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Purpose: This study aimed to evaluate patient- and treatment-related risk factors for late persistent fatigue within the prospective, multicenter EMBRACE-I study.Methods and Materials: Fatigue was prospectively assessed (Common Terminology Criteria for Adverse Events, version 3) at baseline and during regular follow up in 993 patients with locally advanced cervical cancer after treatment with chemoradio-therapy and magnetic resonance imaging-guided brachytherapy. Risk factors for baseline and late persistent fatigue were evaluated with multivariable logistic regression. Late persistent fatigue was defined when either grade >= 1 or >= 2 was scored in at least half of the follow ups.Results: The median follow-up time was 57 months. Baseline fatigue grade >= 1/>= 2 (35.8%/6.3%, respectively) was associated with preexisting comorbidities, World Health Organization performance status, being underweight, severe pain, and tumor volume. Late persistent grade >= 1/>= 2 fatigue (36.3%/5.8%, respectively) was associated with patient-related factors (baseline fatigue, younger age, obesity) along with the size of irradiated volumes and the level of radiation doses from external beam radiation therapy (EBRT) and brachytherapy (EBRT: V43Gy, V57Gy; EBRT + brachytherapy: V60Gy equivalent dose in 2-Gy fractions). Large-volume lymph node (LN) boost increased the risk for late persistent fatigue grade >= 2 by 18% and 5% in patients with and without baseline fatigue, respectively, compared with no LN boost. The risk for late persistent fatigue grade >= 1 increased by 7% and 4% with V43Gy 3000 cm(3) in patients with and without baseline fatigue, respectively. Late persistent grade >= 1 fatigue occurred in 13% of patients without late persistent organ-related symptoms (gastrointestinal, genitourinary, and vaginal) versus 34% to 43%, 50% to 58%, and 73% in patients suffering from persistent symptoms involving 1, 2, or 3 organs, respectively.Conclusions: Late persistent fatigue occurs in a considerable number of patients after chemoradiotherapy, and is associated with patient-related factors, the size of volumes irradiated to intermediate and high EBRT and brachytherapy doses, and other persistent organ-related morbidity. These findings support the importance of ongoing efforts to better tailor the target dose and reduce irradiation of healthy tissue without compromising target coverage, using highly conformal EBRT and brachytherapy techniques. (C) 2021 Elsevier Inc. All rights reserved.

Purpose: To evaluate patient-reported sexual outcomes after chemoradiation therapy and image-guided adaptive brachytherapy for locally advanced cervical cancer in the observational, prospective, multicenter EMBRACE-I study. Methods and Materials: Sexual outcomes were assessed prospectively with the European Organization for Research and Treatment of Cancer Qualify of Life Questionnaire (EORTC-QLQ-CX24) at baseline and follow-up. Crude incidence and prevalence rates of sexual activity, vaginal functioning problems (dryness, shortening, tightening, pain during intercourse), and sexual enjoyment were evaluated. Associations between pain during intercourse and vaginal functioning problems or sexual enjoyment were calculated, pooling observations over all follow-ups (Spearman correlation coefficient). In patients who were frequently sexually active (≥50% of follow-ups), the effects of regular hormonal replacement therapy (HRT) on vaginal functioning problems were evaluated (Pearson χ 2). Results: The analysis involved 1045 patients with a median follow-up of 50 months. Sexual activity was reported by 22% of patients at baseline and by 40% to 47% of patients during follow-up (prevalence rates). Vaginal functioning problems in follow-up were dryness (18%-21%), shortening (15%-22%), tightening (16%-22%), pain during intercourse (9%-21%), and compromised enjoyment (37%-47%). Pain during intercourse was significantly associated with vaginal tightening (r = 0.544), shortening (r = 0.532), and dryness (r = 0.408) and negatively correlated with sexual enjoyment (r = –0.407). Regular HRT was associated with significantly less vaginal dryness (P = .015), shortening (P = .024), pain during intercourse (P = .003), and borderline higher sexual enjoyment (P = .062). Conclusions: Vaginal functioning problems are associated with pain and compromised sexual enjoyment. Further effort is required for the primary prevention of vaginal morbidity with dose optimization and adaptation. Secondary prevention strategies, including HRT for vaginal and sexual health after radiation therapy in locally advanced cervical cancer, should be considered and sexual rehabilitation programs should be developed further.

Purpose: This report describes the persistence of late substantial treatment-related patient-reported symptoms (LAPERS) in the multi-institutional EMBRACE study on magnetic resonance image guided adaptive brachytherapy in locally advanced cervical cancer (LACC).Methods and Materials: Patient-reported symptoms (European Organization for Research and Treatment of Cancer [EORTC]-C30/CX24) and physician-assessed morbidity (Common Terminology Criteria for Adverse Events [CTCAE], version 3.0) were assessed at baseline and regular timepoints during follow-up. Patients with sufficient EORTC follow-up (baseline and >= 3 late follow-up visits) were analyzed. LAPERS events were defined as the presence of substantial EORTC symptoms (quite a bit/very much) for at least half of the assessments (persistence) and progression beyond baseline condition (treatment-related). For each EORTC symptom, the ratio between LAPERS rates and crude incidence rates of substantial symptoms was calculated to represent the proportion of symptomatic patients with persisting symptoms. For 9 symptoms with a corresponding EORTC/CTCAE assessment, the overlap of LAPERS and severe morbidity events (grades 3-5) was evaluated.Results: Of 1047 patients with EORTC available, 741 had sufficient follow-up for the LAPERS analyses. The median follow-up was 59 months (interquartile range, 42-70 months). Across all symptoms, the proportion of patients with LAPERS events (LAPERS rates) was in median 4.6% (range, 0.0% vaginal bleeding to 20.4% tiredness). Urinary frequency, neuropathy, fatigue, insomnia, and menopausal symptoms revealed LAPERS rates of >10%. Vomiting, blood in stool, urinary pain/burning, and abnormal vaginal bleeding displayed LAPERS rates of

On October 5, 2018, a meeting of the Spanish Society of Radiation Oncology (SEOR) Brachytherapy Group was held, in collaboration with the Spanish Society of Medical Physics (SEFM), with the aim of preparing a consensus document on postoperative vaginal-cuff brachytherapy (VCBT). A survey including 42 questions was sent to Spanish Radiation Oncology Centres before the meeting. The survey items included: experience in VCBT, technique indications, previous patient preparation, applicator type, implant procedure, computerized tomography (CT) simulation, definition of target volumes and organs at risk (OAR), dose prescription, fractionation, treatment planning, dosimetric parameters and constraints to OAR. Thirty-three centres answered the survey. Statistical analysis of the survey considered that there was consensus when there was ≥ 85% of agreement related to a survey item, otherwise an item with

