Radiosensitive Tumors Research Articles

PDOC-10 LIMITATIONS IN POST OPERATIVE- ADJUVANT CARE OF PATIENTS WITH BRAIN TUMOURS-A CASE OF SUPRATENTORIAL MEDULLOBLASTOMA IN A PAEDIATRIC PATIENT

Abstract OBJECTIVE To highlight the challenges and limitations in accessing post-operative adjuvant care of patients with brain tumours in Zimbabwe and implications on patient outcomes and to discuss potential strategies to overcome these challenges. METHODS This is a case report on a 6 year old patient with a supratentorial medulloblastoma to demonstrate the challenges encountered on accessing post-operative adjuvant care at a Central hospital in Harare. RESULTS The patient had a near total resection of the tumour done and was managed in the Intensive care unit for 1 week. HE was discharged to the general ward for another week and eventually referred to the paediatric oncologists after a histological diagnosis of a supratentorial medulloblastoma was made. Patient received cycles of chemotherapy but failed to raise money for adjuvant radiotherapy. Patient returned 5 months later with the tumour having recurred. CONCLUSION Limitations in post-operative adjuvant care may have a negative impact on the overall patient outcomes, in this case lack of access to radiotherapy. Medulloblastomas are responsive to radiotherapy and their prognosis improves significantly with a combination of surgical resection and radiotherapy. Addressing these limitations at different levels involving government and non-governmental organizations helps in mitigating inaccessibility of radiotherapy to radio-sensitive brain tumours patients after surgical resection. This case report brings out the urgent need to implement cheaper and sustainable options to address challenges in post-operative adjuvant care in order to get good patient outcomes.

81. Comparison of 3D deep learning models in identifying radiosensitive spine tumors from MRI imaging

81. Comparison of 3D deep learning models in identifying radiosensitive spine tumors from MRI imaging

Using the genomic adjusted radiation dose (GARD) to personalize the radiation dose in nasopharyngeal cancer

BackgroundLocally advanced nasopharyngeal cancer (NPC) patients undergoing radiotherapy are at risk of treatment failure, particularly locoregional recurrence. To optimize the individual radiation dose, we hypothesize that the genomic adjusted radiation dose (GARD) can be used to correlate with locoregional control. MethodsA total of 92 patients with American Joint Committee on Cancer / International Union Against Cancer stage III to stage IVB recruited in a randomized phase III trial were assessed (NPC-0501) (NCT00379262). Patients were treated with concurrent chemo-radiotherapy plus (neo) adjuvant chemotherapy. The primary endpoint is locoregional failure free rate (LRFFR). ResultsDespite the homogenous physical radiation dose prescribed (Median: 70 Gy, range 66–76 Gy), there was a wide range of GARD values (median: 50.7, range 31.1–67.8) in this cohort. In multivariable analysis, a GARD threshold (GARDT) of 45 was independently associated with LRFFR (p = 0.008). By evaluating the physical dose required to achieve the GARDT (RxRSI), three distinct clinical subgroups were identified: (1) radiosensitive tumors that RxRSI at dose < 66 Gy (N = 59, 64.1 %) (b) moderately radiosensitive tumors that RxRSI dose within the current standard of care range (66–74 Gy) (N = 20, 21.7 %), (c) radioresistant tumors that need a significant dose escalation above the current standard of care (>74 Gy) (N = 13, 14.1 %). ConclusionGARD is independently associated with locoregional control in radiotherapy-treated NPC patients from a Phase 3 clinical trial. GARD may be a potential framework to personalize radiotherapy dose for NPC patients.

Dosimetric Impact of Voluntary Deep Inspiration Breath Hold (DIBH) in Mediastinal Hodgkin Lymphomas: A Comparative Evaluation of Three Different Intensity Modulated Radiation Therapy (IMRT) Delivery Methods Using Voluntary DIBH and Free Breathing Techniques.

