The value of brachytherapy in the age of advanced external beam radiotherapy: a review of the literature in terms of dosimetry

Brachytherapy (BT) has long been used for successful treatment of various tumour entities, including prostate, breast and gynaecological cancer. However, particularly due to advances in modern external beam techniques such as intensity-modulated radiotherapy (IMRT), volume modulated arc therapy (VMAT) and stereotactic body radiotherapy (SBRT), there are concerns about its future. Based on a comprehensive literature review, this article aims to summarize the role of BT in cancer treatment and highlight its particular dosimetric advantages. The authors conclude that image-guided BT supported by inverse dose planning will successfully compete with high-tech EBRT in the future and continue to serve as a valuable modality for cancer treatment.

Differences between lung adenocarcinoma and squamous cell carcinoma in histological distribution of residual tumor after induction chemoradiotherapy

Aims To facilitate dose planning for convergent beam radiotherapy in non-small cell lung cancer (NSCLC), tumor response and histological distribution of residual tumors after induction chemoradiotherapy (ICRT) were compared between adenocarcinoma (AD) and squamous cell carcinoma (SQ). Methods Ninety-five patients with N1–2 or T3–4 NSCLC were treated with ICRT followed by surgery; 55 had AD and 40 had SQ. For the evaluation of distribution of residual tumors, the location of the external margin of residual tumors was assessed on surgical materials as follows: radius of whole tumor (“a”); distance between the center of tumor and the external margin of residual tumor (“b”); and its location (“b/a”). Results Of the 55 AD cases, 8 (15%) showed pathological complete remission, which was significantly less frequent than 22 of 40 SQ cases (55%) (p < 0.001). AD showed the residual tumors at the most periphery of tumor (b/a = 1.0) more frequently than SQ, i.e., 39/55 (71%) versus 6/40 (15%), respectively (p < 0.001). Even in 65 cases other than the pathological complete remission, external margins in 47 AD cases located more periphery than those in 18 SQ cases, of which mean b/a values were 0.97 ± 0.17 and 0.70 ± 0.29, respectively (p < 0.001). Conclusion AD showed worse tumor response to ICRT than SQ. After ICRT, AD remained at the periphery of primary tumor more frequently than SQ. It seems that, also in the convergent beam radiotherapy, the periphery part of AD would be more resistant than that of SQ.

A machine learning model that emulates experts’ decision making in vancomycin initial dose planning

Vancomycin is a glycopeptide antibiotic that has been used primarily in the treatment of methicillin-resistant Staphylococcus aureus infections. To enhance its clinical effectiveness and prevent nephrotoxicity, therapeutic drug monitoring (TDM) of trough concentrations is recommended. Initial vancomycin dosing regimens are determined based on patient characteristics such as age, body weight, and renal function, and dosing strategies to achieve therapeutic concentration windows at initial TDM have been extensively studied. Although numerous dosing nomograms for specific populations have been developed, no comprehensive strategy exists for individually tailoring initial dosing regimens; therefore, decision making regarding initial dosing largely depends on each clinician’s experience and expertise. In this study, we applied a machine-learning (ML) approach to integrate clinician knowledge into a predictive model for initial vancomycin dosing. A dataset of vancomycin initial dose plans defined by pharmacists experienced in vancomycin TDM (i.e., experts) was used to build the ML model. The target trough concentration was attained at comparable rates with the model- and expert-recommended dosing regimens, suggesting that the ML model successfully incorporated the experts’ knowledge. The predictive model developed here will contribute to improved decision making for initial vancomycin dosing and early attainment of therapeutic windows.

Differences Between Lung Adenocarcinoma and Squamous Cell Carcinoma in Histological Distribution of Residual Tumor After Induction Chemoradiotherapy

Aims: To facilitate dose planning for convergent beam radiotherapy in non-small cell lung cancer (NSCLC), tumor response and histological distribution of residual tumors after induction chemoradiotherapy (ICRT) were compared between adenocarcinoma (AD) and squamous cell carcinoma (SQ). Methods: Ninety-five patients with N1-2 or T3-4 NSCLC were treated with ICRT followed by surgery; 55 had AD and 40 had SQ. For the evaluation of distribution of residual tumors, the location of the external margin of residual tumors was assessed on surgical materials as follows: radius of whole tumor (“a”); distance between the center of tumor and the external margin of residual tumor (“b”); and its location (“b/a”). Results: Of the 55 AD cases, 8 (15%) showed pathological complete remission, which was significantly less frequent than 22 of 40 SQ cases (55%) (p<0.001). AD showed the residual tumors at the most periphery of tumor (b/a=1.0) more frequently than SQ, i.e., 39/55 (71%) versus 6/40 (15%), respectively (p<0.001). Even in 65 cases other than the pathological complete remission, external margins in 47 AD cases located more periphery than those in 18 SQ cases, of which mean b/a values were 0.97 ± 0.17 and 0.70 ± 0.29, respectively (p < 0.001). Conclusion: AD showed worse tumor response to ICRT than SQ. After ICRT, AD remained at the periphery of primary tumor more frequently than SQ. It seems that, also in the convergent beam radiotherapy, the periphery part of AD would be more resistant than that of SQ.

