Protocol for the SEHNeCa randomised clinical trial assesing Supervised Exercise for Head and Neck Cancer patients.

OBJECTIVES: To evaluate the effectiveness of an innovative supervised exercise programme to mitigate the loss of lean body mass, functional capacity and quality of life in people with head and neck cancer, as well as to identify the optimal moment to apply it, before or after radiotherapy treatment, compared with the prescription of a physical activity plan carried out autonomously. METHODS: Patients with squamous cell carcinoma of the head and neck (n = 144), treated with radiotherapy, will be randomly assigned to one of 3 comparison groups: pre-radiotherapy supervised exercise, post-radiotherapy supervised exercise and autonomous exercise, stratifying by human papillomavirus infection and previous surgery. The exercise programme will be carried out in 36 sessions over 12 weeks, combining moderate and high intensity strength and aerobic exercises. The main outcome variable is the change in lean body mass at 6 months measured by bioimpedance, while secondary variables are functional capacity, symptoms, quality of life and adverse effects. Longitudinal generalised mixed models will be used for the analyses of the repeated measurements at 3, 6, and 12 months after baseline. CONCLUSIONS: The pilot study supports the feasibility and safety of the project. However, as the programme progressed, attendance at the sessions decreased. Strategies will be necessary for increasing attendance, as well as involving the patient in their recovery and other incentives. Follow-up after treatment to assess acute/late toxicity will enable us to know the response to both the exercise programme and its adherence. TRIAL REGISTRATION: NCT04658706 Date and version identifier: March 1, 2023. Version 1.1.

Prospective study of HDR brachytherapy (BT), external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT): 10-years experience of an MRI-guided approach.

OBJECTIVES: To evaluate the predictive factors for biochemical failure and distant metastases in a prospective cohort of patients with localized prostate cancer treated with the combination of HDR BT and EBRT. METHODS AND MATERIALS: Patients with intermediate (IR) or high-risk (HR) prostate adenocarcinoma received a single fraction of HDR of 15 Gy combined with RT of 37.5 Gy in 15 fractions. ADT duration was used depending on risk-group. Descriptive analyses were performed. Univariate and multivariate Hazard Ratios were obtained. Finally, the Kaplan-Meier model was used to describe the survival of the events of interest. RESULTS: 309 patients were treated prospectively (199 were IR and 110 HR). Median age was 72 years; 58.3 % were MRI stage ≤ T2c, 34.1 % T3a and 7.6 % T3b; ISUP-grade 1-3 in 78.9 % and ISUP 4-5 in 21.1 %. 71.8 % of patients had ≤ 50 % positive-cores in biopsy and 28.2 % had > 50 %. Median pre-treatment PSA was 9.9 ng/mL. After a median follow-up of 88 months, 41 patients presented biochemical failure and 18 developed distant metastases. Multivariate cox-regression analyses found that MR-T3b Stage (HR 3.88, p = 0.001) and ADT use (HR 3.99, p = 0.03) were the only predictive factors for biochemical failure and the number of positive cores (>50 %) the only independent predictive factor of distant metastases (HR 4.36, p = 0.002). CONCLUSIONS: Patients with mpMRI evidence of invasion of the SV and involvement of more than 50% of the cores in the prostate biopsy are patients with a higher risk of presenting a biochemical recurrence or developing metastasis due to their prostate cancer, respectively.

SEOR SBRT-SG stereotactic body radiation therapy consensus guidelines for non-spine bone metastasis.

The use of stereotactic body radiation therapy (SBRT) to treat non-spine bone metastases (NSBM) is becoming increasingly common in clinical practice. The clinical advantages of SBRT include good pain control and high local control rates, although only limited data are available. The Spanish Society of Radiation Oncology (SEOR) SBRT group recently convened a task force of experts in the field to address key questions related to SBRT for NSBM, including treatment indications, planning, techniques, and dose fractionation. The task force reviewed the available literature to develop evidence-based recommendations for the safe application of NSBM SBRT and to standardize and optimize SBRT processes. The present document provides a comprehensive analysis of the available data, including ongoing clinical trials and controversies, providing clinically applicable recommendations.

MRI detected extaprostatic extension (EPE) in prostate cancer: Do all T3a patients have the same outcomes?

