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Aim:This study aims to compare the gating signals of patients with lung cancer recorded during the planning computed tomography scan with the ones recorded during treatment fractions. The results provide insights into how representative the respiratory signals from the planning scan are for radiation dose partitioning.Materials and methods:The amplitude and frequency of the respiratory signals of 29 patients with lung carcinoma were analysed and compared with the amplitude and frequency of those recorded during their planning scans. Moreover, a cross-correlation analysis was performed between the difference between the planning scan and fractions and features from the planning scan.Results:Two patients showed significantly different amplitude and frequency during treatment fractions compared to those from the planning scan. These patients showed low variances in frequency and amplitude during the different fractions. The difference between planning scan and fractions is correlated with the variances within the planning scan.Findings:Respiratory signals can differ between the planning scan and the fractions. In this case, a new planning scan may be beneficial. The respiratory signals from the planning scan may be predictive of whether the planning scan will be representative and usable as a control measure during radiotherapy fractions.

The comparative effectiveness of radical prostatectomy (RP) versus radiation therapy (RT) for prostate cancer remains a largely debated topic. Utilizing a provincial population-based linked data set from an equal-access, universal health care system, we sought to compare outcomes among patients treated with either radiation or prostatectomy for nonmetastatic prostate cancer.We performed a retrospective cohort study by linking several administrative data sets to identify patients who were diagnosed with prostate cancer between 2004 and 2016 in Manitoba, Canada and who were subsequently treated with either RP or RT. Cox proportional hazard models with inverse probability of treatment weighting were used to compare rates of all-cause mortality, as well as prostate cancer specific mortality (PCSM) between patients who underwent RP vs RT.During the study period, 2,540 patients underwent RP and 1,895 underwent RT for prostate cancer. Unadjusted overall survival was higher for RP vs RT (5-year overall survival 95.52% for RP compared with 84.55% for RT, p0.0001). In inverse probability of treatment weighting-adjusted Cox regression analysis, compared to patients in the RP groups, patients in the RT group had an increased rate of all-cause mortality (HR 1.93, 95% CI 1.65-2.26, p0.0001), and PCSM (HR 3.98, 95% CI 2.89-5.49; p0.0001).RT was associated with higher all-cause mortality and PCSM rates compared with RP. These findings highlight the importance of comparative effectiveness research to identify treatment disparities and warrant further investigation.

OBJECTIVE Radiotherapy (RT) carries a substantial risk for the development of osteoradionecrosis (ORN) of the jaw. This study was performed to investigate the relationship between dental extractions after RT and the development of ORN. MATERIAL AND METHODS Thirty-two patients with head and neck cancer who underwent tooth extraction after RT were investigated for correlations between the development of ORN and various factors. RESULTS Postextraction ORN was diagnosed in 12 (12.1%) teeth of 9 patients. The RT dose against the site of tooth extraction was 62.0 and 37.4 Gy in the ORN and Non-ORN groups, respectively (p

Introduction Laryngeal squamous cell carcinoma is the second most prevalent malignancy among head and neck tumors, and the treatment of patients with stage I or II disease can be performed with surgery or radiation therapy. National population studies describing therapeutic results comparing these modalities are unusual, but they can be very important to direct treatment guidelines. Objective To evaluate the survival results of patients with laryngeal squamous cell carcinoma at clinical stages I or II, according to the main therapeutic modalities used. Methods Cross-sectional, population-based study using the database of Fundação Oncocentro de São Paulo from January 2000 to March 2019. Inclusion criteria were patients with laryngeal squamous cell carcinoma in clinical stages cT1-2N0. To compensate for the non-random allocation of patients and the imbalance between confounding variables between groups, we used the propensity score methodology. Results A total of 3786 patients met the inclusion criteria. Regarding the cT stage, there were 2171 patients (57.3%) with cT1 tumors. Patients in the public health system had a longer time between diagnosis and treatment (p< 0.001). The analysis by propensity score showed that patients treated with surgery had a tendency towards better disease-specific survival (p = 0.012). Comparing radiotherapy alone versus its combination with radiochemotherapy, radiotherapy alone showed a tendency towards a better survival rate (p< 0.001). Conclusion Analysis by propensity score identified better results for disease-specific survival in patients with laryngeal squamous cell carcinoma at clinical stages I and II treated by surgery when compared to radiotherapy. Resumo Introdução O carcinoma epidermoide de laringe é o segundo mais prevalente entre os tumores de cabeça e pescoço e o tratamento dos pacientes com doença em estádio I ou II pode ser feito com cirurgia ou radioterapia. Estudos populacionais nacionais que descrevem os resultados terapêuticos e compararam essas modalidades são poucos frequentes, mas podem ser muito importantes para orientar diretrizes de tratamento. Objetivo Avaliar os resultados de sobrevida dos pacientes com carcinoma epidermoide de laringe em estádios clínicos I ou II de acordo com as principais modalidades terapêuticas usadas. Método Estudo transversal de base populacional com a base de dados da Fundação Oncocentro de São Paulo de janeiro de 2000 a março de 2019. Os critérios de inclusão foram pacientes com carcinoma epidermoide de laringe em estádios clínicos cT1-2N0. Para compensar pela alocação não randômica dos pacientes e pelo desequilíbrio entre variáveis confundidoras entre os grupos, usamos a metodologia do escore de propensão. Resultados Preencheram os critérios de inclusão 3.786 pacientes. Em relação ao estádio cT, houve 2.171 pacientes (57,3%) com tumores cT1. Os pacientes do sistema único de saúde (SUS) apresentaram um maior tempo entre o diagnóstico e o tratamento (p < 0,001). A análise por escore de propensão mostrou que os pacientes submetidos a cirurgia apresentaram uma tendência de melhor sobrevida doença específica (p = 0,012). Comparando-se radioterapia isolada versus combinação com radioquimioterapia, o tratamento isolado demonstrou tendência a melhor taxa de sobrevida (p< 0,001). Conclusão A análise por escore de propensão identificou melhores resultados de sobrevida doença específica em pacientes com carcinoma epidermoide de laringe estádios clínicos I e II tratados por cirurgia quando comparados a radioterapia.

Objective: To measure 3-year care costs of breast, prostate, colorectal and lung cancers disaggregated by site and clinical stage. Method: A retrospective observational design was employed to investigate care costs of cases recorded in the Registry of the Basque Country between 2010 and 2015. Data gathered included TNM stage and demographic, clinical and resource use variables. Total costs per patient with stage IV disease were calculated by combining generalized linear models with parametric survival analysis. Unit costs were obtained from the analytical accounting system of the Basque Health Service. Results: The sample comprised 23,782 cancer cases (7801 colorectal, 5530 breast, 4802 prostate and 5649 lung cancer). The mean 3-year costs per patient with stage I to III disease were €11,323, €13,727, €8,651 and €12,023 for colorectal, breast, prostate and lung cancer, respectively. The most important cost components were surgery and chemotherapy. Total survival-adjusted costs until death for patients with stage IV disease (€27,568, €26,296, €16,151 and €15,931 for breast, colorectal, lung and prostate cancer, respectively) were higher than the 3-year costs for those with earlier-stage disease. Conclusions: This study quantitatively shows the pattern of changes in the economic burden of cancer throughout its natural history and the great magnitude of this burden for the health system. The use of indicators based on real-world data from each regional health service would allow cancer care in each region to be tailored to local population needs.

Purpose This study aimed to evaluate the radiation-induced adverse effects on ocular structures in head and neck cancer patients and investigate the radiation dose-volume effects on the cornea, lacrimal gland, retina, optic nerve and chiasm.Materials and Methods A total of 38 eyes of 19 patients were included in this prospective, cohort study. All patients underwent complete ophthalmological examination in addition to contrast sensitivity, visual field and visual evoked potentials (VEP) tests. Ophthalmological examinations and psychophysical tests were performed in 6th, 12th, 18th, 24th months and in the last visit. The relationship between the ophthalmologic findings, and the radiation doses below and above the cut-off values was evaluated.Results Contrast sensitivity decrease and visual field deterioration were observed in 42% of the patients in the last visit (median 26 months) whereas a prolonged latency and decreased amplitude of P100 wave in VEP was observed in 58% and 33% of the eyes, respectively at 24th month. Totally 16 patients (84.2%) developed dry eye disease and eight of them received radiotherapy below tolerance doses and had mild to moderate dry eye findings. Radiation-induced retinopathy was observed in three of the eyes in eight patients who received radiation above tolerance dose.Conclusion Head and neck cancers treated with radiotherapy, resulted in various ophthalmic complications. All patients who are treating with radiotherapy should be evaluated by an ophthalmologist in terms of anterior and posterior segment damage, even if the radiation dose is below the tolerance limit.

