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The administration of a dose boost to the tumor bed after breast-conserving surgery has proven to reduce local recurrence. Intra-operative electron radiotherapy (IOERT) offers an alternative method to deliver a boost with several advantages, such as direct visualization of the tumor bed, less inter- and intrafraction motion and a reduction in the number of medical appointments. The objective of our study is to assess chronic toxicity and long-term outcome for our patients after IOERT boost. Forty-six patients treated at our institution between July 2013 and June 2020 with IOERT boost during Breast-Conserving Surgery and consecutive whole breast irradiation were prospectively analyzed. A 10–12 Gy boost was prescribed to 42 patients and 4 patients received a 20 Gy boost. An analysis for overall survival, local relapse and distant progression was performed. Acute and chronic toxicity was assessed by CTCAE 4.0. The median age was 64.5 years (40–90). The median follow-up was 62 months (4–86). We had no local recurrences but 2 patients (4.3%) presented a distant recurrence. Mean pathological tumor size was 16 mm (6–52). 84.8% (39) of the patients had invasive ductal carcinoma. 52.2% (24) presented histological grade II. 52.2% (24) were Luminal A like, 21.7% (10) Luminal B like, 13% (6) HER2 positive, 13% (6) triple negative. No Grade 3–4 chronic toxicity was observed. Grade 1–2 fibrosis was evidenced in 13% (6) of the patients, 4.3% (2) patients presented fat necrosis, 6.5% (3) presented seroma, 4.3% (2) had localized pain, 2.2% (1) presented localized hematoma and 2.2% (1) presented localized edema. IOERT boost in breast cancer treatment during BCS is a safe option with low chronic toxicity. The recurrence rates are comparable to published data and emphasize that IOERT as boost is an effective treatment.

To determine whether brachytherapy with a single hypofractionated dose of 7 Gy provides the similar vaginal-cuff relapses and safety profile in terms of complications compared to schedules of 2 or 3 fractions of lower doses in patients treated previously with external beam irradiation in postoperative endometrial carcinoma. From June 2003 to December 2016, 325 patients were treated with 3 different schedules of high-dose-rate brachytherapy after external beam irradiation for postoperative endometrial carcinoma. The patients were divided into 3 groups: Group-1: 125 patients were treated with 3 fractions of 4–6 Gy per fraction (3 fractions/week) between 2003 and 2008; Group-2: 93 patients were treated with 2 consecutive daily fractions of 5–6 Gy between 2008 and 2011; Group-3: 107 patients received a single fraction of 7 Gy between 2011 and 2016. Bladder and rectum complications were assessed using RTOG scores and with the objective scores of LENT-SOMA for the vagina. Statistics: the chi-square test. The mean follow-up of Groups 1, 2 and 3 was 95, 67 and 51 months, respectively. Three patients in Group-1, 2 in Group-2, 1 in Group-3 developed vaginal-cuff relapse (p = 0.68). No differences were found in late toxicity among the three groups. One single dose of 7 Gy is safe and effective and may be the best treatment schedule with a similar incidence of vaginal-cuff relapses, complications and patient comfort with less hospital attendance.

Purpose To evaluate the preliminary results of the use of 68 Gy EQD2(α/β=3 Gy) as a dose limit to the lowest dose in the most exposed 2 cm3 of the vagina in order to reduce G2 late vaginal problems in postoperative endometrial carcinoma (EC). Methods From November 2016 to October 2019, 69 postoperative EC patients receiving vaginal brachytherapy (VBT) ± external beam radiotherapy (EBRT) were prospectively analyzed. The median EBRT dose was 45 Gy (range: 44–50.4 Gy), 1.8−2 Gy/day, 5 fractions(Fr)/week. VBT was administered with the following schedule: 1Fr of 7 Gy after EBRT and 2 daily Fr × 7.5 Gy in exclusive VBT. The dose was prescribed at 0.5 cm from the applicator surface with an active length of 2.5 cm; 56 patients were treated with vaginal cylinders (49–3.5 cm, 6–3 cm, and 1–2.5 cm) and 13 with the colpostat technique. The overall VBT dose was adjusted to meet the vaginal restriction of (α/β=3 Gy) at 2 cm3. Late toxicity was prospectively assessed using RTOG scores for bladder and rectum, and the objective LENT-SOMA criteria for vagina. Results With a median follow-up of 31.0 months, no vaginal-cuff recurrences were found. Late toxicity: only 1G1(1.4%) rectal toxicity; 21G1(30.4%) and 3G2(4.3%) vaginal complications. Only one (1.4%) of 3 G2 manifested as vaginal shortening. Conclusions In postoperative EC patients treated with VBT, only one developed G2 vaginal stenosis with the use of 68 Gy EQD2(α/β=3 Gy) as a dose constraint. These preliminary results seem to indicate the value of this dose limit for reducing G2 vaginal stenosis. Nonetheless, these findings should be confirmed in a larger number of patients with longer follow-up.

