RTOG 0915-compliant patient specific QA for lung stereotactic body radiotherapy using the new PTW 1600SRS detector array.

PURPOSE: An area of focus in radiotherapy is the treatment of oligometastatic lung cancer using highly conformal techniques such as SBRT, performed using VMAT that involves flattening filter free (FFF) beams. This study proposes a new calibration procedure for PTW Octavius 1600SRS detector array and was designed to also evaluate clinical and dosimetric aspects of a patient-specific quality assurance (PSQA) for lung SBRT patients. METHODS: The cohort consists of 20 patients, treated for lung metastases using SBRT with 50 Gy dose in 5 fractions (10 Gy/fr). The proposed calibration method uses only one calibration factor determined at maximum dose rate of 6MV FFF photon beam. The dosimetric accuracy of achieving a high dose gradient was analyzed using the RTOG 0915 protocol and was confirmed by PSQA procedures using the PTW Octavius 1600SRS detector. RESULTS: Conformity index, gradient index, maximum dose at 2 cm and V20 parameters were evaluated with clinical favorable results, with only two plans with lesions situated in the inferior lobe exceeding the deviation allowed for the gradient index. Gamma passing rates using the new calibration method were 98.93% and 99.38% for different gamma criteria of 2 mm/2% and 1 mm/3%, respectively. CONCLUSIONS: The proposed method for calibration using one calibration factor at maximum dose rate for the involved photon beam shows clinically acceptable gamma passing rates. Employing the RTOG 0915 protocol for lung SBRT treatment plan evaluation brings important dosimetric information about treatment plan quality and dose gradient fall-off which can be correlated with the results achieved during the pretreatment verification procedures.

Dosimetric evaluation of intensity modulated photon versus proton reirradiation of head and neck cancer.

BACKGROUND: Reirradiation of head and neck cancer (HNC) became more accessible in the last decade, owing to modern irradiation techniques which offer a reduction in treatment related toxicities. The aim of this paper was to comparatively evaluate the dosimetric aspects derived from intensity modulated photon vs. proton treatment planning in reirradiated HNC patients. METHODS: Six recurrent HNC patients were enrolled in this retrospective study. For each patient two treatment plans were created: one IMRT/VMAT and one IMPT plan. The prescribed dose for the second irradiation was between 50 and 70 Gy RBE. The study comparatively analyzed the CTV coverage, doses to organs at risk (OARs) and low doses received by the healthy tissue (other than OAR). RESULTS: Similar CTV coverage was achieved for photon vs proton plans, with the latter presenting better homogeneity in four cases. Maximum dose to CTV was generally higher for photon plans, with differences ranging from 0.3 to 1.9%. For parotid glands and body, the mean dose was lower for proton plans. A notable reduction of low dose to healthy tissue (other than OARs) could be achieved with protons, with an average of 60% and 64% for D10% and Dmean, respectively. CONCLUSION: The dosimetric comparison between photon and proton reirradiation of HNC showed a great need for treatment individualization, concluding that protons should be considered for reirradiation on an individual basis.

Affinity of PET-MRI Tracers for Hypoxic Cells in Breast Cancer: A Systematic Review.

Tumour hypoxia is a known microenvironmental culprit for treatment resistance, tumour recurrence and promotion of metastatic spread. Despite the long-known existence of this factor within the tumour milieu, hypoxia is still one of the greatest challenges in cancer management. The transition from invasive and less reliable detection methods to more accurate and non-invasive ways to identify and quantify hypoxia was a long process that eventually led to the promising results showed by functional imaging techniques. Hybrid imaging, such as PET-CT, has the great advantage of combining the structural or anatomical image (offered by CT) with the functional or metabolic one (offered by PET). However, in the context of hypoxia, it is only the PET image taken after appropriate radiotracer administration that would supply hypoxia-specific information. To overcome this limitation, the development of the latest hybrid imaging systems, such as PET-MRI, enables a synergistic approach towards hypoxia imaging, with both methods having the potential to provide functional information on the tumour microenvironment. This study is designed as a systematic review of the literature on the newest developments of PET-MRI for the imaging of hypoxic cells in breast cancer. The analysis includes the affinity of various PET-MRI tracers for hypoxia in this patient group as well as the correlations between PET-specific and MRI-specific parameters, to offer a broader view on the potential for the widespread clinical implementation of this hybrid imaging technique.

