Angeles Rovirosa

GRANULOCYTE MACROPHAGE-COLONY-STIMULATING FACTOR MOUTHWASHES HEAL ORAL ULCERS DURING HEAD AND NECK RADIOTHERAPY

PURPOSE To evaluate the effectiveness of granulocyte macrophage-colony-stimulating factor GM-CSF mouthwashes in the epithelization of radiation-induced oral mucosal ulceration, control of pain, and weight loss. METHODS AND MATERIALS Twelve patients received curative radiotherapy for head and neck carcinoma. All had oropharyngeal and/or oral mucosa irradiation, with a median dose of 72 Gy (range 50-74), with conventional fractionation. A total of 300 microg of GM-CSF in 250 cc of water for 1 h of mouthwashing was prescribed. The procedure started once oral ulceration in the irradiation field was detected. Patients, examined twice a week, were evaluated for oral ulceration, pain, and weight loss. Blood tests were taken weekly during GM-CSF administration. A comparison was carried out with 12 retrospective case-matched controls. RESULTS In the GM-CSF group, mucosa ulcerations healed in 9 of 12 (75%) of the patients during the course of the radiotherapy. Fifty percent of the patients said they felt less pain during the GM-CSF treatment; 30% needed morphine. The mean and median weight loss as a percentage of baseline weight in addition to the actual weight were 4.2% and 3%, respectively (variation ranged between a gain of 1% and a loss of 13%). No GM-CSF-related side effects were found. In the case control group, in the 12 cases, oral ulcerations increased during radiotherapy and two patients needed intubation intake and hospital admission, as opposed to the GM-CSF group. The mean and median percentage of weight loss were 5.8% and 5%, respectively. Sixty percent of patients needed morphine, as opposed to 30% in the GM-CSF group. CONCLUSIONS Granulocyte macrophage-colony-stimulating factor was effective in curing mucosal ulcerations during the course of radiotherapy. This is the first time we have seen a drug with this capacity. Although the GM-CSF seems to be effective in the control of pain, oral intake, and weight loss, we need further studies with a greater number of patients to confirm our premise. Double-blind trials are necessary for future research into the control of pain and weight loss.

Is vascular and lymphatic space invasion a main prognostic factor in uterine neoplasms with a sarcomatous component? A retrospective study of prognostic factors of 60 patients stratified by stages

BACKGROUND Sarcomatous neoplasms of the uterine corpus are still a challenge in terms of obtaining prognostic factors and the most optimum complementary treatment to surgery. The most important prognostic factor is stage; relapses usually appear during the first 2 years, and most patients die within the first 3 years. We have performed a multivariate study of prognostic factors, stratifying patients by stage, to determine their impact on overall survival, disease-free survival, local relapse-free survival, and distant metastasis-free survival. Special emphasis has been given to vascular and lymphatic space invasion (VLSI). METHODS Sixty patients diagnosed with uterine neoplasms with a main sarcomatous component were treated at Hospital Clínic i Universitari of Barcelona between January 1975 and June 1999. Pathologic type: 32 carcinosarcomas, 14 leiomyosarcomas, 9 adenosarcomas, and 5 endometrial stromal sarcomas. TREATMENT 58/60 surgery, 35/60 postoperative radiotherapy, 2/60 exclusive chemotherapy, and 3/60 complementary chemotherapy. FIGO stages: 43 Stage I, 4 Stage II, 11 Stage III, and 2 Stage IV. Variables analyzed: age, stage, vascular and lymphatic space invasion, myometrial invasion, mitotic index, tumor size, unicentricity/multicentricity, necrosis, and radiotherapy. STATISTICS the S and Cox proportional risk models. The partial effect of each risk factor was calculated by hazard ratio (HR) with a confidence interval of 95%. RESULTS Early stages: Multivariate analysis showed that tumor size larger than 8 cm and VLSI had an impact on overall survival (HR = 4.01 and HR = 24.45, respectively). VLSI was present in 23% of the cases. Myometrial invasion greater than 50% had an impact on disease-free survival and local relapse-free survival (HR was 9.75 and 3.20, respectively). VLSI had an impact on distant metastasis-free survival (HR = 2.92). Advanced stages: VLSI was present in 89% of the cases. Only leiomyosarcoma type made the overall survival worse (HR = 10.54). CONCLUSIONS Vascular and lymphatic space invasion was a relevant prognostic factor in our series, with an impact on overall survival and distant metastasis-free survival in early stages. In advanced stages, VLSI had no impact on survival, but was present in 89% of cases. Myometrial invasion >50% had an impact on local relapse. Advanced stages had a more aggressive behavior, and there was a higher incidence of poor prognostic factors in these stages. Nevertheless, prospective studies are still needed on prognostic factors and on the best treatment option.

