Radio-induced apoptosis of peripheral blood CD8 T lymphocytes is a novel prognostic factor for survival in cervical carcinoma patients.

BACKGROUND AND PURPOSE: A close relationship exists between immune response and tumor behavior. This study aimed to explore the associations between radiation-induced apoptosis (RIA) in peripheral blood lymphocytes (PBL) and clinical pathological variables. Furthermore, it assessed the role of RIA as a prognostic factor for survival in cervical carcinoma patients. PATIENTS AND METHODS: Between February 1998 and October 2003, 58 consecutive patients with nonmetastatic, localized stage I-II cervical carcinoma who had been treated with radiotherapy (RT) ± chemotherapy were included in this study. Follow-up ended in January 2013. PBL subpopulations were isolated and irradiated with 0, 1, 2 and 8 Gy then incubated for 24, 48 and 72 h. Apoptosis was measured by flow cytometry and the ß value, a parameter defining RIA of lymphocytes, was calculated. RESULTS: Mean follow-up duration was 111.92 ± 40.31 months. Patients with lower CD8 T lymphocyte ß values were at a higher risk of local relapse: Exp(B) = 5.137, confidence interval (CI) 95 % = 1.044-25.268, p = 0.044. Similar results were observed for regional relapse: Exp(B) = 8.008, CI 95 % = 1.702-37.679, p = 0.008 and disease relapse: Exp(B) = 6.766, CI 95 % = 1.889-24.238, p = 0.003. In multivariate analysis, only the CD8 T lymphocyte ß values were found to be of prognostic significance for local disease-free survival (LDFS, p = 0.049), regional disease-free survival (RDFS, p = 0.002), metastasis-free survival (MFS, p = 0.042), disease-free survival (DFS, p = 0.001) and cause-specific survival (CSS p = 0.028). CONCLUSION: For the first time, RIA in CD8 T lymphocytes was demonstrated to be a predictive factor for survival in cervical carcinoma patients.

Dose-escalated SBRT for borderline and locally advanced pancreatic cancer. Feasibility, safety and preliminary clinical results of a multicenter study.

Background: Pancreatic Stereotactic Body Radiotherapy (SBRT) allows for the administration of a higher biologically effective doses (BED), that would be essential to achieve durable tumor control. Escalating treatment doses need a very accurate tumor positioning and motion control during radiotherapy.The aim of this study to assess the feasibility and safety of a Simultaneous Integrated Boost (SIB) dose-escalated protocol at 45 Gy, 50 Gy and 55 Gy in 5 consecutive daily fractions, in Border Line Resectable Pancreatic Cancer (BRCP) /Locally Advanced Pancreatic Cancer (LAPC) by means of a standard LINAC platform. Methods: Patients diagnosed of BRPC/LAPC, candidates for neoadjuvant chemotherapy and SBRT, in four university hospitals of the province of Las Palmas (Canary Islands, Spain) were included in this prospective study. Radiotherapy was administered using standard technology (LINACS) with advanced positioning (Lipiodol® and metallic stent used as fiducial markers) and tumor motion control (4D, DBH, Calypso®). There were 3 planned dose-escalated SIB groups, 45 Gy/5f (9 patients) 50 Gy/5f (9 + 9 patients) and 55 Gy/5f (9 patients). The defined primary end points of the study were the safety and feasibility of the proposed treatment protocol. Secondary endpoints included radiological tumor response after SBRT, local control and survival. Results: From June 2017 to December 2022, sixty-two patients were initially assessed for eligibility in the study in the four participating centers, and 49 were candidates for chemotherapy (CHT). Forty-one were referred to radiotherapy after CHT and 33 finally were treated by escalated-dose SIB, 45 Gy (9 patients) 50 Gy (16 patients), 55 Gy(8 patients). All patients completed the scheduled treatment and no acute or late severe (≥grade3) gastrointestinal toxicity was observed.Local response was analyzed by CT/MRI two months after the end of SBRT. Ten patients (31,25 %) achieved objective response (2/9:45 Gy, 5/15:50 Gy, 3/8:55 Gy). Follow-up was closed as July 2023. Freedom from local progression at 1-2y were 89,3% (95 %CI:83,4-95,2%) and 66 % (95 %CI:54,6-77,4%) respectively. The 1-2y survival rates were 95,7% (95 %CI:91,4-100 % and 48,6% (95 %CI:37,7-59,5%) respectively. Conclusion: These promising results should be confirmed by further studies with larger sample size and extended follow-up period.

