The Assessment of the Long-Term Impact of Radiotherapy on Biophysical Skin Properties in Patients after Head and Neck Cancer.

Background and Objectives: Chronic radiotherapy-induced skin injury (cRISI) is an irreversible and progressive condition that can significantly impact a patient's quality of life. Despite the limited literature available on the assessment of the epidermal barrier in cRISI, there is a consensus that appropriate skincare, including the use of emollients, is the primary therapeutic approach for this group of patients. The aim of this study was to evaluate the biophysical properties of the skin during the late period (at least 90 days) following radiation therapy (RT) for head and neck cancer. Materials and Methods: This was a single-center prospective non-randomized study. It involved the analysis of 16 adult patients with head and neck cancer who underwent RT at the Greater Poland Cancer Center, along with 15 healthy volunteers. The study and control groups were matched for gender and age (p = 0.51). Clinical assessment, based on the LENT-SOMA scale, was conducted for all patients. Evaluation of the skin's biophysical properties included: an analysis of transepidermal water loss (TEWL), stratum corneum hydration (SCH), and skin visualization using high-frequency ultrasonography (HF-USG). Results: A significantly higher TEWL was observed in the irradiated area compared to the control area in the study group (p = 0.004). However, there was no statistically significant difference in SCH (p = 0.073). Additionally, no significant difference was observed in the values of TEWL and SCH in the irradiated area between the group of patients with and without clinically obvious RISI (p = 0.192 and p = 0.415, respectively). The skin thickness of the irradiated area, assessed by HF-USG, did not differ significantly from the skin thickness of the control area (p = 0.638). Furthermore, no difference in skin thickness was observed in patients with clinical features of cRISI in the irradiated and control areas (p = 0.345). The mean time after RT was 6.1 years. Conclusions: This study marks the first demonstration of epidermal barrier damage in patients in the long term following RT for head and neck cancer. The impairment of the epidermal barrier was observed independently of evident cRISI features. This observation underscores the necessity to recommend appropriate skin care, including the use of emollients, for all patients following RT. We also suggest that HF-USG examination is generally inconclusive in determining the degree of skin damage in the late period after RT.

A convolutional neural network with self-attention for fully automated metabolic tumor volume delineation of head and neck cancer in [Formula: see text]F]FDG PET/CT.

PURPOSE: PET-derived metabolic tumor volume (MTV) and total lesion glycolysis of the primary tumor are known to be prognostic of clinical outcome in head and neck cancer (HNC). Including evaluation of lymph node metastases can further increase the prognostic value of PET but accurate manual delineation and classification of all lesions is time-consuming and prone to interobserver variability. Our goal, therefore, was development and evaluation of an automated tool for MTV delineation/classification of primary tumor and lymph node metastases in PET/CT investigations of HNC patients. METHODS: Automated lesion delineation was performed with a residual 3D U-Net convolutional neural network (CNN) incorporating a multi-head self-attention block. 698 [Formula: see text]F]FDG PET/CT scans from 3 different sites and 5 public databases were used for network training and testing. An external dataset of 181 [Formula: see text]F]FDG PET/CT scans from 2 additional sites was employed to assess the generalizability of the network. In these data, primary tumor and lymph node (LN) metastases were interactively delineated and labeled by two experienced physicians. Performance of the trained network models was assessed by 5-fold cross-validation in the main dataset and by pooling results from the 5 developed models in the external dataset. The Dice similarity coefficient (DSC) for individual delineation tasks and the primary tumor/metastasis classification accuracy were used as evaluation metrics. Additionally, a survival analysis using univariate Cox regression was performed comparing achieved group separation for manual and automated delineation, respectively. RESULTS: In the cross-validation experiment, delineation of all malignant lesions with the trained U-Net models achieves DSC of 0.885, 0.805, and 0.870 for primary tumor, LN metastases, and the union of both, respectively. In external testing, the DSC reaches 0.850, 0.724, and 0.823 for primary tumor, LN metastases, and the union of both, respectively. The voxel classification accuracy was 98.0% and 97.9% in cross-validation and external data, respectively. Univariate Cox analysis in the cross-validation and the external testing reveals that manually and automatically derived total MTVs are both highly prognostic with respect to overall survival, yielding essentially identical hazard ratios (HR) ([Formula: see text]; [Formula: see text] vs. [Formula: see text]; [Formula: see text] in cross-validation and [Formula: see text]; [Formula: see text] vs. [Formula: see text]; [Formula: see text] in external testing). CONCLUSION: To the best of our knowledge, this work presents the first CNN model for successful MTV delineation and lesion classification in HNC. In the vast majority of patients, the network performs satisfactory delineation and classification of primary tumor and lymph node metastases and only rarely requires more than minimal manual correction. It is thus able to massively facilitate study data evaluation in large patient groups and also does have clear potential for supervised clinical application.

