ABSTRACT
Cone-beam computed tomography (CBCT)-based online adaptation is increasingly being introduced into many clinics. Upon implementation of a new treatment technique, a prospective risk analysis is required and enhances workflow safety. We conducted a risk analysis using Failure Mode and Effects Analysis (FMEA) upon the introduction of an online adaptive treatment programme (Wegener et al., Z Med Phys. 2022). A prospective risk analysis, lacking in-depth clinical experience with a treatment modality or treatment machine, relies on imagination and estimates of the occurrence of different failure modes. Therefore, we systematically documented all irregularities during the first year of online adaptation, namely all cases in which quality assurance detected undesired states potentially leading to negative consequences. Additionally, the quality of automatic contouring was evaluated. Based on those quantitative data, the risk analysis was updated by an interprofessional team. Furthermore, a hypothetical radiation therapist-only workflow during adaptive sessions was included in the prospective analysis, as opposed to the involvement of an interprofessional team performing each adaptive treatment. A total of 126 irregularities were recorded during the first year. During that time period, many of the previously anticipated failure modes (almost) occurred, indicating that the initial prospective risk analysis captured relevant failure modes. However, some scenarios were not anticipated, emphasizing the limits of a prospective risk analysis. This underscores the need for regular updates to the risk analysis. The most critical failure modes are presented together with possible mitigation strategies. It was further noted that almost half of the reported irregularities applied to the non-adaptive treatments on this treatment machine, primarily due to a manual plan import step implemented in the institution's workflow.
Subject(s)
Artificial Intelligence , Cone-Beam Computed Tomography , Humans , Prospective Studies , Risk Assessment , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Image-Guided/methods , Healthcare Failure Mode and Effect AnalysisABSTRACT
Sacituzumab govitecan (SG) is a new treatment option for patients with metastatic triple-negative and hormone receptor-positive, HER2-negative breast cancer. This antibody-drug conjugate is currently approved as monotherapy. Palliative radiotherapy is frequently used to treat symptomatic metastases locally. Concurrent use of SG and irradiation was excluded in clinical trials of SG, and there are currently limited published data. We report here a systematic review, as well as a retrospective multi-center study of 17 patients with triple-negative breast cancer who received concurrent SG and radiotherapy. In these patients, concurrent use was found to be efficient, safe and well tolerated. There were no apparent differences in moderate or severe acute toxicity according to the timing of SG administration.
ABSTRACT
BACKGROUND: Incorporating chimeric antigen receptor (CAR)-T cell therapy into relapsed or refractory large B-cell lymphoma (rr LBCL) treatment algorithms has yielded remarkable response rates and durable remissions, yet a substantial portion of patients experience progression or relapse. Variations in outcomes across treatment centers may be attributed to different bridging strategies and remission statuses preceding CAR-T cell therapy. PATIENTS: Twenty-nine consecutive adult patients receiving tisagenlecleucel (tisa-cel) for rr LBCL from December 2019 to February 2023 at Jena University Hospital were analyzed. RESULTS: The median age was 63, with a median of 3 prior treatments. Twenty patients (69%) were refractory to any systemic therapy before CAR-T cell treatment. Following leukapheresis, 25 patients (86%) received bridging therapy with the majority undergoing chemotherapy (52%) or combined modality therapy (32%). Radiotherapy (RT) was part of the bridging strategy in 44%, with moderately hypofractionated involved site RT (30.0 Gy/2.5 Gy) being applied most frequently (64%). Post-CAR-T infusion, the objective response rate at 30 days was 83%, with 55% achieving complete response. Twelve-month progression-free (PFS) and overall survival (OS) were 60% and 74%, respectively, with a median follow up of 11.1 months for PFS and 17.9 months for OS. Factors significantly associated with PFS were chemotherapy sensitivity pre-leukapheresis and response to bridging. CONCLUSION: The study underscores the importance of minimal tumor burden at CAR-T initiation, emphasizing the need for suitable bridging regimens. The findings advocate for clinical trials and further real-world analyses to optimize CAR-T cell therapy outcomes by identifying the most effective bridging strategies.
