The management of brain metastases (BM) remains an important and complex issue in the treatment of cancer-related neurological complications. BM are particularly common in patients diagnosed with lung, melanoma, or breast cancer. Over the past decade, therapeutic approaches for the majority of BM patients have changed. Considering and addressing the fact that patients with BM are living longer, the need to provide effective local control while preserving quality of life and neurocognition is fundamental. Over the past decade, SRS and SRT have become a more commonly chosen treatment option for BM. Despite significant advances in the treatment of BM, numerous questions remain regarding patient selection and optimal treatment sequencing. Clinical trials are critical to advancing our understanding of BM, especially as more therapeutic alternatives become available. Therefore, it is imperative for interdisciplinary teams to improve their understanding of the latest advances in SRS-SRT. This review aims to comprehensively explore SRS and SRT as treatments for BM, covering clinical considerations in their application (e.g., patient selection and eligibility), managing limited and multiple intact BM, addressing brainstem metastases, exploring combination therapies with systemic treatments, and considering the health economic perspective.

This study evaluates the benefit of weekly delineation and peer review by a multidisciplinary team (MDT) of radiation oncologists (ROs), radiologists (RXs), and nuclear medicine (NM) physicians in defining primary and lymph node tumor volumes (GTVp and GTVn) for head and neck cancer (HNC) radiotherapy. This study includes 30 consecutive HNC patients referred for definitive curative (chemo)-radiotherapy. Imaging data including head and neck MRI, [18F]-FDG-PET and CT scan were evaluated by the MDT. The RO identified the 'undeniable' tumor as GTVp_core and determined GTVp_max, representing the maximum tumoral volume. The MDT delineation (MDT-D) by RX and NM physicians outlined their respective primary GTVs (GTVp_RX and GTVp_NM). During the MDT meeting (MDT-M), these contours were discussed to reach a consensus on the final primary GTV (GTVp_final). In the comparative analysis of various GTVp delineations, we performed descriptive statistics and assessed two MDT-M factors: 1) the added value of MDT-M, which includes the section of GTVp_final outside GTVp_core but within GTVp_RX or GTVp_NM, and 2) the part of GTVp_final that deviates from GTVp_max, representing the area missed by the RO. For GTVn, discussions evaluated lymph node extent and malignancy, documenting findings and the frequency of disagreements. The average GTVp core and max volumes were 19.5 cc (range: 0.4-90.1) and 22.1 cc (range: 0.8-106.2), respectively. Compared to GTVp_core, MDT-D to GTVp_final added an average of 3.3 cc (range: 0-25.6) and spared an average of 1.3 cc (0-15.6). Compared to GTVp_max, MDT-D and -M added an average of 2.7 cc (range: 0-20.3) and removed 2.3 cc (0-21.3). The most frequent GTVn discussions included morphologically suspicious nodes not fixing on [18F]-FDG-PET and small [18F]-FDG-PET negative retropharyngeal lymph nodes. Multidisciplinary review of target contours in HNC is essential for accurate treatment planning, ensuring precise tumor and lymph node delineation, potentially improving local control and reducing toxicity.

Objectives: We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intra-prostatic nodule (DIN). Materials and methods: In 33 patients with intermediate–high-risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and 68Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (68Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25–74% for partial overlap, were assessed. Long-term toxicity is reported. Results: All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17–76 months), affecting 13 out of 33 patients (39.4%). Intra-prostatic recurrences occurred in 7 patients (21%), with ≥75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patients. Notably, five patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intra-prostatic recurrences. Extended follow-up revealed late grade ≥ 2 GU and GI toxicity in 18% (n = 6) and 6% (n = 2) of the patients. Conclusions: Among patients with intermediate–high-risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Advances in knowledge: Focal dose-escalated prostate SBRT prevented recurrences in the dominant nodule; however, extra-prostatic recurrence sites were frequent.

Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly diverse disease with low tumor immunogenicity. PDAC is also one of the deadliest solid tumor and will remain a common cause of cancer death in the future. Treatment options are limited, and tumors frequently develop resistance to current treatment modalities. Since PDAC patients do not respond well to immune checkpoint inhibitors (ICIs), novel methods for overcoming resistance are being explored. Compared to other solid tumors, the PDAC's tumor microenvironment (TME) is unique and complex and prevents systemic agents from effectively penetrating and killing tumor cells. Radiotherapy (RT) has the potential to modulate the TME (e.g., by exposing tumor-specific antigens, recruiting, and infiltrating immune cells) and, therefore, enhance the effectiveness of targeted systemic therapies. Interestingly, combining ICI with RT and/or chemotherapy has yielded promising preclinical results which were not successful when translated into clinical trials. In this context, current standards of care need to be challenged and transformed with modern treatment techniques and novel therapeutic combinations. One way to reconcile these findings is to abandon the concept that the TME is a well-compartmented population with spatial, temporal, physical, and chemical elements acting independently. This review will focus on the most interesting advancements of RT and describe the main components of the TME and their known modulation after RT in PDAC. Furthermore, we will provide a summary of current clinical data for combinations of RT/targeted therapy (tRT) and give an overview of the most promising future directions.

This study compares the dosimetric plans of three distinct boost modalities in cervical cancer (CC): intracavitary (IC) with tandem/ovoids brachytherapy (BT), IC + interstitial (IS) BT, and Stereotactic-Body-Radiotherapy (SBRT). The aim is to determine the dosimetric impact in terms of target coverage and organ at risk (OAR) doses. 24 consecutive IC + IS BT boost treatment plans were retrospectively identified. For each plan included, two additional plans were created: IC-BT and SBRT. Importantly, no planning target volume (PTV) or planning (organ at) risk volume (PRV) margins were generated, therefore all structures were identical for any boost modality. Two different normalizations were performed: (1) Normalization to the target: prescription of 7.1 Gy to the D90

Purpose/Objective(s) To compare and measure the potential benefit of time-saving, accuracy and dosimetric impact, the MIM ProtegeAI Prostate 2.0 auto-segmentation™ was compared to the manual delineation of the radiation oncologist. Furthermore, the intra-observer variability and familiarization bias were also assessed. Materials/Methods Forty-eight consecutive prostate cancer cases have been retrospectively investigated. The planning CT scan (3mm slice thickness, from vertebrae L1/2 to 3cm below the ischial tuberosity, without contrast) was used for auto-contouring (AI) and manual delineation by a single observer (Manual). Femur_L/_R, PenileBulb, Rectum, SeminalVes and Bladder were evaluated; while another five AI-generated OARs were discarded. Time (minute: second; [Q1-Q3]) of AI delineation scoring (AIscor: major/minor/no correction needed), AI correction (AIcor), total AI (=AIscor+AIcor) and manual delineation were measured. The potential gain was assessed per individual OARs. To access familiarization half of the cohort started with AIscor and AIcor followed by Manual, while the other half started with Manual, followed by AIscor and AIcor. T-test at p<0.05 significance level was used for comparisons. Dice Similarity Coefficient (DSC), 95% Hausdorff and median surface distance (HD95, MSD) were also determined. Given that both contours were found to be clinically acceptable by the same radiation oncologist, the AIcor/Manual was used to define intra-observer variability. Original dose matrices were used to access median dose differences for each evaluated organ. Results A total of 473 contours were generated by AI, with a fixed of 5 minutes per patient. For 36 patients (75%), AI failed to generate Kidney_L/_R. Major, minor, or no correction was considered in 14%, 72% and 14% of delineations, respectively. Manual delineation took on average 12:52 [7:51-24:19], AIscor and AIcor 2:45 [1:52-5:00] and 6:18 [2:49-14:14], respectively. AI gave up to 16:16 time gain with an average of 5:37 (p<0.001). Per OARs, the average time gain was 0:47 [0:11-1:44]. The familiarization bias, observed for Manual (p=0.09), was on average 1:27 faster when AI workflow started first, while for AIcor no significant bias was observed (p=0.168). Good DSC (>0.8) was observed for AI/AIcor, while HD95 and MSD showed a larger discrepancy. Intra-observer (AIcor/Manual) variability was worse for DSC and better for HD95 and MSD compared to AI vs. AIcor. Relevant (>5%) median dose (Gray) differences were observed for only two OARs: rectum and penile bulb. Conclusion ProtegeAI Prostate 2.0 auto-segmentation™ provides on average more than 4 minutes of gain per patient and requires only minor corrections. The realistic time saving is likely higher, as AIscor+AIcor prior manual delineation significantly reduced manual delineation time. Intra-observer variability remains a substantial source of differences, especially when relying on the DSC. Dose differences may be as high as 5% when using the corrected AI.