Background: The concept of the use of MRI for image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer was introduced 20 years ago. Here, we report on EMBRACE-I, which aimed to evaluate local tumour control and morbidity after chemoradiotherapy and MRI-based IGABT. Methods: EMBRACE-I was a prospective, observational, multicentre cohort study. Data from patients from 24 centres in Europe, Asia, and North America were prospectively collected. The inclusion criteria were patients older than 18 years, with biopsy-proven squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, The International Federation of Gynecology and Obstetrics (FIGO) stage IB–IVA disease or FIGO stage IVB disease restricted to paraaortic lymph metastasis below the L1–L2 interspace, suitable for curative treatment. Treatment consisted of chemoradiotherapy (weekly intravenous cisplatin 40 mg/m2, 5–6 cycles, 1 day per cycle, plus 45–50 Gy external-beam radiotherapy delivered in 1·8–2 Gy fractions) followed by MRI-based IGABT. The MRI-based IGABT target volume definition and dose reporting was according to Groupe Européen de Curiethérapie European Society for Radiation Oncology recommendations. IGABT dose prescription was open according to institutional practice. Local control and late morbidity were selected as primary endpoints in all patients available for analysis. The study was registered with ClinicalTrials.gov, NCT00920920. Findings: Patient accrual began on July 30, 2008, and closed on Dec 29, 2015. A total of 1416 patients were registered in the database. After exclusion for not meeting patient selection criteria before treatment, being registered but not entered in the database, meeting the exclusion criteria, and being falsely excluded, data from 1341 patients were available for analysis of disease and data from 1251 patients were available for assessment of morbidity outcome. MRI-based IGABT including dose optimisation was done in 1317 (98·2%) of 1341 patients. Median high-risk clinical target volume was 28 cm3 (IQR 20–40) and median minimal dose to 90% of the clinical target volume (D90%) was 90 Gy (IQR 85–94) equi-effective dose in 2 Gy per fraction. At a median follow-up of 51 months (IQR 20–64), actuarial overall 5-year local control was 92% (95% CI 90–93). Actuarial cumulative 5-year incidence of grade 3–5 morbidity was 6·8% (95% CI 5·4–8·6) for genitourinary events, 8·5% (6·9–10·6) for gastrointestinal events, 5·7% (4·3–7·6) for vaginal events, and 3·2% (2·2–4·5) for fistulae. Interpretation: Chemoradiotherapy and MRI-based IGABT result in effective and stable long-term local control across all stages of locally advanced cervical cancer, with a limited severe morbidity per organ. These results represent a positive breakthrough in the treatment of locally advanced cervical cancer, which might be used as a benchmark for clinical practice and all future studies. Funding: Medical University of Vienna, Aarhus University Hospital, Elekta AB, and Varian Medical Systems.

Objective: Multiple treatment options are used in early local-stage cervical cancer, including combinations of surgery with neoadjuvant/adjuvant radiotherapy and chemotherapy. Our aim was to determine the outcome for definitive chemoradiation with image guided brachytherapy (IGBT). Methods: FIGO1994 staging system was used in our study. We included 123 patients with stage IB cervical cancer, treated at 12 centers with external beam radiotherapy (EBRT) ± Chemotherapy and IGBT. Three- and 5-year actuarial local control (LC), pelvic control (PC), overall survival (OS), cancer-specific survival (CSS) and late morbidity (CTCAE v 3.0) were computed. Results: Median age was 48 (23–82) years. FIGO1994 stage distribution was: IB1 68% and IB2 32%; 41% of the entire cohort had nodal metastases and 73% squamous-cell carcinoma. MRI-based tumor size was >40 mm in 63%. Median EBRT dose was 45 (40–50) Gy; 84% received chemotherapy. At IGBT, mean CTV-HR D90 was 93 ± 17 Gy (EQD210). D2cc for bladder was 76 ± 14 Gy, rectum 66 ± 11 Gy, sigmoid 66 ± 10 Gy, bowel 67 ± 7 Gy (EQD23). At 43-months median follow-up, 9% of patients had systemic, 6% paraaortic, 3% pelvic-nodal and 2% local failure. Five-year LC was 98%, PC 96%, CSS 90%, OS 83%. Intestinal G3-–4 morbidity was 8%, urinary 7% and vaginal 0%. Conclusions: Chemoradiation with IGBT for FIGO1994 stage IB cervical cancer leads to excellent loco-regional control with limited morbidity. In IB node-negative disease, it can be regarded equivalent to surgery in terms of oncologic outcome. In tumors with unfavorable pre-treatment characteristics, chemoradiation is the first choice to avoid combining surgery with adjuvant therapy.

Introduction/Background To evaluate sexual frequency and vaginal functioning in patients treated with combined external beam radiotherapy ± chemotherapy and image-guided adaptive brachytherapy in the prospective, observational, multi-center EMBRACE study (www.embracestudy.dk). Methodology Patient-reported sexual outcomes were prospectively assessed according to EORTC-QLQ-CX24 questionnaires at baseline (available for 1027 patients) and follow-ups: 1st year every 3M (months), 2nd/3rd year every 6M and yearly thereafter (available for 1044 patients with no evidence of disease). Sexual activity was analysed longitudinally, and defined as frequent if reported (to some degree) in ≥50% of follow-up and as occasional if reported in Results After the diagnosis of cancer, 230/1027 (22.4%) of patients reported some degree of sexual activity. During follow-up (median 36M), 433/1044 (41.5%) patients reported no sexual activity, 128 (12.3%) occasional and 483 (46.3%) frequent sexual activity. Prevalence rates (figure 1A–F) revealed a slow increase of sexual activity during the 1st year of follow-up, reaching a plateau up to 5 years. Vaginal functioning problems during intercourse showed a substantial increase after treatment and remained either elevated or showed signs of slight improvement over time. Sexual enjoyment was impaired, with 37–48% of patients reporting to have ‘not at all’/‘a little’ sexual enjoyment over time. Patient-reported vaginal dryness, shortening and tightening were significantly correlated with dyspareunia to r=0.407, 0.539, 0.552, respectively (figure 2A–C). Conclusion More than half of locally advanced cervical cancer patients are sexually active and the majority of those report frequent sexual activity. Treatment-induced vaginal changes (dryness, shortening and tightening) are associated with dyspareunia. Sexual enjoyment is compromised in almost half of sexually active patients. This underlines the importance of efforts directed towards prevention of vaginal morbidity and sexual rehabilitation after treatment. Disclosure The findings of this abstract were submitted to ESTRO (European Society for Radiotherapy & Oncology, accepted for oral presentation in April 2019, Milano, Italy) and ASTRO (American Society for Radiation Oncology, accepted for oral presentation in September 2019, Chicago, USA). All authors declare no conflict of interest. The EMBRACE study was sponsored by the Medical University of Vienna. Unrestricted research funding was provided by Nucletron, an Elekta company and Varian Medical Systems. Financial support by the Austrian Federal Ministry of Science, Research and Economy, and the Austrian Foundation for Research, Technology, and Development, the Danish Cancer Society and CIRRO - The Lundbeck Foundation Center for Investigational Research in Radiation Oncology is gratefully acknowledged.