Hodgkin lymphomas are radiosensitive and curable tumors that often involve the mediastinum. However, the application of radiation therapy to the mediastinum is associated with late effects including cardiac and pulmonary toxicities and secondary cancers. The adoption of conformal IMRT and deep inspiration breath- hold (DIBH) can reduce the dose to healthy normal tissues (lungs, heart and breast). We compared the dosimetry of organs at risk (OARs) using different IMRT techniques for two breathing conditions, i.e., deep inspiration breath hold (DIBH) and free breathing. Twenty-three patients with early-stage mediastinal Hodgkin lymphomas were accrued in the prospective study. The patients were given treatment plans which utilized full arc volumetric modulated arc therapy (F-VMAT), Butterfly VMAT (B-VMAT), and fixed field IMRT (FF-IMRT) techniques for both DIBH and free breathing methods, respectively. All the plans were optimized to deliver 95% of the prescription dose which was 25.2 Gy to 95% of the PTV volume. The mean dose and standard error of the mean for each OAR, conformity index (CI), and homogeneity index (HI) for the target using the three planning techniques were calculated and compared using Student's t-test for parametric data and Wilcoxon signed-rank test for non-parametric data. The HI and CI of the target was not compromised using the DIBH technique for mediastinal lymphomas. The mean values of CI and HI for both DIBH and FB were comparable. The mean heart doses were reduced by 2.1 Gy, 2.54 Gy, and 2.38 Gy in DIBH compared to FB for the F-VMAT, B-VMAT, and IMRT techniques, respectively. There was a significant reduction in V5Gy, V10Gy, and V15Gy to the heart (p < 0.005) with DIBH. DIBH reduced the mean dose to the total lung by 1.19 Gy, 1.47 Gy, and 1.3 Gy, respectively. Among the 14 female patients, there was a reduction in the mean right breast dose with DIBH compared to FB (4.47 Gy vs. 3.63 Gy, p = 0.004). DIBH results in lower heart, lung, and breast doses than free breathing in mediastinal Hodgkin Lymphoma. Among the different IMRT techniques, FF-IMRT, B-VMAT, and F-VMAT showed similar PTV coverage, with similar conformity and homogeneity indices. However, the time taken for FF-IMRT was much longer than for the F-VMAT and B-VMAT techniques for both breathing methods. B-VMAT and F-VMAT emerged as the optimal planning techniques able to achieve the best target coverage and lower doses to the OARs, with less time required to deliver the prescribed dose.

INFRARED THERMAL IMAGING CONTROL OF RADIATION DERMATITIS DYNAMICS.

Radiation-induced dermatitis impairs the quality of life of cancer patients and may lead to the need of interrupting radiotherapy. The grade of dermatitis is subjectively assessed by the visual examination. There is an urgent need for both objective and quantitative methods for assessing the current grade of dermatitis and predicting its severity at an early stage of radiotherapy. The aim of the study was to evaluate the advantages and limitations of infrared thermography for monitoring the current level of radiation-induced dermatitis and predicting its severity by quantitative analysis of the thermal field dynamics in the irradiated zone. 30 adult patients were examined by infrared thermography during the course of 2D conventional radiotherapy for malignant tumors of various types and localizations. Our approach for quantifying the thermal field caused by dermatitis alone was applied. A statistical (correlation and ROC) analysis was performed. Dermatitis of varying severity was observed in 100% of the patients studied. The dynamics in the intensity of the anomalous thermal fields in the irradiated zone correlated with the dynamics of dermatitis grades, excluding the case of a radiosensitive tumor (correlation coefficient 0.74÷0.84). It was found that the maximum toxicity (dermatitis grade ≥ 3) develops in patients who how significant hyperthermia in the area of interest (≥ 0.7 °C) at an early stage of radiotherapy. The ROC analysis demonstrated the "good quality" of the prognosis method (AUC = 0.871). The non-invasive and cheap infrared thermography is a suitable tool for objective quantitative monitoring the current dermatitis grade during radiotherapy as well as predicting its severity for any tumor location.

A novel immune-related risk-scoring system associated with the prognosis and response of cervical cancer patients treated with radiation therapy.

Objective: The tumor microenvironment plays a critical role in the radiotherapy and immunotherapy response of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). Radioresistance is a key factor in treatment failure among patients who receive radical radiotherapy. Thus, new immune-related biomarkers associated with radiotherapy response in CESC are needed. Methods: In this study, the CIBERSORT and ESTIMATE methods were applied to determine the percentage of tumor-infiltrating cells and the number of immune components in 103 CESCs treated with radiotherapy from The Cancer Genome Atlas (TCGA) database. The main dysregulated genes were subjected to multivariate and univariate analyses. The prognostic value of this system was studied via receiver operating characteristic curve and survival analysis. For further confirmation, the biomarkers' expression levels and predictive value were validated by immunohistochemistry (IHC) and qRT-PCR. The CIBERSORT algorithm was used to calculate the compositional patterns of 22 types of immune cells in cervical cancer patients treated with radiation therapy. Results: Data for 17 radioresistant and 86 radiosensitive tumors were obtained from the The Cancer Genome Atlas database. 53 immune-related DEGs were identified. GO and KEGG analyses revealed that the DEGs were enriched in protein kinase B signaling, growth factors in cytokines, the MAPK pathway and the PI3K-Akt pathway. Then, 14 key immune-related genes built a risk scoring model were deemed prognostic in CESC with radiotherapy. The area under the curve (AUC) of the model was 0.723, and the high-risk group presented worse outcomes than the low-risk group. In addition, the high-risk group tended to have persistent tumors (p = 0.001). The high expression of WT1 and SPOUYT4 were associated with relapse, the high expression of Angiotensinogen and MIEN1 were associated with nonrelapse. Analysis of the immune microenvironment indicated that M0 macrophages, M2 macrophages, activated mast cells and resting memory CD4+ T cells were positively correlated with the risk score (p < 0.05). Conclusion: The novel immune-related risk scoring system has some advantages in predicting the prognosis and treatment response of cervical cancer patients treated with radiotherapy. Moreover, it might provide novel clues for providing targeted immune therapy to these patients.