Circadian rhythm-based cancer therapy in randomised clinical trials.

INTRODUCTION: Since the 2017 Nobel Prize awarded to J. Hall, M. Rosbash and M.W. Young for their discoveries of molecular mechanisms behind the biological clock, circadian rhythm-based therapy, also known as chronotherapy, is receiving more attention in oncology and the number of anatomical sites of interest in this field is increasing. This observation is in line with the clinical evidence provided by trials on head and neck, lung, colorectal and cervical cancers, as well as the presently ongoing chronotherapy trials for breast and brain cancers. AREAS COVERED: The aim of this review was to collate all randomized trials conducted on chronotherapy for various tumor sites and to appraise the evidence for chrono-oncology to advance personalized therapy. Relevant literature was collected from Pubmed/Medline databases and from clinicatrials.gov. EXPERT OPINION: Current randomized clinical trials offer a certain level of evidence for the potential of chronotherapy to personalize oncologic treatment. However, comparison of trial results is hindered by the differences in timing of radiation/chemotherapy, the absence of harmonized recommendations for treatment outcome evaluation and not ultimately, the general lack of considering gender as a matched variable in trials, which was found to be a powerful factor influencing response to treatment.

Opportunities in Cancer Therapies: Deciphering the Role of Cancer Stem Cells in Tumour Repopulation.

Tumour repopulation during treatment is a well acknowledged yet still challenging aspect of cancer management. The latest research results show clear evidence towards the existence of cancer stem cells (CSCs) that are responsible for tumour repopulation, dissemination, and distant metastases in most solid cancers. Cancer stem cell quiescence and the loss of asymmetrical division are two powerful mechanisms behind repopulation. Another important aspect in the context of cancer stem cells is cell plasticity, which was shown to be triggered during fractionated radiotherapy, leading to cell dedifferentiation and thus reactivation of stem-like properties. Repopulation during treatment is not limited to radiotherapy, as there is clinical proof for repopulation mechanisms to be activated through other conventional treatment techniques, such as chemotherapy. The dynamic nature of stem-like cancer cells often elicits resistance to treatment by escaping drug-induced cell death. The aims of this scoping review are (1) to describe the main mechanisms used by cancer stem cells to initiate tumour repopulation during therapy; (2) to present clinical evidence for tumour repopulation during radio- and chemotherapy; (3) to illustrate current trends in the identification of CSCs using specific imaging techniques; and (4) to highlight novel technologies that show potential in the eradication of CSCs.

Dosimetric and clinical aspects of head and neck cancer reirradiation with intensity modulated radiotherapy techniques over the last decade.

PURPOSE: Tumor recurrence in head and neck cancer (HNC) is very common, given that locoregional disease relapse occurs in up to 50% of patients. The clinical approach towards cancer recurrence is either by surgery and/or chemo-radiotherapy. Irrespective of the treatment, the management of HNC recurrence is highly challenging and often administered with palliative intent only. The aim of this work was to analyze clinical and dosimetric aspects, such as dose prescription, organ at risk sparing, overall survival and locoregional control of HNC after reirradiation with intensity modulated radiotherapy techniques based on studies published over the last decade, due to the wide clinical implementation of the intensity modulated radiotherapy and particularly of volumetric modulated arc therapy (VMAT) for this malignancy. METHODS: A systematic search of the literature was conducted within Pub-med/Medline databases to find relevant studies. Of the 130 articles fulfilling the initial search criteria, 15 were selected for final analysis that encompassed all set requirements. RESULTS: Clinical studies revealed the multitude of factors influencing treatment outcome, including anatomical location, histological tumor type, patient-related factors (smoking / comorbidities), cumulative dose and fractionation schedule, reirradiated volume and time between the irradiation of primary and recurrent tumor. CONCLUSIONS: Since the literature reports no specific data related to the type of intensity modulation used in reirradiation or any correlation with treatment outcome, IMRT and VMAT might offer comparable result after HNC reirradiation. Patient selection is potentially the main factor leading to an efficient outcome.