Prostate cancer (PCa) is the second most frequently diagnosed male cancer worldwide. Early diagnosis of PCa, response to therapy and prognosis still represent a challenge. Nearly 60% of PCa patients undergo radiation therapy (RT) which might cause side effects. In spite of numerous researches in this field, predictive biomarkers for radiation toxicity are still not elucidated. MicroRNAs as posttranscriptional regulators of gene expression are shown to be changed during and after irradiation. Manipulation with miRNA levels might be used to modulate response to RT-to reverse radioresistance-to induce radiosensitivity, or if needed, to reduce sensitivity to treatment to avoid side effects. In this review we have listed and described miRNAs involved in response to RT in PCa, and highlighted potential candidates for future biological tests predicting radiation response to RT, with the special focus on side effects of RT. Individual radiation response is a result of the interactions between physical characteristics of radiation treatment and biological background of each patient, and miRNA expression changes among others. According to described literature we concluded that let-7, miR-21, miR-34a, miR-146a, miR-155, and members of miR-17/92 cluster might be promising candidates for biological tests predicting radiosensitivity of PCa patients undergoing radiation treatment, and as future agents for modulation of radiation response. Predictive miRNA panels, especially for acute and late side effects of RT can serve as a starting point for decisions for individualized RT planning. We believe that this review might be one step closer to understanding molecular mechanisms underlying individual radiation response of patients with PCa.

Lung cancer's radiomic phenotype may potentially inform clinical decision-making with respect to radical radiotherapy. At present there are no validated biomarkers available for the individualisation of radical radiotherapy in lung cancer and the mortality rate of this disease remains the highest of all other solid tumours. MEDLINE was searched using the terms 'radiomics' and 'lung cancer' according to the Preferred Reporting Items for Systematic Reviews and Met-Analyses (PRISMA) guidance. Radiomics studies were defined as those manuscripts describing the extraction and analysis of at least 10 quantifiable imaging features. Only those studies assessing disease control, survival or toxicity outcomes for patients with lung cancer following radical radiotherapy ± chemotherapy were included. Study titles and abstracts were reviewed by two independent reviewers. The Radiomics Quality Score was applied to the full text of included papers. Of 244 returned results, 44 studies met the eligibility criteria for inclusion. End points frequently reported were local (17%), regional (17%) and distant control (31%), overall survival (79%) and pulmonary toxicity (4%). Imaging features strongly associated with clinical outcomes include texture features belonging to the subclasses Gray level run length matrix, Gray level co-occurrence matrix and kurtosis. The median cohort size for model development was 100 (15-645); in the 11 studies with external validation in a separate independent population, the median cohort size was 84 (21-295). The median number of imaging features extracted was 184 (10-6538). The median Radiomics Quality Score was 11% (0-47). Patient-reported outcomes were not incorporated within any studies identified. No studies externally validated a radiomics signature in a registered prospective study. Imaging-derived indices attained through radiomic analyses could equip thoracic oncologists with biomarkers for treatment response, patterns of failure, normal tissue toxicity and survival in lung cancer. Based on routine scans, their non-invasive nature and cost-effectiveness are major advantages over conventional pathological assessment. Improved tools are required for the appraisal of radiomics studies, as significant barriers to clinical implementation remain, such as standardisation of input scan data, quality of reporting and external validation of signatures in randomised, interventional clinical trials.

Purpose: Dose-escalated chemoradiation (CRT) for locally advanced rectal cancer did not result in higher complete response rates but initiated more tumor regression in the randomized RECTAL-BOOST trial (Clinicaltrials.gov NCT01951521). This study compared patient reported outcomes between patients who received dose-escalated CRT (5 × 3 gray boost + CRT) or standard CRT for 2 years after randomization.Methods and Materials: Patients with locally advanced rectal cancer who were participating in the RECTAL-BOOST trial filled out European Organisation for Research and Treatment of Cancer QLQ-C30 and CR29 questionnaires on quality of life (QoL) and symptoms at baseline, 3, 6, 12, 18, and 24 months after start of treatment. Between-group differences in functional QoL domains were estimated using a linear mixed-effects model and expressed as effect size (ES). Symptom scores were compared using Mann-Whitney U test.Results: Patients treated with dose–escalated CRT (boost group, n = 51) experienced a significantly stronger decline in global health at 3 and 6 months (ES –0.4 and ES –0.4), physical functioning at 6 months (ES –1.1), role functioning at 3 and 6 months (ES –0.8 and ES –0.6), and social functioning at 6 months (ES –0.6), compared with patients treated with standard CRT (control group, n = 64). The boost group reported significantly more fatigue at 3 and 6 months (83% vs 66% respectively 89% vs 76%), pain at 3 and 6 months (67% vs 36% respectively 80% vs 44%), and diarrhea at 3 months (45% vs 29%) compared with the control group. From 12 months onwards, QoL and symptoms were similar between groups, apart from more blood/mucus in stool in the boost group.Conclusions: In patients with locally advanced rectal cancer, dose-escalated CRT resulted in a transient deterioration in global health, physical, role, and social functioning and more pain, fatigue and diarrhea at 3 and 6 months after start of treatment compared with standard CRT. From 12 months onwards, the effect of dose-escalated CRT on QoL largely resolved.

Background: Survivors of childhood cancer are at risk for therapy-related subsequent malignant neoplasms (SMN), including thyroid SMN. Telomere length (TL) is associated with cancer risk, but the relationship between TL and SMN risk among survivors is less clear. Methods: We conducted a nested, matched case–control study of radiation-exposed 15-year+ adult survivors of childhood cancer with thyroid SMN (cases) and without SMN (controls). Forty-six cases were matched to 46 controls by primary diagnosis, chemotherapy (yes/no), radiation field, and follow-up duration. Lymphocyte TL (LTL) was measured by telomere flow-FISH cytometry using blood samples banked at a mean of 38.9 years (cases), 39.2 years (controls). Genetic variation in telomere genes was assessed by whole genome sequencing. Point estimates for LTL Results: Cases had shorter median LTL than controls in three out of four leukocyte subsets. Cases were more likely to have NK cell LTL Conclusions: Long-term survivors have shorter than expected LTL, a finding that is more pronounced among survivors with thyroid SMN. Impact: The long-term impact of childhood cancer treatment on immune function is poorly understood. Our findings support immune function studies in larger survivor cohorts to assess long-term deficits in adaptive and innate immunity that may underlie SMN risk.

Purpose:Our goal was to compare cancer specific mortality (CSM) rates between radical prostatectomy (RP) vs external beam radiotherapy (EBRT) in National Comprehensive Cancer Network© (NCCN©) high ...

Background Respiratory motion may introduce errors during radiotherapy. This study aims to assess and validate internal gross tumour volume (IGTV) margins in proximal and distal borders of gastroesophageal junction (GEJ) tumours during simultaneous integrated boost radiotherapy. Methods We enrolled 10 patients in group A and 9 patients in group B. For all patients, two markers were placed at the upper and lower borders of the tumour before treatment. In group A, within the simulation and every 5 fractions of radiotherapy, we used 4-dimensional computed tomography (4DCT) to record the intrafractional displacement of the proximal and distal markers. By fusing the average image of each repeated 4DCT with the simulation image based on the lumbar vertebra, the interfractional displacement could be obtained. We calculated the IGTV margin in the proximal and distal borders of the GEJ tumour. In group B, by referring to the simulation images and cone-beam computed tomography (CBCT) images, the range of tumour displacement in proximal and distal borders of GEJ tumour was estimated. We calculated the proportion of marker displacement range in group B lay within the IGTV margin calculated based on the data obtained in group A to estimate the accuracy of the IGTV margin. Results The intrafractional displacement in the cranial–caudal (CC) direction was significantly larger than that in the anterior–posterior (AP) and left–right (LR) directions for both the proximal and distal markers of the tumour. The interfractional displacement in the AP and LR directions was larger than that in the CC direction (p = 0.001, p = 0.017) based on the distal marker. The IGTV margins in the LR, AP and CC directions were 9 mm, 8.5 mm and 12.1 mm for the proximal marker and 15.8 mm, 12.7 mm and 11.5 mm for the distal marker, respectively. In group B, the proportions of markers that located within the IGTV margin in the LR, AP and CC directions were 96.5%, 91.3% and 96.5% for the proximal marker and 100%, 96.5%, 93.1% for the distal marker, respectively. Conclusions Our study proposed individualized IGTV margins for proximal and distal borders of GEJ tumours during neoadjuvant radiotherapy. The IGTV margin determined in this study was acceptable. This margin could be a reference in clinical practice.

