Hypofractionated whole breast irradiation after IORT treatment is safe in patients receiving adjuvant chemotherapy.

INTRODUCTION: Hypofractionated whole breast irradiation (hWBI) and intraoperative radiotherapy (IORT) could be associated in breast cancer patients showing high-risk factors of local recurrence after breast conserving therapy (BSC). The aim of this trial was to evaluate, for the first time, the toxicity and cosmesis of hWBI after photon-IORT in high-risk patients treated by adjuvant chemotherapy. MATERIALS AND METHODS: Thirty-one high-risk localized breast cancer patients treated by BCS, IORT (20 Gy), and adjuvant chemotherapy were included from February 2019 to August 2020 in this prospective trial, of hWBI (40.5 Gy/2.67 Gy/15 fractions). Acute and late toxicity (CTCAEv5.0) and cosmesis (Harvard scale), were assessed after treatment. RESULTS: All patients completed their treatment and were evaluable after treatment. No patients showed severe (G3) acute/late toxicity. Excellent/good cosmesis at least 6 months after completing the treatment, was present in 93.6% of the patients. CONCLUSION: hWBI in high-risk localized breast cancer patients treated by chemotherapy seems to have similar toxicity and cosmetic results than conventionally fractionated WBI in combination to photon-IORT after BCS.

Hypofractionated whole breast irradiation after IORT treatment: evaluation of acute toxicity and cosmesis.

INTRODUCTION: Hypofractionated whole breast irradiation (HWBI) is the current standard of treatment after breast conservative surgery (BCS). Intraoperative radiotherapy (IORT) must be associated to WBI in patients showing high-risk factors of local recurrence in the definitive pathology report. The aim of this trial was to evaluate, for the first time, the acute toxicity and cosmesis of HWBI after photon-IORT. MATERIALS AND METHODS: Twenty-six luminal breast cancer patients treated by BCS and IORT(20 Gy) were included between February and December 2019, in this prospective trial, of adjuvant HWBI (40.5 Gy/2.67 Gy/15 fractions). Acute toxicity (CTCAEv5.0) and cosmesis (Harvard scale), were assessed 3 months after treatment. RESULTS: All patients completed their treatment without interruptions. All cases were evaluable 3 months after treatment showing no toxicity ≥ G3 and excellent/good cosmesis assessment in 88% of the patients. CONCLUSION: HWBI seems to have similar acute toxicity and cosmesis results than conventionally fractionated WBI in combination to photon-IORT after BCS.

Regional deep hyperthermia in combination with whole brain radiotherapy (WBRT) in poor prognosis patients with brain metastases.

PURPOSE: The aim of this study is to assess for the first time, the role of regional deep hyperthermia in combination with radiotherapy and systemic therapy in patients with poor prognosis of brain metastases (GPI ≤ 2.5). METHODS: Patients with confirmed cerebral metastases and classified as GPI score ≤ 2.5 were included in this prospective study. Pretreatment stratification was defined as patients with 0-1 GPI score (Group A) and patients with 1.5-2.5 GPI score (Group B). HT was applied twice a week, 60 min per session, during RT by regional capacitive device (HY-DEEP 600WM system) at 13.56 MHz radiofrequency. RESULTS: Between June 2015 and June 2017, 15 patients and a total of 49 brain metastases were included in the protocol. All patients received all HT sessions as planned. RT and systemic therapy were also completed as prescribed. Tolerance to treatment was excellent and no toxicity was registered. Patients with HT effective treatment time longer than the median (W90time > 88%) showed better actuarial PFS at 6 and 12 months (100% and 66.7%, respectively) compared to those with less HT effective treatment time (50% and 0%, respectively) (p < 0.031). Median OS was 6 months (range 1-36 months). Stratification by GPI score showed a median OS of 3 months (CI 95% 2.49-3.51) in Group A and 8.0 months (CI 95% 5.15-10.41) in Group B (p = 0.035). CONCLUSIONS: Regional hyperthermia is a feasible and safe technique to be used in combination with RT in brain metastases patients, improving PFS and survival in poor prognostic brain metastasis patients.