Significance of neutrophil to lymphocyte ratio as a predictor of outcome in head and neck cancer treated with definitive chemoradiation.

Background: The role of host immune system in carcinogenesis and response to treatment is increasingly studied, including predictive potential of circulating neutrophils and lymphocytes. The objective of the study was to evaluate the prognostic value of pre- and post-treatment neutrophil-to-lymphocyte (NLR) for treatment outcome in patients diagnosed with squamous cell carcinoma of head and neck (HNSCC) treated with definitive chemoradiation. Materials and methods: Electronic medical records of patients were evaluated and NLR was calculated. Cox regression was used to assess the impact of selected variables on overall survival (OS), disease specific survival (DSS), progression free survival (PFS) and distant failure free survival (DFFS). Logistic regression was used to estimate odds ratios of complete response with NLR. Results: 317 patients' records were included in the study. Increases in both pre-and post-NLR were associated with decreased OS in univariable analysis [hazard ratio (HR): 2.26 (1.25-4.07), p = 0.0068 and HR: 1.57 (1.03-2.37), p = 0.035 respectively). Post-NLR remained significant for OS in multivariable analysis [HR: 1.93 (1.22-3.1), p = 0.005] as well as for unfavorable DSS [HR: 2.31 (1.22-4.4), p = 0.01]. Pre-treatment NLR and nodal status correlated with shorter DFFS in multivariable analysis [HR 4.1 (1.14-14), p = 0.03 and HR 5.3: (1.62-18), p = 0.0062, respectively]. Strong correlation of increased both pre- and post-NLR with probability of clinical tumor response (CR) was found [odds ratio (OR): 0.23 (0.08-0.6), p = 0.003, and OR: 0.39 (0.2-0.8), p = 0.01 respectively]. Conclusion: NLR evaluated before and post treatment was a strong predictor of unfavorable treatment outcome and can be used for risk evaluation and clinical decision about treatment and post-treatment surveillance.

Evaluation of physiologic and abnormal glucose uptake in palatine tonsils: differential diagnostics with sequential dual-time-point 2-deoxy-2-[18F]FDG PET/CT.

BACKGROUND: The aim of this article was to evaluate the usefulness of sequential dual-time-point 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (DTP [18F]FDG PET/CT) in distinguishing physiologic, inflammatory and malignant palatine tonsils as difficult to differentiate in the oncological practice. METHODS: A total of 90 patients before the treatment underwent sequential DTP [18F]FDG PET/CT examinations. We analyzed 104 structures in 90 patients: 31 physiologic tonsils, 28 histopathologically confirmed inflammatory tonsils of non-specified origin, 31 histopathologically confirmed palatine tonsils cancer and 14 non-malignant contralateral tonsils in patients with histopathologically confirmed unilateral palatine tonsil malignancy. Patients underwent sequential [18F]FDG PET/CT examinations at 60 and 90 minutes post-injection of the [18F]FDG. We analyzed the SUVmax and SUVmean values at 60 and 90 minutes post-injection changes over time and the Retention Index (RI-SUVmax). To find the predictive SUV value and the RI cut-off between physiology, inflammatory and malignancy, we used the ROC analysis. RESULTS: The average SUVmax values at 60 and 90minutes post-injection within physiologic palatine tonsils were 1.36±0.26 and 1.31±0.26, respectively, P>0.05. The average SUVmax values at 60 and 90 minutes post-injection within inflammatory and malignant tonsils were 3.74±1.45, 3.80±1.47 (P>0.05) and 5.19±2.19, 5.81±2.50 (P<0.05), respectively. The RI-SUVmax fluctuation over time were 5±28% within physiologic, -4±11% within contralateral non-malignant tonsils in patients with one tonsil involved, 2±11% within inflammatory and 13±13% within malignant tonsils. CONCLUSIONS: The sequential dual-time-point [18F]FDG PET/CT examinations may increase the sensitivity and the specificity of the PET/CT method in differential palatine tonsils diagnosis.

