering as inputs the in-field dose, as computed by the treatment planning system, and the patient's anatomy, was trained to predict out-of-field dose maps. The cohort used for learning and performance evaluation included 3151 pediatric patients from the [XXXX] database, treated in 5 clinical centers, whose whole-body dose maps were previously estimated with an empirical analytical method. The test set, composed of 433 patients, was split into 5 subdatasets, each containing patients treated with devices unseen during the training phase. Root mean square deviation (RMSD) evaluated only on non-zero voxels located in the out-of-field areas was computed as performance metric.Results: RMSD of 0.28 and 0.41 cGy.Gy−1 were obtained for the training and validation datasets, respectively. Values of 0.27, 0.26, 0.28, 0.30 and 0.45 cGy.Gy−1 were achieved for the 6 MV linac, 16 MV linac, Alcyon cobalt irradiator, Mobiletron cobalt irradiator, and betatron devices test sets, respectively.Conclusion: This proof-of-concept approach using a convolutional neural network has demonstrated unprecedented generalizability for this task, although it remains limited, and brings us closer to an implementation compatible with clinical routine.

Radiotherapy in younger patients with advanced aggressive B-cell lymphoma—long-term results from the phase 3 R-MegaCHOEP trial

The role of consolidative radiotherapy (RT) for patients with aggressive B-cell lymphoma has not been fully elucidated. The R-MegaCHOEP trial investigated the use of high-dose chemotherapy and rituximab with subsequent autologous stem cell transplantations compared to conventional immunochemotherapy (R-CHOEP) for high-risk patients up to 60 years. The study protocol included RT for patients with bulky (maximum diameter ≥7.5 cm) or extranodal disease. Two-hundred sixty-one patients were analyzed, 120 of whom underwent RT. The most frequently irradiated regions were mediastinum (n = 50) and paraaortic (n = 27). Median RT dose was 36 Gray in median fractions of 1.8 Gray. Acute toxicities were mostly mild to moderate, with only 24 and 8 grade 3 and 4 toxicities reported during RT. Patients with bulky disease who received RT showed significantly better 10-year EFS, PFS and OS (EFS: 64% vs. 35%; p < 0.001; PFS 68% vs. 47%; p = 0.003; OS: 72% vs. 59%; p = 0.011). There was no significant increase in secondary malignancies with the use of RT. RT administered for consolidation of bulky disease after immunochemotherapy improved the prognosis of young high-risk patients with aggressive B-cell lymphoma and should be considered part of first-line therapy. The trial was registered with ClinicalTrials.gov, number NCT00129090.

Abstract 6382: Risk prediction of dyslipidemia in long-term survivors of childhood cancer: A report from the St. Jude Lifetime Cohort

Abstract Background: Dyslipidemia is a significant contributor to the increased risk of cardiovascular morbidity and premature mortality in long-term survivors of childhood cancer. Identifying individuals at risk at an early stage provides an opportunity for tailored prevention approaches. Methods: Long-term childhood cancer survivors from the St. Jude Lifetime Cohort, (SJLIFE, n=2,559; median age 41 years, range 20-77 years) were directly assessed for dyslipidemia. Risk factors under consideration included demographic characteristics, cancer treatment exposures (cumulative doses of anthracyclines, platinum agents, glucocorticoids, and radiation therapy), comorbid conditions at the time of assessment (hypertension, diabetes mellitus, growth hormone deficiency, hypogonadism, hypothyroidism, cardiomyopathy, and chronic kidney disease), and externally validated multi-ancestry general-population polygenic risk scores (PRSs) for lipid values (total cholesterol, LDL-C, HDL-C, and triglycerides). Multivariable logistic regression predicted a 15-year risk of dyslipidemia (CTCAE grade ≥2 hypercholesterolemia and/or hypertriglyceridemia) including variables selected by the stepwise approach. Performance of the model was assessed by the area under the receiver operating characteristic curve (AUC). Results: Dyslipidemia was clinically identified in 543 (25.1%) SJLIFE survivors. AUC of a clinical model with sex, race, age at prediction, and comorbid conditions (diabetes, growth hormone deficiency, hypogonadism, hypothyroidism, and hypertension) was 0.80 (95% CI, 0.78-0.82). Inclusion of cancer treatment exposures (cumulative doses of anthracyclines, cisplatin, carboplatin, glucocorticoids, abdominal and cranial radiation therapy) significantly increased AUC to 0.82 (95% CI, 0.80-0.84; P=2.1×10-4). Addition of two PRSs for LDL-C (one included only genome-wide significant variants adjusted for statins and another consisted of all genome-wide variants) and the PRS for triglycerides provided further significant improvement in AUC to 0.86 (95% CI, 0.84-0.88; P=4.2×10-12). Conclusions: We developed a prediction model with good performance for identifying the risk of dyslipidemia in childhood cancer survivors. In addition to demographics and comorbidities, cancer treatments and inherited genetic factors contributed significantly to improving the risk prediction of dyslipidemia. Results may refine risk stratification for dyslipidemia in survivors and present opportunities for more precise and personalized preventive strategies to address cardiovascular health. Independent validation in survivors from the Childhood Cancer Survivor Study and the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER is currently underway. Citation Format: Kateryna Petrykey, Kendrick Li, Lu Xie, Achal Neupane, Angela Delaney, Christine Yu, Stephanie B. Dixon, Bonnie Ky, Cindy Im, Isaac B. Rhea, Jeffrey A. Towbin, Jason N. Johnson, Melissa Bolier, Vincent G. Pluimakers, Linda Broer, Sebastian J. Neggers, Marry M. van den Heuvel-Eibrink, Rebecca M. Howell, Kirsten K. Ness, Melissa M. Hudson, Gregory T. Armstrong, Yutaka Yasui, Yadav Sapkota. Risk prediction of dyslipidemia in long-term survivors of childhood cancer: A report from the St. Jude Lifetime Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6382.