Purpose/ObjectiveDeep Inspiration Breath Hold (DIBH) is now considered as the standard of care for many breast cancer patients. However, there are still uncertainties about the dose given to the heart, and it is unknown if patients may improve voluntary DIBH depth by gaining experience during treatment. In this study, we will examine the interfractional three-dimensional (3D) heart displacement throughout voluntary DIBH (vDIBH) radiotherapy by means of daily cone-beam computed tomography (CBCT).Material and methodsTwo hundred twenty-five unique CBCTs from 15 patients treated in 15 fractions were analyzed. During CBCT, a vDIBH was conducted without any visual feedback. Patients performed their DIBH freely after receiving explanations and training. After daily CBCT matching to the chest wall (CW), surface-guided radiation therapy (SGRT) tracked DIBH depth to ensure that the CW position was the same as the daily acquired CBCT. The CBCTs were retrospectively registered to the DIBH planning-CT to calculate daily changes in heart displacement relative to the CW.ResultsThe mean displacement of the heart during DIBH treatment relative to the DIBH planning-CT was as follows: 1.1 mm to the right, interquartile range (IQR) 8.0; 0.5 mm superiorly, IQR 4.8; and 0 mm posteriorly, IQR 6.4. The Spearman correlation coefficients (rs) were -0.15 (p=0.025), 0.04 (p=0.549), and 0.03 (p=0.612) for the X, Y, and Z directions, respectively. The differences in median heart displacement were significant: Friedmann rank sum test p=0.031 and pairwise comparison using the Wilcoxon rank-sum test were p=0.008 for X and Y; p=0.33 for X and Z; and p=0.07 for Y and Z. The total median heart motion was δtot median= 7.26 mm, IQR= 6.86 mm.ConclusionDuring DIBH, clinicians must be aware of the wide range of intra- and inter-individual heart position variations. The inter-individual heterogeneity shown in our study should be investigated further in order to avoid unexpected cardiac overexposure and to develop a more accurate heart dose-volume model.

Due to the general aging population and the fashion trend of sun exposure, non-melanoma skin cancer (NMSC) is rising. The management of NMSC is difficult and necessitates a multidisciplinary team (i.e., pathologists, dermatologists, medical oncologists, surgeons, and radiation oncologists). When surgery is not an option or will cause unacceptably functional morbidity, radiation therapy (RT) may be a preferable tissue-preserving option. Whether used alone or in conjunction with other treatments, RT has been shown to be quite effective in terms of cosmetic results and local control. Contact hypofractionated RT, brachytherapy, and electronic brachytherapy are all promising new treatments. However, rigorous, randomized trials are missing, explaining the disparity in dose, fractionation, and technique recommendations. Therefore, it is essential that interdisciplinary teams better understand RT modalities, benefits, and drawbacks. Our review will provide the role and indications for RT in patients with NMSC.

