Pretreatment Spatially Aware Magnetic Resonance Imaging Radiomics Can Predict Distant Brain Metastases (DBMs) After Stereotactic Radiosurgery/Radiation Therapy (SRS/SRT).

Purpose: Stereotactic radiosurgery/radiation therapy (SRS/SRT) increasingly has been used to treat brain metastases. However, the development of distant brain metastases (DBMs) in the untreated brain remains a serious complication. We sought to develop a spatially aware radiomic signature to model the time-to-DBM development in a cohort of patients leveraging pretreatment magnetic resonance imaging (MRI) and radiation therapy treatment planning data including radiation dose distribution maps. Methods and Materials: We retrospectively analyzed a cohort of 105 patients with brain metastases treated by SRS/SRT with pretreatment multiparametric MRI (T1, T1 postcontrast, T2, fluid-attenuated inversion recovery). Three-dimensional radiomic features were extracted from each MRI sequence within 5 isodose regions of interest (ROIs) identified via radiation dose distribution maps and gross target volume (GTV) contours. Clinical features including patient performance status, number of lesions treated, tumor volume, and tumor stage were collected to serve as a baseline for comparison. Cox proportional hazards (CPH) modeling and Kaplan-Meier analysis were used to model time-to-DBM development. Results: CPH models trained using radiomic features achieved a mean concordance index (c-index) of 0.63 (standard deviation [SD], 0.08) compared with a c-index of 0.49 (SD, 0.09) for CPH models trained using clinical factors. A CPH model trained using both radiomic and clinical features achieved a c-index of 0.69 (SD, 0.08). The identified radiomic signature was able to stratify patients into distinct risk groups with statistically significant differences (P = .00007) in time-to-DBM development as measured by log-rank test. Clinical features were unable to do the same. Radiomic features from the peritumoral 50% to 75% isodose ROI and GTV region were most predictive of DBM development. Conclusions: Our results suggest that radiomic features extracted from pretreatment MRI and multiple isodose ROIs can model time-to-DBM development in patients receiving SRS/SRT for brain metastases, outperforming clinical feature baselines. Notably, we believe we are the first to leverage SRS/SRT dose maps for ROI identification and subsequent radiomic analysis of peritumoral and untargeted brain regions using multiparametric MRI. We observed that the peritumoral environment may be implicated in DBM development for SRS/SRT-treated brain metastases. Our preliminary results might enable the identification of patients with predisposition to DBM development and prompt subsequent changes in disease management.

Stereotactic body radiation therapy (SBRT) for the treatment of primary breast cancer in patients not undergoing surgery.

PURPOSE: The purpose was to explore the role of stereotactic body radiation therapy (SBRT) in providing local control (LC) for primary breast cancer in patients unable to undergo surgery. MATERIALS/METHODS: Between 2015 and 2019, 13 non-surgical candidates with 14 lesions were treated with SBRT for primary breast cancer. In 4 cases, SBRT was used after whole breast radiation therapy (WBRT; 40-50 Gy/20-25 fractions). SBRT dose was 30-40 â€‹Gy in 5 fractions for patients treated with SBRT alone and 25-32 â€‹Gy in 4-5 fractions for those treated with SBRT â€‹+ â€‹WBRT. LC and overall survival (OS) were estimated using Kaplan-Meier curves. Response was also assessed using RECIST guidelines. RESULTS: Median follow-up was 32 (range: 3.4-70.4) months. Imaging at median 2.2 (0.6-8.1) months post-SBRT showed median 43.2 â€‹% (range: 2-100 â€‹%) decrease in the largest diameter and median 68.7 â€‹% (range: 27.9-100 â€‹%) SUV reduction. There were 3 cases of local progression at 8.7-10.6 months. Estimated LC was 100 â€‹% at 6 months and 71.6 â€‹% at 12, 24 and 36 months. Estimated median OS was 100 â€‹% at 6 months, 76.9 â€‹% at 12 months, and 61.5 â€‹% at 24 and 36 months. Acute toxicity (n â€‹= â€‹13; 92.9 â€‹%) included grade (G)1 (n â€‹= â€‹8), G2 (n â€‹= â€‹4), and G4 (necrosis; n â€‹= â€‹1). Late toxicity included G2 edema (n â€‹= â€‹1) and G4 necrosis (n â€‹= â€‹2, including 1 consequential late effect). Only patients treated with SBRT â€‹+ â€‹WBRT experienced acute/late G4 toxicity, managed with resection or steroids. CONCLUSIONS: SBRT to primary breast cancer resulted in good LC in non-surgical/metastatic patients. Although necrosis (n â€‹= â€‹2) occurred in the SBRT â€‹+ â€‹WBRT group, it was successfully salvaged.