Dosimetric characteristics of 6MV flattening filter free and flattened beams among beam-matched linacs: a three-institutional study.

BACKGROUND: Beam matching is a concept in radiotherapy applied to clinics where more than one linac is employed to harmonise beam characteristics across linacs for allowing patients interchange without replanning. In view of this, the current study analyzes and compares dosimetric characteristics of 6MV flattening filter free and flattened beams of three beam-matched linear accelerators (linacs) from three different clinics with the aim to evaluate the matching under tight criteria for gamma analysis. METHODS: Three Elekta linacs from three different clinics were included. The linacs have the same collimator assembly, Elekta Agility. Beam data were collected during commissioning process using PTW dosimetry systems. Dose profiles and percentage depth doses (PDD) were analyzed using 1D gamma analysis (1 mm/1%) as well as the following parameters: depth of maximum dose, PDD10, flatness, unflattnes, symmetry, penumbra, output factors. Additionally, five stereotactic treatment plans were optimized in one clinic and calculated by all three planning systems (Monaco) for a dosimetric comparison. RESULTS: Gamma analysis of dose profiles and PDDs showed clinically acceptable results of 96.3% passing rate for profiles and 100% passing rate for PDDs. All dosimetric parameters were in good agreement with the reference data. Furthermore, dosimetric comparisons between stereotactic treatment plans showed a maximum standard deviation of 0.48 Gy for the maximum dose to PTV, and a maximum standard deviation of 0.1 Gy for the dose to the organs at risk. CONCLUSIONS: All three linacs showed a strong agreement between parameters and passed the gamma analysis using 1% DD/1mm DTA criteria. This study confirmed the matching between linacs, offering the possibility to interchange patients with no replanning.

Current Role of Delta Radiomics in Head and Neck Oncology.

The latest developments in the management of head and neck cancer show an increasing trend in the implementation of novel approaches using artificial intelligence for better patient stratification and treatment-related risk evaluation. Radiomics, or the extraction of data from various imaging modalities, is a tool often used to evaluate specific features related to the tumour or normal tissue that are not identifiable by the naked eye and which can add value to existing clinical data. Furthermore, the assessment of feature variations from one time point to another based on subsequent images, known as delta radiomics, was shown to have even higher value for treatment-outcome prediction or patient stratification into risk categories. The information gathered from delta radiomics can, further, be used for decision making regarding treatment adaptation or other interventions found to be beneficial to the patient. The aim of this work is to collate the existing studies on delta radiomics in head and neck cancer and evaluate its role in tumour response and normal-tissue toxicity predictions alike. Moreover, this work also highlights the role of holomics, which brings under the same umbrella clinical and radiomic features, for a more complex patient characterization and treatment optimisation.

Dosimetric Parameters in Hypofractionated Stereotactic Radiotherapy for Brain Metastases: Do Flattening Filter-Free Beams Bring Benefits? A Preliminary Study.