Purpose: In modern conformal radiation therapy of distal esophageal cancer, target coverage can be affected by variations in the diaphragm position. We investigated if daily position verification (PV) extended by a diaphragm position correction would optimize target dose coverage for esophageal cancer treatment.Methods and Materials: For 15 esophageal cancer patients, intensity modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) plans were computed. Displacements of the target volume were correlated with diaphragm displacements using repeated 4-dimensional computed tomography images to determine the correction needed to account for diaphragm variations. Afterwards, target coverage was evaluated for 3 PV approaches based on: (1) bony anatomy (PV_B), (2) bony anatomy corrected for the diaphragm position (PV_BD) and (3) target volume (PV_T).Results: The cranial-caudal mean target displacement was congruent with almost half of the diaphragm displacement (y = 0.459x), which was used for the diaphragm correction in PV_BD. Target dose coverage using PV_B was adequate for most patients with diaphragm displacements up till 10 mm (>= 94% of the dose in 98% of the volume [D-98%]). For larger displacements, the target coverage was better maintained by PV_T and PV_BD. Overall, PV_BD accounted best for target displacements, especially in combination with tissue density variations (D-98%: IMPT 94% +/- 5%, VMAT 96% +/- 5%). Diaphragm displacements of more than 10 mm were observed in 22% of the cases.Conclusions: PV_B was sufficient to achieve adequate target dose coverage in case of small deviations in diaphragm position. However, large deviations of the diaphragm were best mitigated by PV_BD. To detect the cases where target dose coverage could be compromised due to diaphragm position variations, we recommend monitoring of the diaphragm position before treatment through online imaging. (C) 2021 Elsevier Inc. All rights reserved.

OBJECTIVE Olfactory neuroblastoma (ONB) is a rare malignant tumor arising in the upper nasal cleft. Rarely, ONB may originate in ectopic sites and the impact of this on prognosis and treatment strategies continues to be debated. METHODS Retrospective analysis of patients with ectopic ONB treated between 2000 and 2020 in a tertiary-care referral center for skull base tumors. Three patients were included in this analysis: a 37-year-old female with ONB arising from the bulla ethmoidalis; a 28-year-old male with inappropriate secretion of antidiuretic hormone due to a maxillary sinus ONB; and a 41-year-old male with lacrimal sac ONB. Preoperative workup, surgical approach, adjuvant treatments and post-operative surveillance have been analyzed. Relevant literature published between 2000 and January 2021 was fully reviewed in order to investigate oncological outcomes and delineate the standard of care for such rare tumors. RESULTS All patients were treated via endoscopic endonasal resection with radical intent, followed by adjuvant treatments when required. No recurrences of disease were observed after a mean follow-up time of 32 months (range, 12-60 months). Data emerging from current literature suggests that a multidisciplinary treatment approach, including free-margins surgical resection followed by adjuvant radiotherapy or radiochemotherapy is recommended. Olfactory bulb and dura preservation should be attempted whenever feasible. CONCLUSIONS Endoscopic endonasal surgery should be preferred, where possible, to achieve complete excision in order to minimize patients’ morbidity. The ectopic site of origin impacts on prognosis and should be considered when selecting the appropriate multimodal treatment strategy.

Artificial intelligence (AI) has great potential to transform the clinical workflow of radiotherapy. Since the introduction of deep neural networks (DNNs), many AI-based methods have been proposed to address challenges in different aspects of radiotherapy. Commercial vendors have started to release AI-based tools that can be readily integrated to the established clinical workflow. To show the recent progress in AI-aided radiotherapy, we have reviewed AI-based studies in five major aspects of radiotherapy, including image reconstruction, image registration, image segmentation, image synthesis, and automatic treatment planning. In each section, we summarized and categorized the recently published methods, followed by a discussion of the challenges, concerns, and future development. Given the rapid development of AI-aided radiotherapy, the efficiency and effectiveness of radiotherapy in the future could be substantially improved through intelligent automation of various aspects of radiotherapy.

Purpose: Radiation therapy techniques have developed from 3-dimensional conformal radiation therapy (3DCRT) to intensity modulated radiation therapy (IMRT), with better sparing of the surrounding normal tissues. The current analysis aimed to investigate whether IMRT, compared to 3DCRT, resulted in fewer adverse events (AEs) and patient-reported symptoms in the randomized PORTEC-3 trial for high-risk endometrial cancer.Methods and materials: Data on AEs and patient-reported quality of life (QoL) of the PORTEC-3 trial were available for analysis. Physician-reported AEs were graded using Common Terminology Criteria for Adverse Events v3.0. QoL was assessed by the European Organisation for Research and Treatment of Cancer QLQC30, CX24, and OV28 questionnaires. Data were compared between 3DCRT and IMRT. A P value of = .01 was considered statistically significant due to the risk of multiple testing. For QoL, combined scores 1 to 2 ("not at all" and "a little") versus 3 to 4 ("quite a bit" and "very much") were compared between the techniques.Results: Of 658 evaluable patients, 559 received 3DCRT and 99 IMRT. Median follow-up was 74.6 months. During treatment no significant differences were observed, with a trend for more grade =3 AEs, mostly hematologic and gastrointestinal, after 3DCRT (37.7% vs 26.3%, P = .03). During follow-up, 15.4% (vs 4%) had grade >= 2 diarrhea, and 26.1% (vs 13.1%) had grade >= 2 hematologic AEs after 3DCRT (vs IMRT) (both P < .01). Among 574 (87%) patients evaluable for QoL, 494 received 3DCRT and 80 IMRT. During treatment, 37.5% (vs 28.6%) reported diarrhea after 3DCRT (vs IMRT) (P = .125); 22.1% (versus 10.0%) bowel urgency (P = 0039), and 18.2% and 8.6% abdominal cramps (P = .058). Other QoL scores showed no differences.Conclusions: IMRT resulted in fewer grade >= 3 AEs during treatment and significantly lower rates of grade >= 2 diarrhea and hematologic AEs during follow-up. Trends toward fewer patient-reported bowel urgency and abdominal cramps were observed after IMRT compared to 3DCRT. (C) 2021 The Authors. Published by Elsevier Inc.

Background Knowledge regarding cognitive problems in metastatic non-small cell lung cancer (mNSCLC) is limited. Such problems may include both patient-reported cognitive concerns and demonstrable cognitive impairment. Greater understanding of these outcomes is needed to inform rehabilitation strategies for these difficulties. We aimed to identify the frequency of cognitive problems and associated factors in patients with mNSCLC. Methods In this cross-sectional study, adults with mNSCLC completed validated neuropsychological tests and self-report questionnaires measuring cognitive concerns, neurobehavioral concerns, depression, demoralization, illness intrusiveness, self-esteem, and physical symptoms. Cognitive impairment (performance based) was defined according to International Cancer and Cognition Task Force criteria. Clinically significant cognitive concerns were defined by a score ≥1.5 SD below the normative mean on the Functional Assessment of Cancer Therapy-Cognitive Function Perceived Cognitive Impairment (FACT-Cog PCI). Univariate and multivariate logistic regression analyses were performed to identify associated factors. Results Of 238 patients approached, 77 participated (median age: 62 years; range: 37-82). Brain metastases were present in 41 patients (53%), and 23 (29%) received cranial irradiation. Cognitive impairment and cognitive concerns were present in 31 (40%) and 20 patients (26%), respectively. Cognitive impairment and cognitive concerns co-occurred in 10 patients (13%), but their severity was unrelated. Cognitive impairment was associated with cranial irradiation (odds ratio [OR] = 2.89; P = .04), whereas cognitive concerns were associated with greater illness intrusiveness (OR = 1.04; P = .03) and lower self-esteem (OR = 0.86; P = .03). Conclusions Cognitive impairment and cognitive concerns are both common in patients with mNSCLC but are not necessarily related, and their risk factors differ. The association of illness intrusiveness and self-esteem with cognitive concerns can inform therapeutic interventions in this population.