MRI-detected T3a prostate cancer is a heterogeneous disease. This post-hoc analysis of a prospective trial found that patients with T3a disease presenting obliteration of the recto-prostatic angle, contact-asymmetry of neuro-vascular bundle and periprostatic fat invasion, may be at higher risk of biochemical failure and metastases.

Impact of pre-radiation therapy quality of life in lung cancer survival: a prospective, intention-to-treat, multicenter study.

PURPOSE: Lung cancer (LC) has a significant impact on patients' health-related quality of life (HRQoL). We investigate the correlations between pre-radiation therapy HRQoL and survival. MATERIALS AND METHODS: A prospective, intention-to-treat, multicentre study of 437 patients with LC recruited at the radiation oncology departments of three different institutions was conducted between 2012 and 2016. QoL was assessed using the EORTC-QLQ-C30 (v3.0) and EORTC-QLQ-LC13 questionnaires. Global health status (GHS), physical (PF), role functioning (RF), emotional (EF), cognitive (CF), and social functioning (SF) as well as symptoms scores were evaluated in univariate and multivariate analyses. RESULTS: The cohort consisted of 376 men (86%) and 61 women, with a median age of 66 years (range 31-88). Histology was: 72% (n = 315) non-small cell lung cancer and 28% small cell lung cancer. The most common stage was III (80%) and the median follow-up for alive patients was 30 months (range 7-76). Multivariate analysis showed that RF was associated with a lower risk of mortality (HR: 0.693; p = 0.008) and recurrence (HR: 0.737; p = 0.040). Additionally, lower scores on EF and PF were associated with higher mortality (HR: 0.696; p = 0.003 and HR: 0.765; p = 0.044, respectively). Appetite loss, constipation, and dysphagia were associated with a higher risk of mortality (HR: 1.985; p < 0.001, HR: 1.373; p = 0.036, and HR: 1.659; p = 0.002, respectively), while appetite loss was the only symptom associated with a higher risk of recurrence (HR: 1.525; p = 0.014). CONCLUSIONS: Pre-radiation therapy scores on RF, EF, and PF and symptoms like appetite loss, dysphagia, and constipation were associated with the risk of mortality. This information could be added to other prognostic factors to guide our treatment decisions.

Multidisciplinary management of head and neck cancer: First expert consensus using Delphi methodology from the Spanish Society for Head and Neck Cancer (part 2).

Head and neck cancer is one of the most frequent malignances worldwide. Despite the site-specific multimodality therapy, up to half of the patients will develop recurrence. Treatment selection based on a multidisciplinary tumor board represents the cornerstone of head and neck cancer, as it is essential for achieving the best results, not only in terms of outcome, but also in terms of organ-function preservation and quality of life. Evidence-based international and national clinical practice guidelines for head and neck cancer not always provide answers in terms of decision-making that specialists have to deal with in their daily practice. This is the first Expert Consensus on the Multidisciplinary Approach for Head and Neck Squamous Cell Carcinoma (HNSCC) elaborated by the Spanish Society for Head and Neck Cancer and based on a Delphi methodology. It offers a number of specific recommendations based on the available evidence and the expertise of our specialists to facilitate decision-making of all health-care specialists involved.

Prognostic value of maximum standardized uptake value measured by pretreatment 18F-FDG PET/CT in locally advanced head and neck squamous cell carcinoma.