Introduction/Background The aim of this study is to review our initial results in the treatment with surgery and Intraoperative Brachytherapy (HDR-IOBT) in advanced or recurrence gynecologic cancer. Methodology We included two patient groups: Group 1: advanced cervical cancer with poor response to Radiation and chemotherapy; group 2: pelvic recurrence of gynecological tumors of any origin. In all CT and MRI was performed, in recurrences also PET. The surgical procedure depended on the extent of disease with pelvic exenteration, enlarged cystectomy and/or rectal resection. Surgical specimen was confirmed in all cases with intraoperative biopsy to ensure the absence of macroscopic residual disease. We put clips in the surgical bed. Subsequently the applicator Fleipbrup was placed according to the extension of the bed. After intraoperative planning, a dose of 10 Gy prescribed at 0.5 cm bed depth was administered. Finally, the applicator was removed to complete the surgery. Results Between October 2011 and December 2018, 29 patients have been included. In group 1, there were 14 patients with cervical cancer stage IIB in 9 p and IIIB in 6; in group 2 were 15 recurrences. With a median follow-up of 35 months, the Local DFS 3 years was 59.3% Group 1: 74.5%; Group 2: 41.34%; 3 years Overall Survival 63.3%: Group 1: 70.3%, Group 2: 54%. The complications were fistula 5p (17.2%): 1 intestinal, 4 bladder, sigmoid stenosis 2p (6.8%), osteitis pubis in 1p (3.4%). Ureteral stenosis 5p (17.1%). Conclusion HDR-IOBT associated with pelvic exenteration offers good results of pelvic control and overall survival in patients with gynecologic cancer with a poor prognosis. However the number of complications, especially fistulas has been important, so we must take it into account for prevention. These results are possible thanks to the multidisciplinary approach to these patients. Disclosure Nothing to disclose.

Objectives To present a nomogram for prediction of overall survival (OS) in locally advanced cervical cancer patients (LACC) undergoing definitive radiochemotherapy including image guided adaptive brachytherapy (IGABT). Methods We retrospectively reviewed 720 patients with LACC acrrued onto the RetroEMBRACE database (12 international institutions). All patients were treated with External Beam Radiotherapy (EBRT) concurrent with Chemotherapy (CHT) and MRI/CT-guided brachytherapy. Missing data (7.2%) were imputed by multiple imputations and predictive mean matching. Stepwise selection of predictive factors with the Akaike information criterion (AIC) was used to obtain a predictive model and construct a nomogram for OS predictions 60 months from diagnosis. The model was internally validated by concordance probability as a measure of discrimination and a calibration plot (both corrected for optimism using bootstrap cross-validation). Results Through the predictive model (AIC), seven factors were selected to develop the nomogram: FIGO stage (2B vs.1A,1B,2A; 3A,3B,4A,4B vs.1A,1B,2A), age, corpus involvement, lymph node status, concurrent chemotherapy given, overall treatment time, volume of the high risk clinical target volume at the time of first brachytherapy (CTVHR). CTVHR is considered surrogate for response at concurrent EBRT+CHT. This OS nomogram had a satisfactory calibration and useful discrimination (concordance probability c=0.74). Conclusions Prognostic factors were used to develop the first nomogram for 5-year OS in patients with LACC in the setting of IGABT treatment. Response to concurrent EBRT and CHT (CTVHR) seems to be a new essential outcome predictor for OS. These nomograms can be used to better estimate individual and collective outcomes and may facilitate personalized patient counselling during the treatment.

Purpose Image guided adaptive brachytherapy (IGABT) for cervical cancer improves pelvic control and survival across all stages. Improvement in pelvic control is larger in advanced stages, but improvement in survival is similar across stages. This paper analyzes the patterns of failure in the RetroEMBRACE cohort to investigate this discrepancy. Methods and Materials 731 patients from 12 institutions treated with chemoradiation therapy and magnetic resonance imaging or computed tomography–based IGABT were evaluated. The pattern of failure at time of first relapse was analyzed. Results Three hundred twenty-five failures (single and synchronous) occurred in 222 of 731 patients (30%). Among the 325 failures, 9% were local and 6% regional. Pelvic (local or regional) failures made up 13%, paraaortic node (PAN) 9%, systemic 21%, and distant (systemic + PAN) 24%. Of the 222 patients with treatment failure, 21% had pelvic failure alone, 57% had distant failure alone, and 23% had both pelvic and distant failure. Of all failures that occurred, 40% to 50% occurred in the first year, with a further 20% to 30% occurring in the second year. Although local, regional, and PAN failure tended to plateau after year 3, systemic failure continued to occur up to year 10. Conclusions Implementation of IGABT has changed the patterns of relapse after chemoradiation therapy for cervical cancer. The predominant failure after IGABT is systemic, whereas the predominant failure with conventional brachytherapy is pelvic. Effective treatments to eradicate micrometastases in PAN and distant organs are needed in addition to IGABT and chemoradiation therapy to maximize local, regional, PAN, and systemic control and improve survival.

INTRODUCTION: The clinical course in patients with prostate cancer (PCa) after biochemical failure (BF) has received limited attention. This study analyzes survival time from recurrence, patterns of progression, and the efficacy of salvage therapies in patients treated with radical or postoperative radiotherapy (RT). METHODS: This is a multicenter retrospective comparative study of 1135 patients diagnosed with BF and treated with either radical (882) or postoperative (253) RT. Data correspond to the RECAP database. Clinical, tumor, and therapeutic characteristics were collected. Descriptive statistics, survival estimates, and comparisons of survival rates were calculated. RESULTS: Time to BF from initial treatment (RT or surgery) was higher in irradiated patients (51 vs 37months). At a median follow-up of 102months (14-254), the 8-year cause-specific survival (CSS) was 80.5%, without significant differences between the radical (80.1%) and postoperative (83.4%) RT groups. The 8-year metastasis-free survival rate was 57%. 173 patients (15%) died of PCa and 29 (2.5%) of a second cancer. No salvage therapy was given in 15% of pts. Only 5.5% of pts who underwent radical RT had local salvage treatment and 71% received androgen deprivation (AD)±chemotherapy. The worst outcomes were in patients who developed metastases after BF (302pts; 26.5%) and in cases with a Gleason>7. CONCLUSIONS: In PCa treated with radiotherapy, median survival after BF is relatively long. In this sample, no differences in survival rates at 8-years have been found, regardless of the time of radiotherapy administered. AD was the most common treatment after BF. Metastases and high Gleason score are adverse variables. To our knowledge, this is the first study to compare outcomes after BF among patients treated with primary RT vs. those treated with postoperative RT and to evaluate recurrence patterns, treatments administered, and causes of death. The results allow avoiding overtreatment, improving quality of life, without negatively affecting survival.

