Search

The study aimed at examining the relationship among the school heads’ level of servant leadership, level of decision making and instructional leadership practices in elementary schools particularly in the City Schools Division of Cabuyao. Descriptive correlational research design was employed. The study revealed that the there was a significant relationship between the school heads’ level of servant leadership skill and their level of decision-making skill, school heads’ level of servant leadership skill and their instructional leadership practices and school heads’ level of decision-making skill and their instructional leadership practices. Correlations indicated that the higher the level of servant leadership skill of school heads, the higher is their level of decision-making skill, the higher the level of servant leadership skill of school heads, the more they confirm their instructional leadership practices, and the higher the level of decision making skill of school heads, the more they confirm their instructional leadership practices. In essence, the results yield substantial implications to school heads’ leadership and decision making. Similarly, an understanding of the relationship among the school heads’ level of servant leadership skill, level of decision making skill and instructional leadership practices helps the

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

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 85% of agreement would be discussed during the meeting to reach consensus.The results of the survey are reported here. The mean number of patients treated per centre in 2017 was 52 ± 41 (range 7-175), and the mean number of procedures per centre was 175 ± 150 (range 24-701).There was consensus on: the indications, applicator type, the OAR to be considered, the prescription point, standardisation and dosimetric quality parameters. There was no consensus on: patient preparation for the implant, the need for performing CT simulation and the frequency, the length of the vagina to be treated, if CTV should be delimited, the definition of the clinical target volume, fractionation, overall EQD2, active source length, separation between dwelling stepping source positions, if considering the uniformity/maximum values for dwelling stepping sources, the optimization mode, and the limiting doses to the OAR. After presenting the results of the survey, the consensus meeting discussion focused on the issues for which there was no consensus.A consensus document on postoperative VCBT of the Spanish Brachytherapy Groups of SEOR-SEFM was elaborated.

Objetivo: Valorar el significado pronóstico del nadir de PSA (nPSA) y del tiempo a nadir en el periodo libre de enfermedad (PLE) del carcinoma de próstata localizado tratado con radioterapia radical (RTR). Material y métodos: Desde Octubre 1984 hasta Diciembre 1998 se han tratado 86 (p) con el diagnóstico de carcinoma de próstata. Se consideró de Bajo riesgo aquellos pacientes con PSA 5 10 ng/ml, Gleason 5 6 y estadios TI-T2. Riesgo Moderado: aquellos con uno de los tres parámetros elevados. Riesgo Alto: dos o más parámetros elevados. El tratamiento se realizó en un acelerador lineal con fotones de 15MV, con técnicas de tratamiento y fraccionamiento estándar, administrando una mediana de dosis de 66Gy (58-75Gy). Se consideró en el período libre de enfermedad (PLE), tanto el fallo clínico como bioquímico, este último se definió a partir de la fecha del nadir como el ascenso del PSA en tres mediciones consecutivas separadas entre ellas por un tiempo no menor de un mes. Resultados: La mediana de PSA inicial fue de 16 ng/ml (1-270), estadio clínico inicial TI-T2 (70p), estadio T3-T4 (14p), y desconocido en 2p. La mediana de Gleason fue de 6 (2-10). Según el grupo de riesgo se clasificaron como: Bajo en 16 pacientes (19%), Moderado en 22 pacientes (26%), Alto en 21 pacientes (24%), desconocido en 27 pacientes (31%) .La mediana de nPSA fue 0,8 ng/ml (límites: 0-139) y la mediana de tiempo transcurrido entre el PSA inicial y nPSA ha sido de 11 meses (límites: 0-72 meses). El PLE actuarial proyectado a cinco años en aquellos pacientes con nPSA 5 1 ng/ml fue de 67% vs. 47% en pacientes con cifras de nPSA > 1 ng/ml (p= 0,0018). El PLE a 5 años en pacientes con tiempo a nadir (t nadir) < 12 meses fue de 20% vs. 80% de los pacientes con t nadir > 12 meses (p

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.

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.

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.

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.

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.

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.

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

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.

In this work, pore texture characteristics of a series of Ce(IV) or Zr(IV) montmorillonite phosphate cross-linked compounds obtained by precipitation of cerium or zirconium phosphate with dilute H3PO4 on the micelles of an aqueous montmorillonite suspension, previously submitted to ion-exchange processes to replace its exchange ions with Ce(IV) or Zr(IV), are studied. Surface areas and pore volumes of the different materials prepared are determined by N2 adsorption at 77 K and mercury porosimetry techniques. Analysis of the N2 adsorption isotherms by the t-De Boer and Dubinin-Radushkevich methods, revealed the presence of a certain degree of microporosity in all the materials studied. Moreover, analysis of the Hg intrusion data permitted to determine the contribution of the macro- and mesopores to the total surface area and pore volume of the prepared compounds. The results reveal a greater specific surface area for these compounds than for montmorillonite and the evolution of this parameter with thermal treatment is related to the nature and content of phosphate in the different samples. However, the changes recorded in the Vp and S/Vp parameters during the thermal process suggest that surface diffusion is the dominant transport mechanism in the sintering process.

