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1.
Radiother Oncol ; 194: 110217, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38460552

RESUMEN

PURPOSE: To analyze late toxicity after very accelerated partial breast irradiation (VAPBI) for low-risk breast cancer. MATERIALS: Methods: In this retrospective, observational, international multicenter study (HDH F20220713143949), patients with low-risk breast cancer underwent lumpectomy + vAPBI (high-dose rate multicatheter interstitial brachytherapy-MIBT). VAPBI was performed with 4(4x6.2 Gy/2d), 3(3x7.45 Gy/2d) or 1 fraction (1x16Gy or 1x18Gy/1d). Primary endpoint was late toxicity. Secondary endpoints were cumulative incidence of breast cancer local relapse (LR) and distant metastatic relapse (DMR) and specific (SS) and overall (OS) survivals. Prognostic factors for late toxicity were analyzed. RESULTS: From 01/2012 to 06/2022, 516 pts with early breast cancer were enrolled. Median follow-up was 44 months [95 %CI 39-46]. Median age was 71 years [40-100]. Median tumor size was 12 mm [1-35]. VAPBI delivered 1, 3 and 4 fractions for 205pts (39.7 %), 167pts (32.4 %) and 144pts (28 %) respectively. 221 late toxicity events were observed in 168pts (32.6 %) (Fibrosis, dyschromia, pain and telangiectasia). Grade 2 and 3 late toxicities were observed in 7.2 and 0.6 % respectively (no G4) with no difference between 1 and ≥ 2 treatment days. CTV > 50 cc (p = 0.007) and V150 > 40 % (p = 0.027) were prognostic factors for G ≥ 2 late toxicity. Four-year cumulative incidence rates of LR and DMR were 2 % [95 %CI 0-3] and 1 % [95 %CI 0-2] respectively. CONCLUSIONS: VAPBI based on 1 or ≥ 2 days of MIBT represents an attractive de-escalation of irradiation approach for low-risk breast cancer. Late toxicity profile appears acceptable while early oncological outcome shows encouraging local control. Longer follow-up is warranted in order to confirm these preliminary results.


Asunto(s)
Braquiterapia , Neoplasias de la Mama , Humanos , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/patología , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Braquiterapia/efectos adversos , Braquiterapia/métodos , Anciano de 80 o más Años , Adulto , Mastectomía Segmentaria , Resultado del Tratamiento , Recurrencia Local de Neoplasia/radioterapia
2.
Radiother Oncol ; 171: 25-29, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35367528

RESUMEN

BACKGROUND AND PURPOSE: To evaluate the results of low-dose radiation therapy (LD-RT) to lungs in the management of patients with COVID-19 pneumonia. MATERIAL AND METHODS: We conducted a prospective phase I-II trial enrolling COVID-19 patients ≥50 years-old, with bilateral lung involvement at imaging study and oxygen requirement (oxygen saturation ≤93% on room air). Patients received 1 Gy to whole lungs in a single fraction. Primary outcome was a radiological response assessed as severity and extension scores at days +3 and +7. Secondary outcomes were toxicity (CTCAE v5.0), days of hospitalization, changes in inflammatory blood parameters (ferritin, lymphocytes, C-reactive protein, d-dimer and LDH) and SatO2/FiO2 index (SAFI), at day +3 and +7. Descriptive analyses were summarized as means with standard deviation (SD) and/or medians with interquartile ranges (IQR). A Wilcoxon sign rank test for paired data was used to assess the CT scores and Chi Square was used to assess for comparison of categorical variables. RESULTS: Forty-one patients were included. Median age was 71 (IQR 60-84). Eighteen patients (44%) previously received an anti-COVID treatment (tocilizumab, lopinavir/ritonavir, remdesivir) and thirty-two patients (84%) received steroids during LD-RT. The extension score improved significantly (p = 0.02) on day +7. Mean baseline extension score was 13.7 (SD ± 4.9) with a score of 12.2 (±5.2) at day 3, and 12.4 ± 4.7 at day 7. No differences were found in the severity score. SAFI improved significantly on day +3 and +7 (p < 0.01). Median SAFI on day 0 was 147 (IQR 118-264), 230 (IQR 120-343) on day +3 and 293 (IQR 121-353) on day +7. Significant decrease was found in C-reactive protein on day +7 (p = 0.02) and in lymphocytes counts on day +3 and +7 (p = 0.02). The median number of days in hospital after RT was 11 (range 4-78). With a median follow-up of 60 days after LD-RT, 26 (63%) patients were discharged, 11 (27%) died because of COVID respiratory failure and 4 (10%) died of other causes. CONCLUSIONS: LD-RT is a feasible and well-tolerated treatment that could lead to rapid clinical improvement. Large randomized trials would be required to establish the efficacy of LD-RT to treat COVID-19 pneumonia.