Purpose This study aimed to develop a model for predicting pathologic extracapsular extension (ECE) and seminal vesicle invasion (SVI) while integrating magnetic resonance imaging-based T-staging (cTMRI, cT1c-cT3b).Materials and Methods A total of 1,915 who underwent radical prostatectomy between 2006-2016 met the inclusion/exclusion criteria. We performed a multivariate logistic regression analysis as well as Bayesian network (BN) modeling based on possible confounding factors. The BN model was internally validated using 5-fold validation.Results According to the multivariate logistic regression analysis, initial prostate-specific antigen (iPSA) (β=0.050, p < 0.001), percentage of positive biopsy cores (PPC) (β=0.033, p < 0.001), both lobe involvement on biopsy (β=0.359, p=0.009), Gleason score (β=0.358, p < 0.001), and cTMRI (β=0.259, p < 0.001) were significant factors for ECE. For SVI, iPSA (β=0.037, p < 0.001), PPC (β=0.024, p < 0.001), Gleason score (β=0.753, p < 0.001), and cTMRI (β=0.507, p < 0.001) showed statistical significance. BN models to predict ECE and SVI were also successfully established. The overall area under the receiver operating characteristic curve (AUC)/accuracy of the BN models were 0.76/73.0% and 0.88/89.6% for ECE and SVI, respectively. According to internal comparison between the BN model and Roach formula, BN model had improved AUC values for predicting ECE (0.76 vs. 0.74, p=0.060) and SVI (0.88 vs. 0.84, p < 0.001).Conclusion Two models to predict pathologic ECE and SVI integrating cTMRI were established and installed on a separate website for public access to guide radiation oncologists.

Purpose This study aimed to evaluate the role of postoperative radiotherapy (PORT) in intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC).Materials and Methods A total of 133 patients with histologically confirmed HPC were included from eight institutions. Gross total resection (GTR) and subtotal resection (STR) were performed in 86 and 47 patients, respectively. PORT was performed in 85 patients (64%). The prognostic effects of sex, age, performance, World Health Organization (WHO) grade, location, size, Ki-67, surgical extent, and PORT on local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were estimated by univariate and multivariate analyses.Results The 10-year PFS, and OS rates were 45%, and 71%, respectively. The multivariate analysis suggested that PORT significantly improved LC (p < 0.001) and PFS (p < 0.001). The PFS benefit of PORT was maintained in the subgroup of GTR (p=0.001), WHO grade II (p=0.001), or STR (p < 0.001). In the favorable subgroup of GTR and WHO grade II, PORT was also significantly related to better PFS (p=0.028). WHO grade III was significantly associated with poor DMFS (p=0.029). In the PORT subgroup, the 0-0.5 cm margin of the target volume showed an inferior LC to a large margin with 1.0-2.0 cm (p=0.021). Time-dependent Cox proportion analysis showed that distant failures were significantly associated with poor OS (p=0.003).Conclusion This multicenter study supports the role of PORT in disease control of intracranial SFT/HPC, irrespective of the surgical extent and grade. For LC, PORT should enclose the tumor bed with sufficient margin.

Swallowing dysfunction is a prevailing state following radiotherapy in patients with head and neck cancer. Following the advancement of cancer treatment in recent years, the survival rate of head and neck cancer has gradually increased. Simultaneously, patients with head and neck cancer suffer due to the long-duration and more prominent swallowing dysfunction states. Based on an extensive literature review, we aimed to explore the mechanisms, risk factors, and clinical evaluations of swallowing dysfunction and their related symptoms following radiotherapy. These include functional changes of the muscles, trismus, xerostomia, neuropathy, and lymphedema. When swallowing dysfunction occurs, patients usually seek medical help and are referred for rehabilitation therapy, such as muscle strengthening and tongue resistance exercise. Furthermore, clinicians should discuss with patients how and when to place the feeding tube. Only through detailed evaluation and management can swallowing dysfunction resolve and improve the quality of life of patients with head and neck cancer following radiotherapy.

The human microflora is a complex ecosystem composed of diverse microorganisms mainly distributed in the epidermal and mucosal habitats of the entire body, including the mouth, lung, intestines, skin, and vagina. These microbial communities are involved in many essential functions, such as metabolism, immunity, host nutrition, and diseases. Recent studies have focused on the microbiota associated with cancers, particularly the oral and intestinal microbiota. Radiotherapy, the most effective cytotoxic modality available for solid tumors, contributes to the treatment of cancer patients. Mounting evidence supports that the microbiota plays pivotal roles in the efficacy and prognosis of tumor radiotherapy. Here, we review current research on the microbiota and cancer development, and describe knowledge gaps in the study of radiotherapy and the microbiota. Better understanding of the effects of the microbiome in tumorigenesis and radiotherapy will shed light on future novel prevention and treatment strategies based on modulating the microbiome in cancer patients.

Purpose of review To investigate the features and optimal management of pN+ cM0 prostate cancer (PCa) according to registry-based studies. Recent findings Up to 15% of PCa patients harbor lymph node invasion (pN+) at radical prostatectomy plus lymph node dissection. Nonetheless, the optimal management strategy in this setting is not well characterized. Summary We performed a systematic review including n = 13 studies. Management strategies comprised 13 536 men undergoing observation, 11 149 adjuvant androgen deprivation therapy (aADT), 7,075 adjuvant radiotherapy (aRT) +aADT and 705 aRT. Baseline features showed aggressive PCa in the majority of men. At a median follow-up ranging 48-134months, Cancer-related death was 5% and overall-mortality 16.6%. aADT and aRT alone had no cancer-specific survival or overall survival advantages over observation only and over not performing aRT, respectively. aADT plus aRT yielded a survival benefit compared to observation and aADT, which in one study, were limited to certain intermediate-risk categories. Age, Gleason, Charlson score, positive surgical margins, pathological stage, and positive nodes number, but not prostate specific antigen, were most relevant prognostic factors. Our work further confirmed pN+ PCa is a multifaceted disease and will help future research in defining its optimal management based on different risk categories to maximize survival and patient's quality of life.

Purpose:\ud Low-dose whole lung radiotherapy (LDLR) has been proposed as a treatment for patients with acute respiratory distress syndrome associated with SARS-CoV-2 infection and clinical trials are underway. There is an urgent need for preclinical evidence to justify this approach and inform dose, scheduling and mechanisms of action.\ud \ud Materials and methods:\ud Female C57BL/6 mice were treated with intranasal bleomycin sulphate (7.5 or 11.25 units/kg, day 0), then exposed to whole lung radiation therapy (0.5, 1.0, 1.5 Gy or sham, day 3). Bodyweight was measured daily and lung tissue harvested for histology and flow cytometry on day 10. Computed tomography (CT) lung imaging was performed pre-radiation (day 3) and pre-endpoint (day 10).\ud \ud Results:\ud Bleomycin caused pneumonitis of variable severity which correlated with weight loss. LDLR at 1.0 Gy was associated with a significant increase in the proportion of mice recovering to 98% of initial bodyweight and a proportion of these mice exhibited less severe histopathological lung changes. Mice experiencing moderate initial weight loss were more likely to respond to LDLR than those experiencing severe initial weight loss. Additionally, LDLR (1.0 Gy) significantly reduced bleomycin-induced increases in interstitial macrophages, CD103+ dendritic cells and neutrophil-DC hybrids. Overall, bleomycin-treated mice exhibited significantly higher percentages of non-aerated lung in left than right lungs and LDLR (1.0 Gy) limited further reductions in aerated lung volume in right but not left lungs. LDLR at 0.5 and 1.5 Gy did not improve bodyweight, flow cytometric or radiological readouts of bleomycin-induced pneumonitis.\ud \ud Conclusions:\ud Our data support the concept that LDLR can ameliorate acute inflammatory lung injury, identify 1.0 Gy as the most effective dose and provide evidence that it is more effective in the context of moderate than severe pneumonitis. Mechanistically, LDLR at 1.0 Gy significantly suppressed bleomycin-induced accumulation of pulmonary interstitial macrophages, CD103+ dendritic cells and neutrophil-DC hybrids.