Hypofractionation vs. conventional radiotherapy fractionation in the conservative treatment of T1 glottic cancer: a prospective cohort study.

BACKGROUND: Definitive radiotherapy is an effective single-modality in T1 glottic cancer. Hypofractionated schemes could offer excellent results in a shorter treatment period. We aimed to evaluate the clinical outcomes and toxicity comparing conventional vs. hypofractionated radiotherapy treatment in T1N0M0-glottic cancer. PATIENTS AND METHODS: Between Jan-1st, 2005 and August-1st, 2017, in a prospective cohort study, with 10-year follow-up, 138 patients were treated with conventional schedule 2 Gy/day, total dose 70 Gy/7 weeks (N = 71) or hypofractionated schedule 2, 2-2, 25 Gy/day, total dose 63, 8-63 Gy/5, 5 weeks (N = 67). Endpoints were clinical-response rate, local relapse-free survival (LRFS), laryngectomy-free survival (LFS), toxicity rates, relapse-free survival (RFS), metastasis-free survival (MFS), second tumour-free survival (2TFS), and overall survival (OS). RESULTS: All patients showed a complete clinical response. No differences were found for LRFS (p = 0.869), LFS (p = 0.975), RFS (p = 0.767), MFS (p = 0.601), 2TFS (p = 0.293), or OS (p = 0.685). Acute toxicity for skin and mucosae was similar (p = 0.550 and p = 0.698). Acute laryngeal toxicity was higher in the hypofractionation group (p = 0.004), due to an increase in slight moderate grade. No differences in late laryngeal edema were found (p = 0.989). CONCLUSION: Radiotherapy offers high rate survival, local control, and larynx preservation after 5-10-year follow-up. A hypofractionation could be preferable, since it offers the same results as conventional with fewer treatment sessions.

Feasibility of a deep hyperthermia and radiotherapy programme for advanced tumors: first Spanish experience.

BACKGROUND: Hyperthermia (HT) is used to increase the temperature of the tumor-sensitizing cells to the effects of radiation/chemotherapy. We aimed to assess the feasibility, tolerability and safety of hyperthermia treatment in a Radiation Oncology Department. METHODS: Between June 2015 and June 2017, 106 patients and a total of 159 tumor lesions were included in a prospective study (EudraCT 2018-001089-40) of HT concomitant with radiotherapy (RT). Systemic treatment was accepted. HT was given twice a week, 60 min per session, during RT treatment by a regional capacitive device (HY-DEEP 600WM system) at 13.56 MHz radiofrequency. RESULTS: Most lesions (138 cases, 86.8%) received all HT sessions planned. Thirteen lesions (12 patients) withdrew treatment due to grade ≥3 QMHT toxicity. All these 12 patients completed the prescribed radiotherapy and/or systemic treatment. CONCLUSIONS: Regional hyperthermia is a feasible and safe technique to be used in combination with radiotherapy and systemic treatment.

Are there enough radiation oncologists to lead the new Spanish radiotherapy?