Subject(s)
Immunotherapy, Adoptive , Lymphoma, Large B-Cell, Diffuse , Humans , Male , Middle Aged , Female , Aged , Immunotherapy, Adoptive/methods , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Adult , Remission Induction , Neoplasm Recurrence, Local/therapy , Neoplasm Recurrence, Local/pathology , Germany , Receptors, Antigen, T-Cell/therapeutic use , Retrospective Studies , Combined Modality TherapyABSTRACT
BACKGROUND: Surgical resection is the standard of care for patients with large or symptomatic brain metastases (BMs). Despite improved local control after adjuvant stereotactic radiotherapy, the risk of local failure (LF) persists. Therefore, we aimed to develop and externally validate a pre-therapeutic radiomics-based prediction tool to identify patients at high LF risk. METHODS: Data were collected from A Multicenter Analysis of Stereotactic Radiotherapy to the Resection Cavity of Brain Metastases (AURORA) retrospective study (training cohort: 253 patients from two centers; external test cohort: 99 patients from five centers). Radiomic features were extracted from the contrast-enhancing BM (T1-CE MRI sequence) and the surrounding edema (FLAIR sequence). Different combinations of radiomic and clinical features were compared. The final models were trained on the entire training cohort with the best parameter set previously determined by internal 5-fold cross-validation and tested on the external test set. RESULTS: The best performance in the external test was achieved by an elastic net regression model trained with a combination of radiomic and clinical features with a concordance index (CI) of 0.77, outperforming any clinical model (best CI: 0.70). The model effectively stratified patients by LF risk in a Kaplan-Meier analysis (p < 0.001) and demonstrated an incremental net clinical benefit. At 24 months, we found LF in 9% and 74% of the low and high-risk groups, respectively. CONCLUSIONS: A combination of clinical and radiomic features predicted freedom from LF better than any clinical feature set alone. Patients at high risk for LF may benefit from stricter follow-up routines or intensified therapy.
ABSTRACT
Accurate Magnetic Resonance Imaging (MRI) simulation is fundamental for high-precision stereotactic radiosurgery and fractionated stereotactic radiotherapy, collectively referred to as stereotactic radiotherapy (SRT), to deliver doses of high biological effectiveness to well-defined cranial targets. Multiple MRI hardware related factors as well as scanner configuration and sequence protocol parameters can affect the imaging accuracy and need to be optimized for the special purpose of radiotherapy treatment planning. MRI simulation for SRT is possible for different organizational environments including patient referral for imaging as well as dedicated MRI simulation in the radiotherapy department but require radiotherapy-optimized MRI protocols and defined quality standards to ensure geometrically accurate images that form an impeccable foundation for treatment planning. For this guideline, an interdisciplinary panel including experts from the working group for radiosurgery and stereotactic radiotherapy of the German Society for Radiation Oncology (DEGRO), the working group for physics and technology in stereotactic radiotherapy of the German Society for Medical Physics (DGMP), the German Society of Neurosurgery (DGNC), the German Society of Neuroradiology (DGNR) and the German Chapter of the International Society for Magnetic Resonance in Medicine (DS-ISMRM) have defined minimum MRI quality requirements as well as advanced MRI simulation options for cranial SRT.