Asunto(s)
COVID-19 , Anciano , Proteína C-Reactiva , COVID-19/radioterapia , Humanos , Persona de Mediana Edad , Estudios Prospectivos , SARS-CoV-2 , Resultado del Tratamiento
3.
Int J Radiat Oncol Biol Phys ; 109(4): 880-885, 2021 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-33249142

RESUMEN

PURPOSE: Low-dose radiation therapy (LD-RT) has been shown to have an anti-inflammatory effect, and preliminary results suggest it is feasible to treat patients with coronavirus disease 2019 (COVID-19) pneumonia. MATERIALS AND METHODS: We conducted a prospective, single-arm, phase 1/2 clinical trial enrolling patients aged ≥50 years, who were coronavirus disease 2019 (COVID-19) positive, at phase 2 or 3 with lung involvement at imaging study and oxygen requirement. Patients received 100 cGy to total lungs in a single fraction. Primary outcome was radiologic response using severity and extension score on baseline computed tomography (CT), at days 3 and 7 after LD-RT. Secondary outcomes were toxicity using Common Terminology Criteria for Adverse Events v.5.0, duration of hospitalization, blood work evolution, and oxygen requirements using SatO2/FiO2 index (SAFI), at days 3 and 7 after LD-RT. RESULTS: Nine patients were included. Median age was 66 (interquartile range, 57-77). Severity score was stable or decreased in the third CT but was not statistically significant (P = .28); however, there were statistically significant changes in the extension score (P = .03). SAFI index significantly improved 72 hours and 1 week after LD-RT (P = .01). Inflammatory blood parameters decreased 1 week after RT compared with baseline; only lactate dehydrogenase decreased significantly (P = .04). Two patients presented grade 2 lymphopenia after RT and another (with baseline grade 3) worsened to grade 4. Overall, the median number of days of hospitalization was 59 (range, 26-151). After RT the median number of days in the hospital was 13 (range, 4-77). With a median follow-up after RT of 112 days (range, 105-150), 7 patients were discharged and 2 patients died, 1 due to sepsis and the other with severe baseline chronic obstructive pulmonary disease from COVID-19 pneumonia. CONCLUSIONS: Our preliminary results show that LD-RT was a feasible and well-tolerated treatment, with potential clinical improvement. Randomized trials are needed to establish whether LD-RT improves severe pneumonia.


Asunto(s)
COVID-19/radioterapia , Dosis de Radiación , Anciano , Anciano de 80 o más Años , COVID-19/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Dosificación Radioterapéutica , Resultado del Tratamiento
4.
Brachytherapy ; 13(5): 433-41, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24958556