AIM: Radiation oncology services in Spain are undergoing a process of technical modernization, but-in a context of increasing demand by an ageing population-it is unclear whether there are enough radiation oncologists to staff the newly equipped units. This study aims to assess the number of specialists working in radiation oncology services in Spain relative to current and future needs. MATERIALS AND METHODS: In the second half of 2017, the Commission on Infrastructures of the Spanish Society for Radiation Oncology (SEOR) sent a questionnaire on radiation oncology staff to the heads of all 122 public (n = 76, 62%) and private (n = 46, 38%) radiation oncology services in Spain. Data collected were the number of professionals, their position, and their year of birth for specialists and residents in each service. In the descriptive analysis, for continuous variables we calculated means, standard deviations and ranges for each Spanish region and work post. For qualitative variables, we constructed frequency tables. All analyses were performed with R statistical software, version 3.5.1. RESULTS: The survey response rate was 100% among service heads across all 122 centers. The total number of radiation oncologists working in these centers is 721, or 15.4 per million population, with considerable variations between regions. Given the national recommendations to have 20 radiation oncologists per million population, there is currently a deficit of 204 specialists. If the 163 upcoming retirements are also taken into account, there will be 367 fewer radiation oncologists than required to meet the 25% increase in indications for radiotherapy projected for 2025. CONCLUSIONS: The classic model for calculating staff needs based on the number of treatments is outdated, and recommendations should be revised to reflect the current reality. A new model should integrate the most complex technological advances and emerging plans in radiotherapy, without neglecting the other activities carried out in radiation oncology services that are not directly linked to patient care.

Infrastructure and equipment for radiation oncology in the Spanish National Health System: analysis of external beam radiotherapy 2015-2020.

PURPOSE: Planning for radiation oncology requires reliable estimates of both demand for radiotherapy and availability of technological resources. This study compares radiotherapy resources in the 17 regions of the decentralised Spanish National Health System (SNHS). MATERIALS AND METHODS: The Sociedad Española de Oncología Radioterápica (SEOR) performed a cross-sectional survey of all Spanish radiation oncology services (ROS) in 2015. We collected data on SNHS radiotherapy units, recording the year of installation, specific features of linear accelerators (LINACs) and other treatment units, and radiotherapeutic techniques implemented by region. Any machine over 10 years old or lacking a multileaf collimator or portal imaging system was considered obsolete. We performed a k-means clustering analysis using the Hartigan-Wong method to test associations between the gross domestic regional product (GDRP), the number of LINACs per million population and the percentage of LINACs over 10 years old. RESULTS: The SNHS controls 72 (61%) of the 118 Spanish ROS and has 180 LINACs, or 72.5% of the total public and private resources. The mean rate of LINACs per million population is 3.9 for public ROS, and 42% (n = 75) of the public accelerators were obsolete in 2015: 61 due to age and 14 due to technological capability. There was considerable regional variation in terms of the number and technological capacity of radiotherapy units; correlation between GRDP and resource availability was moderate. CONCLUSION: Despite improvements, new investments are still needed to replace obsolete units and increase access to modern radiotherapy. Regular analysis of ROS in each Spanish region is the only strategy for monitoring progress in radiotherapy capacity.

Demand for radiotherapy in Spain.

AIM: Assessing the demand for radiotherapy in Spain based on existing evidence to estimate the human resources and equipment needed so that every person in Spain has access to high-quality radiotherapy when they need it. MATERIAL AND METHODS: We used data from the European Cancer Observatory on the estimated incidence of cancer in Spain in 2012, along with the evidence-based indications for radiotherapy developed by the Australian CCORE project, to obtain an optimal radiotherapy utilisation proportion (OUP) for each tumour. RESULTS: About 50.5 % of new cancers in Spain require radiotherapy at least once over the course of the disease. Additional demand for these services comes from reradiation therapy and non-melanoma skin cancer. Approximately, 25-30 % of cancer patients with an indication for radiotherapy do not receive it due to factors that include access, patient preference, familiarity with the treatment among physicians, and especially resource shortages, all of which contribute to its underutilisation. CONCLUSIONS: Radiotherapy is underused in Spain. The increasing incidence of cancer expected over the next decade and the greater frequency of reradiations necessitate the incorporation of radiotherapy demand into need-based calculations for cancer services planning.

New biological markers in the decision of treatment of head and neck cancer patients.