Biochemical markers of bone turnover and clinical outcome in patients with renal cell and bladder carcinoma with bone metastases following treatment with zoledronic acid: The TUGAMO study.

BACKGROUND: Levels of bone turnover markers (BTM) might be correlated with outcome in terms of skeletal-related events (SRE), disease progression, and death in patients with bladder cancer (BC) and renal cell carcinoma (RCC) with bone metastases (BM). We try to evaluate this possible correlation in patients who receive treatment with zoledronic acid (ZOL). METHODS: This observational, prospective, and multicenter study analysed BTM and clinical outcome in these patients. Serum levels of bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), and beta-isomer of carboxy-terminal telopeptide of type I collagen (ß-CTX) were analysed. RESULTS: Patients with RCC who died or progressed had higher baseline ß-CTX levels and those who experienced SRE during follow-up showed high baseline BALP levels. In BC, a poor rate of survival was related with high baseline ß-CTX and BALP levels, and new SRE with increased PINP levels. Cox univariate analysis showed that ß-CTX levels were associated with higher mortality and disease progression in RCC and higher mortality in BC. Bone alkaline phosphatase was associated with increased risk of premature SRE appearance in RCC and death in BC. CONCLUSION: Beta-isomer of carboxy-terminal telopeptide of type I collagen and BALP can be considered a complementary tool for prediction of clinical outcomes in patients with BC and RCC with BM treated with ZOL.

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study.

BACKGROUND: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). METHODS: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (ß-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. RESULTS: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with ß-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. CONCLUSION: In patients with PCa and bone metastases treated with ZA, ß-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.

Novel unconventional radiotherapy techniques: Current status and future perspectives - Report from the 2nd international radiation oncology online seminar.

•Improvement of therapeutic ratio by novel unconventional radiotherapy approaches.•Immunomodulation using high-dose spatially fractionated radiotherapy.•Boosting radiation anti-tumor effects by adding an immune-mediated cell killing.

Prospective Pilot study of Quality of Life in patients with severe late-radiation-toxicity treated by Low hyperbaric-oxigen-therapy.

Background/purpose: The aim of this study is to assess for the first time the immediate and long term impact on quality-of-life of HBO treatments(HBOT) at 1.45 ATA (Absolute Atmospheric Pressure) Medical Hyperbaric chamber. Methods: Patients over 18 years-old, suffering of grade 3 Common Terminology Criteria for Adverse Events (CTCAE) 4.0 radiation induced late toxicity and progressing to standard support therapy were included in this prospective study. HBOT was given daily, sixty minutes per session by a Medical Hyperbaric Chamber Biobarica System at 1.45 ATA at 100% O2. Forty sessions were prescribed for all patients given in 8 weeks. Patients reported outcomes (PROs) was assessed by the QLQ-C30 questionnaire, before starting, in the last week of the treatment, as well as during follow up. Results: Between February-2018/June-2021, 48 patients fulfilled the inclusion criteria. A total of 37 patients (77%) completed the treatment prescribed HBOT sessions. Patients with anal fibrosis (9/37) and brain necrosis (7/37) were the most frequently treated. The most common symptoms were pain (65%) and bleeding (54%). In addition, thirty out of the 37 patients who completed the pre- and post-treatment Patients Reported Outcomes (PROs) assessment also completed the follow up European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire C30 (EORTC-QLQ-C30), and were evaluated in the present study. Mean follow up was 22,10 (6-39) months.The Median score of the EORTC-QLQ-C30, at the end of HBOT and during follow-up, was improved in all assessed domains, except in the cognitive aspect (p = 0.106). Conclusions: HBOT at 1.45 ATA is a feasible and well tolerated treatment, improving long term quality of life in terms of physical function, daily activities and general health subjective state of patients suffering severe late radiation-induced toxicity.

Anti-inflammatory effects of low-dose radiotherapy. Indications, dose, and radiobiological mechanisms involved.

Low-dose radiotherapy (LD-RT) has been used for several benign diseases, including arthrodegenerative and inflammatory pathologies. Despite its effectiveness in clinical practice, little is known about the mechanisms through which LD-RT modulates the various phases of the inflammatory response and about the optimal dose fractionation. The objective of this review is to deepen knowledge about the most effective LD-RT treatment schedule and radiobiological mechanisms underlying the anti-inflammatory effects of LD-RT in various in vitro experiments, in vivo studies, and clinical studies.