PURPOSE/OBJECTIVES: To evaluate the prognostic impact of maximum standardized uptake value (SUVmax) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) undergoing pretreatment [F-18] fluoro-D-glucose-positron emission tomography/computed tomography (FDG PET/CT) imaging. MATERIALS/METHODS: Fifty-eight patients undergoing FDG PET/CT before radical treatment with definitive radiotherapy (±concomitant chemotherapy) or surgery + postoperative (chemo)radiation were analyzed. The effects of clinicopathological factors (age, gender, tumor location, stage, Karnofsky Performance Status (KPS), and treatment strategy) including primary tumor SUVmax and nodal SUVmax on overall survival (OS), disease-free survival (DFS), locoregional control (LRC), and distant metastasis-free survival (DMFS) were evaluated. Kaplan-Meier survival curves were generated and compared with the log-rank test. RESULTS: Median follow-up for the whole population was 31 months (range 2.3-53.5). Two-year OS, LRC, DFS and DMFS, for the entire cohort were 62.1, 78.3, 55.2 and 67.2%, respectively. Median pretreatment SUVmax for the primary tumor and lymph nodes was 11.85 and 5.4, respectively. According to univariate analysis, patients with KPS < 80% (p < 0.001), AJCC stage IVa or IVb vs III (p = 0.037) and patients undergoing radiotherapy vs surgery (p = 0.042) were significantly associated with worse OS. Patients with KPS < 80% (p = 0.003) or age ≥65 years (p = 0.007) had worse LRC. The KPS < 80% was the only factor associated with decreased DFS (p = 0.001). SUVmax of the primary tumor or the lymph nodes were not associated with OS, DFS or LRC. The KPS < 80% (p = 0.002), tumor location (p = 0.047) and AJCC stage (p = 0.025) were associated with worse cancer-specific survival (CSS). According to Cox regression analysis, on multivariate analysis KPS < 80% was the only independent parameter determining worse OS, DFS, CSS. Regarding LRC only patients with IK < 80% (p = 0.01) and ≥65 years (p = 0.01) remained statistically significant. Nodal SUVmax was the only factor associated with decreased DMFS. Patients with a nodal SUVmax > 5.4 presented an increased risk for distant metastases (HR, 3.3; 95% CI 1.17-9.25; p = 0.023). CONCLUSIONS: The pretreatment nodal SUVmax in patients with locally advanced HNSCC is prognostic for DMFS. However, according to our results primary tumor SUVmax and nodal SUVmax were not significantly related to OS, DFS or LRC. Patients presenting KPS < 80% had worse OS, DFS, CSS and LRC.

A prospective analysis of inter- and intrafractional errors to calculate CTV to PTV margins in head and neck patients.

PURPOSE: To evaluate an institute-specific CTV-PTV margin for head and neck (HN) patients according to a 3-mm action level protocol. METHODS/PATIENTS: Twenty-three HN patients were prospectively analysed. Patients were immobilized with a thermoplastic mask. Inter- and intrafractional set-up errors (in the three dimensions) were assessed from portal images (PI) registration. Digitally reconstructed radiographs (DRRs) were compared with two orthogonal PI by matching bone anatomy landmarks. The isocenter was verified during the first five consecutive days of treatment: if the mean error detected was greater than 2 mm the isocenter position was corrected for the rest of the treatment. Isocenter was checked weekly thereafter. Set-up images were obtained before and after treatment administration on 10, 20 and 30 fractions to quantify the intrafractional displacement. For the set-up errors, systematic (Σ), random (σ), overall standard deviations, and the overall mean displacement (M), were determined. CTV to PTV margin was calculated considering both inter- and intrafractional errors. RESULTS: A total of 396 portal images was analysed in 23 patients. Systematic interfractional (Σ(inter)) set-up errors ranged between 0.77 and 1.42 mm in the three directions, whereas the random (σ (inter)) errors were around 1-1.31 mm. Systematic intrafractional (Σ(intra)) errors ranged between 0.65 and 1.11 mm, whereas the random (σ (intra)) errors were around 1.13-1.16 mm. CONCLUSIONS: A verification protocol (3-mm action level) provided by EPIDs improves the set-up accuracy. Intrafractional error is not negligible and contributes to create a larger CTV-PTV margin. The appropriate CTV-PTV margin for our institute is between 3 and 4.5 mm considering both inter- and intrafractional errors.

[Mediastinal chordoma]. / Cordoma mediastínico.

We describe a patient with chordoma located in the mid-posterior mediastinum whose first clinical symptoms were respiratory. This, together with the patient's age at presentation, made this case unusual.

Definitive radiotherapy for T1 glottic squamous cell carcinoma: a 15-year Cruces University Hospital experience.