PurposeTo retrospectively assess outcomes and to identify prognostic factors in patients diagnosed with intermediate-risk (IR) prostate cancer (PCa) treated with primary external beam radiotherapy (EBRT).Materials and methodsData were obtained from the multi-institutional Spanish RECAP database, a population-based prostate cancer registry in Spain. All IR patients (NCCN criteria) who underwent primary EBRT were included. The following variables were assessed: age; prostate-specific antigen (PSA); Gleason score; clinical T stage; percentage of positive biopsy cores (PPBC); androgen deprivation therapy (ADT); and radiotherapy dose. The patients were stratified into one of three risk subcategories: (1) favourable IR (FIR; GS 6,T2b or GS 3+4,T1c), (2) marginal IR (MIR; GS 3+4, T2a-b), and (3) unfavourable IR (UIR; GS 4+3 or T2c). Biochemical relapse-free survival (BRFS), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) were assessed.ResultsA total of 1754 patients from the RECAP database were included and stratified by risk group: FIR, n=781 (44.5%); MIR, n=252 (14.4%); and UIR, n=721 (41.1%). Mean age was 71years (range 47-86). Mean PSA was 10.4ng/ml (range 6-20). The median radiotherapy dose was 74Gy, with mean doses of 72.5Gy (FIR), 73.4Gy (MIR), and 72.8Gy (UIR). Most patients (88%) received ADT for a median of 7.1months. By risk group (FIR, MIR, UIR), ADT rates were, respectively, 88.9, 86.5, and 86.9%. Only patients with24months of follow-up post-EBRT were included in the survival analysis (n=1294). At a median follow-up of 52months (range 24-173), respective 5- and 10-year outcomes were: OS 93.6% and 79%; BRFS 88.9% and 71.4%; DFS 96.1% and 89%; CSS 98.9% and 94.6%. Complication rates (grade 3) were: acute genitourinary (GU) 2%; late GU 1%; acute gastrointestinal (GI) 2%; late GI 1%. There was no significant association between risk group and BRFS or OS. However, patients with favourable-risk disease had significantly better 5- and 10-year DFS than patients with UIR: 98.7% vs. 92.4% and 92% vs. 85.8% (p=0.0005). CSS was significantly higher (p=0.0057) in the FIR group at 5 (99.7% vs. 97.3%) and 10 years (96.1% vs. 93.4%). On the multivariate analyses, the following were significant predictors of survival: ADT (BRFS and DFS); dose74Gy (BRFS); age (OS).ConclusionsThis is the first nationwide study in Spain to report long-term outcomes of patients with intermediate-risk PCa treated with EBRT. Survival outcomes were good, with a low incidence of both acute and late toxicity. Patients with unfavourable risk characteristics had significantly lower 5- and 10-year disease-free survival rates. ADT and radiotherapy dose74Gy were both significant predictors of treatment outcomes.

PurposeImage guided brachytherapy (IGBT) for locally advanced cervical cancer allows dose escalation to the high-risk clinical target volume (HRCTV) while sparing organs at risk (OAR). This is the first comprehensive report on clinical outcome in a large multi-institutional cohort.Patients and methodsFrom twelve centres 731 patients, treated with definitive EBRT ± concurrent chemotherapy followed by IGBT, were analysed. Kaplan–Meier estimates at 3/5 years were calculated for local control (LC, primary endpoint), pelvic control (PC), overall survival (OS), cancer specific survival (CSS). In 610 patients, G3–4 late toxicity (CTCAEv3.0) was reported.ResultsMedian follow up was 43 months, percent of patients per FIGO stage IA/IB/IIA 22.8%, IIB 50.4%, IIIA–IVB 26.8%. 84.8% had squamous cell carcinomas; 40.5% lymph node involvement. Mean EBRT dose was 46 ± 2.5 Gy; 77.4% received concurrent chemotherapy. Mean D90 HRCTV was 87 ± 15 Gy (EQD210), mean D2cc was: bladder 81 ± 22 Gy, rectum 64 ± 9 Gy, sigmoid 66 ± 10 Gy and bowel 64 ± 9 Gy (all EQD23). The 3/5-year actuarial LC, PC, CSS, OS were 91%/89%, 87%/84%, 79%/73%, 74%/65%. Actuarial LC at 3/5 years for IB, IIB, IIIB was 98%/98%, 93%/91%, 79%/75%. Actuarial PC at 3/5 years for IB, IIB, IIIB was 96%/96%, 89%/87%, 73%/67%. Actuarial 5-year G3–G5 morbidity was 5%, 7%, 5% for bladder, gastrointestinal tract, vagina.ConclusionIGBT combined with radio-chemotherapy leads to excellent LC (91%), PC (87%), OS (74%), CSS (79%) with limited severe morbidity.

Objective The aim of the study is to assess the safety and efficacy of transperitoneal laparoscopic para-aortic and pelvic lymphadenectomy in the setting of surgical staging of patients with locally advanced cervical cancer (LACC), and to analyse the prognostic value and impact of this staging on the survival prognosis of this condition. Study Design Data from 67 patients with LACC who underwent transperitoneal laparoscopic para-aortic and pelvic lymphadenectomy and who received chemo-radiation therapy were retrospectively analysed. Results Metastatic lymph nodes (LN) were identified in 32 patients (47.7%), 20 (29.8%) had metastatic LN in the pelvic area and 12 (17.9%) had metastatic LN in the pelvic and para-aortic area. There were no skip metastases in the para-aortic area. After a median follow-up of 54.6 months (5–122.2 months), the 5-year local control and disease-free survival (DFS) rates for the whole group were 91.1% and 60.5% respectively. The five-year DFS for patients without LN metastasis was 86.4%, while for patients with pelvic LN metastases or pelvic and para-aortic metastases was 34.2% and 24.2% respectively (p The five-year overall survival (OS) for the whole group was 67.3%. The mortality rate in patients with para-aortic nodal metastases was increased compared to patients with negative nodes (5-year OS 21.3% vs 81.6% respectively, p = 0.005), but the OS rate was similar in patients with negative nodes and those with only pelvic nodes affected (5-year OS 81.6% vs 70.8% respectively, p = 0.380). This approach allowed the modification of the initial treatment plan in the para-aortic area in 13.4% of patients and in the pelvic area in 28.3%. The overall intraoperative morbidity rate was 5.9%, while the postoperative morbidity rate was 10.4%, with only 3 patients presenting grade 3 morbidity. Conclusions Transperitoneal para-aortic and pelvic lymphadenectomy provides precise information about nodal state and allows personalized treatment planning in patients with LACC, avoiding false negative (FN) and false positive (FP) imaging results. In 17.9% of patients, the external beam radiotherapy (EBRT) field had to include the aortic area, whilst 47.7% received pelvic boost to the involved nodes.