To evaluate the level of anaemia monitoring and to determine the prevalence of anaemia in patients with endometrial carcinoma (EC) undergoing postoperative pelvic radiotherapy (RT). We evaluated 233 consecutive patients diagnosed with EC receiving RT in our institution between January 2011 and December 2015. One hundred and fifty-two patients (65.2%) received a combination of external beam radiotherapy (EBRT) and high dose rate brachytherapy (HDR-BT) (mean dose 53.4 Gy, range 21–75), and 71 patients (30.5%) were exclusively treated with HDR-BT (mean dose 10.2 Gy, range 7–20). Blood test results with haemoglobin (Hb) levels were collected at three specific time points were: pre-RT (Hb1), during RT (Hb2) and post-RT (Hb3). Anaemia was defined as Hb

Although the chemotherapy-induced depletion of circulating white blood cells (WBC) is well recognized, the impact of exclusive radiotherapy (RT) on the different subpopulations of WBC remains unexplored. This may be important for immunotherapy administrated in combination with radiation, especially in malignant tumors usually treated with RT or chemoradiotherapy (CRT), and characterized by a high mutational burden, such as endometrial (EC) or cervical cancer (CC). We aimed to evaluate the impact of RT and CRT on circulating WBC in uterine cancers and its correlation with survival. A total of 202 consecutive patients with uterine cancers treated with RT or CRT between 2009 and 2016 in a large European center and with available basal and post-treatment blood tests were retrospectively evaluated. EC and CC patients were analyzed separately. The differences between pre- and post- treatment WBC mean values were evaluated independently in patients treated with CRT and exclusive RT. Two-sided T test for paired samples and Kaplan–Meier curves were applied for analysis (p value

To evaluate the effect of boost radiotherapy on ipsilateral breast tumor recurrence (IBTR) for ductal carcinoma in situ (DCIS) after breast-conserving surgery and whole breast radiotherapy (WBRT) with or without boost.Retrospective, multicentre study of 622 patients (624 tumors) diagnosed with pure DCIS from 1993-2011.Most tumors (377/624; 60.4%) received a boost. At a median follow-up of 8.8 years, IBTR occurred in 64 cases (10.3%). A higher percentage of patients with risk factors for IBTR received a boost (p 0.05). Boost was not associated with lower rates of IBTR than WBRT alone (HR 0.75, 95% CI 0.42-1.35). On the univariate analyses, IBTR was significantly associated with tumor size (11-20 mm, HR 2.32, 95% CI 1.27-4.24; and 20 mm, HR 2.10, 95% CI 1.14-3.88), re-excision (HR 1.76, 95% CI 1.04-2.96), and tamoxifen (HR 2.03, 95% CI 1.12-3.70). Boost dose 16 Gy had a protective effect (HR 0.39, 95% CI 0.187-0.824). Multivariate analyses confirmed the independent associations between IBTR and 11-20 mm (p = 0.02) and 20 mm (p = 0.009) tumours, and re-excision (p = 0.006). On the margin-stratified multivariate analysis, tamoxifen was a poor prognostic factor in the close/positive margin subgroup (HR 4.28 95% CI 1.23-14.88), while the highest boost dose ( 16 Gy) had a significant positive effect (HR 0.34, 95% CI 0.13-0.86) in the negative margin subgroup.Radiotherapy boost did not improve the risk of IBTR. Boost radiotherapy was more common in patients with high-risk disease. Tumor size and re-excision were significant independent prognostic factors.