Dual-time-point PET/CT study protocol can improve the larynx cancer diagnosis.

AIM: To evaluate whether the sequential dual-time-point fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (DTP 18F-FDG PET/CT) study improves the differential diagnosis in the larynx. BACKGROUND: In some cases, the clinical and metabolic similarity of laryngitis and larynx cancer make differential diagnostics difficult when performing standard 18F-FDG PET/CT examinations; therefore, an additional study protocol performance seems to be of reasonable value. MATERIALS AND METHODS: 90 patients (mean age: 61 ± 11 years, range: 41-84 years): 23 women (mean age: 63 ± 10 years, range: 51-84 years) and 67 men (mean age: 61 ± 11 years, range: 41-80 years) underwent delayed 18F-FDG PET/CT examinations at 60 and 90 min post intravenous injection (p.i.) of the radiopharmaceutical 18F-FDG. We compared the metabolic activity of 90 structures divided into following groups: normal larynx (30 patients), laryngitis (30 lesions) and larynx cancer (30 tumors) with maximal and mean standardized uptake value (SUVmax, SUVmean) and the retention index (RI-SUVmax). We used the receiver operating characteristics (ROC) curve to evaluate the SUVmax cut-off values. RESULTS: The SUVmax cut-off value at 60 and 90 min p.i. of 2.3 (sensitivity/specificity: 96.4%/100%) and 2.4 (94.2%/100%), respectively, distinguished normal and abnormal metabolic activity in the larynx. When laryngitis and tumors were compared, the SUVmax cut-off values obtained after initial and delayed imaging were 3.6 (87.5%/52.0%) and 6.1 (58.3%/84%), respectively. The RI-SUVmax of 1.3% (71.4%/88.1%) suggested abnormality, while RI-SUVmax of 6.6%, malignant etiology (75.0%/80.0%). CONCLUSIONS: In this study, the sequential DTP scanning protocol improved the sensitivity and specificity of the PET/CT method in terms of differential diagnosis within the larynx.

An ultrasonographic monitoring of skin condition in patients receiving radiotherapy for head and neck cancers.

Radiodermatitis is one of the commonest side effects of radiotherapy. They are usually assessed by semi-quantitative clinical scores, which are not validated and may be subject to inter-observer variability. A few previous studies suggested that high-frequency ultrasonography (HF-USG) is useful in the assessment of the acute phase of radiation dermatitis in breast cancer patients. (a) To monitor skin changes by HF-USG during the course of radiotherapy due to head and neck cancers, and (b) to determine whether there is any connection between skin sonograms and the skin scoring criteria. This prospective, observational study includes patients diagnosed with head and neck cancers, treated with radiotherapy or concomitant chemoradiation. The final analysis includes six patients. In every patient, the HF-USG as well as dermatological assessment (target lesion score-TLS and CACE v. 4.0) were performed 4×: before, in the middle, day after, and 3 months after radiotherapy. There were significant differences between non-irradiated skin thickness and thickness of skin with clinically obvious radiodermatitis (TLS grade 1-4; P < .0001), as well as between irradiated, unchanged skin thickness (TLS grade 0) and thickness of skin with clinically obvious radiodermatitis (TLS grade 1-4; P = .0002). There was no significant difference between non-irradiated and irradiated, unchanged skin thickness (TLS grade 0; P = .9318). In four patients, we demonstrated subepidermal low echogenic band (SLEB). HF-USG can be useful tool to noninvasive and objective assessment of skin changes during radiotherapy.

Skin barrier function in patients under radiation therapy due to the head and neck cancers - Preliminary study.