Utility of Stereotactic Body Radiation Therapy in Establishing Local Control for Patients With Invasive Breast Cancer Not Undergoing Definitive Surgery.

PURPOSE: Surgery is the backbone of breast cancer (BC) treatment. For patients who cannot undergo surgery, improving local control (LC) of the primary tumor is paramount. To that end, this study explored the role of stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Between 2015 and 2022, 21 nonsurgical candidates (10 metastatic, 11 stage IA-IIIC) received 23 SBRT courses to primary BC. Seven were analyzed retrospectively; 15 are currently enrolled in a prospective study. SBRT (40 Gy/5 fractions) was delivered every other day. Follow-up imaging was reviewed. Acute (≤3 months) and late toxicities were evaluated using Common Terminology Criteria for Adverse Events, version 5. LC and overall survival (OS) were estimated using Kaplan-Meier curves. RESULTS: Median age was 78.4 years (45.9-97.3). Median follow-up was 14.7 months (3.3-70.3). Median pre-SBRT index lesion size was 3.1 cm (0.5-14.5) and planning treatment volume was 32.4 cc (11.5-522.4). Initial posttreatment imaging performed at a median 4.0 months (0.6-11.9) post-SBRT demonstrated median decrease in index lesion size of 20.8% (0%-100%); SUV reduction of 65.2% (20.8%-100%). Second follow-up scans at a median 7.8 months post-SBRT showed 62% (0%-100%) and 88% (33.3%-100%) median reduction in tumor size and SUV, respectively, compared with pre-SBRT values. The estimated LC rate was 100% at 6 months and 93.3% at 12, 24, and 36 months. Local progression occurred in 1 case 9.5 months after SBRT, after an initial response. Regional progression occurred in 4 cases (17.4%) at a median 18.6 months (5.2-22.7) post-SBRT. Six patients (35.3%) developed distant progression at a median 2.7 months (0.9-16.2). The estimated OS was 85.7% at 6 months, 69.6% at 12 months, and 63.8% at 24 and 36 months. The rates of acute toxicity were G1: 47.8%, G2: 4.3%, G3: 8.7%, and G4: 0%. CONCLUSIONS: Definitive SBRT for primary BC resulted in good LC in nonsurgical patients and was well-tolerated. Considering the pattern of progression, additional approaches to improve regional/distant control should be investigated.

Estrogen Receptor-negative Ductal Carcinoma In Situ (DCIS) of the Breast - an Institutional Review of Outcomes.

BACKGROUND/AIM: Estrogen receptor (ER)-negative [ER(-)] invasive breast cancers (IBCs) are known to be more aggressive than their ER(+) counterparts. This is less well defined for ductal carcinoma in situ (DCIS). This study investigated the outcomes following the treatment of ER(-) DCIS. PATIENTS AND METHODS: A total of 103 ER(-) DCIS patients diagnosed between 2004-2018 were retrospectively analyzed. Median follow-up was 63.9 months. Statistical analysis included descriptive statistics, non-parametric tests, T-test, logistic regression. The outcomes were compared to a group of 102 ER(+) DCIS patients from our institution. RESULTS: Any breast event (BE) occurred in 10 (9.7%) patients at a median of 3.2 (1.7-7.2) years. The incidence of ipsilateral breast events (IBEs) was 5.8% (6/103). All IBE cases were ER(-) DCIS. All (n=4) contralateral breast events (CBEs) were ER(+) including 3 IBCs. Cumulative incidence of any BEs at 1, 2, and 5 years was 0%, 1.1%, and 9.1%, respectively. Among patients with ER(-) DCIS who developed BE, breast conserving surgery (BCS) had been performed for the initial DCIS in 90% of cases. In those without any BE, the BCS rate (vs. mastectomy) was 58.1% (p=0.08). Adjuvant radiotherapy after BCS was used less often among patients with vs. without subsequent BE (55.5% vs. 77.4%) (p=0.22). Predictors for BE occurrence were not identified. The incidence of any BE among patients with ER(+) DCIS was 6.9% and was not significantly different compared to ER(-) DCIS group (p=0.46). CONCLUSION: ER(-) DCIS outcomes were similar to our institutional ER-positive DCIS group and the previously reported ones for predominantly ER-positive DCIS cohorts.