PURPOSE: This study aimed to compare the dosimetric results of flattening filter-free (FFF) vs. flattened (FF) treatment plans for fractionated stereotactic radiotherapy (fSRT), with the goal to highlight potential advantages of FFF beams. METHODS: A group of 18 patients with brain metastases treated with fSRT (30 Gy delivered in 5 fractions) were included. The dosimetric parameters evaluated were: (1) physical dosimetric parameters (number of monitor units (MUs), conformity index (CI), dose gradient index (DGI), beam on time (BOT)); (2) clinical dosimetric parameters pertaining to target volume (PTV) and organs at risk (OARs). Two treatment plans were performed for all patients: one used 6 MV FFF beams and the other used 6 MV flattened beams. RESULTS: A slight increase in MUs was observed for the FFF mode (+23.3 MUs). The CI showed a difference of -2.7% for the FF plans (p = 0.28), correlated with a poorer coverage of the PTV. DGI values reported in terms of PTV are in line with international recommendations and showed a +1.9% difference for FFF plans. An average BOT of 90.3 s was reported for FFF plans, which was 2.3 times shorter than that required for FF plans delivery (p ≤ 0.001). A slight decrease of PTV coverage (-1.26%, p = 0.036) for FF plans can be considered relevant, but no other significant differences were observed between the two optimizations. No statistically significant benefit of using FFF beams to reduce V20 for normal brain could be demonstrated. CONCLUSION: These dosimetric results encourage the implementation of fSRT with standard flattened beams in centers where FFF linacs are not available.

Cannot Target What Cannot Be Seen: Molecular Imaging of Cancer Stem Cells.

Cancer stem cells are known to play a key role in tumour development, proliferation, and metastases. Their unique properties confer resistance to therapy, often leading to treatment failure. It is believed that research into the identification, targeting, and eradication of these cells can revolutionise oncological treatment. Based on the principle that what cannot be seen, cannot be targeted, a primary step in cancer management is the identification of these cells. The current review aims to encompass the state-of-the-art functional imaging techniques that enable the identification of cancer stem cells via various pathways and mechanisms. The paper presents in vivo molecular techniques that are currently available or await clinical implementation. Challenges and future prospects are highlighted to open new research avenues in cancer stem cell imaging.

Developments on tumour site-specific chrono-oncology towards personalised treatment.

Research into chronotherapy has seen notable developments over the past decades, with a clear focus on the identification of circadian clock genes as potential treatment targets. Moreover, new factors are investigated, such as gender and the role of cancer stem cells in influencing the outcome of chronomodulated treatments. These factors could add to the arsenal of parameters that assist with patient stratification and treatment personalisation. Literature analysis showed that certain anatomical sites received more attention and the associated studies reported clinically significant results, even though some findings are contradictory. The aim of this work was to review the existing studies on chrono-oncology using a tumour site-specific approach and to highlight the status of research in various cancers. Inconsistencies in data reporting, the nature of the studies and the highly heterogeneous patient characteristics, highlight the need for well-designed randomised controlled trials to elucidate the real potential of chronotherapy in oncology.

Factors impacting on patient setup analysis and error management during breast cancer radiotherapy.

Radiotherapy is required to deliver an accurate dose to the tumor while protecting surrounding normal tissues. Breast cancer radiotherapy involves a number of factors that can influence patient setup and error management, including the immobilization device used, the verification system and the patient's treatment position. The aim of this review is to compile and discuss the setup errors that occur due to the above-mentioned factors. In view of this, a systematic search of the scientific literature in the Medline/PubMed databases was performed over the 1990-2021 time period, with 93 articles found to be relevant for the study. To be accessible to all, this study not only aims to identify factors impacting on patient setup analysis, but also seeks to evaluate the role of each verification device, board immobilization and position in influencing these errors.

The role of medical physicists in clinical trials across Europe.

INTRODUCTION: The roles and responsibilities of medical physicists (MPs) are growing together with the evolving science and technology. The complexity of today's clinical trials requires the skills and knowledge of MPs for their safe and efficient implementation. However, it is unclear to what extent the skillsets offered by MPs are being exploited in clinical trials across Europe. METHODS: The EFOMP Working Group on the role of Medical Physics Experts in Clinical Trials has designed a survey that targeted all 36 current National Member Organisations, receiving a response from 31 countries. The survey included both quantitative and qualitative queries regarding the involvement of MPs in trial design, setup, and coordination, either as trial team members or principal investigators. RESULTS: The extent of MPs involvement in clinical trials greatly varies across European countries. The results showed disparities between the roles played by MPs in trial design, conduct or data processing. Similarly, differences among the 31 European countries that responded to the survey were found regarding the existence of national bodies responsible for trials or the available training offered to MPs. The role of principal investigator or co-investigator was reported by 12 countries (39%), a sign of efficient collaboration with medical doctors in designing and implementing clinical studies. CONCLUSION: Organisation of specific training courses and guideline development for clinical trial design and conduct would encourage the involvement of a larger number of MPs in all stages of trials across Europe, leading to a better standardisation of clinical practice.