AIM: To present the possibility of non-invasive monitoring of the skin after radiotherapy in regards of epidermal barrier function. BACKGROUND: Radiodermatitis constitutes 95% of all side effects in patients after radiotherapy. The proper assessment of the severity of radiodermatitis can be determined using semi-quantitative clinical scores [Common Terminology Criteria for Adverse Events v 4.0 (CTCAE)].The most accepted way to analyze the epidermal barrier function is to determine Transepidermal Water Loss (TEWL). MATERIAL AND METHODS: In prospective study, we included 16 patients diagnosed with head and neck cancer treated with radiotherapy or concomitant chemoradiation in whom we performed non-invasive assessments of the skin barrier function, including TEWL measurement. The final analysis included 6 patients (4 treated with adjuvant radiotherapy, 2 with radical chemoradiation). Clinical assessment of irradiated skin was based on target lesion score (TLS) and CTCAE v 4.0. RESULTS: The mean TLS score in the middle of irradiation was 1.6 points, after last irradiation it was 2.3 points; 3 months later the mean TLS score was: 0. CTCAE v 4.0 criteria: 2 patients had grade 0, 3 patients - grade 1; 1 patient - grade 2. There were statistically significant differences in TEWL related to irradiated skin in the following time intervals: before vs. in the middle; before vs. day after; in the middle vs. day after; in the middle vs. 3 months after; day after vs. 3 months after. CONCLUSIONS: The study showed that radiotherapy causes skin barrier dysfunction in all patients independently of clinical radiodermatitis. The biophysical features of this dysfunction can precede clinical symptoms and they can be assessed by non-invasive and objective methods.

Prospective study on dosimetric comparison of helical tomotherapy and 3DCRT for craniospinal irradiation - A single institution experience.

AIM: This prospective study aims to assess feasibility of helical tomotherapy (HT) for craniospinal irradiation (CSI) and perform dosimetric comparison of treatment plans for both HT and 3D conformal radiotherapy (3DCRT). BACKGROUND: CSI is a challenging procedure. Large PTV size requires field matching due to technical limitations of standard linear accelerators, which cannot irradiate such volumes as a single field. HT could help to avoid these limitations as irradiation of long fields is possible without field matching. MATERIALS AND METHODS: Three adults were enrolled from 2009 to 2010. All patients received radiochemotherapy. Treatment plans in prone position for 3DCRT and in supine position for HT were generated. The superior plan was used for patients' irradiation. Plans were compared with the application of DVH, Dx parameters - where x represents a percentage of the structure volume receiving a normalized dose and homogeneity index (HI). RESULTS: All patients received HT irradiation. The treatment was well tolerated. The HT plans resulted in a better dose coverage and uniformity in the PTV: HI were 5.4, 7.8, 6.8 for HT vs. 10.3, 6.6, 10.4 for 3DCRT. For most organs at risk (OARs), the D(V80) was higher for HT than for 3DCRT, whereas D(V5) was lower for HT. CONCLUSIONS: HT is feasible for CSI, and in comparison with 3DCRT it improves PTV coverage. HT reduces high dose volumes of OARs, but larger volumes of normal tissue receive low radiation dose. HT requires further study to establish correlations between dosimetrical findings and clinical outcomes, especially with regard to late sequelae of treatment.

Clinical results of the total skin electron irradiation of the mycosis fungoides in adults. Conventional fractionation and low dose schemes.

BACKGROUND: Mycosis fungoides (MF) is a rare skin condition, effectively treated by irradiation. Since 1951, different methods of total skin irradiation have been developed. Although dose-response effect has been demonstrated in many publications, controversies about low dose treatment still exist. AIM: The analysis of results of the total skin electron irradiation (TSEI), especially low dose TSEI in comparison with standard dose treatment is the subject of this review. Also, acute and late side effects of radiotherapy in MF are discussed. MATERIALS AND METHODS: Medline search and analysis of studies published between 1995 and 2012, containing key words: mycosis fungoides, standard dose TSEI, low dose TSEI, total skin electron beam therapy (TSEBT). RESULTS: Detailed analysis of relevant studies demonstrated that standard dose radiotherapy 30-36 Gy is the most effective treatment used in clinical practice. Objective response rate (ORR) is high, especially for less advanced stages of disease. Complete response rate (CR), although slightly lower, is still relatively high. For more advanced MF, TSEI serves as a very good method of palliative treatment and relief of symptoms, like pruritus, pain or desquamation. There is no consensus regarding low dose TSEI; the method is widely accepted as a palliative treatment or in case of reirradiation. CONCLUSIONS: Standard dose TSEI is an effective method of MF treatment for radical and palliative treatment, producing high rate of ORR and reasonably long time to progression (TTP). Acute and late side effect of treatment are mostly mild and easy to manage. Low dose TSEI is still in the phase of clinical studies.