Acoustic analysis after radiotherapy in T1 vocal cord carcinoma: a new approach to the analysis of voice quality

PURPOSE The study of acoustic voice parameters (fundamental frequency, jitter, shimmer, and harmonics-to-noise ratio) in extended vowel production, oral reading of a standard paragraph, spontaneous speech and a song in irradiated patients for Tis-T1 vocal cord carcinoma. METHODS AND MATERIALS Eighteen male patients irradiated for Tis-T1 vocal cord carcinoma and a control group of 31 nonirradiated subjects of the same age were included in a study of acoustic voice analysis. The control group had been rigorously selected for voice quality and the irradiated group had previous history of smoking in two-thirds of the cases and a vocal cord biopsy. Radiotherapy patients were treated with a 6MV Linac receiving a total dose of 66 Gy, 2 Gy/day, with median treatment areas of 28 cm(2). Acoustic voice analysis was performed 1 year after radiotherapy, the voice of patients in extended vowel production, oral reading of a standard paragraph, spontaneous speech, and in a song was tape registered and analyzed by a Kay Elemetrics Computerized Speech Lab (model CSL# 4300). Fundamental frequency, jitter, shimmer, and harmonics-to-noise ratio were obtained in each case. Mann Whitney analysis was used for statistical tests. RESULTS The irradiated group presented higher values of fundamental frequency, jitter, shimmer, and harmonics-to-noise ratio. Mann-Whitney analysis showed significant differences for fundamental frequency and jitter in vowel production, oral reading, spontaneous speech, and song. Shimmer only showed differences in vowel production and harmonics-to-noise ratio in oral reading and song. CONCLUSIONS In our study only fundamental frequency and jitter showed significant increased values to the control group in all the acoustic situations. Sustained vowel production showed the worst values of the acoustic parameters in comparison with the other acoustic situations. This study seems to suggest that more work should be done in this field.

Quality assurance of interstitial brachytherapy technique in lip cancer: comparison of actual performance with the Paris System recommendations

This study takes a quality assurance approach to assessing staff application of Paris System recommendations for brachytherapy. Between 1988 and 1992, 72 patients were treated with brachytherapy for cancer of the lip at Hospital Clinic in Barcelona. Because of the relatively high number of total local recurrences (11%) and the fact that several radiotherapists had come from other hospitals to join the staff, we analysed the technique actually used compared with the recommendations of the Paris System. Results indicate our staff did not, in fact, use the active length prescribed by the Paris System in 71% of cases but that the discrepancies had no observable impact on the actuarial local control in the short follow-up period (28 +/- 15 months). When we compared, in time sequence, the first 35 patients treated between 1988 and 1989 (Early group) with the last 37 treated between 1990 and 1992 (Later group), we saw that staff members had improved their application of the therapy by more often using the recommended length of active lines. Staff performance in the Later group was still far from ideal, however, as the actual length used differed from the length recommended in 51% of the cases. At present we are insisting on stricter application of the Paris System guidelines for lip brachytherapy. Our study suggests that auditing performance is worthwhile and we recommend that radiotherapists apply this analytical quality assurance method, especially when several new physicians join a department.

Three or Four Fractions of 4–5 Gy per Week in Postoperative High-Dose-Rate Brachytherapy for Endometrial Carcinoma