Introduction/Background In Luxembourg, brachytherapy (BT) is not widely available. The focus of this research was to assess the feasibility, safety, and efficacy of Stereotactic Body Radiation Therapy (SBRT) as a boost in locally advanced cervical cancer. Methodology Between 2017–2019, patients with histologically proven FIGO (2018) stages IB-IVA treated by external radiotherapy (VMAT): 50 Gy in 28 fractions to the pelvic +/- lomboaortic lymph nodes and 60.04 Gy using a simultaneous integrated boost to the macroscopic tumor +/- positive FDG-PET-CT scan nodes were included. Concurrent weekly cisplatin (40 mg/m2) was given. Following concurrent radio-chemotherapy (CCRT), a pelvic computed tomography scan with a magnetic resonance imaging simulation were performed within the 1st week after CCRT. Target volumes (GTV-T, HR-CTV, PTV) and organs at risk (bladder, rectum, sigmoid, and bowel bag) were define on the MRI. The boost prescription was 13Gy in two fractions delivered in two consecutive days. SBRT boost was delivered using a Cyberknife®M6 and tracking based fiducial markers. A 12-week MRI and Pet-Ct were used to determine the therapeutic outcomes. Results Eleven patients were included, median age was 59 years (57–68), 100% had a squamous cell carcinoma, 45% had a stage ≥ IIIC. The median overall treatment time was 52 days (Q1–3: 49.5–56). With a median follow up of 20 months (12.5–31), the local control was 73%. Three patients relapsed: external parametrial areas (n=2), pre-sacral node (n=1). No acute genito-urinary toxicity (Grade > II) was observed, 18% had acute grade III gastrointestinal toxicity. The most common long-term toxicity were grade I-II genito-urinary and gastro intestinal, no Grade ≥ III was observed. Progression free survival during the median follow-up of 20 months was 71.7%. Conclusion SBRT boost seems feasible and well tolerable, although it cannot substitute BT. Further studies with longer follow-up periods are warranted to confirm long-term outcomes.

Xeroderma pigmentosum (XP) is a rare genetic disease, which vital prognosis is conditioned by the occurrence of cancers essentially of the skin and ocular surfaces, requiring an early and adapted management. Radiation therapy (RT) is a very effective modality in the therapeutic arsenal alongside surgery, but it remains underused as it is wrongly considered to be deleterious for these patients. In this article, we report the case of a 10-years-old girl with XP treated with external beam RT for a squamous cell carcinoma (SCC) of the right ocular conjunctiva. The clinical tolerance was excellent and we obtained a good tumoral response. Therefore, the place of RT in these patients could/should be reconsidered, especially since these suspicions have still not been confirmed.

Purpose Concurrent chemo radiotherapy (CCRT) has been the standard of care in locally advanced nasopharyngeal carcinoma (LA-NPC) for many years. The role of induction chemotherapy (ICT) has always been controversial. This systematic review and meta-analysis investigates the value of adding ICT to CCRT in LA-NPC. Materials and Methods Two reviewers independently assessed the eligibility of randomized controlled trials (RCTs) comparing ICT followed by CCRT versus CCRT alone, including treatment-naive adult patients with histologically proven nonmetastatic LA-NPC. Results Eight RCTs with in total 2,384 randomized patients, of whom 69% had N2-N3 disease, were selected. ICT was the allocated treatment in 1,200 patients, of whom 1,161 actually received this. Treatment compliance varied, with a median rate of 92% (range, 86%-100%) of patients receiving all cycles of ICT. The percentage of patients completing radiotherapy was 96% and 95% [(Combined Risk difference(CRD)= 0.004; 95% Confidence Interval (CI) -0.001-0.01;p= 0.14)] in the ICT group and CCRT group, respectively, whereas chemotherapy during radiotherapy could be completed in only 28% of the ICT group versus 61% in the CCRT group (CRD, -0.243; 95% CI, -0.403 to -0.083;p= .003). Grade 3-4 acute toxicity was mostly hematologic during the ICT phase (496 events vs. 191 nonhematologic) and was predominant in the ICT group (1,596 events vs. 1,073 in the CCRT alone group) during the CCRT. Adding ICT to CCRT provided a significant benefit in overall survival (hazard ratio [HR], 0.680; 95% CI, 0.511-0.905;p= .001) and progression-free survival (HR, 0.657; 95% CI, 0.568-0.760;p< .001). Conclusion Although ICT followed by CCRT is associated with more acute toxicity and a lower compliance of the chemotherapy during the CCRT phase, this association resulted in a clinically meaningful survival benefit. ICT should be considered as a standard option in patients with LA-NPC, but further study on optimal patient selection for this treatment is warranted. Implications for Practice Locally advanced nasopharyngeal carcinoma (LA-NPC) is a relatively common disease in some parts of the world, with a rather poor prognosis due to its high metastatic potential. The role of induction chemotherapy (ICT) has always been controversial. This meta-analysis found that ICT followed by concurrent chemoradiotherapy (CCRT) in LA-NPC is associated with a significant clinical improvement in both overall survival and progression-free survival compared with CCRT alone. ICT should be considered as a standard option in patients with LA-NPC.