Multi-institutional Prognostic Modeling in Head and Neck Cancer: Evaluating Impact and Generalizability of Deep Learning and Radiomics.

Artificial intelligence (AI) and machine learning (ML) are becoming critical in developing and deploying personalized medicine and targeted clinical trials. Recent advances in ML have enabled the integration of wider ranges of data including both medical records and imaging (radiomics). However, the development of prognostic models is complex as no modeling strategy is universally superior to others and validation of developed models requires large and diverse datasets to demonstrate that prognostic models developed (regardless of method) from one dataset are applicable to other datasets both internally and externally. Using a retrospective dataset of 2,552 patients from a single institution and a strict evaluation framework that included external validation on three external patient cohorts (873 patients), we crowdsourced the development of ML models to predict overall survival in head and neck cancer (HNC) using electronic medical records (EMR) and pretreatment radiological images. To assess the relative contributions of radiomics in predicting HNC prognosis, we compared 12 different models using imaging and/or EMR data. The model with the highest accuracy used multitask learning on clinical data and tumor volume, achieving high prognostic accuracy for 2-year and lifetime survival prediction, outperforming models relying on clinical data only, engineered radiomics, or complex deep neural network architecture. However, when we attempted to extend the best performing models from this large training dataset to other institutions, we observed significant reductions in the performance of the model in those datasets, highlighting the importance of detailed population-based reporting for AI/ML model utility and stronger validation frameworks. We have developed highly prognostic models for overall survival in HNC using EMRs and pretreatment radiological images based on a large, retrospective dataset of 2,552 patients from our institution.Diverse ML approaches were used by independent investigators. The model with the highest accuracy used multitask learning on clinical data and tumor volume.External validation of the top three performing models on three datasets (873 patients) with significant differences in the distributions of clinical and demographic variables demonstrated significant decreases in model performance. Significance: ML combined with simple prognostic factors outperformed multiple advanced CT radiomics and deep learning methods. ML models provided diverse solutions for prognosis of patients with HNC but their prognostic value is affected by differences in patient populations and require extensive validation.

Appropriateness of the 30-day expected mortality metric in palliative radiation treatment: a narrative review.

BACKGROUND AND OBJECTIVE: The 30-day expected mortality rate is frequently used as a metric to determine which patients benefit from palliative radiation treatment (RT). We conducted a narrative review to examine whether its use as a metric might be appropriate for patient selection. METHODS: A literature review was conducted to identify relevant studies that highlight the benefits of palliative RT in timely symptom management among patients with a poor performance status, the accuracy of predicting survival near the end of life and ways to speed up the process of RT administration through rapid response clinics. KEY CONTENT AND FINDINGS: Several trials have demonstrated substantial response rates for pain and/or bleeding by four weeks and sometimes within the first two weeks after RT. Models of patient survival have limited accuracy, particularly for predicting whether patients will die within the next 30 days. Dedicated Rapid Access Palliative RT (RAPRT) clinics, in which patients are assessed, simulated and treated on the same day, reduce the number of patient visits to the radiation oncology department and hence the burden on the patient as well as costs. CONCLUSIONS: Single-fraction palliative RT should be offered to eligible patients if they are able to attend treatment and could potentially benefit from symptom palliation, irrespective of predicted life expectancy. We discourage the routine use of the 30-day mortality as the only metric to decide whether to offer RT. More common implementation of RAPRT clinics could result in a significant benefit for patients of all life expectancies, but particularly those having short ones.

A critical appraisal of the four systematic reviews and meta-analysis on stereotactic body radiation therapy versus external beam radiotherapy for painful bone metastases and where we go from here.