Examining the Efficacy and Safety Profile of Palliative Radiotherapy Using 30 Gy in 5 Fractions

Higher biological equivalent doses of radiotherapy (RT) can improve symptom palliation and local control in select tumor sites. However, not all patients meet criteria for treatment with stereotactic ablative radiotherapy (SABR). Furthermore, SABR is a resource intensive technique which may limit its use in many centers. The 30 Gray in 5 fractions regimen (30/5) stems from a modification of 5-fraction SABR regimens. It is a conformal, homogenous hypo-fractionated regimen that delivers higher dose than conventional palliative RT while still respecting the normal tissue constraints for 5-fraction SABR. It uses streamlined contouring and planning with less stringent requirements for immobilization and image guidance, compared to what is required for SABR. This study evaluates the clinical outcomes of patients receiving 30/5. A single institution retrospective review of clinical and treatment data was performed for patients who received 30/5 from October 2020 to August 2022. Local control (LC) was calculated for all treatment courses. Distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were calculated for all patients. Survival analyses were analyzed by the Kaplan-Meier method and curves compared by log-rank test. Univariate and multivariate analyses were performed using cox-regression analysis. A total of 77 patients and 92 courses of 30/5 were available for analysis. The most common primary tumor was lung (44%), followed by gastrointestinal (GI; 20%), breast (10%), and genitourinary (10%). The median age of patients was 64 years (range: 37-93). The median tumor size treated was 11.4 cm^3 (range: 0.3 - 210.9 cm^3). Treatment sites included lung (31%), lymph nodes (22%), non-spine bone (20%), and spine (15%). At median follow-up of 10.1 months (mo), 25 deaths occurred. Median LC after receiving 30/5 was 18.5 mo (95% CI: 15.7-21.3 mo), median DMFS was 6.6 months (95% CI: 4.6-8.6 mo), median PFS was 6.4 mo (95% CI: 4.9-8.0 mo), and median OS was 18.1 mo (95% CI: 13.1-23.1 mo). Median time to initiating, restarting, or changing systemic therapy was 12.8 mo (95% CI: 7.6-18.0 mo). Radiosensitive (lung, prostate, breast, gynecological, and head/neck) tumors had better LC than radioresistant (GI, renal cell, sarcoma, melanoma) tumors (median 20.9 vs 12.1 mo, p < 0.02). Six grade 2 toxicities occurred (6.5% of all treatments). No grade 3 or higher toxicities occurred. The 30/5 regimen is a safe, well-tolerated, and resource efficient regimen with effective local control. This may serve as a practical alternative for patients who require palliative RT but not optimal candidates for SABR. As expected, radiosensitive tumors had better local control than radioresistant tumors. Future research can further explore the safety, efficacy, and indications of 30/5 as a palliative RT option.

Stereotactic Radiosurgery for Small Intact Brain Metastasis: A Comparative Evaluation of 3 Different Single Fraction Prescription Doses