Background In our department, during lung stereotactic body radiation therapy (SBRT), all patients receive an intra-fractional midpoint cone beam computed tomography (CBCT). This study aimed to quantify the benefit of adding a second midpoint CBCT over a course of peripheral lung SBRT. Materials and methods Six-hundred-sixty-four CBCTs from 166 patients were retrospectively analyzed. Treatments were based on the internal target volume (ITV) approach. An isotropic 0.5 cm margin was used to create the planning target volume (PTV) around the ITV. The prescribed dose was 48 Gy in 4 fractions to the PTV. Patients were divided into two groups: patients for whom the 3D-intra-fractional-variation (IFV) was < 0.5 cm (105 patients, low risk group) and patients with at least one 3D-IFV ≥ 0.5 cm (61 patients, high-risk group). Plans simulating the dosimetric impact of the IFV were created as follows: the original 2 arcs (ARC ) were copied into a new plan consisting of 4 times ARC 1 and 4 times ARC 2. The delivery of ARC 1 was always assumed to have occurred with the isocenter initially coordinated, whereas the positions of ARC 2 were modified for each arc by the measured the 3D-IFV. Results For the PTV, we obtained: D99% (Gy) = 45.2 vs. 48.2 Gy (p < 0.0001); Dmean = 53 vs. 54 Gy (p < .0001) for the reconstructed vs. planned dose values, respectively. For the ITV, the changes are less pronounced: D99% (Gy) = 52.2 vs. 53.6 Gy (p = 0.0007); Dmean = 56 vs. 56.8 Gy (p = 0.0144). The V48 Gy(%)-ITV coverage did not statistically change between the delivered vs. planned dose (p = 0.1803). Regarding the organs at risk for both groups, dose-volume-histograms were near-identical. Conclusion We demonstrated that a single CBCT is sufficient and reliable to manage the IFV during peripheral lung SBRT.

BACKGROUND:Rhabdomyosarcoma (RMS) is a highly malignant soft tissue sarcoma (STS), usually of adults, displaying skeletal muscle differentiation. STS principally metastasize to the lungs with more than 50% of metastatic patients presenting with isolated pulmonary metastasis. Paradoxically, the majority of drugs prescribed to treat RMS are associated with multidrug resistance. CASE REPORT:We report the case of a 53 year-old patient who developed three synchronous chemoresistant lung metastasis from pleomorphic RMS. Considering the poor prognosis, the patient's preference and the chemoresistance of her lung metastasis, we decided to perform two consecutive stereotactic body radiotherapy (SBRT) on two of these three lesions. DISCUSSION:Initially, the patient was referred to our institute with a painful mass in the anterior part of the left thigh increasing in volume for 3 months. Biopsy revealed a high-grade pleomorphic RMS. The cancer being staged IB, she had neoadjuvant radiotherapy. After complete surgical excision, pathology examination revealed a 6 cm Grade II pleomorphic RMS, with clear margins. Six months later, she developed three synchronous lung metastases. She got 4 courses of doxorubicin-ifosfamide which were poorly supported. After two courses, a heterogeneous (morphological and metabolic) response was observed, hence SBRT was delivered with a Biologically Equivalent Dose (α/β10)> 100 Gray on the two more chemoresistant lesions. This SBRT was very well tolerated, no side effects were reported. The patient remained alive and achieved a complete response of these three metastases, which sustains after more than 3 years. CONCLUSION:Early recognition and proper management of these oligometastatic patients may lead to motivating results in a poor prognosis disease.