Radiotherapy is an important treatment modality for pain control in patients with bone metastases. Stereotactic body radiation therapy (SBRT), which allows delivering a much higher dose per fraction while sparing critical structures compared to conventional external beam radiotherapy (cEBRT), has become more widely used, especially in the oligometastatic setting. Randomized controlled trials (RCTs) comparing the pain response rate of SBRT and cEBRT for bone metastases have shown conflicting results, as have four recent systematic reviews with meta-analyses of these trials. Possible reasons for the different outcomes between these reviews include differences in methodology, which trials were included, and the endpoints examined and how they were defined. We suggest ways to improve analysis of these RCTs, particularly performing an individual patient-level meta-analysis since the trials included heterogeneous populations. The results of such studies will help guide future investigations needed to validate patient selection criteria, optimize SBRT dose schedules, include additional endpoints (such as the time to onset of pain response, durability of pain response, quality of life (QOL), and side effects of SBRT), and better assess the cost-effectiveness and trade-offs of SBRT compared to cEBRT. An international Delphi consensus to guide selection of optimal candidates for SBRT is warranted before more prospective data is available.

Tomotherapy - a different way of dose delivery in radiotherapy.

AIM OF THE STUDY: Helical tomotherapy is one of the methods of radiotherapy. This method enables treatment implementation for a wide spectrum of clinical cases. The vast array of therapeutic uses of helical tomotherapy results directly from the method of dose delivery, which is significantly different from the classic method developed for conventional linear accelerators. The paper discusses the method of dose delivery by a tomotherapy machine. Moreover, an analysis and presentation of treatment plans was performed in order to show the therapeutic possibilities of the applied technology. Dose distributions were obtained for anaplastic medulloblastoma, multifocal metastases to brain, vulva cancer, tongue cancer, metastases to bones, and advanced skin cancer. Tomotherapy treatment plans were compared with conventional linear accelerator plans. RESULTS: Following the comparative analysis of tomotherapy and conventional linear accelerator plans, in each case we obtained the increase in dose distribution conformity manifested in greater homogeneity of doses in the radiation target area for anaplastic medulloblastoma, multifocal metastases to brain, vulva cancer, metastases to bones, and advanced skin cancer, and the reduction of doses in organs at risk (OAR) for anaplastic medulloblastoma, vulva cancer, tongue cancer, and advanced skin cancer. The time of treatment delivery in the case of a tomotherapy machine is comparable to the implementation of the plan prepared in intensity-modulated radiotherapy (IMRT) technique for a conventional linear accelerator. In the case of tomotherapy the application of a fractional dose was carried out in each case during one working period of the machine. For a conventional linear accelerator the total value of the fractional dose in the case of anaplastic medulloblastoma and metastases to bones was delivered using several treatment plans, for which a change of set-up was necessary during a fraction. CONCLUSION: The obtained results confirm that tomotherapy offers the possibility to obtain precise treatment plans together with the simplification of the therapeutic system.

Do we protect or discriminate? Representation of senior adults in clinical trials.

AIM: The analysis of barriers responsible for low recruitment of older patients in clinical trials and presentation of possible solutions are the subject of this review. BACKGROUND: Europe's population is ageing, and the group of people who more frequently develop neoplasms increases. Oncologists are confronted with a new challenge - how to treat cancer in this group of patients, especially considering the lack of Evidence Based Medicine (EBM) guidelines for treatment of cancer in the elderly population. MATERIALS AND METHODS: Medline search and analysis of studies published between 1999 and 2012, containing key words: senior adults, cancer, elderly in clinical trials. RESULTS: Detailed analysis of relevant studies demonstrated that senior adults are underrepresented in clinical trials. Moreover, there is a lack of trials exclusively designed for this heterogeneous group of patients. The analysis of reasons for low recruitment of older patients in clinical trials revealed barriers dependent on patient's and physician's attitudes as well as institutional and logistic problems. CONCLUSIONS: It is necessary to widen the scale of trials of all phases in the group of seniors with appropriate assessment of toxicity. This will allow a proper stratification and obtaining representative groups for statistical analysis and credible trial results. Another priority is the design of trials dedicated exclusively to the elderly.

Assessment of health status in elderly patients with cancer.