Inflammatory biomarkers have recently attracted attention as valuable prognosticators and predictors of survival outcomes in many cancers. We describe a new pre-treatment biomarker, expressed as the eosinophil–lymphocytes ratio (ELR) and validate other biomarkers such as the level of circulating eosinophils, neutrophil–lymphocytes ratio (NLR), platelet–lymphocytes ratio (PLR) and systemic immune-inflammatory index (SII) as prognostic factors in cervical cancer (CC) patients. A retrospective cohort of 151 consecutive patients diagnosed with CC and treated according to the European guidelines with radiotherapy and/or chemotherapy and/or surgery in our institution from 2009 to 2016 were evaluated. Patients were categorized into two different groups based on the optimal cut-off for each biomarker, according to the receiver operating characteristic (ROC) curves. Impact of blood biomarkers on overall survival (OS), cancer-specific survival (CCS) and progression-free survival (PFS) were examined. Higher values of ELR, eosinophils and age ≥ 50 years were associated with better OS in univariate Cox analysis, while high NLR, PLR, SII, neutrophils ≥ 7.0, Bulky tumor and FIGO stage III–IV at diagnosis were prognosticators of worse survival outcomes. In multivariate analysis, the only factors independently impacting OS were ELR ≥ 0.07 (HR = 0.49, p = 0.048) and FIGO stage III–IV (HR = 2.5, p = 0.018). High PLR and SII were associated with shorter PFR. Increased values of ELR and eosinophils portend better OS in CC. To our best knowledge, this is the first report describing eosinophils-related biomarker as an independent prognostic factor in CC.

Objectives The aim of the study was to evaluate the clinical outcome and toxicity after adjuvant whole abdominal radiotherapy (WART) in patients with ovarian cancer. Material and methods Ten patients with optimal cytoreduced ovarian cancer, with a mean age of 58 years (40–70) and stage Ic: 4, stage II: 2, stage III: 4, were treated with WART and adjuvant chemotherapy (9/10). The total radiation dose was 22.5 Gy in the whole abdomen and 42–45 Gy in the pelvis. Results The mean follow-up was 8 years. The 5-year actuarial disease-free survival (DFS) was 60%, and the overall survival (OS) was 70%. Four patients had disease recurrence. The sites of recurrence were the abdomen in 2 patients and distant metastases in the other 2 patients (liver and brain metastasis). Gastrointestinal toxicity was as follows: acute 3/10 grades I and II, and late toxicity: 2/10 grades I and II, and only 1 patient developed small bowel obstruction (SBO) that required surgery. Conclusions Whole abdominal radiotherapy after surgery and platinum-based chemotherapy achieves high locoregional disease control with an acceptable risk of acute toxicity.

The concurrent use of erythropoietin beta (EPO) and radiotherapy in head and neck cancer patients has been reported by Henke et al (Lancet 2003; 362:1255–60) to correct anemia and impair cancer control. Due to the potential impact in daily clinical practice of this information a systematic critical review of the mentioned article was performed. Authors selected 10 arguments to question the contents regarding methodological and statistical aspects of the trial, and added 14 comments of controversy in more basic scientific concepts mentioned in the text as published. The panel including epidemiologist and radiation oncologists with expertise in clinical research concluded with 5 additional remarks recommending caution in interpretation of these results in terms of changes in daily practice of anemic patients support and advising not to use EPO at experimental doses or after reaching physiological concentrations of hemoglobin.