Highlights • Rapid improvement observed in a patient with a large cardiac metastasis. • There is today no curative therapeutic option when the tumor is inoperable. • Transcoronary tumor embolization plus moderate targeted radiotherapy should be a new option for tumor control., Purpose Cardiac metastasis is a rare fatal event. An intracavitary right tumor mainly in the ventricle is difficult to manage. Literature reports suggest that cardiac surgery in oligometastatic patients could offer median survival of 1 year. We investigated salvage treatment comprising transcoronary tumor embolization followed 15 days later by cardiac radiotherapy (40.5 Gy/15 fractions). Cases We report two cases of severe right cardiac metastasis with a history of abdominal cancer managed by this salvage treatment following residual cardiac mass after previous cardiac surgery. Conclusion Both symptomatic patients improved progressively and were locally controlled for at least 1 year without toxicity.

The immunogenicity of SARS-CoV-2 vaccines in cancer patients receiving radiotherapy is unknown. This prospective cohort study demonstrates that anti-SARS-CoV-2 spike antibody and neutralization titers are reduced in a subset of thoracic radiotherapy patients, possibly due to immunosuppressive conditions. Antibody testing may be useful to identify candidates for additional vaccine doses.

PURPOSE: Heart dose and heart disease increase risk for RT-associated cardiac toxicity. We hypothesized that CT coronary calcifications are associated with cardiac toxicity and may help ascertain baseline heart disease. METHODS AND MATERIALS: We analyzed the cumulative incidence of cardiac events in patients with Stage III non-small-cell lung cancer receiving median 74 Gy on prospective dose-escalation trials. Events were defined as symptomatic effusion, pericarditis, unstable angina, infarction, significant arrhythmia, and/or heart failure. Coronary calcifications were delineated on simulation CT’s using MIM (130 HU threshold). Calcifications were defined “None,” “Low,” and “High,” with median volume dividing Low and High. RESULTS: Of 109 patients, 26 had cardiac events at median 26 months (range, 1-84 months) post-RT. Median follow-up in surviving patients was 8.8 years (range, 2.3-17.3). On simulation CT’s, 64 (59%) had coronary calcifications with median volume 0.2 cc (range 0.01-8.3). Only 16 patients (15%) had baseline coronary artery disease. Cardiac events occurred in 7% (3/45), 29% (9/31), and 42% (14/33) of patients with No, Low, and High calcifications, respectively. Calcification burden was associated with cardiac toxicity on univariate (Low vs. None: HR 5.0, p=0.015, High vs. None: HR 8.1, p

Highlights • Radiotherapy can trigger cytokine release syndrome and tumor lysis syndrome in association with chemotherapy drugs. • Extreme caution must be given when irradiating large tumor volumes at high risk of tumor lysis. • Evidence of cytokine release following radiotherapy unveils the systemic interactions of radiotherapy with the immune system., We present the case of a 53-year-old woman treated with analgesic radiotherapy for a multiple myeloma bone lesion of the forearm. After a first fraction of 5 Gray (Gy), she presented with an acute respiratory syndrome with fever a few hours after the treatment. The same symptoms occurred after the second fraction 3 days later. The patient recovered quickly thanks to intravenous hydration and suspension of the radiotherapy. Biological tests revealed a tumor lysis syndrome. We concluded that the clinical symptoms could be defined as cytokine release syndrome. This is the second time in the literature that cytokine release syndrome has been described following radiotherapy. First, we synthesize TLS and radiotherapy to determine how radiotherapy could be a trigger associated with other well-known factors. Furthermore, we discuss radiotherapy and cytokine release syndrome. Summary We present the case of a woman treated with analgesic radiotherapy for a multiple myeloma bone lesion. Following the first and the second treatment fraction, the patient presented with an acute respiratory syndrome with fever and biological tests revealed a tumor lysis syndrome. We concluded that the clinical symptoms could be defined as cytokine release syndrome. Furthermore, we discuss how radiotherapy could be a trigger of cytokine release syndrome and tumor lysis syndrome in association with chemotherapy drugs.

Objective: The objective was to assess swallowing, mouth opening and speech function during the first year after radiation-based treatment (RT(+)) after introduction of a dedicated preventive rehabilitation program for stage III–IV oropharyngeal carcinoma (OPC). Methods: Swallowing, mouth opening and speech function were collected before and at six- and twelve-month follow-up after RT(+) for OPC as part of ongoing prospective assessments by speech-language pathologists. Results: Objective and patient-perceived function deteriorated until 6 months and improved until 12 months after treatment, but did not return to baseline levels with 25%, 20% and 58% of the patients with objective dysphagia, trismus and speech problems, respectively. Feeding tube dependency and pneumonia prevalence was low. Conclusion: Despite successful implementation, a substantial proportion of patients still experience functional limitations after RT(+) for OPC, suggesting room for improvement of the current rehabilitation program. Pretreatment sarcopenia seems associated with worse functional outcomes and might be a relevant new target for rehabilitation strategies.

Background & aims: Patients who receive chemoradiotherapy or bioradiotherapy (CRT/BRT) for locally advanced head and neck squamous cell carcinoma (LAHNSCC) often experience high toxicity rates interfering with oral intake, causing tube feeding (TF) dependency. International guidelines recommend gastrostomy insertion when the expected use of TF exceeds 4 weeks. We aimed to develop and externally validate a prediction model to identify patients who need TF > 4 weeks and would benefit from prophylactic gastrostomy insertion. Methods: A retrospective multicenter cohort study was performed in four tertiary head and neck cancer centers in the Netherlands. The prediction model was developed using data from University Medical Center Utrecht and the Netherlands Cancer Institute and externally validated using data from Maastricht University Medical Center and Radboud University Medical Center. The primary endpoint was TF dependency >4 weeks initiated during CRT/BRT or within 30 days after CRT/BRT completion. Potential predictors were extracted from electronic health records and radiotherapy dose-volume parameters were calculated. Results: The developmental and validation cohort included 409 and 334 patients respectively. Multi variable analysis showed predictive value for pretreatment weight change, texture modified diet at baseline, ECOG performance status, tumor site, N classification, mean radiation dose to the contralateral parotid gland and oral cavity. The area under the receiver operating characteristics curve for this model was 0.73 and after external validation 0.62. Positive and negative predictive value for a risk of 90% or higher for TF dependency >4 weeks were 81.8% and 42.3% respectively. Conclusions: We developed and externally validated a prediction model to estimate TF-dependency >4 weeks in LAHNSCC patients treated with CRT/BRT. This model can be used to guide personalized decision-making on prophylactic gastrostomy insertion in clinical practice. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

PurposeTo test effects of positron emission tomography (PET)-based bone marrow-sparing (BMS) image-guided intensity modulated radiation therapy (IG-IMRT) on efficacy and toxicity for patients with locoregionally advanced cervical cancer.Methods and materialsIn an international phase II/III trial, patients with stage IB-IVA cervical carcinoma were treated with either PET-based BMS-IG-IMRT (PET-BMS-IMRT group) or standard image-guided IMRT (IMRT group), with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy. The phase II component nonrandomly assigned patients to PET-BMS-IMRT or standard IMRT. The phase III trial randomized patients to PET-BMS-IMRT versus IMRT, with a primary endpoint of progression-free survival (PFS) but was closed early for futility. Phase III patients were analyzed separately and in combination with phase II patients, comparing acute hematologic toxicity, cisplatin delivery, PFS, overall survival (OS), and patterns of failure. In a post-hoc exploratory analysis, we investigated the association between pretreatment absolute lymphocyte count (ALC) and OS.ResultsIn total, 101 patients were enrolled on the phase II/III trial, including 29 enrolled in phase III (PET-BMS-IMRT group: 16; IMRT group: 13) before early closure. Median follow-up was 33 months for phase III patients and 39 months for all patients. PFS and OS at 5 years for all patients were 73.6% (95% confidence interval [CI], 64.9%-84.3%) and 84% (95% CI, 76%-92.9%]), respectively. There were no differences in number of cisplatin cycles, OS, PFS, or patterns of failure between groups for the combined cohort. The incidence of acute grade ≥ 3 neutropenia was significantly lower in the PET-BMS-IMRT group compared with IMRT for randomized patients (19% vs 54%, χ2P=.048) and in the combined cohort (13% vs 35%, χ2P=.01). Patients with pretreatment ALC ≤ 1.5 k/µL had nonsignificantly worse OS on multivariable analysis (HR 2.85; 95% CI, 0.94-8.62; adjusted P=.216), compared with patients with ALC > 1.5 k/µL. There was no difference in posttreatment ALC by treatment group.ConclusionsPET-BMS-IMRT significantly reduced acute grade ≥3 neutropenia, but not treatment-related lymphopenia, compared with standard IMRT. We found no evidence that PET-BMS-IMRT affected chemotherapy delivery or long-term outcomes, and weak evidence of an association between pretreatment ALC and OS.