Feasibility Of Radiation Dose Planning Guided Surgical Resection In Spinal Tumours

The objective of high dose stereotactic radiotherapy regardless of application is to treat the malignancy while minimizing the radiation dose to the surrounding healthy tissue. In the context of spinal tumours this paradigm is difficult since the rigid dose tolerance of the spinal cord precludes optimal dose coverage of the epidural disease. To achieve adequate coverage spine separation surgery is performed, increasing the distance from the spinal cord to the malignancy and facilitating adequate radiation treatment planning. This approach has been validated with delivery of maximum tolerable dose and local control rates over 90%. The objective of this dissertation is to establish the feasibility of intraoperative, dose guided, spine separation surgery. In the current clinical context, spine separation surgery is performed prior to radiation treatment planning and contours are placed based on postoperative resected tumour volumes. The extent of surgical resection is not dictated by the dosimetric constraints of the spinal cord and relies solely on the clinical expertise of the operating neurosurgeon. Further, though a skilled surgeon can perform precise tumour debulking with or without the aid of millimetre resolution neuronavigation devices, determination of surgical debulking progress with accuracy comparable to treatment delivery cannot be recognized without intraoperative imaging. To achieve this goal, we introduced pre-surgical dosimetric planning with tracked high frequency micro-ultrasound imaging into the operating theatre to inform the surgeon of the surgical progress while considering the dosimetric objectives. In this dissertation, we assessed the dosimetric advantage of spine separation surgery on a millimetre by millimetre basis in a retrospective simulation study. Feasibility of intraoperative navigation with submillimetre resolution was established by quantifying the application accuracy of surgical navigation in the context of cranial and spinal surgery. Accuracy quantification was performed, assessing our revolutionary optical topographical imaging system and benchmarked versus existing commercially available neuronavigation systems. Finally, to establish feasibility of radiation dose planning guided surgical resection we integrated a high frequency micro-ultrasound system into the operating theater during spine separation surgery. Thus, by implementing sub-millimetre high frequency micro-ultrasound imaging and neuronavigation, incremental gains towards establishing the feasibility of in traoperative dose planning by iteratively updating the extent of tumour resection were recognized.

MRI based physiological parameters are biomarkers of tumor and non tumor tissue response following radiation to brain metastases

We sought to determine the utility of early relative blood volume (rCBV), relative blood flow (rCBF) and permeability (K2 trans) measurements as biomarkers of radiation response or progression for brain metastases and to characterize early normal tissue changes following stereotactic radiosurgery. Patients were imaged with dynamic susceptibility and dynamic contrast enhanced magnetic resonance imaging at baseline, 1 week and 1 month post-treatment. Tumors outcomes were stratified using volumetric data obtained from structural images. K2trans at 1 week and rCBV at 1 month were identified as predictors of tumor response and progressive disease respectively. Pre-treatment localized dose planning CT images with overlaid isodose distributions outside the tumor were evaluated within all tissue, and segmented gray and white matter. rCBV and rCBF ratio differences between baseline, 1 week and 1 month were compared. Subsequent analysis identified increases in rCBF and rCBV ratios occurring in a dose, tissue, and time specific manner.

Feasibility Of Radiation Dose Planning Guided Surgical Resection In Spinal Tumours

The objective of high dose stereotactic radiotherapy regardless of application is to treat the malignancy while minimizing the radiation dose to the surrounding healthy tissue. In the context of spinal tumours this paradigm is difficult since the rigid dose tolerance of the spinal cord precludes optimal dose coverage of the epidural disease. To achieve adequate coverage spine separation surgery is performed, increasing the distance from the spinal cord to the malignancy and facilitating adequate radiation treatment planning. This approach has been validated with delivery of maximum tolerable dose and local control rates over 90%. The objective of this dissertation is to establish the feasibility of intraoperative, dose guided, spine separation surgery. In the current clinical context, spine separation surgery is performed prior to radiation treatment planning and contours are placed based on postoperative resected tumour volumes. The extent of surgical resection is not dictated by the dosimetric constraints of the spinal cord and relies solely on the clinical expertise of the operating neurosurgeon. Further, though a skilled surgeon can perform precise tumour debulking with or without the aid of millimetre resolution neuronavigation devices, determination of surgical debulking progress with accuracy comparable to treatment delivery cannot be recognized without intraoperative imaging. To achieve this goal, we introduced pre-surgical dosimetric planning with tracked high frequency micro-ultrasound imaging into the operating theatre to inform the surgeon of the surgical progress while considering the dosimetric objectives. In this dissertation, we assessed the dosimetric advantage of spine separation surgery on a millimetre by millimetre basis in a retrospective simulation study. Feasibility of intraoperative navigation with submillimetre resolution was established by quantifying the application accuracy of surgical navigation in the context of cranial and spinal surgery. Accuracy quantification was performed, assessing our revolutionary optical topographical imaging system and benchmarked versus existing commercially available neuronavigation systems. Finally, to establish feasibility of radiation dose planning guided surgical resection we integrated a high frequency micro-ultrasound system into the operating theater during spine separation surgery. Thus, by implementing sub-millimetre high frequency micro-ultrasound imaging and neuronavigation, incremental gains towards establishing the feasibility of in traoperative dose planning by iteratively updating the extent of tumour resection were recognized.