Purpose To analyze the frequency in determining pathologically proven metastatic involvement of internal mammary nodes (IMN) after sentinel lymph node (SLN) technique in breast cancer and to evaluate the implications for radiotherapy (RT) management of patients. Methods and materials Two hundred and twenty-five patients who underwent lymphatic mapping for early breast cancer treated with breast-conserving surgery and radiation (80%) or mastectomy (20%) were evaluated. There were two phases in the study: the validation phase (105 patients, 52 T1, 53 T2 ≤ 4 cm), and the application phase (120 patients, 70 T1, 50 T2 ≤ 2.5 cm). In the validation, if a drainage pathway to the IMN was identified, no biopsy was performed in this phase. In the application, if the study showed metastases in the IMNs, biopsy was performed. When histologically proven IMN metastases were detected, RT was included on the IMN chain planned with a 3D treatment system using conformal techniques. At the beginning of the study the injection site was subdermal and subsequently, the injection site was changed to peritumoral and intratumoral to search for IMN. Results In 31 patients of 225 (14%) hot spots were observed in the internal mammary chain (11.5% and 17.2% in the validation and application phases, respectively). In the validation phase, in 11 cases (11.5%) IMN drainage was observed, and in the application phase, in 20 cases (17.2%). Sampling of the internal mammary basin based on lymphoscintigraphy results was successful in 69% of the cases (14 of 20) and revealed metastatic involvement in 14% (2 of 14). This represents incidence of only 1.7% (2 of 116) in early breast cancer patients with SLN study in the application phase. In both cases the axillary SLN was also positive. Both patients with metastatic involvement of the IMN area received RT on the IMN chain next to the remaining breast after conservative surgery. Conclusions We can conclude that 14% of the patients with intraoperative drainage into the IMN surgical examination of the lymph nodes had pathologically positive metastases. The percentage in pathologically proven metastatic involvement of IMN after the SLN technique in early breast cancer is low, but it is not negligible. Moreover, it is expected to increase since the international recommendations have established a 3-cm cutoff for practicing the SLN technique. Although the real value of IMN irradiation in early breast cancer is not known, including this chain in postoperative radiotherapy is not recommended unless pathologically proven IMNs have been produced by the SLN technique. To avoid overdosage or underdosage in the joint between the medial tangential and IMN fields, an individualized 3D dosimetry study is mandatory to enhance dose distribution and reduce the heart volume to lessen side effects.

Objetivo Describir las caracteristicas de los pacientes incluidos en el registro de tumoraciones pancreaticas del Hospital Clinic de Barcelona. Pacientes y metodo Se ha incluido a todos los pacientes con tumoraciones pancreaticas atendidos desde julio de 1990 a marzo de 2003. Las variables recogidas fueron: edad, sexo, fecha de diagnostico, diagnostico fundamental, diagnostico histologico, tamano, localizacion y estadio del tumor, y tratamiento efectuado. Por otra parte, se ha evaluado la correlacion del estadio tumoral con la edad del paciente, la fecha de diagnostico y la localizacion de la tumoracion. Resultados Durante el periodo de estudio, se ha incluido a 630 pacientes con tumoraciones pancreaticas, lo que supone una incidencia de 60 pacientes/ano. La edad media fue de 66 anos y la relacion varon/mujer, de 1,18:1. Las lesiones malignas de pancreas fueron las mas frecuentes (92%), y el adenocarcinoma ductal pancreatico fue el tipo histologico mas comun (73%). La localizacion mas frecuente fue la cabeza pancreatica (64%). En el 28% de los pacientes el tumor se diagnostico en estadios I y II. El 31% de los pacientes fue resecado, mientras que el 48% no recibio ningun tipo de tratamiento. La relacion enfermedad localizada (estadio I)/diseminada (estadio IV) fue de 0,34. El cociente estadio I/IV aumento con la edad, el diagnostico anterior a 1994 y la localizacion en la cabeza pancreatica. ConclusiOn Los registros hospitalarios de tumores permiten establecer con precision el perfil de la poblacion atendida, lo que puede contribuir a delinear la mejor estrategia diagnostico-terapeutica y ser de utilidad en la investigacion clinica.