While single-fraction stereotactic radiosurgery (SRS) in the treatment of small brain metastases (SBM, ≤ 2 cm) is well established, prescription dosing varies considerably across institutions and clinical trials. The choice of prescription dose is a delicate balance between local failure (LF) and radiation necrosis (RN) risks. In the modern era, historically-established dosing thresholds may no longer be applicable. To evaluate the impact of prescription dose on outcomes, we performed a comparative analysis of patients with SBM treated with definitive SRS using three different prescriptions, at a single tertiary institution. Consecutive patients with intact SBM treated with SRS from January 2017 and December 2021 were analyzed. Baseline patient characteristics and dosing parameters were abstracted from the medical record. To limit the integral brain dose when treating multiple brain metastases, the institutional practice was to reduce prescription dose as the total number of lesions increased (i.e., 24 Gy for ≤10 lesions, 22 Gy for 11-20, and 20 Gy for >20). A per lesion analysis, where each lesion was followed from the date of SRS to the last follow-up, was conducted with primary endpoints of LF and RN. Gray's test was used to compare the cumulative incidence of the LF and RN, with death as a competing risk. Factors affecting LF were analyzed using Cox hazard regression analysis. A total of 1318 SBM in 250 patients received SRS and met the inclusion criteria. The median age was 62 years (range: 18-90), median KPS was 90 (range: 50-100) and 66% were female. The most common primary tumors were lung (55.5%) and breast cancers (26.4%). With a median follow-up of 12 months, 136 (11%) LF in 44 patients and 70 (5.7%) RN events in 46 patients occurred. The actuarial 1-year cumulative rate of LF was lower in lesions treated with 24 Gy (6.4%, 95% CI: 4.7-8.6%) or 22 Gy (5.8%, 95% CI: 3.7-8.7%) compared to 20 Gy (15.4%, 95% CI: 10.9-20.5%) (p<0.01). 22 Gy and 24 Gy prescription doses were associated with a 44% and 52% reduction in risk in LF compared to 20 Gy (HR: 0.56; 95% CI: 0.36-0.9; p = 0.01 and HR: 0.48; 95% CI: 0.31-0.74; p<0.01, respectively). In a subset analysis of radiosensitive tumors, 1-year LF rate was still lower with 24 Gy (7.4%, 95% CI: 5.3-9.9%) and 22 Gy (6.1%, 95% CI: 3.7-9.4%) than 20 Gy (15.7%, 95% CI: 11.2-21%) (p = 0.01). The cumulative 1-year RN rate numerically declined with dose, but was not statistically significantly different, with 3.6% (95% CI: 2.3-5.3%) for 24 Gy, 2.6% (95% CI: 1.3-4.8%) for 22 Gy and 1.4% (95% CI: 0.4-3.7%) for 20 Gy. Patients treated with single fraction SRS to intact SBM were at increased risk of LF with prescription doses of 20 Gy compared to 22-24 Gy, without an increased risk of RN. Even in patients with radiosensitive histologies, higher LF rates were still observed following 20 Gy compared to 22-24 Gy.

Primary central nervous system lymphoma (PCNSL) in older patients.

Primary central nervous system lymphoma (PCNSL) is a rare, chemo and radio-sensitive tumor limited to the central nervous system. The incidence of PCSNL increases notably in the elderly population which represented approximately half of the patients. The limit of 'elderly' population remained debated and nonuniform, including 60 years as a cutoff for brain radiotherapy, 65 years for autologous stem-cell transplantation, and 70 years for the last clinical trials. Current therapeutic options include first line treatment based on high-dose methotrexate based polychemotherapy, consolidation chemotherapy, and adapted autologous stem cell transplantation for highly selected patients. At relapse, single agent targeted therapies or salvage chemotherapy followed by intensive consolidation are promising therapeutic options. Nevertheless, improving management of elderly patients is an urgent medical need that currently remains unresolved. We will focus on elderly patients with PCNSL and their specificities including clinical presentations, available therapeutic options and adaptations to be made. To improve survival, it will be necessary to personalized and adapt the treatments, to each patient and his comorbidities, to increase their effectiveness and limit their toxicity in this frail population. Finally, inclusion of these patients in clinical trials is one of the major challenges to significantly change PCNSL elderly patient prognosis.

PD-1 blockade attenuates surgery-mediated immunosuppression and boosts Th1 immunity perioperatively in oesophagogastric junctional adenocarcinoma.

This timely study assesses the immunosuppressive effects of surgery on cytotoxic Th1-like immunity and investigates if immune checkpoint blockade (ICB) can boost Th1-like immunity in the perioperative window in upper gastrointestinal cancer (UGI) patients. PBMCs were isolated from 11 UGI patients undergoing tumour resection on post-operative days (POD) 0, 1, 7 and 42 and expanded ex vivo using anti-CD3/28 and IL-2 for 5 days in the absence/presence of nivolumab or ipilimumab. T cells were subsequently immunophenotyped via flow cytometry to determine the frequency of T helper (Th)1-like, Th1/17-like, Th17-like and regulatory T cell (Tregs) subsets and their immune checkpoint expression profile. Lymphocyte secretions were also assessed via multiplex ELISA (IFN-γ, granzyme B, IL-17 and IL-10). The 48h cytotoxic ability of vehicle-, nivolumab- and ipilimumab-expanded PBMCs isolated on POD 0, 1, 7 and 42 against radiosensitive and radioresistant oesophageal adenocarcinoma tumour cells (OE33 P and OE33 R) was also examined using a cell counting kit-8 (CCK-8) assay to determine if surgery affected the killing ability of lymphocytes and whether the use of ICB could enhance cytotoxicity. Th1-like immunity was suppressed in expanded PBMCs in the immediate post-operative setting. The frequency of expanded circulating Th1-like cells was significantly decreased post-operatively accompanied by a decrease in IFN-γ production and a concomitant increase in the frequency of expanded regulatory T cells with an increase in circulating levels of IL-10. Interestingly, PD-L1 and CTLA-4 immune checkpoint proteins were also upregulated on expanded Th1-like cells post-operatively. Additionally, the cytotoxic ability of expanded lymphocytes against oesophageal adenocarcinoma tumour cells was abrogated post-surgery. Of note, the addition of nivolumab or ipilimumab attenuated the surgery-mediated suppression of lymphocyte cytotoxicity, demonstrated by a significant increase in tumour cell killing and an increase in the frequency of Th1-like cells and Th1 cytokine production. These findings support the hypothesis of a surgery-mediated suppression in Th1-like cytotoxic immunity and highlights a rationale for the use of ICB within the perioperative setting to abrogate tumour-promoting effects of surgery and ameliorate the risk of recurrence.