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.

The nucleotide exchange process is one of the key activation steps regulating the ras protein. This report describes the development of potent, non-nucleotide, small organic inhibitors of the ras nucleotide exchange process. These inhibitors bind to the ras protein in a previously unidentified binding pocket, without displacing bound nucleotide. This report also describes the development and use of mass spectrometry, NMR spectroscopy and molecular modeling techniques to elucidate the structure of a drug-protein complex, and aid in designing new ras inhibitor targets.

In the past year, the three-dimensional structures of two serine/threonine phosphatases, protein phosphatase-1 and protein phosphatase-2b (calcineurin), have been determined. The new information puts previous sequence comparisons and mutagenesis studies into a detailed structural perspective. The active-site structure and catalytic mechanism appear to be common to a variety of phosphoesterase enzymes.

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.

Resonance Raman (RR) spectra are reported for the ternary complex of Escherichia coli thymidylate synthase with the cofactor 5,10-methylenetetrahydrofolate (CH2-H4-folate) and the inhibitor 5-fluoro-2'-deoxyuridylate, excited at 337 or 356 nm, in resonance with perturbed absorption bands of the p-aminobenzoylglutamate (PABA-Glu) portion of the cofactor. For comparison, RR spectra were obtained with 260 nm excitation for PABA-Glu in various solvents, and for CH2H4-folate and H4-folate in aqueous solution. These reference spectra are assigned to modes of PABA-Glu in its benzenoid form. The ternary complex RR spectra are very different, however, and are assigned, with the aid of isotopic data, to the PABA-Glu in a predominantly quinoid form. Similar spectra were obtained for the ternary complexes of the E58Q and K48Q mutants, indicating that neither Glu58 nor Lys48 are essential for maintaining the quinoid structure, even though their side chains complement the dipolar charge distribution of the quinoid form of PABA-Glu. Since these are the only charged residues in the PABA-Glu vicinity, electrostatic stabilization is not essential to maintenance of the quinoid structure. It is proposed that quinoid formation results from steric forces, probably resulting from the protein conformation change known to accompany cofactor binding, which enforce coplanarity of the PABA-Glu ring and substituents. This stereoelectronic change activates the cofactor by opening the methylene bridge. A second RR spectrum of the ternary complex, previously proposed to reflect an alternate structure, is shown to result instead from irreversible formation of a laser-induced photoproduct.

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.

In this article we detail some questions related to managing the treatment of mobile tumors, that is, those tumors that shift with respiratory movements, integrating movement into the plan of treatment. This fact complicates the administration of high doses of radiotherapy since, in such cases, the radiation margin must be wider than that required by the tumor itself, representing a greater risk to surrounding healthy tissue. However, the new technologies offer an alternative in these cases, such as tracking and respiratory gating in radiotherapy (RT), that is, the synchronization of treatment with respiratory movement. In gating we capture the tumor and other organs at risk at a specific moment in the breathing cycle, while in tracking we trace the tumor and the organs at risk throughout the breathing cycle. It is therefore essential to obtain good images and to correlate them with each phase of the breathing cycle. The tumors with which these strategies have been most employed are those of the lung, breast and lymphomas, and less frequently with some abdominal tumors such as pancreas, liver and prostate.

Brachytherapy consists in the administration of radiation in intimate contact with the tumour, with a low exposure of neighbouring healthy tissues. Its use began in the early XX century and it has developed since then: different radioisotopes, systems of remote treatment, computer programs making individual dose calculation possible. In recent years there have been changes affecting two aspects of brachytherapy. In the first place, the incorporation of imaging techniques such as echography, computerised tomography (CT) and magnetic resonance (MR), indispensable for diagnosis and tumoural staging. Their use when the implant is being done helps in guiding and carrying out the operation with greater precision. In the second place, the use of CT, MR and echography makes better coverage of the tumour possible, or reduces the dose to healthy organs. They are used in inverse planning systems, which carry out dose calculation on the basis of the doses to be administered to the tumour and healthy organs. In these planning programs it is possible to make calculations more rapidly, taking account of the placement of the source at each moment in time. This technique, called real-time planning, is starting to show advantages in the treatment of prostate cancer. Incorporation of imaging techniques and improvements in calculation systems mean that brachytherapy is currently playing an important role in treating cancer of the prostate, cervix, breast, head and neck tumours, bronchial tubes or oesophagus.

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.