Purpose To report the disease-free Grade ≥3 complication-free survival of a Phase II protocol of reirradiation with high-dose-rate (HDR) interstitial brachytherapy (ITB) in previously irradiated gynecologic cancer. Methods and Materials Fifteen patients with previously irradiated cervical (n = 6), endometrial (n = 6), and vulvovaginal tumors (n = 3) were treated with HDR-ITB alone to a median dose of 38 Gy in 8 b.i.d. fractions over 4 consecutive days. Prior treatments included surgery (n = 12; 80%), external irradiation (n = 15; 100%), and brachytherapy (n = 9; 60%). Average clinical target volume Size was 60.9 cc (range, 14.8–165.3 cc), and median time to reirradiation was 3.9 years (range, 0.4–22.7 years). Results With a median followup of 2.8 years (range, 1.2–9.2 years), 3 patients (20.0%) developed Grade ≥3 toxicity consisting of Grade 3 intestinal obstruction (n = 1), Grade 4 rectovesical fistula (n = 1), and Grade 5 intestinal obstruction (n = 1). Six patients remain alive and without evidence of disease at last followup. Two patients are alive with disease progression, and 7 patients have died, 4 of them from disease progression and 3 from other causes. The 2-year disease-free Grade ≥3 complication-free survival was 40%. Conclusions HDR-ITB alone is a reasonable salvage treatment option in a significant number of patients with previously irradiated gynecologic tumors.

In the present study we compared three different Stereotactic body radiation therapy (SBRT) treatment delivery techniques in terms of treatment time (TT) and their relation with intrafraction variation (IFV). Besides that, we analyzed if different clinical factors could have an influence on IFV. Finally, we appreciated the soundness of our margins. Forty-five patients undergoing SBRT for stage I lung cancer or lung metastases up to 5 cm were included in the study. All underwent 4DCT scan to create an internal target volume (ITV) and a 5 mm margin was added to establish the planning target volume (PTV). Cone-beam CTs (CBCTs) were acquired before and after each treatment to quantify the IFV. Three different treatment delivery techniques were employed: fixed fields (FF), dynamically collimated arcs (AA) or a combination of both (FA). We studied if TT was different among these modalities of SBRT and whether TT and IFV were correlated. Clinical data related to patients and tumors were recorded as potential influential factors over the IFV. A total of 52 lesions and 147 fractions were analyzed. Mean IFV for x-, y- and z-axis were 1 ± 1.16 mm, 1.29 ± 1.38 mm and 1.17 ± 1.08 mm, respectively. Displacements were encompassed by the 5 mm margin in 96.1 % of fractions. TT was significantly longer in FF therapy (24.76 ± 5.4 min), when compared with AA (15.30 ± 3.68 min) or FA (17.79 ± 3.52 min) (p

There are few studies on the effect on quality of life (QL) of cancer-related illness and treatment in elderly patients. The aim of this work was to evaluate prospectively QL in a sample of elderly patients with stages I.III breast cancer who started radiotherapy treatment and compare their QL with that of a sample of younger patients.Forty-eight patients,or = 65 years of age completed the European Organization for Research and Treatment of Cancer (EORTC) QL questionnaires QLQ-C30 and QLQ-BR23, and the Interview for Deterioration in Daily Living Activities in Dementia (IDDD) daily activities scale three times throughout treatment and follow-up periods. Clinical and demographic data were also recorded. Fifty patients ages 40-64 years with the same disease stage and treatment modality had previously completed the QL questionnaires. QL scores, changes in them among the three assessments, differences between groups based on clinical factors, and differences between the two samples were calculated.QL scoring was good and stable (70/100 points) in most areas, in line with clinical data. Light and moderate limitations occurred in global QL and some emotional, sexual, and treatment-related areas. Moderate decreases (10-20) appeared in some toxicity-related areas, which recovered during the follow-up period. Breast-conservation and sentinel-node patients presented higher scores in emotional areas. There were few QL differences among agebased samples.QL and clinical data indicate radiotherapy was well tolerated. Age should not be the only factor evaluated when deciding upon treatment for breast cancer patients.

SUMMARY ABSTRACT The purpose of this study was to achieve locoregional control of locally advanced laryngeal carcinoma, survival, and organ preservation using split hyperfractionated accelerated radiation therapy and cisplatin concomitantly. This study was a phase II trial of chemoradiotherapy with split hyperfractionated accelerated radiation therapy, 1.6 Gy per fraction given twice per day to a total dose of 64 to 67.2 Gy for a total of 6 weeks with a 2-week gap, and cisplatin 20 mg/m2, days 1 to 5, in continuous perfusion, concomitantly. Seventy-three patients were treated (stage IV, 64%). At a median follow-up of 55 months for living patients, median survival was 44 months, and 5-year overall survival and disease-free survival were 42% and 39%, respectively. Toxicities included mucositis (grade III, 40%; grade IV, 28%), epithelitis (grade III, 28%). Of the 73 patients, 32 (44%) have continued with their larynx free of disease. Split hyperfractionated accelerated radiation therapy and concomitant cisplatin has been demonstrated to be an active treatment for locally advanced laryngeal carcinomas, but more active combinations of chemotherapy and radiotherapy, without increase of toxicity, are necessary to increase the rate of locoregional control, organ preservation, and survival.

Simultaneous chemoradiation is used in unresectable pancreatic cancer for palliation. It is not known if the use of adjuvant surgery will benefit this group of patients. From November 1991 to September 1998, 47 patients with unresectable pancreatic cancer were treated with simultaneous preoperative radiation therapy (45 Gy) and chemotherapy. Chemotherapy followed three different protocols: cisplatin, 5-fluorouracil +/- paclitaxel; cisplatin, 5-fluorouracil (protracted infusion); and docetaxel and gemcitabine. Whipple pancreatoduodenectomy was performed 1 month after the end of radiation in patients selected for resection. Twenty-three unresectable tumors after preoperative treatment (47%) received an additional dose (10-12 Gy) of radiotherapy using intraoperative or external radiation therapy. Twelve patients (26%) were considered to have clinically resectable tumors after the preoperative treatment. Nine patients had surgery (19% of the total number of patients), and 2 of them had complete pathologic response. After chemoradiation, two patients died of pneumonia and gastrointestinal bleeding, respectively, and another two patients died in the postoperative period. Local recurrence was observed in 22% of the patients and 57% had distant metastases. Three-year survival rates for patients with unresectable and resectable tumors was 0% (median survival 10 months) and 48% (median survival 23 months), respectively (p = 0.0004). Preoperative treatment with chemotherapy and radiotherapy in patients with unresectable pancreatic cancer is feasible. In some patients, the tumor can be resected, and in addition some cases of complete pathologic response were found. Long-term survivors were observed in the group of resected tumors. More effective chemotherapy regimens are needed because the majority of the patients died of metastatic disease.