A theranostic approach: Imaging and therapy of delta-like ligand 3–expressing small cell lung cancers.

8575 Background: Small cell lung cancer (SCLC) is a highly radiosensitive tumor, with selective cell surface expression of the inhibitory Notch ligand Delta-like ligand 3 (DLL3). This facilitates targeted radionuclide therapy accompanied by complementary imaging agents to evaluate and monitor disease progression. The project aims to identify the next generation of DLL3-targeting radioimmunoconjugates to improve the clinical outcome for SCLC patients. Methods: In collaboration with the Tri-Institutional Therapeutics Discovery Institute, we screened and assessed &gt;100 humanized antibodies for their binding affinities, internalization rates, and other pharmacodynamic properties. Here, we present data on two leading candidates (mAb1 and mAb2) holding highest promise in both imaging and therapy studies conducted in DLL3-expressing SCLC tumors. For in vivo imaging, antibodies were radiolabeled with Zirconium-89 (89Zr), which allows for immuno-positron emission tomography (immunoPET). Therapeutic studies were performed with the same antibodies conjugated with Lutetium-177 (177Lu). Human SCLC NCI-H82 xenografts were implanted in nude athymic female mice. ImmunoPET scans were acquired during multiple time points post-injection of the imaging agent, and terminal biodistribution analysis was performed. Treatment studies included administration of 400 and 600 Ci 177Lu-conjugated antibodies in cohorts of mice, with appropriate positive and negative controls. Results: Both lead antibodies demonstrated efficient radioconjugation with either isotope. ImmunoPET imaging utilizing 89Zr showed specific high-level tumor uptake for both clones with low background in non-tumor organs. Ex vivo gamma counting biodistribution analysis, performed 120 hours post-injection, confirmed these findings. Dosimetry estimates suggested a similar therapeutic index between the two clones, with the bone marrow being the dose-limiting organ. Preliminary results from therapy studies demonstrate a statistically significant (p &lt;0.05) prolonged overall survival for the experimental arms compared to controls, and include durable tumor responses. As expected for radionuclide therapy, transient hematologic suppression was observed within 7-10 days after the beginning of the treatment, with normalization of blood cell counts for all groups within three weeks. Conclusions: This study highlights the promise held by novel DLL3-direct radioimmunoconjugates as a diagnostic tracer, prognostic biomarker, and therapeutic agent. Both lead candidates appear promising for translation as both imaging and therapeutic agents for patients with SCLC.

Prognostic Value of Serum Transferrin Level before Radiotherapy on Radio-Sensitivity and Survival in Patients with Nasopharyngeal Carcinoma.

To investigate the prognostic value of serum transferrin (TRF) level before intensity-modulated radiation therapy (IMRT) on radio-sensitivity and overall survival (OS) in patients with nasopharyngeal carcinoma (NPC). From October 2012 to October 2016, a total of 348 patients with NPC in the First Affiliated Hospital of Fujian Medical University were retrospectively analyzed in our study. The concentration of serum TRF was detected by the method of enzyme-linked immunosorbent assay (ELISA). In the whole group, 46 patients received IMRT, and 302 patients received IMRT plus chemotherapy. The radio-sensitive tumor was defined when the local tumor lesions disappeared completely in the nasopharyngeal MRI scan and no tumor residues were found under the electronic nasopharyngoscope one month after the end of radiotherapy. The serum TRF level before IMRT was (1.34-3.89) g/L, with a median of 2.16 g/L and a mean of (2.20 ± 0.42) g/L. In the whole group, 242 cases (69.5%) were radiosensitive, and 106 cases (30.5%) were insensitive. The number of radiosensitive patients in the group of HTRF (transferrin > 2.16 g/L) and LTRF (transferrin ≤ 2.16 g/L) before radiotherapy was 129 (74.6%) and 113 (64.6%), respectively. The difference in radio-sensitivity between the two groups was statistically significant (χ2 = 4.103, p = 0.043). Logistic regression analysis showed that the level of TRF before radiotherapy (OR = 1.702; 95% CI 1.044~2.775; p = 0.033) was an independent factor for radio-sensitivity. The log-rank test showed that patients in the LTRF group achieved a significantly worse OS (χ2 = 5.388, p = 0.02) than those in the HTRF group. Cox regression analysis showed that baseline TRF level (HR = 1.706; 95% CI 1.065~2.731; p = 0.026) was an independent prognostic factor for overall survival. The low level of TRF before IMRT is a risk factor for radio-sensitivity and a prognostic factor for poor OS in NPC patients. It may be a promising marker to predict radio-sensitivity and OS in NPC patients who accept IMRT.