PURPOSE To evaluate the results of high-dose-rate brachytherapy (HDRBT) using a schedule of three or four fractions per week, when possible, in 89 patients on local control and toxicity in postoperative treatment of endometrial carcinoma. The effect of the overall HDRBT treatment time (OTT) on toxicity was also evaluated. PATIENTS AND METHODS Fédération Internationale de Gynécologie Obstétrique Stage: 24 IB, 45 IC, 4 IIA, 6 IIB, 4 IIIA, 2 IIIB, and 4 IIIC. Radiotherapy: Group 1-67 of 89 patients received external beam irradiation (EBI; 44-50 Gy) plus HDRBT (3 fractions of 4-6 Gy); Group 2-22 of 89 patients received HDRBT alone (6 fractions of 4-5 Gy). OTT: Group 1-HDRBT was completed in a median of 5 days in 32 patients and in >5 days in 35; Group 2-HDRBT was completed in <15 days in 11 patients and in ≥16 days in 11. Toxicity was evaluated using Radiation Therapy Oncology Group scores and the bioequivalent dose (BED) study was performed in vaginal mucosa surface. Statistics included Students t test, chi-square test, and receiving operator curves. RESULTS With a mean follow-up of 31 months (range, 6-70), 1 of 89 patients had vaginal relapse. Early toxicity appeared in 8 of 89 (9%) patients and was resolved. Late toxicity appeared in 13/89 (14%): vaginal nine Grade 1, three Grade 2, one Grade 4; bladder two Grade 2; rectal three Grade 1, one Grade 2. No differences were found in relation to OTT in Groups 1 and 2. Mean BED was 88.48 Gy in Group 1 and 165.28 Gy in Group 2. Cases with Grade 2 late vaginal toxicity received >75 Gy after EBI and >165 Gy in Group 2. CONCLUSIONS Three fractions of 4-5 Gy in 3-5 days after EBI or 6 fractions in <15 days in patients receiving HDRBT alone was a safe treatment in relation to toxicity and local control. Vaginal surface BED less than 75 Gy after EBI and less than 160 Gy in HDRBT alone may be safe to avoid G2 toxicity.

GEC-ESTRO ACROP recommendations for head & neck brachytherapy in squamous cell carcinomas: 1st update – Improvement by cross sectional imaging based treatment planning and stepping source technology

The Head and Neck Working Group of the GEC-ESTRO (Groupe Européen de Curiethérapie - European Society for Therapeutic Radiology and Oncology) published in 2009 the consensus recommendations for low-dose rate, pulsed-dose rate and high-dose rate brachytherapy in head & neck cancers. The use of brachytherapy in combination with external beam radiotherapy and/or surgery was also covered as well as the use of brachytherapy in previously irradiated patients. Given the developments in the field, these recommendations needed to be updated to reflect up-to-date knowledge. The present update does not repeat basic knowledge which was published in the first recommendation but covers in a general part developments in (1) dose and fractionation, (2) aspects of treatment selection for brachytherapy alone versus combined BT+EBRT and (3) quality assurance issues. Detailed expert committee opinion intends to help the clinical practice in lip-, oral cavity-, oropharynx-, nasopharynx-, and superficial cancers. Different aspects of adjuvant treatment techniques and their results are discussed, as well the possibilities of salvage brachytherapy applications.

Analysing the integration of MR images acquired in a non-radiotherapy treatment position into the radiotherapy workflow using deformable and rigid registration

AIM Our aim was to analyse the feasibility of integrating an MRI acquired in a non-radiotherapy set-up into the prostate cancer radiotherapy workflow. MATERIAL AND METHODS The MRIs of 15 prostate cancer patients, acquired with a flat table-top (MRI-flat), and with a curved tabletop (MRI-curve) were analysed. MRIs were rigidly (RIR) and non-rigidly registered (DIR) with CT images. The prostate and rectum were contoured in each image set and translated to the CT, and IMRT plans were computed taking into account structural changes after RIR and DIR (P-flatRIR, P-curveRIR and P-curveDIR). In addition the P-curveDIR was overlaid with RIR structures. Spatial overlap parameters and dose-volume histogram metrics were generated. RESULTS No significant differences were observed among P-flatRIR and P-curveRIR or P-flatRIR and P-curveDIR. Median gamma-values: P-curveRIR, 95.3%; P-curveDIR, 96%, translated-P-curveDIR, 95%. DVH metrics for translated-P-curveDIR were: Dmin, 64.5Gy; Dmean, 70.06Gy; V95%, 100%. No statistically significant differences were found in the dosimetric MRI-flatDIR values. CONCLUSIONS The dosimetric reproduction of treatment position image following image registration of non-radiotherapy set-up images suggests that it is feasible to integrate these images into the radiotherapy workflow.