Subject(s)
Radiation Oncology , Radiosurgery , Humans , Radiosurgery/methods , Magnetic Resonance Imaging , Radiotherapy Dosage , Imaging, Three-DimensionalABSTRACT
BACKGROUND: Many automatic approaches to brain tumor segmentation employ multiple magnetic resonance imaging (MRI) sequences. The goal of this project was to compare different combinations of input sequences to determine which MRI sequences are needed for effective automated brain metastasis (BM) segmentation. METHODS: We analyzed preoperative imaging (T1-weighted sequence ± contrast-enhancement (T1/T1-CE), T2-weighted sequence (T2), and T2 fluid-attenuated inversion recovery (T2-FLAIR) sequence) from 339 patients with BMs from seven centers. A baseline 3D U-Net with all four sequences and six U-Nets with plausible sequence combinations (T1-CE, T1, T2-FLAIR, T1-CE + T2-FLAIR, T1-CE + T1 + T2-FLAIR, T1-CE + T1) were trained on 239 patients from two centers and subsequently tested on an external cohort of 100 patients from five centers. RESULTS: The model based on T1-CE alone achieved the best segmentation performance for BM segmentation with a median Dice similarity coefficient (DSC) of 0.96. Models trained without T1-CE performed worse (T1-only: DSC = 0.70 and T2-FLAIR-only: DSC = 0.73). For edema segmentation, models that included both T1-CE and T2-FLAIR performed best (DSC = 0.93), while the remaining four models without simultaneous inclusion of these both sequences reached a median DSC of 0.81-0.89. CONCLUSIONS: A T1-CE-only protocol suffices for the segmentation of BMs. The combination of T1-CE and T2-FLAIR is important for edema segmentation. Missing either T1-CE or T2-FLAIR decreases performance. These findings may improve imaging routines by omitting unnecessary sequences, thus allowing for faster procedures in daily clinical practice while enabling optimal neural network-based target definitions.
ABSTRACT
PURPOSE: Tumor boards serve as established platforms for interdisciplinary expert discussions and therapeutic recommendations tailored to individual patient characteristics. Despite their significance, medical students often lack exposure to such interdisciplinary discussions as tumor boards are currently not integrated into medical curricula. To address this, we aimed to enhance future physicians' interdisciplinary communication skills and subject-specific knowledge by introducing an interactive series of five linked tumor board seminars within the domain of neuro-oncology. METHODS: We developed a neuro-oncological student tumor board using a flipped-classroom format. The primary objectives of this case-centered approach included fostering an understanding of the tumor board process, active participation in multidisciplinary case discussions, honing appropriate communication strategies, and creating personalized therapy plans that consider inputs from all relevant disciplines, individual patient factors, and ethical considerations. To gauge the effectiveness of the seminar series, we administered structured pre- and post-course questionnaires. RESULTS: Fourteen medical students in third to fifth year participated in the pilot series. Despite its organizational complexity, the interdisciplinary seminars were feasible. Students demonstrated significant growth in competence, aligned with predefined learning objectives. Notably, they appreciated the supportive learning environment and interactive teaching format, which kindled their interest in interdisciplinary oncology. CONCLUSION: Active participation in a student tumor board can empower students to tackle the diverse challenges of caring for cancer patients within an interdisciplinary team during the early stages of their careers. The student tumor board represents an innovative, learner-centered approach to teach interdisciplinary cancer treatment, communication strategies, and ethical aspects of medical practice.
Subject(s)
Students, Medical , Humans , Learning , CurriculumABSTRACT
BACKGROUND: Objective and subjective assessment of image quality of brain metastases on dual-energy computed tomography (DECT) virtual monoenergetic imaging (VMI) and its impact on target volume delineation. MATERIALS AND METHODS: 26 patients with 37 brain metastases receiving Magnetic Resonance Imaging (MRI) and DECT for stereotactic radiotherapy planning were included in this retrospective analysis. Lesion contrast (LC), contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were assessed for reconstructed VMI at 63 keV and artificial 120 kV Computed Tomography (CT). Image contrast and demarcation of metastases between 120 kV CT, VMI and MRI were subjectively assessed. Brain metastases were delineated by four radiation oncologists on VMI with a fixed or free brain window and contours were compared to solely MRI-based delineation using the Dice similarity coefficient. RESULTS: LC, CNR and SNR were significantly higher in VMI than in 120 kV CT (p < 0.0001). Image contrast and lesion demarcation were significantly better on VMI compared to 120 kV CT (p < 0.0001). Mean gross tumor volume (GTV)/planning target volume (PTV) Dice similarity coefficients were 0.87/0.9 for metastases without imaging uncertainties (no artifacts, calcification or impaired visibility with MRI) but worse for metastases with imaging uncertainties (0.71/0.74). Target volumes delineated on VMI were around 5-10% smaller compared to MRI. CONCLUSION: Image quality of VMI is objectively and subjectively superior to conventional CT. VMI provides significant advantages in stereotactic radiotherapy planning with improved visibility of brain metastases and geometrically distortion-free representation of brain metastases. Beside a plausibility check of MRI-based target volume delineation, VMI might improve reliability and accuracy in target volume definition particularly in cases with imaging uncertainties with MRI.