BACKGROUND: Health status assessment of senior adults is one of the most important aspects of a treatment decision making process. A group of elderly cancer patients is very heterogeneous according to the health status - some of them are fit enough for aggressive treatment, but others are frail and vulnerable. Treatment for the latter group has to be adapted and carefully monitored. AIM: To review and analyze relevant literature on the usage and optimization of Comprehensive Geriatric Assessment (CGA). MATERIALS AND METHODS: Medline search of studies published between 2000 and 2011, containing key words: Comprehensive Geriatric Assessment, aging, cancer in senior adults, frailty. RESULTS: To recognize and address individual needs of senior adults, a special holistic approach has been developed - comprehensive geriatric assessment (CGA). This tool is a gold standard in gerontooncology, recommended by International Society of Geriatric Oncology. CGA evaluates all important health domains, from physiology to social and economical problems, using sets of different tests. Assessment has to be performed by a trained team, including a physician, nurse and social worker. CGA has been clinically validated in many studies, but it is still not clear whether CGA improves the outcome of treatment of the elderly with cancer. CONCLUSIONS: Complexity and multidimensionality of CGA pose a logistic challenge for everyday clinical practice. Special senior programs, which could be developed inside comprehensive cancer center, focusing attention on seniors' problems and needs seem to be a way forward for geriatric oncology.

Criteria for Verification and Replanning Based on the Adaptive Radiotherapy Protocol "Best for Adaptive Radiotherapy" in Head and Neck Cancer.

No clear criteria have yet been established to guide decision-making for patient selection and the optimal timing of adaptive radiotherapy (ART) based on image-guided radiotherapy (IGRT). We have developed a novel protocol­the Best for Adaptive Radiotherapy (B-ART) protocol­to guide patient selection for ART. The aim of the present study is to describe this protocol, to evaluate its validity in patients with head and neck (HN) cancer, and to identify the anatomical and clinical predictors of the need for replanning. We retrospectively evaluated 82 patients with HN cancer who underwent helical tomotherapy (HT) and subsequently required replanning due to soft tissue changes upon daily MVCT. Under the proposed criteria, patients with anatomical changes >3 mm on three to four consecutive scans are candidates for ART. We compared the volumes on the initial CT scan (iCT) and the replanning CT (rCT) scan for the clinical target volumes (CTV1, referring to primary tumor or tumor bed and CTV2, metastatic lymph nodes) and for the parotid glands (PG) and body contour (B-body). The patients were stratified by primary tumor localization, clinical stage, and treatment scheme. The main reasons for replanning were: (1) a planning target volume (PTV) outside the body contour (n = 70; 85.4%), (2) PG shrinkage (n = 69; 84.1%), (3) B-body deviations (n = 69; 84.1%), and (4) setup deviations (n = 40; 48.8%). The replanning decision was made, on average, during the fourth week of treatment (n = 47; 57.3%). The mean reductions in the size of the right and left PG volumes were 6.31 cc (20.9%) and 5.98 cc (20.5%), respectively (p < 0.001). The reduction in PG volume was ≥30% in 30 patients (36.6%). The volume reduction in all of the anatomical structures was statistically significant. Four variables­advanced stage disease (T3−T4), chemoradiation, increased weight loss, and oropharyngeal localization­were significantly associated with the need for ART. The B-ART protocol provides clear criteria to eliminate random errors, and to allow for an early response to relevant changes in target volumes.

Prediction of Incomplete Response of Primary Tumour Based on Clinical and Radiomics Features in Inoperable Head and Neck Cancers after Definitive Treatment.

Radical treatment of patients diagnosed with inoperable and locally advanced head and neck cancers (LAHNC) is still a challenge for clinicians. Prediction of incomplete response (IR) of primary tumour would be of value to the treatment optimization for patients with LAHNC. Aim of this study was to develop and evaluate models based on clinical and radiomics features for prediction of IR in patients diagnosed with LAHNC and treated with definitive chemoradiation or radiotherapy. Clinical and imaging data of 290 patients were included into this retrospective study. Clinical model was built based on tumour and patient related features. Radiomics features were extracted based on imaging data, consisting of contrast- and non-contrast-enhanced pre-treatment CT images, obtained in process of diagnosis and radiotherapy planning. Performance of clinical and combined models were evaluated with area under the ROC curve (AUROC). Classification performance was evaluated using 5-fold cross validation. Model based on selected clinical features including ECOG performance, tumour stage T3/4, primary site: oral cavity and tumour volume were significantly predictive for IR, with AUROC of 0.78. Combining clinical and radiomics features did not improve model's performance, achieving AUROC 0.77 and 0.68 for non-contrast enhanced and contrast-enhanced images respectively. The model based on clinical features showed good performance in IR prediction. Combined model performance suggests that real-world imaging data might not yet be ready for use in predictive models.