Central Nervous System Lymphoma: The Great Mimicker-A Single-Institution Retrospective Study.

Background: Primary central nervous system lymphoma (PCNSL) is a rare, aggressive form of non-Hodgkin lymphoma contained in the brain and the spinal cord as well as the meninges, cranial nerves, eyes, and cerebrospinal fluid (CSF). Due to its variable presentation and lack of associated B-symptoms, it is quite challenging to diagnose PCNSL, if there is not a high level of suspicion. Methods: This is a retrospective case series examining 13 human immunodeficiency virus- (HIV-) negative patients with PCNSL and DLBCL type, with a median age of 75 years old. Results: The most common presenting symptom was altered mental status. The frontal lobes, basal ganglia, cerebellum, and corpus callosum were most affected. Prior to brain biopsy, 4/13 patients were on steroids, which did not affect biopsy results and the average time to diagnosis was 1 month. 9/13 patients who did not receive steroids had an average time to diagnosis of less than 1 month. Conclusion: Although steroid administration did not appear to diminish the yield of the biopsy, it is a best practice to withhold steroids prior to biopsy to decrease the time to diagnose PCNSL.

Thromboprophylaxis in the End-of-Life Cancer Care: The Update.

Cancer patients are at increased risk for venous thromboembolism (VTE), which further increases with advanced stages of malignancy, prolonged immobilization, or prior history of thrombosis. To reduce VTE-related mortality, many official guidelines encourage the use of thromboprophylaxis (TPX) in cancer patients in certain situations, e.g., during chemotherapy or in the perioperative period. TPX in the end-of-life care, however, remains controversial. Most recommendations on VTE prophylaxis in cancer patients are based on the outcomes of clinical trials that excluded patients under palliative or hospice care. This translates to the paucity of official guidelines on TPX dedicated to this group of patients. The problem should not be underestimated as VTE is known to be associated with symptoms adversely impacting the quality of life (QoL), i.e., limb or chest pain, dyspnea, hemoptysis. In end-of-life care, where the assurance of the best possible QoL should be the highest priority, VTE prophylaxis may eliminate the symptom burden related to thrombosis. However, large randomized studies determining the benefits and risks profiles of TPX in patients nearing the end of life are lacking. This review summarized available data on TPX in this population, analyzed potential tools for VTE risk prediction in the view of this group of patients, and summarized the most current recommendations on TPX pertaining to terminal care.

Co-localization of Coagulation Factor X and its Inhibitory System, PZ/ZPI, in Human Endometrial Cancer Tissue.

BACKGROUND/AIM: Hemostatic system components contribute to cancer progression independently from their roles in hemostasis. It has been shown that protein Z (PZ)/protein Z-dependent protease inhibitor (ZPI) inhibit coagulation factor X (FX). The aim of the study was to analyze the expression of PZ/ZPI in relation to the main coagulation factor - FX in human endometrial cancer tissue. MATERIALS AND METHODS: Immunohistochemical analysis was performed on 21 endometrial cancer specimens employing antibodies against ZPI, PZ and FX. RESULTS: Endometrial cancer cells showed a strong expression of ZPI and PZ and medium expression of FX. Normal endometrial tissue showed no expression of ZPI, PZ or FX. CONCLUSION: Strong expression of PZ and ZPI in endometrial cancer cells suggests a role of these proteins in endometrial cancer.

Endothelial Microparticles and Vascular Endothelial Growth Factor in Patients With Head and Neck Cancer Undergoing Radiotherapy or Radiochemotherapy.

BACKGROUND: Endothelial microparticles (EMPs) released from activated or apoptotic endothelial cells may play a role in coagulation and thrombus formation. However, there is insufficient evidence regarding the impact of EMPs on angiogenesis in patients with cancer. MATERIALS AND METHODS: Sixteen patients with head and neck cancer (HNC) undergoing radiotherapy/radiochemotherapy (RT/RCT) and 10 healthy controls were studied. Serum EMPs were counted by flow cytometry, and vascular endothelial growth factor (VEGF) was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean EMP level was significantly higher in patients with HNC before RT/RCT (1,601±1,479 EMP/µl) compared to the control group (782±698 EMP/µl). The number of EMPs was not notably increased after RT/RCT (1,629±769 EMP/µl). There was no significant correlation between the plasma EMP number and concentration of VEGF before (r=0.131; p=0.625), 1 day after (r=-0.042, p=0.874), nor 3 months after RT/RCT (r=0.454, p=0.076). CONCLUSION: Released EMPs may not influence promotion of neovascularization in patients with HNC.