PURPOSE: Thymidylate synthase (TS) is an important target enzyme for the fluoropyrimidines. TS gene promoter possesses regulatory tandemly repeated (TR) sequences that are polymorphic in humans, depending on ethnic factors. These polymorphisms have been reported to influence TS expression. TS expression levels affect tumor downstaging after preoperative fluoruracil (5-FU)–based chemoradiation. Tumor downstaging correlates with improved local control and disease-free survival. The aim of this study is to correlate TR polymorphisms with downstaging and disease-free survival. PATIENTS AND METHODS: Sixty-five patients with rectal cancer underwent tumor resection after preoperative 5-FU–based chemoradiation. Tumor downstaging was evaluated by comparing the pretreatment T stage with the pathologic stage observed in the surgical specimen. TS polymorphism genotype was determined by polymerase chain reaction amplification of the corresponding TS promoter region, and products of amplification were electrophoresed, obtaining products of 220 bp (2/2), 248 bp (3/3), or both (2/3). The TS polymorphism genotype results were subsequently compared with the downstaging observed and with disease-free survival. RESULTS: Patients who were homozygous for triple TR (3/3) had a lower probability of downstaging than patients who were homozygous with double TR or heterozygous patients (2/2 and 2/3): 22% versus 60% (P = .036; logistic regression). Furthermore, a trend toward improved 3-year disease-free survival was detected in the 2/2 and 2/3 groups, compared with that in the 3/3 group (81% v 41%; P = .17). CONCLUSION: This preliminary study suggests that TS repetitive-sequence polymorphisms are predictive for tumor downstaging. TR sequences in TS promoter may be useful as a novel means of predicting response to preoperative 5-FU–based chemoradiation.

BACKGROUND Chemoradiotherapy is becoming an alternative to radical cystectomy among patients with bladder carcinoma invading muscle. In 1988, the authors began a protocol with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC regimen) and radiotherapy for these patients. Traditionally, age has been considered a determinant factor thereby excluding the older patients from the oncologic protocols that are considered to be more aggressive. The authors analyzed 20 patients (age > 70 years) who were treated during this period with the same protocol as the authors' other patients. METHODS The study included 20 patients (age range, 70-78 years; median age, 74 years) including 4 patients with T2 disease, 9 with T3 disease, and 7 with T4 disease. All patients had a Karnofsky performance status of > 60. Treatment protocol included cytoreductive transurethral resection, 2 cycles of M-VAC chemotherapy, and radiotherapy (45 grays [Gy] on pelvic volume) with concurrent cisplatin (20 mg/m2 on Days 1-5. Response was determined by cystoscopic evaluation. If there was a complete response, radiotherapy continued until a total dose of 65 Gy; if there was not a complete response, cystectomy was performed. RESULTS Tumor response after a dose of 45 Gy included 11 complete responses (55%), 5 partial responses (25%), and 4 nonresponses (20%). Overall survival was 75%, 34%, and 27% in the 2nd, 3rd, and 5th years of follow-up, respectively. Cause specific survival was 79%, 54%, and 38%, respectively. Survival for patients with complete response was 100%, 60%, and 48%, respectively. Severe toxicity was uncommon, with the most frequent toxicities being leukopenia and cystitis. No treatment-related death occurred with either treatment protocol. CONCLUSIONS The age of the individual must not become a strict exclusion criterion for the radical treatment of old patients with invasive bladder carcinoma. Cancer 1997; 80:115-20. © 1997 American Cancer Society.

Purpose : The feasibility and activity of an intensive chemoradiotherapeutic scheme for patients with locally advanced squamous cells head and neck cancers were tested in a single institution Phase II pilot study. Methods and materials : Between January 1990 and February 1992, 40 patients were entered into this trial. The treatment protocol consisted of split hyperfractionated accelerated radiation therapy (SHART), 1.6 Gy per fraction given twice per day to a total dose of 64–67.2 Gy for a total of 6 weeks with a 2-week gap, and cisplatin (20 mg/sqm/Days 1 to 5, in continuous perfusion) concomitantly. Results : All of the 40 patients were evaluable for response and survival. Toxicity was significant, but tolerable. A complete tumor response to this treatment was acheived by 37 patients (92.5%). With a minimal follow-up of 22 months (median 30 months) there have been 16 local relapses and 19 patients have died, 2 without tumor. The projected 2- and 3-year overall survival rates are 64% (confidence interval (CI) 95%, 49–79%) and 47%, respectively. The 2-year local control probability has been 56% (CI 95%, 39–73%). Conclusion : This treatment obtains a high rate of complete responses with increased acute toxicity but tolerable late effects. Preliminary results are encouraging for laryngeal neoplasms. A longer follow-up is needed to evaluate the impact of this treatment on patient survival.

Objective To compare the biologic equivalence in terms of local control and toxicity of a short course of high-dose-rate intravaginal brachytherapy alone (IVBa) delivered over five consecutive days (25 Gy/5 Rx/5 days) to other more protracted classical schemes 21 Gy/3 Rx/14–28 days (Postoperative Radiation Therapy in Endometrial Carcinoma [PORTEC]-2/Memorial Sloan-Kettering Cancer Center). Methods and Materials From February 2001 to May 2008, 122 patients with International Federation of Gynecology and Obstetrics Stage IaG3–IIIaG2 endometrial adenocarcinoma were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by postoperative IVBa. Seventy-seven patients (63.1%) underwent surgical staging. Total IVBa dose was 25 Gy in five consecutive daily fractions prescribed at 0.5-cm depth. Results After a median followup of 4.1 years, the rates of Radiation Therapy Oncology Group Grades 1, 2, and ≥3 complications were 12.9%, 3.4%, and 0.8%, respectively. Five patients (4.1%) presented locoregional failures: two isolated nodal pelvic failures, one vaginal pelvic relapse (intra-abdominal lymph node metastases), one vaginal distant failure, and one combined locoregional and distant failure. The 8.5-year actuarial vaginal control rate was 97.5%, and the pelvic control rate was 94.3%. Six other patients developed distant metastases alone. The 8.5-year actuarial overall and disease-free survival rates were 90.3% and 87.2%, respectively. Univariate analysis revealed that histologic grade, deep myometrial invasion, advanced age, and categorization as high intermediate–risk patient according to the PORTEC-2 and the Gynecologic Oncology Group (GOG)-99 stratifications were statistically significant prognostic factors. After multivariate analysis, histologic grade ( p = 0.001) and high intermediate risk according to GOG-99 ( p = 0.004) and PORTEC-2 ( p = 0.001) remained significant. Conclusions The proposed scheme reproduces the excellent results obtained with more protracted schemes and has the added advantage of shortened overall treatment time.

Gastric carcinoma is the second most common cancer in the world. Adenocarcinoma of the stomach has a rate of incidence of 21% in men and 9% in women in Navarra and represents the fifth most common. The incidence of gastric cancer has decreased during the last decades. Although the causes of this decline are unknown, adenocarcinoma of the stomach appears to be related to the environment factors. Several specific patiens conditions appear to be associated with an increased risk of gastric cancer: age, socio-economic status and the weight loss. Multiple factors associated with the tumor include histologic type, tumor invasion of the gastric wall, lymph nodes involvement, tumor markers (CEA; Ca 19.9...), biologic factors as gen p53 mutations, the urokynase-type plasminogen activator system and the angiogenesis. Another prognostic factors have been correlated with the type treatment: total or subtotal gastrectomy, the extent of lymphadenectomy or the adjuvant treatment with chemoradiation. Although the majority of patients are diagnosed at a locally advanced or metastasis disease, the identification of prognostic factors has attracted particular interest to select different treatment modalities in an attempt to increase tumor response and survival.