RESUMEN

PURPOSE: To demonstrate the feasibility of using high-dose-rate (HDR) brachytherapy to deliver 125% of the prescription dose to the dominant intraprostatic lesion (DIL) as defined on multiparametric MRI while respecting critical organ dose constraints. METHODS AND MATERIALS: Twenty-six patients with biopsy-proven predominantly unilateral prostate cancer consented to a university ethics-approved Phase 2 study of selective dose escalation. Combined information from endorectal T2 MRI sequences, dynamic contrast enhancement, and apparent diffusion coefficient maps was used to contour the DIL and prostate. Images were fused to intraoperative transrectal ultrasound for transposition of the DIL. Treatment consisted of two fractions of 10 Gy HDR brachytherapy to the entire prostate with 12.5 Gy to the DIL, combined with 46 Gy in 23 fractions of external beam radiotherapy. RESULTS: All patients had intermediate- or high-risk disease; 25 of 26 had a visible DIL (mean volume, 2.9 cm(3); SD, 1.8). Mean percentage of prostate receiving prescription dose (V100) was 98.1% (SD, 1.2). Mean dose to 90% of the DIL was 13.4 Gy (SD, 1.0). The coverage of the DIL was excellent with a mean of 95.7% (SD, 5.0) receiving the planned escalation of 25%. Established dose constraints to rectum and urethra were respected in all cases; where DIL coverage was limited by proximity to urethra or rectum, a mean dose to 90% of the DIL of 12.3 Gy was achieved. CONCLUSIONS: Modest dose escalation to the DIL (25-30%) using ultrasound-planned HDR brachytherapy is feasible for selected intermediate- and high-risk patients while respecting critical organ constraints and is achievable within the practice setting of a community cancer center.


Asunto(s)
Adenocarcinoma/radioterapia , Braquiterapia/métodos , Neoplasias de la Próstata/radioterapia , Ultrasonografía Intervencional , Adenocarcinoma/diagnóstico por imagen , Anciano , Estudios de Factibilidad , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Órganos en Riesgo , Neoplasias de la Próstata/diagnóstico por imagen , Dosificación Radioterapéutica , Recto , Resultado del Tratamiento , Uretra
5.
Brachytherapy ; 13(1): 75-9, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24080299

RESUMEN

PURPOSE: The use of transrectal ultrasound (TRUS) to both guide and plan high-dose-rate (HDR) brachytherapy (BT) for prostate is increasing. Studies using prostate phantoms have demonstrated the accuracy of ultrasound (US) needle tip reconstruction compared with CT imaging standard. We have assessed the in vivo accuracy of needle tip localization by TRUS using cone-beam CT (CBCT) as our reference standard. METHODS AND MATERIALS: Needle positions from 37 implants have been analyzed. A median of 16 needles (range, 16-18) per implant were inserted, advanced to the prostate base, and their tips identified using live TRUS images and real-time planning BT software. Needle protrusion length from the template was recorded to allow for reverification before capturing images for planning. The needles remained locked in the template, which was fixed to the stepper, while a set of three-dimensional TRUS images was acquired for needle path reconstruction and HDR-BT treatment planning. Following treatment, CBCT images were acquired for subsequent needle reconstruction using a BT Treatment Planning System. The coordinates of each needle tip were recorded from the Treatment Planning System for CT and US and compared. RESULTS: A total of 574 needle tip positions have been compared between TRUS and CBCT. Of these, 59% agreed within 1 mm, 27% within 1-2 mm, and 11% agreed within 2-3 mm. The discrepancy between tip positions in the two modalities was greater than 3 mm for only 20 needles (3%). CONCLUSIONS: The US needle tip identification in vivo is at least as accurate as CT identification, while providing all the advantages of a one-step procedure.


Asunto(s)
Braquiterapia/métodos , Tomografía Computarizada de Haz Cónico/métodos , Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Planificación de la Radioterapia Asistida por Computador/métodos , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Radioterapia de Alta Energía/métodos , Reproducibilidad de los Resultados , Ultrasonografía
6.
Brachytherapy ; 12(4): 362-7, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23477886

RESUMEN

PURPOSE: To compare 30-day seed displacement and seed loss of standard loose seeds to specially engineered coated seeds. METHODS AND MATERIALS: Forty patients with prostate cancer were randomized and treated with either loose seeds or loose "coated" seeds. Implants were preplanned using transrectal ultrasound and performed using preloaded needles containing either standard or coated iodine-125 seeds according to randomization. Pelvic X-rays and CT were performed on Days 0 and 30 and a pelvic magnetic resonance scan on Day 30. Cranial-caudal displacement relative to the center of mass (COM) of the seed cloud of the six most peripheral basal and apical seeds was determined from Day 0 and 30 CT scans using custom software. Day 30 magnetic resonance-CT fusion was performed using a seed-to-seed match for soft tissue contouring on MRI. RESULTS: The mean displacement for the six basal seeds was 0.32 cm (standard deviation [SD], 0.25 cm) and 0.33 cm (SD, 0.27 cm) toward the COM for the regular and coated seeds, respectively (p = 0.35). For the apical seeds, mean displacement was 0.31 cm (SD, 0.35 cm) and 0.43 cm (SD, 0.26 cm) (p = 0.003) toward the COM. More regular seeds (n = 8) were lost from the apical region as compared with one coated seed (p = 0.015). There was a trend to reduction in total seeds lost: 1% for regular seeds as compared with 0.3% for coated seeds. CONCLUSIONS: Coated seeds were found to have a significant anchoring effect that was effective in reducing the number of apical seeds lost because of venous migration.