Can we shorten the overall treatment time in postoperative brachytherapy of endometrial carcinoma? Comparison of two brachytherapy schedules

PURPOSE To analyze vaginal-cuff relapses (VCR) and toxicity of two brachytherapy (BT) schedules in postoperative endometrial carcinoma and to correlate vaginal toxicity with vaginal-surface-EQD2Gy3 dose (VS-EQD2Gy3). METHODS/MATERIALS 319 patients (p) I-IIIC-Figo-stage were treated with 2 BT schedules. One schedule included 166p (Group-1) to whom 3 fractions (Fr) of 4-6Gy per week (w) of BT were administered after external beam radiotherapy (EBI) (125p) and 6Fr/2w of 4-6Gy in exclusive-BT (41p). The second schedule included 153p (Group-2) with BT administered daily with 2Fr/w of 5-6Gy after EBI (94p) and 5-6Gy/4Fr/w in exclusive-BT (59p). Doses were prescribed at 5mm from the vaginal surface. Toxicity was evaluated using RTOG scores for the rectum and bladder and objective LENT-SOMA scores for the vagina. STATISTICS Chi-square, Fisher and Students-t tests. RESULTS Mean follow-up (months): Group-1: 66.55 (7.73-115.40), Group-2: 41.49 (3.13-87.90). VCR: Group-1: 3p (1.88%); Group-2: 2p (1.3%). No differences were found between the two schedules comparing rectal (p=0.170), bladder (p=0.125) and vagina (p=0.680) late toxicities and comparing vagina EBI+BTp vs. exclusive-BTp (p=0.667). Significant differences in VS-EQD23Gy were observed considering EBI+BT (Groups 1+2) vs. exclusive-BT (Groups 1+2) (p<0.0001); nevertheless, no association was found between VS-EQD23Gy and vaginal complications. CONCLUSIONS No differences were found between the two schedules. No association was found between vaginal toxicity and VS-EQD23Gy. Consequently, treatment with the least number of fractions is preferable.

ENT COBRA (Consortium for Brachytherapy Data Analysis): Interdisciplinary standardized data collection system for head and neck patients treated with interventional radiotherapy (brachytherapy)

Purpose Aim of the COBRA (Consortium for Brachytherapy Data Analysis) project is to create a multicenter group (consortium) and a web-based system for standardized data collection. Material and methods GEC-ESTRO (Groupe Européen de Curiethérapie – European Society for Radiotherapy & Oncology) Head and Neck (H&N) Working Group participated in the project and in the implementation of the consortium agreement, the ontology (data-set) and the necessary COBRA software services as well as the peer reviewing of the general anatomic site-specific COBRA protocol. The ontology was defined by a multicenter task-group. Results Eleven centers from 6 countries signed an agreement and the consortium approved the ontology. We identified 3 tiers for the data set: Registry (epidemiology analysis), Procedures (prediction models and DSS), and Research (radiomics). The COBRA-Storage System (C-SS) is not time-consuming as, thanks to the use of “brokers”, data can be extracted directly from the single centers storage systems through a connection with “structured query language database” (SQL-DB), Microsoft Access®, FileMaker Pro®, or Microsoft Excel®. The system is also structured to perform automatic archiving directly from the treatment planning system or afterloading machine. The architecture is based on the concept of “on-purpose data projection”. The C-SS architecture is privacy protecting because it will never make visible data that could identify an individual patient. This C-SS can also benefit from the so called “distributed learning” approaches, in which data never leave the collecting institution, while learning algorithms and proposed predictive models are commonly shared. Conclusions Setting up a consortium is a feasible and practicable tool in the creation of an international and multi-system data sharing system. COBRA C-SS seems to be well accepted by all involved parties, primarily because it does not influence the centers own data storing technologies, procedures, and habits. Furthermore, the method preserves the privacy of all patients.

Activity of chemotherapy with carboplatin plus paclitaxel in a recurrent mesonephric adenocarcinoma of the uterine corpus

BACKGROUND Malignant lesions derived from mesonephric (Wolffian) remnants are uncommon. The course of these tumors is usually indolent, and the recurrence has only been documented in nine cases. Because of the small number of cases, no current recommendations exist regarding treatment, and little is known about the response to chemotherapeutic agents. CASE A 33-year-old woman was diagnosed with a mesonephric adenocarcinoma arising in the uterine corpus. Ten months after initial surgery and radiotherapy she presented with local and pulmonary relapse. Salvage chemotherapy with carboplatin plus paclitaxel was administered with a good response. CONCLUSIONS Mesonephric adenocarcinomas are uncommon neoplasms. Their treatment remains elusive. We report a case of a recurrent uterine mesonephric adenocarcinoma that presented a good response to therapy with carboplatin plus paclitaxel. A review of the previous literature is also presented.