In the last years they observed an increased of malignant melanoma incidence. This and the new techniques in treatment and diagnosis- the sentinel node biopsy and the new protocols of inmunotherapy- have made to increase the factor prognosis importance. In this study they do a revision of literature that had established the valour prognostic of the different factors; moreover they are denoting the staging change that are promoted by the prognosis factors knowledge.

The detection and quantification of circulating tumour markers can provide useful information that contributes to establishing the diagnosis, the stage and the prognosis of specific tumours. Its fundamental role continues to be that of monitoring the evolution of the disease and evaluating the efficacy of treatment. On very limited occasions, the determination of a tumour marker can direct therapeutic conduct.

En el presente trabajo, se detallan algunas cuestiones relacionadas con el manejo del tratamiento con radioterapia de los tumores móviles, es decir, aquellos que se desplazan con los movimientos respiratorios, integrando el movimiento en el plan de tratamiento. Este hecho complica la administración de dosis altas de radioterapia ya que, en estos casos, el margen de radiación debe ser más amplio de lo que el tumor en sí exige, suponiendo un mayor riesgo para el tejido sano circundante. Sin embargo, las nuevas tecnologías ofrecen una alternativa en estos casos, como son el traking y el gating respiratorio en radioterapia (RT), es decir, la sincronización del tratamiento con el movimiento respiratorio. En el gating capturamos el tumor y demás órganos de riesgo en un momento determinado del ciclo respiratorio, mientras que en el traking realizamos un «rastreo» del tumor y de los órganos de riesgo a lo largo del ciclo respiratorio, siendo entonces fundamental contar con una buena adquisición de imágenes y una correlación de las mismas con cada fase del ciclo respiratorio. Los tumores en los que más se han utilizado estas estrategias son los de pulmón, mama y linfomas y con menos frecuencia en algunos abdominales como páncreas, hígado y próstata.

La radioterapia guiada por imagen (RTGI) es un concepto que engloba la manera más moderna de administrar el tratamiento radioterápico El objetivo es maximizar la dosis depositada en el volumen a tratar (target), minimizando la dosis en los órganos sanos. Esto no sería posible sin el continuo desarrollo tecnológico y de los software, sobre todo en las siguientes áreas: registrar imágenes deformables, replanificar nuevos tratamientos, imagen en tiempo real y cálculo de dosis acumulada. El impacto clínico es evidente, pero poco se habla del impacto en la reorganización de los servicios de Oncología Radioterápica. La RTGI supone un entrenamiento de todo el equipo involucrado, con un periodo de aprendizaje y puesta en marcha. Con la experiencia adquirida, el tiempo dedicado a cada paciente (en todas las etapas de su tratamiento: simulación, planificación, puesta en marcha, sistemas de verificación de posicionamiento, correcciones on-line, off-line, replanificación, controles clínicos periódicos), es muy superior al que se precisa en la radioterapia convencional, motivo por el que aparecen nuevas responsabilidades y roles. Image guided radiotherapy (IGR) is a concept that encompasses the most modern way of administering radiotherapy treatment. The aim is to maximise the dose deposited in the target volume, minimising the dose in healthy organs. This would not be possible without the continuous development of technology and software, above all in the following areas: deformable image registration, replanning new treatments, real time image and calculation of accumulated dose. While the clinical impact is evident, little is said about the impact on the reorganisation of the Radiotherapy Oncology services. IGR supposes training all team members involved, with a training and a starting period. With the experience acquired, the time dedicated to each patient (in all stages of treatment: simulation, planning, starting out, systems for verifying position, on-line, off-line corrections, replanning, periodic clinical controls) is far higher than that required in conventional radiotherapy, which gives rise to new responsibilities and roles.

La braquiterapia consiste en la administración de radiación en contacto íntimo con el tumor, con una baja exposición de los tejidos sanos circundantes. Empezó a utilizarse a comienzos del siglo XX y desde entonces ha ido desarrollándose: diferentes radioisótopos, sistemas de tratamiento a distancia, programas informáticos que permiten un cálculo individualizado de la dosis. Los cambios en los últimos años dentro de la braquiterapia han afectado a dos aspectos. En primer lugar, la incorporación de las técnicas de imagen como la ecografía, la tomografía computarizada (TC) y la resonancia magnética (RM), imprescindibles para el diagnóstico y la estadificación tumoral. Su utilización mientras se realiza el implante ayuda a guiarlo y realizarlo con mayor precisión. En segundo lugar, la utilización de TC, RM y ecografía permiten mejorar la cobertura del tumor o reducir la dosis a los órganos sanos. Se utilizan dentro de sistemas de planificación inversa, que realizan el cálculo de dosis a partir de las recomendaciones de las dosis a administrar al tumor y a los órganos sanos. En estos programas de planificación es posible hacer los cálculos con mucha rapidez, teniendo en cuenta la colocación en cada momento de la fuente. Esta técnica, llamada planificación en tiempo real, empieza a mostrar ventajas en el tratamiento de los cánceres de próstata. La incorporación de las técnicas de imagen y las mejoras en los sistemas de cálculo han hecho que en la actualidad la braquiterapia juegue un papel importante en el tratamiento del cáncer de próstata, cérvix, mama, tumores de cabeza y cuello, bronquio o esófago.

Replacement of methionine (Met) residues by selenomethionine (SeMet) was recently shown to facilitate the crystallographic analysis of protein structure through the application of multi-wavelength anomalous diffraction techniques [Yang et al. (1990) Science (Washington, D.C.) 249, 1398-1405]. The availability of SeMet-containing proteins provides an excellent opportunity to evaluate the effects of the complete replacement of Met by SeMet. We chose to compare the properties of selenomethionyl thymidylate synthase isolated from Escherichia coli DL41 (a methionine auxotroph) and wild-type (wt) enzyme obtained from E. coli Rue10. An improved purification procedure for thymidylate synthase was developed which permitted the isolation of 25 mg of pure protein from 2 g of E. coli in 90% yield in no more than 8 h. The pure wt and SeMet enzymes exhibited specific activities 40% higher than published values. Thermal stability studies at 30 degrees C in degassed buffer showed that the SeMet enzyme (t1/2 67 h) was 8-fold less stable than wt enzyme (t1/2 557 h). The half-lives for the latter enzymes in nondegassed buffers at 30 degrees C were decreased by 2-fold, thus indicating the sensitivity of the enzyme to dissolved oxygen. Both enzymes exhibited essentially the same kinetic and binding properties, including Km(dUMP) (1.2 x 10(-6) M), specificity constant (1.6 x 10(6) s-1 M-1), and Kd for 5-fluorodeoxyuridylate binding (1.2 nM) in covalent inhibitory ternary complexes. In addition, X-ray crystallographic analysis by difference Fourier synthesis showed there was no significant difference in conformation between the SeMet enzyme and the wt enzyme.