A 53-year-old man presented to his optician with blurring of vision in the right eye and was diagnosed to have branch retinal vein occlusion. Over the following 3 months, he had further progressive visual impairment due to right central retinal vein occlusion (CRVO) and then left CRVO. Soon thereafter, during a hospital admission for infected submandibular gland, he was noted to have secondary hypothyroidism and persistent hypokalaemia which led to the diagnosis of Cushing’s syndrome. This case was unusual as the patient did not manifest any classical features of Cushing’s syndrome at the time of presentation with bilateral CRVO, and only 3 months later had dramatic weight loss, muscle weakness and acute psychosis. He received intravenous etomidate and underwent emergency transsphenoidal hypophysectomy with dramatic clinical and biochemical improvement and complete visual recovery in the left eye but unfortunately vision in the right eye remained limited to hand movements.

Injury of the afferent limb of the baroreflex from neck radiation causes radiation-induced afferent baroreflex failure (R-ABF). Identification and management of R-ABF is challenging. We aimed to investigate the pattern of autonomic dysfunction on standardized autonomic testing in patients with probable R-ABF. We retrospectively analyzed all autonomic reflex screens performed at Mayo Clinic in Rochester, MN, between 2000 and 2020 in patients with probable R-ABF. Additional tests reviewed included ambulatory blood pressure monitoring, plasma norepinephrine, and thermoregulatory sweat test. We identified 90 patients with probable R-ABF. Median total composite autonomic severity score (range, 0–10) was 7 (interquartile range, 6–7). Cardiovascular adrenergic impairment was seen in 85 patients (94.4%), increased blood pressure recovery time after Valsalva maneuver in 71 patients (78.9%; median 17.4 seconds), and orthostatic hypotension in 68 patients (75.6%). Cardiovagal impairment was demonstrated by abnormal heart rate responses to deep breathing (79.5%), Valsalva ratio (87.2%), and vagal baroreflex sensitivity (57.9%). Plasma norepinephrine was elevated and rose appropriately upon standing (722–1207 pg/mL). Ambulatory blood pressure monitoring revealed hypertension, postural hypotension, hypertensive surges, tachycardia, and absence of nocturnal dipping. Blood pressure lability correlated with impaired vagal baroreflex function. Postganglionic sympathetic sudomotor function was normal in most cases; the most frequent thermoregulatory sweat test finding was focal neck anhidrosis (78.9%). Standardized autonomic testing in R-ABF demonstrates cardiovascular adrenergic impairment with orthostatic hypotension, blood pressure lability, and elevated plasma norepinephrine. Cardiovagal impairment is common, while sudomotor deficits are limited to direct radiation effects.

BACKGROUND: In the context of high-grade gliomas (HGGs), very little evidence is available concerning the optimal radiotherapy (RT) schedule to be used in radioimmunotherapy combinations. This studied was aimed at shedding new light in this field by analyzing the effects of RT dose escalation and dose fractionation on the tumor microenvironment of experimental HGGs. METHODS: Neurospheres (NS) CT-2A HGG-bearing C57BL/6 mice were treated with stereotactic RT. For dose-escalation experiments, mice received 2, 4 or 8 Gy as single administrations. For dose-fractionation experiments, mice received 4 Gy as a single fraction or multiple (1.33x3 Gy) fractions. The impact of the RT schedule on murine survival and tumor immunity was evaluated. Modifications of glioma stem cells (GSCs), tumor vasculature and tumor cell replication were also assessed. RESULTS: RT dose-escalation was associated with an improved immune profile, with higher CD8+ T cells and CD8+ T cells/regulatory T cells (Tregs) ratio (P=0.0003 and P=0.0022, respectively) and lower total tumor associated microglia/macrophages (TAMs), M2 TAMs and monocytic myeloid derived suppressor cells (mMDSCs) (P=0.0011, P=0.0024 and P

Purpose: Re-irradiation is a treatment option for recurrent esophageal cancer patients with a history of radiotherapy, but there is a risk of severe late adverse effects. This study focused on the efficacy and safety of re-irradiation using hyperfractionated radiotherapy. Materials and Methods: Twenty-six patients who underwent re-irradiation by the hyperfraction technique using twice-daily irradiation of 1.2 Gy per fraction for recurrent esophageal cancer were retrospectively included in this study. The overall survival period after the start of secondary radiotherapy and the occurrence of late adverse effects were investigated. Results: Of 26 patients, 21 (81%) received re-irradiation with definitive intention and 21 (81%) underwent concurrent chemotherapy. The median re-irradiation dose was 60 Gy in 50 fractions in 25 treatment days, and the median accumulated irradiation dose in equivalent dose in 2 Gy per fraction was 85.4 Gy with an α/β value of 3. The median interval between two courses of radiotherapy was 21.0 months. The median overall survival period was 15.8 months and the 1-year and 3-year overall survival rates were 64.3% and 28.3%, respectively. Higher dose of re-irradiation and concurrent chemotherapy significantly improved survival (p < 0.001 and p = 0.019, respectively). Severe late adverse effects with the Common Terminology Criteria for Adverse Events grade 3 or higher were observed in 5 (19.2%) patients, and 2 (7.7%) of them developed a grade 5 late adverse effect. Conclusion: High-dose re-irradiation using a hyperfractionated schedule with concurrent chemotherapy might be related to good prognosis, while the rate of late severe adverse effects is not high compared with the rates in past reports.

Neoadjuvant immunotherapy, given before surgical resection, is a promising approach to develop systemic antitumor immunity for the treatment of high-risk resectable disease. Here, using syngeneic and orthotopic mouse models of triple-negative breast cancer, we have tested the hypothesis that generation of tumor-specific T-cell responses by induction and activation of tumor-residing Batf3-dependent conventional type 1 dendritic cells (cDC1) before resection improves control of distant metastatic disease and survival. Mice bearing highly metastatic orthotopic tumors were treated with a combinatorial in situ immunomodulation (ISIM) regimen comprised of intratumoral administration of Flt3L, local radiotherapy, and in situ TLR3/CD40 stimulations, followed by surgical resection. Neoadjuvant ISIM (neo-ISIM) generated tumor-specific CD8+ T cells that infiltrated into distant nonirradiated metastatic sites, which delayed the progression of lung metastases and improved survival after the resection of primary tumors. The efficacy of neo-ISIM was dependent on de novo adaptive T-cell immunity elicited by Batf3-dependent dendritic cells and was enhanced by increasing dose and fractionation of radiotherapy, and early surgical resection after the completion of neo-ISIM. Importantly, neo-ISIM synergized with programmed cell death protein-1 ligand-1 (PD-L1) blockade to improve control of distant metastases and prolong survival, while removal of tumor-draining lymph nodes abrogated the antimetastatic efficacy of neo-ISIM. Our findings illustrate the therapeutic potential of neoadjuvant multimodal intralesional therapy for the treatment of resectable tumors with high risk of relapse. Significance: Neoadjuvant induction and activation of cDC1s in primary tumors enhances systemic antitumor immunity, suppresses metastatic progression, improves survival, and synergizes with anti–PD-L1 therapy.