Asunto(s)
Braquiterapia/efectos adversos , Braquiterapia/métodos , Migración de Cuerpo Extraño , Neoplasias de la Próstata/radioterapia , Prótesis e Implantes/efectos adversos , Anciano , Anciano de 80 o más Años , Humanos , Radioisótopos de Yodo , Masculino , Persona de Mediana Edad , Polímeros , Dosificación Radioterapéutica
7.
Int J Urol ; 20(2): 142-7, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22905916

RESUMEN

The aim of the present study was to review the English language literature on the topic of prostate-specific antigen bounce after brachytherapy and present a summary of the current knowledge. Although ultimately prostate-specific antigen is a reliable measure of success after prostate brachytherapy, it can be very misleading in the first 3 years because of the frequency with which temporary benign rises in prostate-specific antigen occur. We have reviewed the English language literature on the topic of prostate-specific antigen bounce under the following headings: prostate neoplasms, brachytherapy, biochemical definition of prostate-specific antigen failure, "benign prostate-specific antigen bounce" and "prostate-specific antigen spike". We included brachytherapy delivered as either low dose rate or high dose rate, and either as monotherapy or as a boost combined with external beam radiotherapy. A benign self-limited rise in prostate-specific antigen after prostate brachytherapy is seen in an average of 35% of patients, but increases in frequency with younger age. In patients aged less than 55 years, it is observed in up to 68%. Other factors, such as sexual activity, dose, prostate volume and the use of high dose rate versus low dose rate have been implicated in affecting the frequency of the benign bounce. Benign increases in prostate-specific antigen are frequent after prostate brachytherapy. It is important to recognize and correctly diagnose this phenomenon in order to avoid unnecessary salvage treatment.


Asunto(s)
Biomarcadores de Tumor/sangre , Braquiterapia/métodos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/radioterapia , Factores de Edad , Anciano , Anciano de 80 o más Años , Biopsia con Aguja , Braquiterapia/efectos adversos , Supervivencia sin Enfermedad , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Pronóstico , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Medición de Riesgo , Sensibilidad y Especificidad , Análisis de Supervivencia
8.
Brachytherapy ; 12(4): 338-42, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-22748289

RESUMEN

PURPOSE: To describe the management of a patient with locally recurrent prostate cancer in the prostate bed, 10 years after a radical prostatectomy. METHODS AND MATERIALS: A 71-year-old man had a radical prostatectomy for a Gleason 7 clinical T2a carcinoma of the prostate in 2000. Final pathologic stage was pT3a pN0. Postoperatively his prostate-specific antigen was undetectable, but by 2008 it was 1.0ng/mL and in 2011 it reached to 1.43ng/mL. He was referred for consideration of salvage radiotherapy. Staging workup was negative but transrectal ultrasound revealed a 15cc recurrence in the prostate bed. A combination of external beam radiation therapy (4600/23/4.5 weeks to the pelvis) and a brachytherapy boost (115Gy) was selected for definitive management. Androgen ablation was not used. RESULTS: The treatment was well tolerated. The brachytherapy boost was planned in a similar fashion to a de novo implant for an intact prostate. The postimplant dosimetry was evaluated using magnetic resonance imaging-computed tomography (MR-CT) fusion and appeared satisfactory. Acute toxicity was minimal. Six months after brachytherapy, the prostate-specific antigen had fallen from 1.43 to 0.05ng/mL. CONCLUSIONS: Dose escalation with combined external beam and brachytherapy may be feasible if recurrent disease can be visualized using transrectal ultrasound and encompassed in an implanted volume. Although longer followup and a larger series of patients are required to demonstrate safety and efficacy, consideration should be given this approach.