Orthovoltage X-Ray Therapy of Large Cell Invasive Nasal Lymphoma in Cat

Abstract Feline nasal lymphoma is generally a localized radiosensitive tumor. Treatment options include radiation therapy, chemotherapy, or a combination of both modalities. Radiation therapy (RT) in a combination with chemotherapy lead to median survival from 19 months to 955 days. The objective of this paper is to report a case of a large cell late stage invasive feline nasal lymphoma and to evaluate the results of orthovoltage radiation therapy and its side effects. A 12-year-old female mixed breed cat was presented with nasal discharge, sneezing and hyporexia. Definitive histopathology diagnosis was diffuse large cell lymphoma. Computed tomography revealed an advanced stage of the disease, an intranasal mass, bone lysis, invasion of the orbital space and central nervous system. A radical course of X-ray therapy was performed (SFD = 4 Gy, TSD = 40 Gy, 10 sessions, 3 times a week). Radiation side effects were well tolerated and resolved with supportive treatment. Lymphoma is a systemic process and requires a multidisciplinary approach. On most cases, the penetrating ability of radiation therapy of 3.5 cm in depth is enough for small domestic animals. A significant effect is noted in the middle of the treatment course. The fractionated regime did not cause early radiation damage. The relapse-free period was up to 8 months. The patient had a satisfying quality of life for 5 months. Orthovoltage X-ray therapy can be considered as a treatment choice for local nasal lymphoma. X-ray therapy is a widely used modality in veterinary medicine considering the price of machines and costs of treatment.

Solitary Extraosseous Plasmacytoma of Submandibular Gland - Report of a Rare Case.

Plasmacytomas are tumors involving plasma cells that can be either osseous or extraosseous. Solitary extraosseous plasmacytomas are rarely found in the head and neck region. Various pathological, immuno-histochemistry, and radiological investigations must be done to distinguish it from multiple myeloma. A 41-year-old female presented with a progressively increasing mass in right submandibular region for 1 year. She also had complaints of dysphagia and dyspnea for 3 months. Histopathological examinations showed lymphoplasmacytic infiltrate and possibility of plasma cell neoplasm was suspected. On further investigations like immunohistochemistry, bone marrow biopsy, quantitative immunoglobulin, immunoelectrophoresis, and urine analysis, diagnosis of extraosseous plasmacytoma was made. Positron emission tomography-computed tomography (PET-CT) scan did not show any distant foci of the disease. The patient received definitive radiotherapy to the primary region and tolerated well. The patient is asymptomatic after 1 month of radiotherapy and is on regular follow-up. Extraosseous plasmacytoma of the submandibular region is very rare but radiosensitive tumor. Multiple myeloma must be ruled out prior to start of any treatment. Long term follow ups are required to comment on disease progression, dissemination, or recurrence.

Small-Molecule Polθ Inhibitors Provide Safe and Effective Tumor Radiosensitization in Preclinical Models.

DNA polymerase theta (Polθ, encoded by the POLQ gene) is a DNA repair enzyme critical for microhomology mediated end joining (MMEJ). Polθ has limited expression in normal tissues but is frequently overexpressed in cancer cells and, therefore, represents an ideal target for tumor-specific radiosensitization. In this study we evaluate whether targeting Polθ with novel small-molecule inhibitors is a feasible strategy to improve the efficacy of radiotherapy. We characterized the response to Polθ inhibition in combination with ionizing radiation in different cancer cell models in vitro and in vivo. Here, we show that ART558 and ART899, two novel and specific allosteric inhibitors of the Polθ DNA polymerase domain, potently radiosensitize tumor cells, particularly when combined with fractionated radiation. Importantly, noncancerous cells were not radiosensitized by Polθ inhibition. Mechanistically, we show that the radiosensitization caused by Polθ inhibition is most effective in replicating cells and is due to impaired DNA damage repair. We also show that radiosensitization is still effective under hypoxia, suggesting that these inhibitors may help overcome hypoxia-induced radioresistance. In addition, we describe for the first time ART899 and characterize it as a potent and specific Polθ inhibitor with improved metabolic stability. In vivo, the combination of Polθ inhibition using ART899 with fractionated radiation is well tolerated and results in a significant reduction in tumor growth compared with radiation alone. These results pave the way for future clinical trials of Polθ inhibitors in combination with radiotherapy.