Influence of Semiquantitative [18F]FDG PET and Hematological Parameters on Survival in HNSCC Patients Using Neural Network Analysis.

The aim of this study is to assess the influence of semiquantitative PET-derived parameters as well as hematological parameters in overall survival in HNSCC patients using neural network analysis. Retrospective analysis was performed on 106 previously untreated HNSCC patients. Several PET-derived parameters (SUVmax, SUVmean, TotalSUV, MTV, TLG, TLRmax, TLRmean, TLRTLG, and HI) for primary tumor and lymph node with highest activity were assessed. Additionally, hematological parameters (LEU, LEU%, NEU, NEU%, MON, MON%, PLT, PLT%, NRL, and LMR) were also assessed. Patients were divided according to the diagnosis into the good and bad group. The data were evaluated using an artificial neural network (Neural Analyzer version 2.9.5) and conventional statistic. Statistically significant differences in PET-derived parameters in 5-year survival rate between group of patients with worse prognosis and good prognosis were shown in primary tumor SUVmax (10.0 vs. 7.7; p = 0.040), SUVmean (5.4 vs. 4.4; p = 0.047), MTV (23.2 vs. 14.5; p = 0.010), and TLG (155.0 vs. 87.5; p = 0.05), and mean liver TLG (27.8 vs. 30.4; p = 0.031), TLRmax (3.8 vs. 2.6; p = 0.019), TLRmean (2.8 vs. 1.9; p = 0.018), and in TLRTLG (5.6 vs. 2.3; p = 0.042). From hematological parameters, only LMR showed significant differences (2.5 vs. 3.2; p = 0.009). Final neural network showed that for ages above 60, primary tumors SUVmax, TotalSUV, MTV, TLG, TLRmax, and TLRmean over (9.7, 2255, 20.6, 145, 3.6, 2.6, respectively) are associated with worse survival. Our study shows that the neural network could serve as a supplement to PET-derived parameters and is helpful in finding prognostic parameters for overall survival in HNSCC.

ESTRO ACROP guidelines for external beam radiotherapy of patients with complicated bone metastases.

This is the second part of the guidelines on the management of bone metastases. In the first part, the diagnosis and management of uncomplicated bone metastases have been addressed. Bone metastases may significantly reduce quality of life due to related symptoms and possible complications. The most common symptoms include pain and neurologic deficits. The most serious complications of bone metastases are skeletal-related events (SRE), defined as pathologic fracture, spinal cord compression, pain, or other symptoms requiring an urgent intervention such as surgery or radiotherapy. Diffuse bone metastases may lead to hypercalcaemia that can be fatal if untreated. The growing access to modern diagnostic tools allows early detection of asymptomatic bone metastases that could be successfully managed with local treatment if oligometastatic or systemic treatment for diffuse bone metastases to try to avoid the development of SRE.

ESTRO ACROP guidelines for external beam radiotherapy of patients with uncomplicated bone metastases.

After liver and lungs, bone is the third most common metastatic site (Nystrom et al., 1977). Almost all malignancies can metastasize to the skeleton but 80% of bone metastases originate from breast, prostate, lung, kidney and thyroid cancer (Mundy, 2002). Introduction of effective systemic treatment in many cancers has prolonged patients' survival, including those with bone metastases. Bone metastases may significantly reduce quality of life due to related symptoms and possible complications, such as pain and neurologic compromise. The most serious complications of bone metastases are skeletal-related events (SRE), defined as pathologic fracture, spinal cord compression, pain, or other symptoms requiring an urgent intervention such as surgery or radiotherapy. In turn, growing access to modern diagnostic tools allows early detection of asymptomatic bone metastases that could be successfully managed with local treatment avoiding development of SRE. The treatment for bone metastases should focus on relieving existing symptoms and preventing new ones. Radiotherapy is the standard of care for patients with symptomatic bone metastases, providing durable pain relief with minimal toxicity and reasonable cost-effectiveness. Historically, the dose was prescribed in one to five fractions and delivered using simple planning techniques. While 3D-conformal radiotherapy is still widely used for treating bone metastases, introduction of highlyconformal radiotherapy techniques such as stereotactic body radiotherapy (SBRT) have opened new therapeutic possibilities that should be considered in selected patients with bone metastases.