Oligometastatic breast cancer (OMBC) is a heterogeneous disease with intrinsic biological diversity. It is increasingly accepted in clinical practice that patients with OMBC could be treated with the expectation of long-term disease remission. Local ablative treatments, such as radiotherapy or surgery have a role in this setting. At present, patients that may benefit are characterised by low tumour burden, long disease-free interval and the capacity to completely ablate all sites of disease. In the future, biological or genomic classifiers may help predict which patients may benefit the most from local ablative treatments. This review provides an overview of the proposed classifications of oligometastatic disease and outlines the standard systemic treatment options of endocrine therapy, chemotherapy, and immunotherapy. The evidence for localized treatment with stereotactic ablative body radiotherapy (SABR) is presented. We discuss current active trials in oligometastatic cancer and discuss potential future directions for the use of SABR in the treatment of OMBC., Highlights • The oligometastatic disease state is being increasingly recognised in breast cancer. • Breast cancer is a heterogenous disease with varied subtypes and treatment paths. • Stereotactic ablative body radiotherapy in addition to systemic therapy has merit. • Evidence suggests benefit for cure, stable disease maintenance, and symptom control. • Study of targeted strategies to treat oligometastatic breast cancer is encouraged.

Introduction Cyclin-dependent kinase (CDK)4/6 inhibitor is a first-line therapy for metastatic ER+/HER2-breast cancer. However, there are limited data on safety of combined radiotherapy (RT) and CDK4/6 inhibition. Methods We conducted a retrospective study of women with metastatic breast cancer who received palliative RT within 14 days of CDK4/6 inhibitor use. The primary endpoint was toxicity per Common Terminology Criteria for Adverse Events v5. Secondary endpoints were pain response and local control based on clinical assessment and imaging. Results Thirty patients underwent 36 RT courses with palbociclib (n = 34 courses, 94.4%) or abemaciclib (n = 2, 5.6%). RT was delivered before, concurrently or after CDK4/6 inhibitors in 7 (19.4%), 8 (22.2%), and 21 (58.3%) of cases with median 3.5 days from RT to closest CDK4/6 inhibitor administration. Median RT dose was 30Gy (range 8–40.05Gy). Treated sites included brain (n = 5, 11.6%), spine (n = 19, 44.2%), pelvis (n = 9, 20.9%), other bony sites (n = 6, 14.0%) and others (n = 4, 9.3%). No acute grade ≥3 non-hematologic toxicity occurred. No increased hematologic toxicity was attributable to RT with grade 3 hematologic toxicities rates 16.7%, 0%, and 6.7% before, during, and 2 weeks after RT completion. All but one patient (29/30) achieved symptom relief. Local control rates were 94.4%, 91.7% at 6 and 12 months. Conclusions The use of RT within 2 weeks of CDK4/6 inhibitors had low acceptable toxicity and high efficacy, suggesting that it is safe for palliation of metastatic breast cancer., Highlights • CDK4/6 inhibitors with endocrine therapy is a preferred first line therapy for HR+, HER2-metastatic breast cancer. • Limited data exists on safety of combined radiotherapy and CDK4/6 inhibition in patients with metastatic breast cancer. • This retrospective cohort study included 30 patients who underwent palliative RT with combined CDK4/6 inhibitor use. • RT within 2 weeks of CDK4/6 inhibitor had low toxicity and high efficacy, supporting its safety in metastatic breast cancer.

BackgroundTrimodality therapy (TMT) with preoperative chemoradiation followed by surgical resection is used for locally-advanced non-small-cell lung cancer (LA-NSCLC). Traditionally, preoperative radiation doses ≤54Gy are used due to concerns regarding excess morbidity, but little is known about outcomes and toxicities after TMT with intensity-modulated radiotherapy (IMRT) to higher doses.MethodsA retrospective analysis of patients who received planned TMT with IMRT for LA-NSCLC at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 2008 and 2017 was performed. Clinical and treatment characteristics, pathologic response, and surgical toxicity were assessed. Kaplan-Meier method and log-rank test was used for survival outcomes. Cox proportional-hazards regression was used for multivariable analysis.ResultsForty-six patients received less than definitive doses of 7days were associated with OS.ConclusionsWith IMRT, there was no increased rate of surgical complications in patients receiving higher doses of radiation. Survival outcomes or LOS did not differ based on radiation dose, but increased LOS was associated with worse OS. Larger prospective studies are needed to further examine outcomes after IMRT in patients with LA-NSCLC receiving TMT.

Background and purpose: Accelerated partial breast irradiation (APBI) may benefit from the MR-Linac for target definition, patient setup, and motion monitoring. In this planning study, we investigated whether prone or supine position is dosimetrically beneficial for APBI on an MR-Linac and we evaluated patient comfort. Materials and methods: Twenty-patients (9 postoperative, 11 preoperative) with a DCIS or breast tumor

Objective: The primary aim was to compare the psychometric properties among the Patient Health Questionnaire (PHQ-9) (both including and excluding somatic symptom items), the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D), and the Center for Epidemiologic Studies Depression Scale (CES-D) in detecting depression in cancer patients receiving radiotherapy. The secondary aim was to investigate the prevalence of depression in this group of patients.Materials and Methods: Overall, 198 participants with cancer diagnosis from a radiology clinic took part in the study. They completed PHQ-9, HADS-D, and CES-D questionnaires and were interviewed in line with the Mini-International Neuropsychiatric Interview (M.I.N.I.) to confirm the diagnosis. The PHQ-9 was analyzed for three scoring methods: sum-score, inclusive (including all items), and exclusive (excluding 4 somatic symptom items) methods. The psychometric properties of each questionnaire were analyzed. The prevalence of depression measured by the M.I.N.I. was evaluated.Results: The sum-score method of the PHQ-9 had an equal sensitivity (100%) to the HADS-D and CES-D, and had a slightly higher specificity (91.1%) than the HADS-D (87.4%) and CES-D (90.6%). When compared results within the PHQ-9, the sum-score method had greater sensitivity than the inclusive (71.4%) and exclusive (42.9%) methods, and had a slightly lower specificity than the inclusive (96.9%) and exclusive (97.4%) methods. The prevalence of depression assessed by the M.I.N.I was 3.5%.Conclusion: The sum-score method of the PHQ-9 seemed to be the best tool to use for depression screening in cancer patients receiving radiotherapy due to its excellent sensitivity and specificity.

During radiation therapy treatments patients may require medications to manage radiation toxicities. Since patients are assessed daily by Radiation Therapists (RTs) it would be optimal and timely for patients to receive medication prescriptions for relief of common radiation side effects from the RTs.The purpose of this study was to determine the perceptions that RTs and Radiation Oncologists (ROs) have of frontline treatment RTs prescribing medications to patients for treatment-related side effects.A qualitative and quantitative survey consisting of twenty-five questions on a five-point Likert scale, one open-ended question, and three demographic questions was designed. While the survey sought to examine the perceptions that RTs and ROs have of RTs prescribing medications, the survey also proposed eight different medications that RTs could potentially prescribe. The medications that were proposed are commonly prescribed to radiation therapy patients and included anti-emetic, topical anti-bacterial, hydrocortisone cream, topical anaesthetic, anti-diarrheal, anti-spasmodic, urinary analgesic and anti-fungal medications. After the survey was approved by the Research Ethics Board, RTs and ROs at a large, academic cancer centre were invited to complete the survey. To analyze the survey results, several statistical tests were performed separately for the RTs' surveys and the ROs' surveys. The chi-squared test was used to determine if the sample RT and RO populations were representative of the actual RT and RO populations (p0.05). Additionally, the Sign test for medians was used to analyze statistically the responses to the Likert scale questions (p0.05), while the Kruskal-Wallis test was used to compare the responses to the Likert scale questions across the demographic groups identified in the demographic questions (p0.05).The response rate was 34% (31/90) for the RT population and 42% (10/24) for the RO population. The statistical analysis of the RT population's surveys showed that the majority of the RTs shared positive perceptions towards having RTs prescribe medications, while some respondents highlighted negative perceptions in the open-ended qualitative question. The majority of the RTs agreed that RTs should prescribe five of the eight proposed medications, excluding anti-spasmodic, urinary analgesic, and anti-fungal medications. In contrast to the RTs, there was no statistically significant consensus from the ROs on RTs prescribing medications. Furthermore, the ROs had varying opinions on RTs prescribing the eight proposed medications.Although the sample size in this study was small, the results from the RT population's surveys supported RTs prescribing medications. The positive results from the RTs and the equivocal response from the ROs suggest that future research should be conducted. Additionally, a future pilot study could be implemented where RTs prescribe one or more of the five medications that were supported to prescribe by the RTs. By having RTs prescribe medications to patients in a pilot study, the effectiveness on patient care could be measured.