Carcinoembryonic antigen (CEA) and squamous cell carcinoma(SCC) serum levels were prospectively determined in 159 untreated patients diagnosed with carcinoma of the uterine cervix from 1991 to 2001. The histological analysis showed epidermoid cancer in 117 patients, adenocarcinoma in 26 patients, adenosquamous carcinoma in 12 patients and other histological types in the remaining 4 patients. Tumor marker sensitivity was related to the histological type with abnormal SCC (>2 ng/ml) in 51.3% of squamous tumors in contrast to the 7.1% found in other histologies. By contrast, CEA sensitivity was not related to histology with abnormal values (>5 ng/ml) in 25% of squamous tumors, 19% of adenocarcinomas, 33% of adenosquamous carcinomas and 25% of other histologies. CEA and SCC serum levels were clearly related to tumor stage, parametrial invasion, tumor size and nodal involvement. Elevated pretreatment CEA indicates parametrial invasion with a probability of 82%. Likewise, pretreatment CEA and SCC serum levels were of prognostic value, with a shorter disease-free survival and overall survival in patients with abnormal levels. All patients with adenocarcinomas and abnormal CEA had relapse during follow-up. Multivariate analysis indicated that parametrial invasion, age, tumor size and SCC were independent prognostic factors. In conclusion, CEA and SCC are useful tumor markers in carcinomas of the uterine cervix, with a clear relationship with well-known prognostic factors (parametrial invasion, nodal involvement), and are of prognostic value.

High-dose-rate brachytherapy (HDR-BT) is an accepted part of treatment for endometrial carcinoma and is usually performed in 1–2 fractions per week using different total doses and doses per fraction. To reduce the overall treatment time, HDR-BT was administered with a 3–4 days/week schedule. From June 2003 to December 2008, 164 patients with stage I-IIIc endometrial carcinoma were treated with HDR-BT (4–5 Gy per fraction). The patients were divided into two groups; Group 1 (40/164 patients) was treated with HDR-BT alone (6 fractions; 4 fractions/week) and Group 2 (124/164 patients) was treated with both (External Beam Radiotherapy [EBRT] + HDR-BT: 3 fractions/week). Complications were analyzed using RTOG scores for rectum and bladder and the objective scores of LENT-SOMA for vaginal complications. The mean followup was 48 months. In Group 1, 35 % of patients underwent treatment in ≤10 days and 65 % in >10 days. In Group 2, 53.2 % received treatment in ≤5 days and in 46.8 % in >5 days. Vaginal relapse was observed in only two patients (1.2 %), both having received adjuvant EBRT + HDR-BT. Acute vaginal toxicity appeared in 8.5 % and late vaginal toxicity in 20.7 % of patients with 13.4 % being G1, 6.7 % G2 and only 0.6 % being G4. No statistically significant differences were found in complications in either brachytherapy group regardless of the overall time. In our series, three fractions given in 3–5/days after EBRT or six fractions in 10 days, is a safe regimen in terms of complications and local control.

During the last 30 years many groups have carried out experiments and trials to develop new imaging and radiotherapy techniques in oncology, based on the use of synchrotron X-rays. There are several synchrotron biomedical stations around the world, which offer an excellent platform to improve either the imaging diagnosis or radiotherapy treatment for different tumour types. In the coming months the first radiotherapy clinical trials will be seen at the Biomedical Beamline at the ESRF synchrotron in Grenoble (France). In this article we highlight the results of some of the techniques and strategies that have been developed at different biomedical synchrotron stations.