Subject(s)
Brain Neoplasms , Radiography, Dual-Energy Scanned Projection , Humans , Retrospective Studies , Reproducibility of Results , Radiography, Dual-Energy Scanned Projection/methods , Tomography, X-Ray Computed/methods , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/radiotherapy , Radiographic Image Interpretation, Computer-Assisted/methodsABSTRACT
Intensified preoperative chemotherapy after (chemo)radiotherapy, (Total Neoadjuvant Therapy-TNT), increases pathological complete response (pCR) rates and local control. In cases of clinically complete response (cCR) and close follow-up, non-operative management (NOM) is feasible. We report early outcomes and toxicities of a long-term TNT regime in a single-center cohort. Fifteen consecutive patients with distal or middle-third locally advanced rectal cancer (UICC stage II-III) were investigated, who received neoadjuvant chemoradiotherapy (total adsorbed dose: 50.4 Gy in 28 fractions and two concomitant courses 5-fluorouracil (250 mg/m2/d)/oxaliplatin (50 mg/m2), followed by consolidating chemotherapy (nine courses of FOLFOX4). NOM was offered if staging revealed cCR 2 months after TNT, with resection performed otherwise. The primary endpoint was complete response (pCR + cCR). Treatment-related side effects were quantified for up two years after TNT. Ten patients achieved cCR, of whom five opted for NOM. Ten patients (five cCR and five non-cCR) underwent surgery, with pCR confirmed in the five patients with cCR. The main toxicities comprised leukocytopenia (13/15), fatigue (12/15) and polyneuropathy (11/15). The most relevant CTC °III + IV events were leukocytopenia (4/15), neutropenia (2/15) and diarrhea (1/15). The long-term TNT regime resulted in promising response rates that are higher than the response rates of short TNT regimes. Overall tolerability and toxicity were comparable with the results of prospective trials.
Subject(s)
Leukopenia , Rectal Neoplasms , Humans , Neoadjuvant Therapy/methods , Prospective Studies , Treatment Outcome , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Rectal Neoplasms/drug therapy , Chemoradiotherapy, Adjuvant/adverse effects , Chemoradiotherapy, Adjuvant/methods , Leukopenia/etiologyABSTRACT
Boron neutron capture therapy (BNCT) involves infusion of cancer patients with a tumor-seeking, boron-loaded compound and irradiation by a beam of neutrons, with an energy range of 1 eV-10 keV. Neutron capture in the 10B atoms results in an effective lethal radiation dose to the tumor cells, while sparing the healthy tissue. Recently available accelerator-based irradiation facilities facilitate developing BNCT to a treatment modality. However, the binary principle of BNCT, together with other points, is challenging in designing clinical trials that allow a timely and safe introduction of this innovative targeted modality into clinical practice. We propose a methodological framework to work toward a systematic, coordinated, and internationally accepted and evidence-based approach.