Microcystic adnexal carcinoma (MAC) is an infiltrative rare cutaneous neoplasm for which there are no consensus management guidelines because of the paucity of evidence-based practice; hence, the utility of their management is based only on previously published case reports. We report a case of a scalp lesion that was successfully treated using a combination of surgical resection, chemotherapy, and radiotherapy.

Radiotherapy (RT) is a major modality of postoperative treatment in breast cancer. The maximal standardized value (SUVmax) is 18FDG-PET/CT derived parameter that reported to be a valuable prognostic factor in cancer patients. Herein, we aimed to identify a prognostic gene signature associated with glucose uptake for breast cancer patients after RT by leveraging the mRNA expression profiling on public datasets. The glucose uptake signature was constructed using the single sample gene set enrichment analysis (ssGSEA) algorithm and evaluated in GSE21217 where SUVmax value was measured by PET-CT directly. The prognostic value was validated in three post-RT breast cancer cohorts (GSE103744, NKI, and FUSCC databases). The patients were stratified into glucose uptake signature score-high and low groups. Patients with a higher score had worse survival than those with a lower score. Mechanistically, the glucose uptake signature was calculated in each cell type of a single-cell RNA-seq database from five breast cancer patients. Glucose uptake signature score was significantly elevated in the malignant epithelial cells compared with normal ones. The immunosuppression markers including PDCD1, TIGIT, LAG3, and HAVCR2 were significantly upregulated in the T cells bearing a high glucose uptake signature score. Collectively, our results demonstrated the potential prognostic value of a glucose uptake signature in the post-RT breast cancer patients., Graphical abstract, A glucose uptake gene signature was constructed and validated to predict survival in radiotherapy-treated breast cancer patients. The correlation between this gene signature and immunosuppressive markers has been explored.

Background: The present paper reports on analysis of 184 patients who were diagnosed with endometrial cancer. The main objective of this study was to address parameter V rec(30Gy) which determines a volume of the rectum irradiated with a dose of 30 Gy during radiotherapy. Material and methods: All patients were irradiated with an IMRT technique on linear accelerators. The planning target volume (PTV) contour was determined by a radiation oncologist. The clinical target volume (CTV) was drawn on CT images obtained in a prone position. For statistical analysis, appropriate tests (e.g. the Shapiro-Wilk, Wilcoxon) were used. Results and discussion: The performed analysis showed that the recommended condition for V rec(30Gy) is met only in 3% of patients and the observed median value exceeds 90%. The obtained results were compared with the studies in which the V rec(30Gy) values were related to various radiotherapy techniques. Conclusions: The analysis showed that the condition for V rec(30Gy) is satisfied in the case of only 3% of patients. Due to the difficulty with meeting the condition, it should be reconsidered based on real results.

The aim of this review was to examine the theoretical, preclinical and clinical bases of the combination radiotherapy immunotherapy in the management of non-small cell lung cancer (NSCLC). Preclinical studies have shown that in addition to its well-established tumoricidal effects, radiotherapy can activate the host immune system and modify the tumor microenvironment. Immunotherapy is currently part of the therapeutic arsenal of the NSCLC given its capacity to restore the host's immune system's ability to recognize and destroy tumor cells. The combination of radiotherapy and immunotherapy seems to be synergistic, particularly with inhibitors of immune checkpoints. This association has become standard in the metastatic stages and especially in consolidation after radiochemotherapy in the locally advanced, unresectable and stable stages. Several questions remain unanswered including the optimal sequence of this combination, the type of radiotherapy (hypo-fractionated or normofractionated), the association of several immunotherapies and the cross-toxicity of the combination. The association of radiotherapy and immunotherapy is a promising treatment.

Background Machine learning studies require a large number of images often obtained on different PET scanners. When merging these images, the use of harmonized images following EARL-standards is essential. However, when including retrospective images, EARL accreditation might not have been in place. The aim of this study was to develop a convolutional neural network (CNN) that can identify retrospectively if an image is EARL compliant and if it is meeting older or newer EARL-standards. Materials and methods 96 PET images acquired on three PET/CT systems were included in the study. All images were reconstructed with the locally clinically preferred, EARL1, and EARL2 compliant reconstruction protocols. After image pre-processing, one CNN was trained to separate clinical and EARL compliant reconstructions. A second CNN was optimized to identify EARL1 and EARL2 compliant images. The accuracy of both CNNs was assessed using fivefold cross-validation. The CNNs were validated on 24 images acquired on a PET scanner not included in the training data. To assess the impact of image noise on the CNN decision, the 24 images were reconstructed with different scan durations. Results In the cross-validation, the first CNN classified all images correctly. When identifying EARL1 and EARL2 compliant images, the second CNN identified 100% EARL1 compliant and 85% EARL2 compliant images correctly. The accuracy in the independent dataset was comparable to the cross-validation accuracy. The scan duration had almost no impact on the results. Conclusion The two CNNs trained in this study can be used to retrospectively include images in a multi-center setting by, e.g., adding additional smoothing. This method is especially important for machine learning studies where the harmonization of images from different PET systems is essential.

Paratesticular Rhabdomyosarcoma is a rare mesenchymal tumor. The Alveolar variant is the one with the worse prognosis. It comprehend 20% of cases. The treatment is multimodal combining surgery, chemotherapy and radiotherapy. Depending on the extent of disease and the staging group, the approach of treatment is different. Here we report the case of an alveolar Paratesticular rhabdomyosarcoma and review the literature regarding this unusual clinical entity.

The present study aimed to reduce the parotid gland dose in the hippocampus avoidance with whole-brain radiotherapy (HA-WBRT) using the helical tomotherapy (HT). Ten patients who had previously undergone WBRT were randomly selected and enrolled in this study. During the treatment planning, two different techniques to the jaw were applied for each patient, namely, 1.0 cm fixed jaw and 2.5 cm dynamic jaw. To efficiently reduce the dose in the bilateral parotid glands, directional block (DB) mode was set. The DB is a function of a treatment planning system for the dose reduction in organs at risk. The standard HA-WBRT plan which did not reduce the parotid gland dose was also designed to compare the plan quality. Compared with the standard HA-WBRT plan, the parotid gland dose could be reduced by approximately 70% without extending the delivery time by adding the parotid gland on the DB mode to the dose constraint. In addition, the differences in dosimetric parameters observed between the plans employing the 1.0 cm fixed jaw and 2.5 cm dynamic jaw were almost negligible. Moreover, delivery time in the 2.5 cm dynamic jaw could be greatly reduced by 60% compared with that in the 1.0 cm fixed jaw.

Purpose Radiation-induced toxicity (RIT) is usually assessed by inspection and palpation. Due to their subjective and unquantitative nature, objective methods are required. This study aimed to determine whether a quantitative tool is able to assess RIT and establish an underlying BED-response relationship in breast cancer. Methods Patients following seven different breast radiation protocols were recruited to this study for RIT assessment with qualitative and quantitative examination. The biologically equivalent dose (BED) was used to directly compare different radiation regimens. RIT was subjectively evaluated by physicians using the Radiation Therapy Oncology Group (RTOG) late toxicity scores. Simultaneously an objective multiprobe device was also used to quantitatively assess late RIT in terms of erythema, hyperpigmentation, elasticity and skin hydration. Results In 194 patients, in terms of the objective measurements, treated breasts showed higher erythema and hyperpigmentation and lower elasticity and hydration than untreated breasts (p p p p = 0.019, respectively). As the BED increased, Δerythema and Δpigmentation gradually increased as well (p = 0.006 and p = 0.002, respectively). Regarding the clinical assessment, the increase in BED resulted in a higher RTOG toxicity grade (p p p = 0.016, p = 0.005, respectively). Conclusions The multiprobe device can be a sensitive and simple tool for research purpose and quantitatively assessing RIT in patients undergoing radiotherapy for breast cancer. Physician-assessed toxicity scores and objective measurements revealed that the BED was positively associated with the severity of RIT.