Background: The treatment of nasopharyngeal carcinoma (NPC) consists of radiotherapy alone (stage I) or radiotherapy concomitant with chemotherapy (stage II-V). Acute side effects management forms a major challenge for practitioners. Substantial literature is available from endemic areas, whereas data from Europe is scarce. This study examines clinical characteristics, therapeutic results, acute and late side effects of patients treated at the Jules Bordet Institute. Materials and Methods: Twenty-two consecutive non-metastatic NPC patients treated between May 2012 and September 2015 were retrospectively analyzed. All patients were treated by Intensity Modulated Radiation Therapy (IMRT) with or without chemotherapy (CT). Results: Thirteen patients have North-African ancestry while nine are of European origin. Seventy-three percent had a non-keratinizing carcinoma and 90% had an advanced stage disease (III-IVb). Ninety-five percent of the patients received concomitant CT. After a median follow-up time of 31 months, overall survival was 77%. Local, regional and distant control rates were 95%, 86% and 73%. Main acute grade 3 toxicities were swallowing disorders (91%), vomiting (82%), oropharyngeal mucositis (64%) and dermatitis (23%). Only one patient developed grade 4 dermatitis, requiring treatment discontinuation in the sixth week. In the seventh week of treatment, 86% of the patients had lost more than 10% of their starting weight. Univariate analysis identified three factors driving the weight loss: grade 3 mucositis of the soft palate (p=0.027), vomiting (p=0.019) and pre-treatment dental extraction (p=0.006). In multivariate analysis, weight loss is only linked to dental extraction (p=0.042, Odds Ratio 1.62, [95% CI: 1.16-2.80]). Late toxicities were xerostomia (68%), auditory symptoms (55%), hypothyroidism (45%) and swallowing disorders (23%). Conclusion: Our clinical characteristics outcome and toxicity are comparable to published data from endemic regions. Interestingly, weight loss of u003e10% is correlated to pre-treatment dental extraction. This finding should be confirmed and analyzed in a prospective manner.

Purpose or ObjectiveCarcinoma buccal mucosa is a major health problem in India and Sqamous cell carcinoma (SCC) is the most common histology.Early stage disease (Stage I&II) is treated with Radical Radiotherapy (RT) or Surgery.The locally advanced patients are treated with Surgery followed by adjuvant treatment.The purpose of this retrospective analysis is to analyse the clinical profile and treatment outcomes of patients with SCC Buccal mucosa who were treated with Radical RT between 2010 and 2012 at Regional Cancer Centre, Trivandrum, South India. Material and MethodsData was collected using a structured proforma.Record of 418 patients evaluated and 226 patients were treated with Radical RT.The primary end point was Disease free survival (DFS).Secondary end points were Overall survival (OS) and second malignancies.DFS and OS were generated by Kaplan Meier Curves.

Purpose: The term “oligo-metastasis” could be defined as a transition state between localized and widespread systemic cancer. In the uro-oncology field, very few cases of oligo-metastases of bladder cancer have been described, probably because of the high metastatic potential of muscle invasive bladder cancer. In fact, bladder cancer remains an important cause of morbidity and mortality, the latter being predominantly related to metastasis. Herein we report a case of an oligometastatic bladder cancer treated by SBRT and we review the literature on the treatment of this disease. Methods: We describe a case of pulmonary and lymph-node metastases of a high grade bladder cancer, which relapsed after surgical resection and chemotherapy. Results: After the patient was treated with SBRT at his 3 metastatic lesions, and dispite a transient episode of grade 2 dyspnea, he was clinically in good condition without any evidence of disease on PET-CT scan after 22 months. Conclusion: SBRT is an efficient metastasis-directed treatment, and may be an alternative to chemotherapy or surgery. However, our case highlights that SBRT although easily feasible is not without any risk and should be use with caution, especially outside recognize indications and clinical trials.