Subject(s)
Boron Neutron Capture Therapy , Neoplasms , Humans , Boron Neutron Capture Therapy/methods , Clinical Trials as Topic , Neoplasms/radiotherapy , Neutrons , Dose-Response Relationship, RadiationSubject(s)
Quality of Life , Rectal Neoplasms , Humans , Rectum , Rectal Neoplasms/therapy , Treatment OutcomeABSTRACT
INTRODUCTION: Conducting neoadjuvant chemoradiotherapy (CRT) and additional preoperative consolidating chemotherapy (CTx), that is, total neoadjuvant therapy (TNT), improves local control and complete response (CR) rates in locally advanced rectal cancer (LARC), putting the focus on organ preservation concepts. Therefore, assessing response before surgery is crucial. Some LARC patients would either not benefit from intensification by TNT or may reach CR, making resection not mandatory. Treatment of LARC should therefore be based on patient individual risk and response to avoid overtreatment.The "PRIMO" pilot study aims to determine early response assessment to form a basis for development and validation of a noninvasive response prediction model by a subsequent prospective multicenter trial, which is highly needed for individual, response-driven therapy adaptions. METHODS: PRIMO is a prospective observational cohort study including adult patients with LARC receiving neoadjuvant CRT. At least 4 multiparametric magnetic resonance imaging (MRI) scans (diffusion-weighted imaging [DWI] and hypoxia-sensitive sequences) as well as repeated blood samples in order to analyze circulating tumor cells (CTC) and cell-free tumor DNA (ctDNA) are scheduled. Pelvic radiotherapy (RT, 50.4 Gy) will be performed in combination with a 5-fluorouracil/oxaliplatin regimen in all patients (planned: N = 50), succeeded by consolidation CTx (FOLFOX4) if feasible. Additional (immuno)histochemical markers, such as tumor-infiltrating lymphocytes (TIL) and programmed death ligand 1 (PD-L1) status will be analyzed before and after CRT. Routine resection is scheduled subsequently, nonoperative management is offered alternatively in case of clinical CR (cCR).The primary endpoint is pathological response; secondary endpoints comprise longitudinal changes in MRI as well as in CTCs and TIL. These are evaluated for early response prediction during neoadjuvant therapy, in order to develop a noninvasive response prediction model for subsequent analyses. DISCUSSION: Early response assessment is the key in differentiating "good" and "bad" responders during neoadjuvant CRT, allowing adaption of subsequent therapies (additional consolidating CTx, organ preservation). This study will contribute in this regard, by advancing MR imaging and substantiating new surrogate markers. Adaptive treatment strategies might build on these results in further studies.
Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Adult , Humans , Neoadjuvant Therapy/methods , Prospective Studies , Pilot Projects , Chemoradiotherapy/methods , Rectal Neoplasms/therapy , Rectal Neoplasms/drug therapy , Magnetic Resonance Imaging , Liquid Biopsy , Treatment Outcome , Tumor MicroenvironmentABSTRACT
PURPOSE: The new Medical Licensing Regulations 2025 (Ärztliche Approbationsordnung, ÄApprO) require the development of competence-oriented teaching formats. In addition, there is a great need for high-quality teaching in the field of radiation oncology, which manifests itself already during medical school. For this reason, we developed a simulation-based, hands-on medical education format to teach competency in performing accelerated partial breast irradiation (APBI) with interstitial multicatheter brachytherapy for early breast cancer. In addition, we designed realistic breast models suitable for teaching both palpation of the female breast and implantation of brachytherapy catheters. METHODS: From June 2021 to July 2022, 70 medical students took part in the hands-on brachytherapy workshop. After a propaedeutic introduction, the participants simulated the implantation of single-lead catheters under supervision using the silicone-based breast models. Correct catheter placement was subsequently assessed by CT scans. Participants rated their skills before and after the workshop on a six-point Likert scale in a standardized questionnaire. RESULTS: Participants significantly improved their knowledge-based and practical skills on APBI in all items as assessed by a standardized questionnaire (mean sum score 42.4 before and 16.0 after the course, pâ¯< 0.001). The majority of respondents fully agreed that the workshop increased their interest in brachytherapy (mean 1.15, standard deviation [SD] 0.40 on the six-point Likert scale). The silicone-based breast model was found to be suitable for achieving the previously defined learning objectives (1.19, SD 0.47). The learning atmosphere and didactic quality were rated particularly well (mean 1.07, SD 0.26 and 1.13, SD 0.3 on the six-point Likert scale). CONCLUSION: The simulation-based medical education course for multicatheter brachytherapy can improve self-assessed technical competence. Residency programs should provide resources for this essential component of radiation oncology. This course is exemplary for the development of innovative practical and competence-based teaching formats to meet the current reforms in medical education.