PURPOSE: To evaluate the treatment outcomes for T1 N0 glottic carcinoma after definitive radiotherapy. METHODS: One hundred and seventeen patients treated with radical radiotherapy from 1990 to 2006 were retrospectively reviewed. The median follow-up duration for the entire group was 92 months (range 4-227). A median dose of 70 Gy (range 63-70 Gy) was administered. We determined the rates of local control (LC), regional control, overall survival (OS) and cause-specific survival (CSS) at 5, 10 and 15 years by Kaplan-Meier product-limit method. The Cox regression analysis was performed to identify significant prognostic factors for LC and survival. The incidence of secondary malignancies is also reported. RESULTS: The 5-, 10- and 15-year LC rates for the whole group were 84, 80.2 and 80.2 %, respectively. There were 20 local recurrences, of which 19 were salvaged with laryngectomy, giving an ultimate control rate of 90.6 %. The 5-/10-/15-year OS and CSS rates were 81.2 %/66.1 %/48.3 % and 90.6 %/90.6 %/90.6 %, respectively. None of the parameters analyzed exhibited a statistically significant relationship with LC. The age ≥65 years had a statistically significant effect on OS (but not in CSS), with a hazard ratio of 2.45 (95 % confidence interval 1.29-4.66; p = 0.006). During follow-up, 26 patients (22 %) developed a secondary malignancy. Only two patients (1.7 %) presented with severe toxicity (edema and mucositis). CONCLUSIONS: Radiotherapy alone offers a high likelihood of LC and an excellent CSS rate. In addition, the surgical approach for the salvage is a successful option.

Prognostic value of maximum standardized uptake value measured by pretreatment 18F-FDG PET/CT in locally advanced head and neck squamous cell carcinoma

Purpose/objectives. To evaluate the prognostic impact of maximum standardized uptake value (SUVmax) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) undergoing pretreatment [F-18] fluoro-d-glucose-positron emission tomography/computed tomography (FDG PET/CT) imaging. Materials/methods. Fifty-eight patients undergoing FDG PET/CT before radical treatment with definitive radiotherapy (±concomitant chemotherapy) or surgery + postoperative (chemo)radiation were analyzed. The effects of clinicopathological factors (age, gender, tumor location, stage, Karnofsky Performance Status (KPS), and treatment strategy) including primary tumor SUVmax and nodal SUVmax on overall survival (OS), disease-free survival (DFS), locoregional control (LRC), and distant metastasis-free survival (DMFS) were evaluated. Kaplan–Meier survival curves were generated and compared with the log-rank test. Results. Median follow-up for the whole population was 31 months (range 2.3–53.5). Two-year OS, LRC, DFS and DMFS, for the entire cohort were 62.1, 78.3, 55.2 and 67.2%, respectively. Median pretreatment SUVmax for the primary tumor and lymph nodes was 11.85 and 5.4, respectively. According to univariate analysis, patients with KPS < 80% (p < 0.001), AJCC stage IVa or IVb vs III (p = 0.037) and patients undergoing radiotherapy vs surgery (p = 0.042) were significantly associated with worse OS. Patients with KPS < 80% (p = 0.003) or age ≥65 years (p = 0.007) had worse LRC. The KPS < 80% was the only factor associated with decreased DFS (p = 0.001). SUVmax of the primary tumor or the lymph nodes were not associated with OS, DFS or LRC. The KPS < 80% (p = 0.002), tumor location (p = 0.047) and AJCC stage (p = 0.025) were associated with worse cancer-specific survival (CSS). According to Cox regression analysis, on multivariate analysis KPS < 80% was the only independent parameter determining worse OS, DFS, CSS. Regarding LRC only patients with IK < 80% (p = 0.01) and ≥65 years (p = 0.01) remained statistically significant. Nodal SUVmax was the only factor associated with decreased DMFS. Patients with a nodal SUVmax > 5.4 presented an increased risk for distant metastases (HR, 3.3; 95% CI 1.17–9.25; p = 0.023). Conclusions. The pretreatment nodal SUVmax in patients with locally advanced HNSCC is prognostic for DMFS. However, according to our results primary tumor SUVmax and nodal SUVmax were not significantly related to OS, DFS or LRC. Patients presenting KPS < 80% had worse OS, DFS, CSS and LRC (AU)

No disponible

A prospective analysis of inter- and intrafractional errors to calculate CTV to PTV margins in head and neck patients