Endothelial Microparticles and Blood Coagulation Activation in Head and Neck Cancer Patients Undergoing Radiotherapy or Radiochemotherapy.

BACKGROUND/AIM: Endothelial microparticles (EMP) are small vesicles which are released from the endothelium and contribute to blood coagulation activation in various clinical settings. The aim of this study was to examine whether EMP influence blood coagulation activation in cancer patients during radiotherapy/radiochemotherapy (RT/RCT). MATERIALS AND METHODS: Sixteen head and neck cancer (HNC) patients undergoing RT/RCT and 10 controls were examined. EMP and thrombin-antithrombin complex (TAT) were measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. Tissue factor-positive EMP (TF+EMP) were defined as CD31+/CD142+/CD42b- Results: TF+EMP were significantly elevated in HNC patients before RT/RCT (T0) (1299±1154/µl), one day after RT/RCT (T1d) (1257±603/µl) and 3 months after RT/RCT (T3m) (1289±372/µl) compared to controls (688±647/µl). TF+EMP levels at T0/T1d and T0, as well as at T1d and T3m were not significantly different. TAT levels at T0 and T1d did not differ significantly but at T3m were significantly lower compared to T0 and T1d TF+EMP and TAT concentrations were not significantly correlated at T0 (r=0.058; p=0.828), T1d (r=0.373, p=0.154) and T3m (r=-0.302, p=0.204). CONCLUSION: TF+EMP may not contribute to hemostatic abnormalities in HNC patients.

Thromboprophylaxis in cancer patients in hospice.

Advanced cancer patients in hospice are at notably increased risk of venous thromboembolism (VTE) due to age, local and distal advancement of the malignancy and bed confinement, among other factors. Asymptomatic VTE prevalence among palliative care patients has been found to reach 50%, whereas the clinically overt form occurs in 10%. Hospice patients are frequently given medications increasing VTE risk, for instance megestrol which is a drug commonly used in cancer cachexia. Many of the available guidelines encourage the implementation of thromboprophylaxis (TPX) in cancer patients, e.g., in the perioperative period or over the course of chemotherapy. However, concerning patients remaining under hospice care where the priority goal is not life extension but assurance of the best possible quality of life (QoL), the main benefit from the TPX would be a decrease in the risk of symptom burden associated with VTE, i.e., pain, edema or dyspnea. Nevertheless, studies performed on a sufficiently large study group, which could unequivocally determine the influence of anticoagulation on VTE symptom burden in hospice patients, are still lacking. VTE prophylaxis is challenging for many reasons: its unknown effect on QoL, vague risk of its discontinuation, and risk of bleeding complications which is additionally increased in conditions prevalent in hospice population, i.e., malnutrition, renal or liver insufficiency. So far, most of the guidelines issued by oncological societies do not precisely refer to the problem of TPX in hospice patients. Therefore, the decisions on the implementation of anticoagulation should be taken individually, with previous assessment of VTE risk, comorbidities and possible hemorrhagic complications.

Positron Emission Tomography Scanning in the Management of Hodgkin Lymphoma Patients: A Single-Institution Experience.

BACKGROUND: Positron emission tomography (PET-CT) has become a valuable implement in the management of Hodgkin lymphoma (HL). However, since PET-CT is a relatively new imaging method, its capabilities have not been fully explored. OBJECTIVES: The aim of the study was to evaluate the role of PET-CT at different points in HL management. MATERIAL AND METHODS: The medical documentation of 47 HL patients treated at the Comprehensive Cancer Center in Bialystok, Poland, was analyzed retrospectively. The study group consisted of 15 men and 32 women, aged 18-59 years, in HL clinical stages II-IV, treated either with chemotherapy or sequential chemoradiotherapy. RESULTS: In 65.2% of the patients who underwent post-chemotherapy PET-CT scanning before their qualification for adjuvant radiotherapy (RT), PET-CT was decisive in qualifying them for RT, by establishing whether or not metabolic partial remission (PR) had occurred. With regard to the achievement of partial or complete response (CR), computed tomography (CT) and PET-CT results correlated in 45.5% of the patients after the completion of chemotherapy, and in 18.7% after the completion of the entire treatment (chemotherapy or chemoradiotherapy). Among the patients from the advanced-stage group (stages III/IV stage and/or bulky HL), morphological PR in CT scans after two to three courses of chemotherapy was more often associated with a lack of metabolic CR in posttreatment PET-CT scanning (p = 0.022) than in other patients. Post-treatment PET-CT scanning was shown to be highly prognostic of a relapse-free follow-up (p < 0.0001) and superior to post-treatment CT imaging in relapse prediction (p < 0.0001). CONCLUSIONS: Compared to CT, PET-CT was more accurate in residual masses assessment. Notable ability of PET-CT in relapse-free follow-up prediction encourages to more common use of PET-CT in clinical practice. Further clinical research on the need for RT in patients with PR in CT parallel to CR in PET-CT is required.