Subject(s)
Brachytherapy , Breast Neoplasms , Students, Medical , Female , Humans , Mastectomy, Segmental/methods , Brachytherapy/methods , Breast/radiation effects , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgeryABSTRACT
BACKGROUND: Stereotactic radiotherapy is a standard treatment option for patients with brain metastases. The planning target volume is based on gross tumor volume (GTV) segmentation. The aim of this work is to develop and validate a neural network for automatic GTV segmentation to accelerate clinical daily routine practice and minimize interobserver variability. METHODS: We analyzed MRIs (T1-weighted sequence ± contrast-enhancement, T2-weighted sequence, and FLAIR sequence) from 348 patients with at least one brain metastasis from different cancer primaries treated in six centers. To generate reference segmentations, all GTVs and the FLAIR hyperintense edematous regions were segmented manually. A 3D-U-Net was trained on a cohort of 260 patients from two centers to segment the GTV and the surrounding FLAIR hyperintense region. During training varying degrees of data augmentation were applied. Model validation was performed using an independent international multicenter test cohort (n = 88) including four centers. RESULTS: Our proposed U-Net reached a mean overall Dice similarity coefficient (DSC) of 0.92 ± 0.08 and a mean individual metastasis-wise DSC of 0.89 ± 0.11 in the external test cohort for GTV segmentation. Data augmentation improved the segmentation performance significantly. Detection of brain metastases was effective with a mean F1-Score of 0.93 ± 0.16. The model performance was stable independent of the center (p = 0.3). There was no correlation between metastasis volume and DSC (Pearson correlation coefficient 0.07). CONCLUSION: Reliable automated segmentation of brain metastases with neural networks is possible and may support radiotherapy planning by providing more objective GTV definitions.
Subject(s)
Brain Neoplasms , Radiosurgery , Humans , Neural Networks, Computer , Magnetic Resonance Imaging , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/radiotherapy , Radiotherapy Planning, Computer-Assisted , Image Processing, Computer-AssistedABSTRACT
Population-based studies on early mortality in head and neck cancer (HNC) are sparse. This retrospective population-based study investigated early mortality of HNC and the influence of patients' tumor and treatment characteristics. All 8288 patients with primary HNC of the German federal state Thuringia from 1996 to 2016 were included. Univariate and multivariate analysis were performed to identify independent factors for 30-day, 90-day, and 180-day mortality. The 30-, 90-, and 180-day mortality risks were 1.8%, 5.1%, and 9.6%, respectively. In multivariable analysis, male sex (odds ratio (OR) 1.41; 95% confidence interval (CI) 1.08-1.84), increasing age (OR 1.81; CI 1.49-2.19), higher T (T4: OR 3.09; CI 1.96-4.88) and M1 classification (OR 1.97; CI 1.43-2.73), advanced stage (IV: OR 3.97; CI 1.97-8.00), tumors of the cavity of mouth (OR 3.47; CI 1.23-9.75), oropharynx (OR 3.01; CI 1.06-8.51), and hypopharynx (OR 3.27; CI 1.14-9.40) had a significantly greater 180-day mortality. Surgery (OR 0.51; CI 0.36-0.73), radiotherapy (OR 0.37; CI 0.25-0.53), and multimodal therapy (OR 0.10; CI 0.07-0.13) were associated with decreased 180-day mortality. Typical factors associated with worse overall survival had the most important impact on early mortality in a population-based setting.