Plasminogen activator inhibitor-1 (PAI-1) expression in relation to hypoxia and oncoproteins in clinical cervical tumors.

PURPOSE: Explore the role of plasminogen activator inhibitor-1 (PAI-1) in cervical cancer and its relationship to hypoxia and the expression of p53, Ku70/80, and cyclin D1. MATERIAL AND METHODS: The expression of PAI-1, cyclin D1, and p53, together with tumor oxygenation, were determined in 43 consecutive patients suffering from localized cervical carcinoma. Oncoprotein expression was determined by immunohistochemistry. Tumor oxygenation was measured using a polarographic probe system, "pO2 histography." RESULTS: PAI expression was considered negative in 32.6% and overexpressed in 18.6% of cases. Cyclin D1 showed a median expression of 5.0 (range 0-70). We observed a positive association between PAI expression and altered p53 (p = 0.049) and cyclin D1 (p = 0.020). An inverse association was detected between PAI and Ku70/80 expression (p = 0.042). Cyclin D1 staining increased according to tumor volume (r = 0.314, p = 0.009). We did not observe a significant association between PAI and hypoxia or other clinicopathological parameters. CONCLUSION: The present results show that PAI-1 overexpression is associated with nonhomologous end-joining DNA repair down-regulation (low Ku70/80 expression) and with increased p53 and cyclin D1 expression, and they suggest that PAI-1 plays a role in the tumor behavior in cervical carcinoma.

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.

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.

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.

Morphologic Features on MR Imaging Classify Multifocal Glioblastomas in Different Prognostic Groups.

BACKGROUND AND PURPOSE: Multifocal glioblastomas (ie, glioblastomas with multiple foci, unconnected in postcontrast pretreatment T1-weighted images) represent a challenge in clinical practice due to their poor prognosis. We wished to obtain imaging biomarkers with prognostic value that have not been found previously. MATERIALS AND METHODS: A retrospective review of 1155 patients with glioblastomas from 10 local institutions during 2006-2017 provided 97 patients satisfying the inclusion criteria of the study and classified as having multifocal glioblastomas. Tumors were segmented and morphologic features were computed using different methodologies: 1) measured on the largest focus, 2) aggregating the different foci as a whole, and 3) recording the extreme value obtained for each focus. Kaplan-Meier, Cox proportional hazards, correlations, and Harrell concordance indices (c-indices) were used for the statistical analysis. RESULTS: Age (P < .001, hazard ratio = 2.11, c-index = 0.705), surgery (P < .001, hazard ratio = 2.04, c-index = 0.712), contrast-enhancing rim width (P < .001, hazard ratio = 2.15, c-index = 0.704), and surface regularity (P = .021, hazard ratio = 1.66, c-index = 0.639) measured on the largest focus were significant independent predictors of survival. Maximum contrast-enhancing rim width (P = .002, hazard ratio = 2.05, c-index = 0.668) and minimal surface regularity (P = .036, hazard ratio = 1.64, c-index = 0.600) were also significant. A multivariate model using age, surgery, and contrast-enhancing rim width measured on the largest foci classified multifocal glioblastomas into groups with different outcomes (P < .001, hazard ratio = 3.00, c-index = 0.853, median survival difference = 10.55 months). Moreover, quartiles with the highest and lowest individual prognostic scores based on the focus with the largest volume and surgery were identified as extreme groups in terms of survival (P < .001, hazard ratio = 18.67, c-index = 0.967). CONCLUSIONS: A prognostic model incorporating imaging findings on pretreatment postcontrast T1-weighted MRI classified patients with glioblastoma into different prognostic groups.

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.

Androgen deprivation in prostate cancer and the long-term risk of fracture. / Deprivación andrógenica en cáncer de próstata y riesgo de fractura a largo plazo.