Simultaneous occurrence of non-Hodgkin lymphoma, renal cell carcinoma and oncocytoma: A case report.

We herein report the case of a 74 year-old woman with a diffuse large B-cell lymphoma and bilateral renal masses identified on computed tomography scans during the initial staging process. Following partial bilateral nephrectomy, histopathological examination revealed renal cell carcinoma (RCC) and oncocytoma in the left and the right kidneys, respectively. Shortly afterwards, lymphoma of the left palatine tonsil was diagnosed and the patient received chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP regimen), followed by radiotherapy. Due to metastasis of the RCC to the right breast, pancreas and the area of the left psoas major muscle, systemic treatment with pazopanib was commenced. To the best of our knowledge, this is the first reported case of simultaneous diagnosis of non-Hodgkin lymphoma (NHL), RCC and oncocytoma. The aim of this study was to review the related literature, discuss issues regarding the management of this unusual case and identify possible common etiopathological mechanisms underlying the simultaneous occurrence of NHL, RCC and oncocytoma.

Adipokines and Insulin Resistance in Young Adult Survivors of Childhood Cancer.

We examined the association between adipokines (leptin, adiponectin, and resistin), radiotherapy, measurement of body fat, and insulin resistance among young adult survivors of childhood cancer (CCS). Materials and Methods. Seventy-six survivors were included (mean age 24.1 ± 3.5 years). Insulin resistance (IR) was calculated using the homeostasis model assessment (HOMA-IR). The serum levels of adipokines were assayed by immunoassays. Fat mass was evaluated by DXA. Results. Mean adiponectin level and mean body FAT were higher in the examined females than in males (10009 ± 6367 ng/mL versus 6433 ± 4136 ng/mL, p < 0.01; 35.98 ± 9.61% versus 22.7 ± 7.46%, p < 0.001). Among CCS, one of 75 patients met the criteria of insulin resistance, and in 14 patients there was impaired fasting glucose. The multiple regression model for females showed that leptin/adiponectin ratio (LA ratio) significantly affected HOMA-IR (increase of 0.024 per each unit of LA ratio; p < 0.05). Radiotherapy had no effect on serum adipokines and IR. Conclusion. The observed results support the hypothesis that adiponectin might be associated with insulin resistance and it can not be ruled out that changes in the mean level of adiponectin per FAT mass or leptin/adiponectin ratio may precede the occurrence of insulin resistance in the future.

Pain management during radiotherapy and radiochemotherapy in oropharyngeal cancer patients: single-institution experience.

AIM OF THE STUDY: Radiotherapy (RT) is a radical therapeutic option for patients with oropharyngeal cancer (OPC). It induces an acute postradiation reaction that may cause significant pain. The aim of this study was to analyse pain occurrence and intensity, as well as type and effectiveness of analgesic treatment, in OPC patients undergoing RT or radiochemotherapy (RT-CT). MATERIAL AND METHODS: Retrospective data were obtained for 42 OPC patients at clinical stages I-IVA, treated with adjuvant RT or RT-CT or definite RT or RT-CcT at the Comprehensive Cancer Center in Bialystok, Poland. Pain intensity and type of analgesic treatment during the therapy were analysed and compared with the intensity of the radiation-induced acute reaction, assessed weekly according to the Dische score. RESULTS: Thirty-nine (92.9%) patients received analgesic treatment. Analgesic therapy was started in 27 (64.3%) patients with administration of non-steroidal anti-inflammatory drugs (NSAIDs) and/or paracetamol, in seven (16.7%) with mild opioids and in five (11.9%) with strong opioids. Strong opioids were used during therapy in 21 (50%) patients. Co-analgesics were administered to six patients. Breakthrough pain was observed in 10 (23.8%) patients. CONCLUSIONS: High incidence of pain during RT and RT-CT calls for increased awareness of the importance of pain monitoring and treatment during RT of OPC patients. The analgesic treatment had to be adjusted individually.