ABSTRACT
INTRODUCTION: Since the beginning of the pandemic in 2020, COVID-19 has changed the medical landscape. International recommendations for localized prostate cancer (PCa) include deferred treatment and adjusted therapeutic routines. MATERIALS AND METHODS: To longitudinally evaluate changes in PCa treatment strategies in urological and radiotherapy departments in Germany, a link to a survey was sent to 134 institutions covering two representative baseline weeks prior to the pandemic and 13 weeks from March 2020 to February 2021. The questionnaire captured the numbers of radical prostatectomies, prostate biopsies and case numbers for conventional and hypofractionation radiotherapy. The results were evaluated using descriptive analyses. RESULTS: A total of 35% of the questionnaires were completed. PCa therapy increased by 6% in 2020 compared to 2019. At baseline, a total of 69 radiotherapy series and 164 radical prostatectomies (RPs) were documented. The decrease to 60% during the first wave of COVID-19 particularly affected low-risk PCa. The recovery throughout the summer months was followed by a renewed reduction to 58% at the end of 2020. After a gradual decline to 61% until July 2020, the number of prostate biopsies remained stable (89% to 98%) during the second wave. The use of RP fluctuated after an initial decrease without apparent prioritization of risk groups. Conventional fractionation was used in 66% of patients, followed by moderate hypofractionation (30%) and ultrahypofractionation (4%). One limitation was a potential selection bias of the selected weeks and the low response rate. CONCLUSION: While the diagnosis and therapy of PCa were affected in both waves of the pandemic, the interim increase between the peaks led to a higher total number of patients in 2020 than in 2019. Recommendations regarding prioritization and fractionation routines were implemented heterogeneously, leaving unexplored potential for future pandemic challenges.
Subject(s)
COVID-19 , Prostatic Neoplasms , Humans , Male , Prostate/pathology , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/radiotherapy , Surveys and Questionnaires , UrologistsABSTRACT
This population-based study investigated the prognostic role of intraparotid (PAR) and cervical lymph node (LN) metastasis on overall survival (OS) of primary parotid cancer. All 345 patients (median age: 66 years; 43% female, 49% N+, 31% stage IV) of the Thuringian cancer registries with parotid cancer from 1996 to 2016 were included. OS was assessed in relation to the total number of removed PAR and cervical LN, number of positive intraparotid (PAR+), positive cervical LN, LN ratio, log odds of positive LN (LODDS), as well as including the PAR as LODDS-PAR. PAR was assessed in 42% of the patients (22% of these PAR+). T and N classification were not independent predictors of OS. When combining T with LODDS instead of N, higher T (T3/T4) became a prognosticator (hazard ratio (HR) = 2.588; CI = 1.329−5.040; p = 0.005) but not LODDS (p > 0.05). When combining T classification with LODDS-PAR, both higher T classification (HR = 2.256; CI = 1.288−3.950; p = 0.004) and the alternative classification with LODDS-PAR (≥median −1.11; HR 2.078; CI = 1.155−3.739; p = 0.015) became independent predictors of worse OS. LODDS-PAR was the only independent prognosticator out of the LN assessment for primary parotid cancer.
ABSTRACT
Optimal doses for the treatment of adrenal metastases with stereotactic radiotherapy (SBRT) are unknown. We aimed to identify dose-volume cut-points associated with decreased local recurrence rates (LRR). A multicenter database of patients with adrenal metastases of any histology treated with SBRT (biologically effective dose, BED10 ≥50 Gy, ≤12 fractions) was analyzed. Details on dose-volume parameters were required (planning target volume: PTV-D98%, PTV-D50%, PTV-D2%; gross tumor volume: GTV-D50%, GTV-mean). Cut-points for LRR were optimized using the R maxstat package. One hundred and ninety-six patients with 218 lesions were included, the largest histopathological subgroup was adenocarcinoma (n = 101). Cut-point optimization resulted in significant cut-points for PTV-D50% (BED10: 73.2 Gy; P = .003), GTV-D50% (BED10: 74.2 Gy; P = .006), GTV-mean (BED10: 73.0 Gy; P = .007), and PTV-D2% (BED10: 78.0 Gy; P = .02) but not for the PTV-D98% (P = .06). Differences in LRR were clinically relevant (LRR ≥ doubled for cut-points that were not achieved). Further dose-escalation was not associated with further improved LRR. PTV-D50%, GTV-D50%, and GTV-mean cut-points were also associated with significantly improved LRR in the adenocarcinoma subgroup. Separate dose optimizations indicated a lower cut-point for the PTV-D50% (BED10: 69.1 Gy) in adenocarcinoma lesions, other values were similar (<2% difference). Associations of cut-points with overall survival (OS) and progression-free survival were not significant but durable freedom from local recurrence was associated with OS in a landmark model (P < .001). To achieve a significant improvement of LRR for adrenal SBRT, a moderate escalation of PTV-D50% BED10 >73.2 Gy (adenocarcinoma: 69.1 Gy) should be considered.