The etiologies and management of spinal cord compression in childhood cancers: Are we aware of the emergency of cord compression?

The spinal cord compression causes irreversible long-term permanent neurological sequelae. This study aims to increase awareness of childhood cancers that cause cord compression by comparing histopathological diagnosis, treatments, and survival rates to the literature. Seventy-three patients (38 male, 35 female) with spinal cord compression, among 1085 patients diagnosed with solid tumors at Gazi University Department of Pediatric Oncology between 1991 and 2021 were retrospectively evaluated. The mean time between the onset of complaints and diagnosis was 27.5± 24.9 (2-150) days. The first three most common tumors that caused cord compression; were central nervous system tumors in 22 (30%), neuroblastoma in 17 (23%), and malignant germ cell tumors in 8 (10%) cases. Of the patients, 46 (63%) had compression due to extradural masses, and 27 (37%) patients had an intradural compression. The most common symptoms were pain in 60 (82%), weakness in 57 (78%), and pins and needles in 28 (38%) patients, respectively. The clinical physical neurological examination findings were motor deficit in 62 (84%), and deep tendon reflex changes in 54 patients (73.9%). Compression findings were detected in 58 (79.5%) patients at diagnosis, and in 15 (20.5%) of them during follow-up. The most common level of compression was seen in the thoracolumbar region in 19 (26%) cases. In 65 (89%) patients with cord compression, corticosteroids were given as anti-edema treatment. Surgical excision was performed in 39 (53%) patients. Spinal radiotherapy was given to 35 patients (48%) with radiosensitive tumors. Chemotherapy protocols were started in 52 (71.2%) cases according to their diagnoses. Complete neurological recovery was achieved in 33 (45%) patients. The 5-year overall survival rates for solid tumors with extradural compression and intradural compression were 62% and 22%, respectively (p=0.002). Neurological sequela-free recovery is possible with early diagnosis and urgent treatment. Spinal compression must be detected by detailed systemic and neurological examination and imaging methods. Patients should be rapidly transferred to pediatric oncology units after starting anti-edema treatment.

Uloga radioterapije u lečenju Ewing sarkoma kostiju

Ewing sarcoma (ES) is the second most common primary bone malignancy after osteosarcoma. The disease most often occurs in adolescence, with peak incidence around the age of fourteen. The most common primary location of the tumor is the bones of the pelvis, followed by the ribs, spine and long bones of the extremities such as the tibia and the fibula. ES shows a tendency towards hematogenous dissemination, primarily in the lungs and bones, much less often lymphogenously. One third of patients have distant metastases present at initial diagnosis, which is why ES is considered a systemic disease. The treatment of Ewing sarcoma is based on a multimodal approach that includes the use of chemotherapy, surgery and/or radiotherapy. The identification of prognostic parameters enabled the individual treatment of patients based on the assessed risk group. With the application of modern therapeutic protocols, five-year survival for patients with localized disease lies between 60% and 68%, while for patients with metastatic disease, five-year survival is still unsatisfactory and is around 17%. ES belongs to the group of radiosensitive tumors, and radiotherapy plays a very important role in the local control of the disease, in combination with surgical treatment or independently, and can be applied as radical, preoperative or postoperative radiation therapy. Also, radiation therapy has a role in the palliative approach to the treatment of lung metastases and other metastatic sites. Considering that the modern multimodal treatment of Ewing sarcoma leads to long-term survival, it is necessary to take into account the expected side effects of the therapy that can reduce the quality of life of treated patients. Modern radiotherapy techniques such as three-dimensional conformal radiation therapy (3D CRT), intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT) enable precise delivery of the prescribed dose of radiation to target volumes with better sparing of surrounding normal tissues and organs, which leads to a lower incidence of late sequelae of radiation therapy and enables the preservation of the quality of life of treated patients.

Optimizing Palliative Focal Radiation Therapy Dose in Cutaneous T-Cell Lymphoma: How Low Can You Go?