Is there a dosimetric advantage of volumetric modulated arc therapy over intensity modulated radiotherapy in head and neck cancer?

OBJECTIVE: A planning study was performed to evaluate dosimetric differences between intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) for head and neck cancer (HNC) for sequential boost (Seq-boost) and simultaneous integrated boost techniques (SIB). METHODS: 30 patients with HNC were included, 15 treated with SIB and 15 with Seq-Boost. For all patients both VMAT and IMRT plans were completed. The planning objective for PTV was 95% of dose covering minimum 95% of PTV; for spinal cord and brainstem Dmax was limited to 45 Gy and 54 Gy respectively. The parotids had a mean dose < 26 Gy limitation. The number of monitor units (MU) were scored for treatment delivery time efficiency. RESULTS: Both techniques achieved the set objectives regarding PTV coverage and organ sparing. SIB plans presented a statistically significant better homogeneity for VMAT (p = 0.0096), while Seq-boost showed a statistically significant better conformity for VMAT (p = 0.0049). For parotids only SIB plans showed a lower Dmean value obtained with VMAT, while Seq-boost plans showed statistically insignificant differences. For SIB plans the MU was reduced by 33.4% with VMAT, whereas in Seq-boost plans the reduction was by 19.1%. CONCLUSION: VMAT shows dosimetric superiority to IMRT in some cases, however an adequate coverage of the target volumes and a suitable OAR sparing can be achieved with both techniques. Though IMRT is still the standard in HNC radiotherapy, VMAT can be safely implemented, offering at least similar target coverage and organ sparing, with significantly reduced MU.

Adaptive Radiotherapy in Head and Neck Cancer Using Volumetric Modulated Arc Therapy.

A dosimetric study was performed to show the importance of adaptive radiotherapy (ART) for head and neck cancer (HNC) patients using volumetric modulated arc therapy (VMAT). A total of 13 patients with HNC who required replanning during radiotherapy were included in this study. All plans succeeded to achieve the set objectives regarding target volume coverage and organ sparing. All target volumes presented a significant decrease with an average of 76.44 cm3 (p = 0.007) for PTVlow risk, 102.81 cm3 (p = 0.021) for PTVintermediate risk, and 47.10 cm3 (p = 0.003) for PTVhigh risk. Additionally, a positive correlation was found between PTV shrinkage and the number of fractions completed before replanning. Significant volume decrease was also observed for the parotid glands. The ipsilateral parotid decreased in volume by a mean of 3.75 cm3 (14.43%) (p = 0.067), while the contralateral decreased by 4.23 cm3 (13.23%) (p = 0.033). For all analyzed organs, a reduction in the final dose received after replanning was found. Our study showed that ART via rescanning, recontouring, and replanning using VMAT is essential whenever anatomical and positional variations occur. Furthermore, comparison with the literature has confirmed that ART using VMAT offers similar results to ART with intensity modulated radiotherapy.

Radiobiological and Treatment-Related Aspects of Spatially Fractionated Radiotherapy.