Purpose: To analyze the therapeutic value of Cu/Zn-superoxide dismutase (SOD1) supplementation in an experimental model of radiation-induced intestinal inflammation and explore its mechanistic effects. Methods and Materials: Mice were subjected to abdominal irradiation with 10 Gy or sham irradiation and studied 24 or 72 hours after radiation. Groups of mice were treated with 0.1, 4, or 6 mg/kg/day of SOD1 or vehicle. Leukocyte-endothelial cell interactions in intestinal venules were assessed by intravital microscopy. Endothelial intercellular adhesion molecule-1 (ICAM-1) expression was determined with radiolabeled antibodies. Effects of SOD1 on histologic damage and levels of lipid hydroperoxides were also measured. Results: A significant increase in the flux of rolling leukocytes and number of firmly adherent leukocytes in intestinal venules was observed at 24 and 72 hours after irradiation. Treatment with SOD1 had no effect on leukocyte rolling but significantly and dose-dependently decreased firm leukocyte adhesion to intestinal venules. Treatment with SOD1 at doses that reduced leukocyte recruitment abrogated the increase in hydroperoxides in intestinal tissue and ICAM-1 upregulation in intestinal endothelial cells. The inflammatory score, but not a combined histology damage score, was also significantly reduced by SOD1. Conclusions: Treatment with SOD1 decreases oxidative stress and adhesion molecule upregulation in response to abdominal irradiation. This is associated with an attenuation of the radiation-induced intestinal inflammatory response. © 2005 Elsevier Inc.

occurred in 17.5% of cases. Median time to progression was 20.7 months (range 2-40.5). By Kaplan-Meier estimate, 3 year vaginal recurrence free survival (RFS) was 95%, pelvis RFS was 94%, distant metastasis free survival was 83.8% and both cancer-specific and overall survival (OS) were 83%. Of variables examined by univariate log-rank analysis, we found only lower stage to be significantly associated with better cancerspecific (90% vs 64%, pZ 0.038) and OS (83% vs 55%, pZ 0.03). Of the two patients observed who progressed, one had distant failure alone and the other presented with vaginal cuff recurrence with progression to omental involvement and positive ascites 10 months later despite salvage radiation and chemotherapy. The five adjuvantly treated patients who progressed had all received radiation alone without chemotherapy. Of these, pattern of failure was comprised of three with simultaneous locoregional (vaginal cuff or pelvic lymphadenopathy; although 3 lacked staging LND) and distant failures, one with vaginal failure with distant metastasis only 3 months later, and one with distant metastasis alone. All patients who progressed had distant failures (either during or after initial recurrence) and eventually died of disease. Distant sites included brain, pleural effusion, bone, positive ascites, inguinal nodes and supraclavicular lymph node. Conclusions: In our report of a large series for a rare cancer we found relatively high rates of distant metastasis despite early stage disease. Recurrences were uniformly fatal and worse outcomes were found in those with stage II disease. Based on patterns of failure, more aggressive systemic therapy may be warranted for those with higher stage disease. Author Disclosure: C.N. Chang-Halpenny: None. S. Natarajan: None. J.M. Hwang-Graziano: None.

To analyze the vaginal-cuff local control (VCC) and toxicity in postoperative endometrial carcinoma patients (EC) underwent high-dose-rate brachytherapy (HDR-BT) administered daily. 154 consecutive patients received postoperative HDR-BT for EC from January 2007 to September 2011. FIGO-staging I–IIIC2 patients were divided into two groups according to risk classification: Group 1 (94/154) included high-risk or advanced disease patients and Group 2 (60/154) included intermediate-risk EC patients. Group 1 underwent external beam irradiation (EBI) plus HDR-BT (2 fractions of 5 Gy) and Group 2 underwent HDR-BT alone (4 fractions of 5 Gy). Toxicity evaluation was done with RTOG scores for bladder and rectum, and the objective criteria of LENT–SOMA for vagina. With a median follow-up of 46.7 months (36.6–61 months) only two patients developed vaginal-cuff recurrence in Group 1 (2.1 %) and none in group 2 (0 %). Early toxicity in Group 1 appeared 5.3 % in rectum, 7.5 % in bladder (G1–G2) and 2.1 % in vagina (G1); late toxicity was present in 7.3 % in rectum (all G1–G2 but 1 G3) and in 27.7 % in vagina (all G1–G2 but one G4). In Group 2, 6.7 % developed acute G1–G2 bladder and 6.6 % acute vaginal (G1–G2) toxicity. No late rectal or bladder toxicity was observed; 21.7 % of G1–G2 presented late problems in vagina. The present HDR-BT schedule of 2 fractions of 5 Gy after EBI and 4 fractions of 5 Gy administered daily showed excellent results in terms of VCC and toxicity.