PurposePrimary cutaneous T-cell lymphomas (CTCLs) are radiosensitive tumors with variable and often relapsing courses. Local disease can be treated with low-dose focal palliative radiation therapy (RT), though little data supports the use of a specific dose. This study assesses clinical outcomes after focal RT to a total dose of 4 Gy, 8 Gy, or 12 Gy. Methods and MaterialsAn International Review Board-approved, retrospective, single-institution study was performed of 225 lesions in 41 patients with primary CTCL treated with low-dose focal RT from 2015 to 2020. Patient, tumor, and treatment characteristics were reviewed. The primary outcome was freedom from treatment failure (FFTF), defined as time to requiring local retreatment, and secondary outcomes included response rates and toxicities. ResultsOf the 225 lesions, 90 received 4 Gy, 106 received 8 Gy, and 29 received 12 Gy. Lesions treated with 12 Gy (96%) or 8 Gy (92%) had a significantly higher 1-year FFTF compared with 4 Gy (77%) (P = .034). Overall response rate and complete response rate were not significantly different between different doses (P = .117), though there was a trend toward higher overall response rate at initial assessment with 8 Gy versus 4 Gy (91.5% vs 82.2%, P = .057). Toxicity was low, with 7.1% of lesions having grade 2 or higher radiation dermatitis. ConclusionsIn primary CTCL lesions treated with focal palliative RT, a dose response was noted favoring 8 to 12 Gy, with 1-year FFTF rates over 90%. However, 4 Gy resulted in substantially better outcomes than previously reported, with 77% requiring no further treatment at 1 year and comparable response rates to higher doses. While our data substantiates 8 to 12 Gy as the standard of care, it also suggests that 4 Gy should be considered an acceptable alternative in situations with concern for radiation toxicities, such as with fragile or heavily pretreated skin.

EVALUATION OF NASOPHARYNGEAL CARCINOMA CELLS TREATED WITH REPEATED DOSING OF EPIGALLOCATECHIN-3-GALLATE, THYMOQUINONE, OR 5 – FLUOROURACIL

Nasopharyngeal carcinoma (NPC) is a malignancy arising from the epithelium of the nasopharynx. Ethnic background, being exposed to the Epstein Barr virus, and increased alcohol use are risk factors for the development of NPC. The majority of patients are diagnosed when the cancer has spread beyond the local area. Radiation therapy, chemotherapy, and surgery are options for treating NPC and are dependent upon location and stage of the disease. Although NPC is a radiosensitive tumor, long-term survival for patients with advanced disease remains poor. The goal of this study was to determine if natural products (thymoqunione (TQ) and Epigallo-catechin-3-gallate (EgCg)) when given by continuous delivery methods rather than a single dose method would destroy cells over a shorter period of time than conventional delivery. The FaDu squamous cell carcinoma cell line was used to test repeated doses of natural (EgCg and TQ) drugs to determine if repeated doses would be as effective at destroying cancer cells as repeated doses of a known chemotherapeutic (5-FU) drug. Cells were treated repeatedly with IC50 concentrations of EgCg, TQ, and 5-FU at 24, 48, and 72 hours. Cells showed similar levels of cellular reduction at 72 hours. Increases in cellular membrane damage were observed in all treated groups with a significant difference seen in 5-FU treated cells compared to EgCg and TQ treated cells. Nitric oxide levels increased in a time dependent manner in EgCg and TQ treated groups. Overall, EgCg and TQ were proved they are as effective as 5-FU in cellular reduction and disrupting cellular function.

Insight of a Metabolic Prognostic Model to Identify Tumor Environment and Drug Vulnerability for Lung Adenocarcinoma.

Metabolic reprogramming is a novel method for the treatment of malignant tumors. The exploration of metabolism procedures between radiosensitive and radioresistant tumors may provide novel perspectives for lung adenocarcinoma (LUAD) patients after radiation therapy. In our study, metabolic reprogramming and immune response changes were found between radioresistant cell line (A549RR) and its parent cells (A549) using gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Nucleotide/amino acid, lipid, and glucose metabolic process, including Alanine, aspartate and glutamate metabolism, Tryptophan/Tyrosine metabolism, Butanoate metabolism, Purine/Pyrimidine metabolism, were screened out. Then molecular signatures database and The Cancer Genome Atlas Program (TCGA) lung adenocarcinoma datasets were used to identify metabolism-related genes (MRGs) between radiosensitive and radioresistant lung adenocarcinoma (LUAD) cells. A metabolism-based prognostic model, receiver operating characteristic (ROC) curve and nomogram were constructed using Metabolism Score calculated by 14 metabolism-related genes (MRGs). Three independent public datasets, (GSE72094, GSE3141, GSE8894) and one immunotherapy cohort (IMvigor210) were used as external validation cohorts. Expression of 14 hub genes in cells, normal and LUAD specimens were explored by Human Protein Atlas, TIMER2.0 and RT-qPCR. Patients with low-Metabolism Scores were correlated with longer survival times, higher response rates to immune checkpoint inhibitors (ICIs), different immune cell infiltrations and drug vulnerability. Our study demonstrated a comprehensive landscape between radiosensitive and radioresistant LUAD, and provide novel targets for NSCLC, especially those patients received radiation therapy. Moreover, this metabolism-based prognostic model may help to investigate connections between radiosensitivity, immune response, metabolic reprogramming, and patients’ prognosis.