The continuously evolving field of radiotherapy aims to devise and implement techniques that allow for greater tumour control and better sparing of critical organs. Investigations into the complexity of tumour radiobiology confirmed the high heterogeneity of tumours as being responsible for the often poor treatment outcome. Hypoxic subvolumes, a subpopulation of cancer stem cells, as well as the inherent or acquired radioresistance define tumour aggressiveness and metastatic potential, which remain a therapeutic challenge. Non-conventional irradiation techniques, such as spatially fractionated radiotherapy, have been developed to tackle some of these challenges and to offer a high therapeutic index when treating radioresistant tumours. The goal of this article was to highlight the current knowledge on the molecular and radiobiological mechanisms behind spatially fractionated radiotherapy and to present the up-to-date preclinical and clinical evidence towards the therapeutic potential of this technique involving both photon and proton beams.

Gender and Sex-Related Differences in Normal Tissue Effects Induced by Platinum Compounds.

Gender medicine in the field of oncology is an under-researched area, despite the existing evidence towards gender-dependent response to therapy and treatment-induced adverse effects. Oncological treatment aims to fulfil its main goal of achieving high tumour control by also protecting normal tissue from acute or chronic damage. Chemotherapy is an important component of cancer treatment, with a large number of drugs being currently in clinical use. Cisplatin is one of the most commonly employed chemotherapeutic agents, used either as a sole drug or in combination with other agents. Cisplatin-induced toxicities are well documented, and they include nephrotoxicity, neurotoxicity, gastrointestinal toxicity, ototoxicity, just to name the most frequent ones. Some of these toxicities have short-term sequelae, while others are irreversible. Furthermore, research showed that there is a strong gender-dependent aspect of side effects caused by the administration of cisplatin. While evidence towards sex differences in animal models is substantial, clinical studies considering sex/gender as a variable factor are limited. This work summarises the current knowledge on sex/gender-related side effects induced by platinum compounds and highlights the gaps in research that require more attention to open new therapeutic possibilities and preventative measures to alleviate normal tissue toxicity and increase patients' quality of life in both males and females.

Current Omics Trends in Personalised Head and Neck Cancer Chemoradiotherapy.

Chemoradiotherapy remains the most common management of locally advanced head and neck cancer. While both treatment components have greatly developed over the years, the quality of life and long-term survival of patients undergoing treatment for head and neck malignancies are still poor. Research in head and neck oncology is equally focused on the improvement of tumour response to treatment and on the limitation of normal tissue toxicity. In this regard, personalised therapy through a multi-omics approach targeting patient management from diagnosis to treatment shows promising results. The aim of this paper is to discuss the latest results regarding the personalised approach to chemoradiotherapy of head and neck cancer by gathering the findings of the newest omics, involving radiotherapy (dosiomics), chemotherapy (pharmacomics), and medical imaging for treatment monitoring (radiomics). The incorporation of these omics into head and neck cancer management offers multiple viewpoints to treatment that represent the foundation of personalised therapy.

Dosimetric justification for the use of volumetric modulated arc therapy in head and neck cancer-A systematic review of the literature.

INTRODUCTION: Radiotherapy for head and neck cancer (HNC) has evolved rapidly in the past decades from conformal three-dimensional technique (3D-CRT) to intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT). This paper presents a dosimetric comparative study between VMAT and IMRT delivery based on current literature, while also presenting the potential challenges encountered with volumetric arc therapy. METHODS: A systematic search of the scientific literature was conducted within Medline/Pubmed databases. A number of 13 papers fulfilled the search criteria which was based on the main objective to evaluate dosimetric characteristics of comparative treatment delivery with VMAT vs IMRT in HNC. RESULTS: Overall, from a dosimetric perspective, dose delivery via VMAT and IMRT present comparable results. Beside the delivery technique, target volume coverage also depends on the planner's expertise as well as the employed planning algorithm. At times, the superiority of VMAT emerges from the improved sparing of normal tissue, reduction of monitor units (MU) and of treatment delivery time. Similar to IMRT, one of the most important challenges of VMAT is the risk of developing secondary cancer due to the higher number of MUs compared to 3D-CRT. CONCLUSIONS: Based on the comparative results with the more established IMRT, VMAT in HNC can be safely delivered either as a single treatment or combined with other techniques.