OBJECTIVES: To determine the rate of bone mass loss and the risk of fracture induced by androgen deprivation therapy in patients with prostate cancer. MATERIAL AND METHODS: Prospective study in 2 phases. In the first phase, demographic variables, FRAX®, bone mineral density and clinical fractures were collected, before starting the therapy and up to 1 year after ending the therapy. In the second phase, we conducted a telephone interview a mean of 8.5 years after the start of the study to assess new fractures. RESULTS: We included 150 patients with a mean age of 67 years and a mean therapy duration of 24 months. Before starting the treatment, 62 patients (41%) showed osteoporosis or low bone mass in the densitometry. After the first year of treatment, the bone mineral density decreased a mean of 3.7% and 2.1% in the lumbar spine and femoral neck, respectively. At the end of the second and third year, the loss rate was lower. During the first phase of the study, 4 patients (2.7%) experienced a fracture. In the telephone interviews with 80 patients (53%), only 1 had experienced a fracture. CONCLUSIONS: In the patients with prostate cancer and androgen deprivation therapy, greater bone loss occurred during the first year. When the treatment did not exceed 2 years, the absolute risk of fracture was low, and clinical fractures were uncommon in the short and long term.

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.

Association between single-nucleotide polymorphisms in DNA double-strand break repair genes and prostate cancer aggressiveness in the Spanish population.

BACKGROUND: Novel predictors of prognosis and treatment response for prostate cancer (PCa) are required to better individualize treatment. Single-nucleotide polymorphisms (SNPs) in four genes directly (XRCC5 (X-ray repair complementing defective repair in Chinese hamster cells 5) and XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6)) or indirectly (PARP1 and major vault protein (MVP)) involved in non-homologous end joining were examined in 494 Spanish PCa patients. METHODS: A total of 22 SNPs were genotyped in a Biotrove OpenArray NT Cycler. Clinical tumor stage, diagnostic PSA serum levels and Gleason score at diagnosis were obtained for all participants. Genotypic and allelic frequencies were determined using the web-based environment SNPator. RESULTS: (XRCC6) rs2267437 appeared as a risk factor for developing more aggressive PCa tumors. Those patients carrying the GG genotype were at higher risk of developing bigger tumors (odds ratio (OR)=2.04, 95% confidence interval (CI) 1.26-3.29, P=0.004), present higher diagnostic PSA levels (OR=2.12, 95% CI 1.19-3.78, P=0.011), higher Gleason score (OR=1.65, 95% CI 1.01-2.68, P=0.044) and D'Amico higher risk tumors (OR=2.38, 95% CI 1.24-4.58, P=0.009) than those patients carrying the CC/CG genotypes. Those patients carrying the (MVP) rs3815824 TT genotype were at higher risk of presenting higher diagnostic PSA levels (OR=4.74, 95% CI 1.40-16.07, P=0.013) than those patients carrying the CC genotype. When both SNPs were analyzed in combination, those patients carrying the risk genotypes were at higher risk of developing D'Amico higher risk tumors (OR=3.33, 95% CI 1.56-7.17, P=0.002). CONCLUSIONS: We believe that for the first time, genetic variants at XRCC6 and MVP genes are associated with risk of more aggressive disease, and would be taken into account when assessing the malignancy of PCa.

Apoptosis in carcinoma of the bladder: relation with radiation treatment results.

PURPOSE: Radiotherapy is widely used in the treatment of bladder cancer. The search for biological parameters that could select patients who will respond to radiation treatment has become essential. The aim of this study is to assess whether the pretreatment apoptotic index is useful in predicting local control and survival in a group of bladder cancer patients treated by radiotherapy. METHODS AND MATERIALS: Fifty-five patients with invasive bladder carcinoma treated between 1983 and 1996 were included in this study. Radiotherapy was given to a median dose of 66 Gy, mean 63.28 Gy, in 1.8-2 Gy daily fractions. Apoptotic cells were studied in hematoxylin-eosin slides. Clinicopathological tumor characteristics were studied in relation to the apoptotic index, and as prognostic factors for local control and survival in both univariate and multivariate analysis. RESULTS: Pretreatment apoptotic indexes were related to tumor stage, mitotic index, and Ki67 proliferation index. Five-year actuarial local control for the whole group was 45%. Patients with tumors showing low pretreatment apoptotic indexes had better local control (p < 0.037) and survival (p < 0.01) than highly apoptotic tumors. Tumor stage (T2 vs. T3-4) and the pretreatment apoptotic index were significant predictive factors for local control and survival in multivariate analysis. CONCLUSIONS: The pretreatment apoptotic index is useful in predicting the clinical outcome of bladder cancer patients treated by radiotherapy. Assessment of biological tumor characteristics could allow the selection of patients for different treatment strategies.