Purpose. To evaluate an institute-specific CTV–PTV margin for head and neck (HN) patients according to a 3-mm action level protocol. Methods/patients. Twenty-three HN patients were prospectively analysed. Patients were immobilized with a thermoplastic mask. Inter- and intrafractional set-up errors (in the three dimensions) were assessed from portal images (PI) registration. Digitally reconstructed radiographs (DRRs) were compared with two orthogonal PI by matching bone anatomy landmarks. The isocenter was verified during the first five consecutive days of treatment: if the mean error detected was greater than 2 mm the isocenter position was corrected for the rest of the treatment. Isocenter was checked weekly thereafter. Set-up images were obtained before and after treatment administration on 10, 20 and 30 fractions to quantify the intrafractional displacement. For the set-up errors, systematic (Σ), random (σ), overall standard deviations, and the overall mean displacement (M), were determined. CTV to PTV margin was calculated considering both inter- and intrafractional errors. Results. A total of 396 portal images was analysed in 23 patients. Systematic interfractional (Σinter) set-up errors ranged between 0.77 and 1.42 mm in the three directions, whereas the random (σ inter) errors were around 1–1.31 mm. Systematic intrafractional (Σintra) errors ranged between 0.65 and 1.11 mm, whereas the random (σ intra) errors were around 1.13–1.16 mm. Conclusions. A verification protocol (3-mm action level) provided by EPIDs improves the set-up accuracy. Intrafractional error is not negligible and contributes to create a larger CTV–PTV margin. The appropriate CTV–PTV margin for our institute is between 3 and 4.5 mm considering both inter- and intrafractional errors (AU)

No disponible

Malonyl-CoA and AMP-activated protein kinase (AMPK): possible links between insulin resistance in muscle and early endothelial cell damage in diabetes.

Based on available evidence, we would propose the following. (i) Excesses of glucose and free fatty acids cause insulin resistance in skeletal muscle and damage to the endothelial cell by a similar mechanism. (ii) Key pathogenetic events in this mechanism very likely include increased fatty acid esterification, protein kinase C activation, an increase in oxidative stress (demonstrated to date in endothelium) and alterations in the inhibitor kappa B kinase/nuclear factor kappa B system. (iii) Activation of AMP-activated protein kinase (AMPK) inhibits all of these events and enhances insulin signalling in the endothelial cell. It also enhances insulin action in muscle; however, the mechanism by which it does so has not been well studied. (iv) The reported beneficial effects of exercise and metformin on cardiovascular disease and insulin resistance in humans could be related to the fact that they activate AMPK. (v) The comparative roles of AMPK in regulating metabolism, signalling and gene expression in muscle and endothelial cells warrant further study.

Definitive radiotherapy for T1 glottic squamous cell carcinoma: a 15-years Cruces University Hospital experience

PURPOSE: To evaluate the treatment outcomes for T1 N0 glottic carcinoma after definitive radiotherapy. METHODS: One hundred and seventeen patients treated with radical radiotherapy from 1990 to 2006 were retrospectively reviewed. The median follow-up duration for the entire group was 92 months (range 4-227). A median dose of 70 Gy (range 63-70 Gy) was administered. We determined the rates of local control (LC), regional control, overall survival (OS) and cause-specific survival (CSS) at 5, 10 and 15 years by Kaplan-Meier product-limit method. The Cox regression analysis was performed to identify significant prognostic factors for LC and survival. The incidence of secondary malignancies is also reported. RESULTS: The 5-, 10- and 15-year LC rates for the whole group were 84, 80.2 and 80.2 %, respectively. There were 20 local recurrences, of which 19 were salvaged with laryngectomy, giving an ultimate control rate of 90.6 %. The 5-/10-/15-year OS and CSS rates were 81.2 %/66.1 %/48.3 % and 90.6 %/90.6 %/90.6 %, respectively. None of the parameters analyzed exhibited a statistically significant relationship with LC. The age ≥65 years had a statistically significant effect on OS (but not in CSS), with a hazard ratio of 2.45 (95 % confidence interval 1.29-4.66; p = 0.006). During follow-up, 26 patients (22 %) developed a secondary malignancy. Only two patients (1.7 %) presented with severe toxicity (edema and mucositis). CONCLUSIONS: Radiotherapy alone offers a high likelihood of LC and an excellent CSS rate. In addition, the surgical approach for the salvage is a successful option (AU)