Objective To evaluate the feasibility and intermediate-term results of a short course of high-dose-rate (HDR) intravaginal brachytherapy only after hysterectomy. Methods and materials From December 1999 to February 2005, 50 patients with International federation of gynecology and obstetrics Stages IA–IIB endometrioid endometrial adenocarcinoma were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by postoperative HDR brachytherapy alone. The mean age of the patients was 62.6 years (range 42–86). International federation of gynecology and obstetrics patient grouping included IaG3N x ( n = 1), IbG1N 0 ( n = 1), IbG1N x ( n = 2), IbG2N 0 ( n = 10), IbG2N x ( n = 20), IbG3N 0 ( n = 3), IbG3N x ( n = 1), IcG1N x ( n = 2), IcG2N 0 ( n = 3), IcG3N 0 ( n = 3), IIaG1N x ( n = 2), IIaG2N x ( n = 1), and IIbG1N 0 ( n = 1). Twenty-one patients (42.0%) had been surgically staged. Four to 16 weeks after surgery (median 42 d, range 28–112), all patients received HDR intravaginal brachytherapy to 25 Gy in five consecutive 5-Gy daily fractions prescribed at 0.5-cm depth. Median HDR brachytherapy treatment duration was 5 days (range 5–12). Results After a median followup of 37 months (range 12–80), the overall survival and disease-free survival were 96%. No vaginal or pelvic recurrences have been observed. One patient (2%) developed distant metastases. No late toxicities of Grade 3 or greater have been reported. Conclusions The results reported in this study are in agreement with previous reports of postoperative HDR brachytherapy alone in early-stage endometrial cancer. HDR brachytherapy alone seems to provide adequate tumor control. The fractionation schedule proposed (25 Gy in five consecutive daily treatments) was well tolerated and is convenient for patients living far from the radiation center.

Purpose To determine the long-term results of a Phase II trial of perioperative high-dose-rate brachytherapy (PHDRB) in primary advanced or recurrent gynecological cancer. Methods and Materials Fifty patients with locally advanced and recurrent gynecological cancer suitable for salvage surgery were included. Unirradiated patients (n = 25) received preoperative chemoradiation followed by surgery and PHDRB (16–24 Gy). Previously irradiated patients (n = 25) received surgery and PHDRB alone (32–40 Gy). Results Median followup was 11.5 years. Eight unirradiated patients (32%) developed Grade ≥3 toxic events including two fatal events. Local and locoregional control rates at 16 years were 87.3% and 78.9%, respectively. Sixteen-year disease-free and overall survival rates were 42.9% and 46.4%, respectively. Ten previously irradiated patients (40.0%) developed Grade ≥3 adverse events, including four fatal events. Local and locoregional control rates at 14 years were 59.6% and 42.6%, respectively. Fourteen-year disease-free and overall survival rates were 16.0% and 19.2%, respectively. Conclusions PHDRB allows effective salvage of a subset of unfavorable gynecological tumors with high-risk surgical margins. Toxicity was unacceptable at the initial dose levels but deescalation resulted in the absence of severe toxicity without a negative impact on locoregional control. A substantial percentage of patients remain alive and controlled at >10 years including a few previously irradiated cases with positive margins.

La alta incidencia de metástasis óseas secundarias a carcinomas y la grave repercusión funcional que provocan, son motivos de constante estudio y avance en los métodos de evaluación, diagnóstico y tratamiento. El dolor es el síntoma más frecuente de presentación, aunque a veces el comienzo es una fractura patológica. Las pruebas clásicas de detección y valoración de extensión en la enfermedad metastásica, la radiología simple y la gammagrafía, se complementan en la actualidad con otras como la tomografía computarizada (TC) y la resonancia magnética (RM), mejorando la información sobre las características de la lesión tanto dentro como fuera del hueso. Por otra parte la tomografía por emisión de positrones (PET) está mostrando una sensibilidad muy superior a la gammagrafía y se perfila como la prueba de futuro para la detección precoz de metástasis y de tumores primarios de curso silente. Las posibilidades de tratamiento de las metástasis óseas se basan en el empleo de los regeneradores óseos, la radioterapia y la cirugía. Los dos primeros tienen su indicación en las lesiones ya detectadas en la radiología, sintomáticas o no, si no existe riesgo previsible de fractura. La cirugía tiene su indicación en situaciones de pobre o nula respuesta a estos tratamientos, cuando el riesgo de fractura es alto o ya se ha producido una fractura patológica. Antes de cualquier planificación terapéutica se debe realizar una valoración minuciosa del paciente, tanto a nivel local (tamaño, localización, extensión de la metástasis) como general (tipo de tumor primario, fase de tratamiento y respuesta, supervivencia estimada).

La disfagia es uno de los síntomas más frecuentes en los pacientes con tumores de cabeza y cuello, y esófago. Éste puede ser el síntoma inicial o, más frecuentemente, relacionado con el tratamiento oncológico. Se revisan los aspectos fisiopatológicos y terapéuticos más importantes de la disfagia aguda de causa oncológica. La deglución es un proceso complejo en el que intervienen numerosas estructuras músculo-esqueléticas bajo el control neurológico de diversos pares craneales. La compleja coordinación neuromuscular necesaria para una correcta deglución puede verse afectada por numerosas situaciones tanto por efecto de los tumores como de su tratamiento, fundamentalmente la cirugía o la radioterapia. En conclusión, se puede afirmar que para un adecuado tratamiento de la disfagia oncológica, es preciso una correcta evaluación inicial y un tratamiento activo, ya que del control de la disfagia, depende no sólo la calidad de vida del paciente, sino en numerosas ocasiones la posibilidad de continuar el tratamiento y por tanto de mantener las posibilidades de curación.

En el presente trabajo se revisan los síndromes de la vena cava superior malignos, sus manifestaciones clínicas, relacionadas con las características anatómicas del compartimento por donde discurre la vena cava superior, los requerimientos diagnósticos para abordar el tratamiento en las mejores condiciones y el conjunto de medidas que deben adoptarse para su manejo.

Los pacientes afectos de enfermedades neoplásicas consultan a menudo en los servicios de urgencias de nuestros hospitales. Buena parte de esas consultas ocurren por complicaciones de tipo urológico, sea cual sea el origen del tumor que presenta el paciente. La patología puede ser secundaria a la neoplasia o a los medios utilizados para tratarla, aunque muchas veces son complicaciones que aparecen independientemente del curso de su enfermedad. Pretendemos dar unas pinceladas acerca de las causas de consulta urgente por problemas urológicos más frecuentes en el paciente afecto de enfermedades neoplásicas, ya sean del aparato urogenital o no. Comentaremos sobre todo el estudio y tratamiento iniciales por parte del médico de urgencias o del oncólogo.