Subject(s)
Adenocarcinoma , Adrenal Gland Neoplasms , Lung Neoplasms , Neoplasms, Second Primary , Radiosurgery , Adenocarcinoma/radiotherapy , Adrenal Gland Neoplasms/radiotherapy , Adrenal Gland Neoplasms/secondary , Humans , Lung Neoplasms/pathology , Radiosurgery/methods , Radiotherapy Dosage , Retrospective StudiesABSTRACT
BACKGROUND: This retrospective study investigated factors influencing time to treatment initiation (TTI) and the influence of TTI on overall survival (OS) of primary head and neck cancer (HNC) patients in cohorts from 2003, 2008 and 2013. METHODS: Two hundred and ninenty seven patients (78.8% men; median age: 62 years) were included. Kaplan-Meier analyses and multivariate Cox regression were performed to investigate OS. RESULTS: Mean times to treatment initiation (TTI) of 2003, 2008 and 2013 were 17.11 ± 18.00, 30.26 ± 30.08 and 17.30 ± 37.04 days, respectively. TTI for patients with T3/T4 tumors was higher than for T1/T2 (p = 0.010). In univariable analysis on OS, TTI > 5 days showed lower OS (p = 0.047). In multivariate analysis, longer TTI had no influence on lower OS [hazard ratio (HR) 1.236; 95% CI 0.852-1.791; p = 0.264], but male gender [HR 2.342; 95% CI 1.229-4.466; p = 0.010], increased age [HR 1.026; 95% CI 1.008-1.045; p = 0.005], M1 [HR 5.823; 95% CI 2.252-15.058; p = 0.003], hypopharynx tumor [HR 2.508; 95% CI 1.571-4.003; p < 0.001] and oral cavity tumor [HR 1.712; CI 1.101-2.661; p = 0.017]. The year of treatment showed no significant effect on OS. CONCLUSION: Median TTI seemed to be very short compared to other studies. There was no clear trend in the impact of TTI on OS from 2003 to 2013.
Subject(s)
Head and Neck Neoplasms , Time-to-Treatment , Female , Head and Neck Neoplasms/therapy , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Retrospective Studies , UniversitiesABSTRACT
BACKGROUND: Adjuvant radiotherapy (RT) is an integral component of a multidisciplinary treatment strategy for early-stage breast cancer. It significantly reduces the incidence of loco-regional recurrence but also of distant events. Distant events are due to tumor cells disseminated from the primary tumor into lymphatic fluid or blood, circulating epithelial tumor cells (CETC/CTC), which can reach distant tissues and regrow into metastases. The purpose of this study is to determine changes in the number of CETC/CTC in the course of adjuvant RT, and to evaluate whether they are correlated to local recurrence and distant metastases in breast cancer patients. METHODS: Blood from 165 patients irradiated between 2002 and 2012 was analyzed 0-6 weeks prior to and 0-6 weeks after RT using the maintrac® method, and patients were followed over a median period of 8.97 (1.16-19.09) years. RESULTS: Patients with an increase in CETC/CTC numbers over the course of adjuvant RT had a significantly worse disease-free survival (p = 0.004) than patients with stable or decreasing CETC/CTC numbers. CETC/CTC behavior was the most important factor in predicting subsequent relapse-free survival. In particular, patients who had received neoadjuvant chemotherapy were disproportionately more likely to develop metastases when cell counts increased over the course of RT (p = 0.003; hazard ratio 4.886). CONCLUSIONS: Using the maintrac® method, CETC/CTC were detected in almost all breast cancer patients after surgery. The increase in CETC/CTC numbers over the course of RT represents a potential predictive biomarker to judge relative risk/benefit in patients with early breast cancer. The results of this study highlight the need for prospective clinical trials on CETC/CTC status as a predictive criterion and for individualization of treatment. CLINICAL TRIAL REGISTRATION: The trial is registered (2 May 2019) at trials.gov under NCT03935802.