Head and neck squamous cell carcinoma is the sixth most common cancer type worldwide. Also the 5-year survival rate of less than 50 % seems to be lower than other cancer types. There are some reasons behind this high mortality rate; one of them is the lack of knowledge about the biology and genomic instability behind the carcinogenic processes. These biological features could condition the failure of frontline treatment, in which case rescue treatment should be used, representing an overtreatment for the patients. For years many biological factors have been tested as prognostic and predictive factors in relation to treatment with a modest success. To find appropriate tests which could be used in the context of the individualized treatment decision, we have reviewed new biological markers, not only in tumor tissue, but also in normal tissue from head and neck carcinoma patients.

ET AAS evaluation of the stability and pH-sensitivity of, pH-sensitive stealth liposomes containing cisplatin in mouse plasma.

In this work, stability and the pH-sensitivity of pH-sensitive stealth liposomes containing cisplatin exposed to plasma medium and their subsequent responses to pH modifications were evaluated. A method to determine platin in mouse plasma by electrothermal atomic absorption spectroscopy (ET AAS) was developed and validated. At first, a comparative study of sample preparation treatments with basic, acidic, and acidic added with Triton X-100 as a modifier was done. The best treatment was obtained with HCl 3% (v/v). The ET AAS method with acid treatment presented linearity at a range of 10-160 ng Pt/mL. The limits of detection (LOD) was 3.1 ng/mL Pt for acid treatment, while the limit quantification (LOQ) was 10 ng/mL Pt. The acid treatment presented good repeatability (VC<15.0%) and recovery close to 100%. This treatment was chosen for subsequent studies due to its best value of repeatability, recovery, LOD and lowest cost. pH-sensitive stealth liposomes, containing cisplatin, demonstrated low stability and poor response to pH variation after plasma incubation. These findings suggest that further studies are needed to improve liposome formulation i.e., to reduce its size.

Molecular biomarkers in the decision of treatment of cervical carcinoma patients.

Cervical carcinoma is the third most common cancer in women worldwide. The programs developed for early detection have made that most patients are diagnosed in early stages. Treatment for those patients consists of conservative techniques as surgery or radical radiotherapy; however, the decision between those two therapies is still controversial. Even though in many cases this decision varies according to classical associated risk factors (i.e. tumor stage or age), in the clinical practice, a significant number of patients treated by surgery also receive post-surgery radiotherapy, with the consequent over-treatment and toxic effects. Since response to treatments is conditioned by individual factors, the use of new biological markers as novel predictive factors for both tumor and normal tissues could help clinicians to choose the best treatment schedule for each patient individually. Based on the experience of our institution, we have reviewed the new biological markers in cervical carcinoma patients treated by radiotherapy.

Development and validation of a method for Cd, Pb and As analysis in bovine, equine and poultry liver by inductively coupled plasma mass spectrometry.

A method for the determination of As, Cd and Pb in bovine, equine and poultry liver by ICP-MS was developed and validated. Samples were digested in a microwave oven using a 10% HNO(3) solution. A set of experiments was made according to a central composite design (CCD) for optimisation of the plasma argon flow, nebuliser argon flow and radiofrequency power applied to the plasma. During the validation, Rh and Ru were evaluated as internal standards and, after validation, the best was Rh for Pb and Cd analysis, but for As better results were obtained without an internal standard. The method allowed As, Cd and Pb determination with a 3.3% HNO(3) solution for the calibration curves ranging from 0 to 40 µg l(-1) for As and from 0 to 20 µg l(-1) for Cd and Pb. The recovery values obtained showed averages of 100%, 106% and 96% for As, Cd and Pb, respectively. Limits of quantification obtained were 85 µg kg(-1) for As, 6.5 µg kg(-1) for Cd and 12.5 µg kg(-1) for Pb. Repeatability and within-laboratory reproducibility were evaluated through the indicators HORRAT(r) and HORRAT(R), and the results were less than 0.30. The method is simple, fast and showed adequate precision and accuracy for the determination of As, Cd and Pb in bovine, equine and poultry liver. The precision, recovery, uncertainties, and limits of detection and quantification for each analyte were in accordance to European Union Commission Regulation 2007/333/EC.