Asunto(s)
Braquiterapia/métodos , Neoplasias de la Próstata/radioterapia , Anciano , Humanos , Radioisótopos de Yodo , Masculino , Recurrencia Local de Neoplasia , Antígeno Prostático Específico , Prostatectomía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Dosificación Radioterapéutica
9.
J Natl Compr Canc Netw ; 10(9): 1088-95; quiz 1088, 1096, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22956808

RESUMEN

Despite common and occasionally serious side effects, androgen deprivation therapy (ADT) is widely used in the management of prostate cancer at all stages and presentations. ADT is frequently used in situations in which evidence of benefit is lacking, such as combined with definitive radiotherapy for favorable-risk prostate cancer, or in the primary management of elderly patients with low-risk disease. In intermediate- and high-risk disease, the role of ADT is being challenged and is decreasing in importance, as the ability to deliver very high biologically effective doses becomes more widely available, especially through the combination of external radiotherapy and brachytherapy. Appropriately selecting patients for ADT according to established indications will minimize the number exposed, whereas systematic patient education before initiating treatment can ameliorate the side effects. Minimizing the exposure to ADT and efforts to mitigate the side effects may have a beneficial effect on quality of life for many men with prostate cancer.


Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Braquiterapia , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Terapia Combinada , Humanos , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/prevención & control , Recurrencia Local de Neoplasia/radioterapia , Medición de Riesgo
10.
Head Neck ; 34(8): 1081-8, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22267124

RESUMEN

BACKGROUND: This study aimed to test the safety of using perioperative high-dose-rate brachytherapy (PHDRB) in resected head and neck cancer. METHODS: From 2000 to 2008, 97 patients received PHDRB after complete macroscopic resection. Group 1 (previously irradiated patients) received 32 to 40 Gray (Gy) of PHDRB in 8 to 10 twice-daily (bid) treatments (R0-R1 resections). Group 2 (unirradiated patients) received 16 to 24 Gy of PHDRB in 4 to 6 bid treatments (R0-R1 resections) followed by external beam irradiation (EBRT) of 45 Gy/25 daily fractions ± concomitant chemotherapy. RESULTS: The median follow-up was 4.3 years. The cumulative hazard of 2-year grade ≥ 3 complications in group 1 was 45.9%, and the rate of grade ≥ 3 complications in group 2 was 24.6%. Actuarial locoregional control at 2 and 5 years for group 1 was 60.9% and for group 2, 84.1% and 79.4%. CONCLUSIONS: Complications and locoregional failure rates were similar to those reported in the reference standards despite a much smaller treatment volume.


Asunto(s)
Braquiterapia , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeza y Cuello/terapia , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/mortalidad , Quimioradioterapia Adyuvante , Cisplatino/administración & dosificación , Femenino , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Paclitaxel/administración & dosificación , Dosificación Radioterapéutica
11.
Int J Radiat Oncol Biol Phys ; 82(3): e469-76, 2012 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-22284039

RESUMEN

PURPOSE: To determine the feasibility of combined long-term androgen deprivation therapy (ADT) and dose escalation with high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS: Between 2001 and 2007, 200 patients with high-risk prostate cancer (32.5%) or very high-risk prostate cancer (67.5%) were prospectively enrolled in this Phase II trial. Tumor characteristics included a median pretreatment prostate-specific antigen of 15.2 ng/mL, a clinical stage of T2c, and a Gleason score of 7. Treatment consisted of 54 Gy of external irradiation (three-dimensional conformal radiotherapy [3DCRT]) followed by 19 Gy of HDR brachytherapy in four twice-daily treatments. ADT started 0-3 months before 3DCRT and continued for 2 years. RESULTS: One hundred and ninety patients (95%) received 2 years of ADT. After a median follow-up of 3.7 years (range, 2-9), late Grade ≥2 urinary toxicity was observed in 18% of the patients and Grade ≥3 was observed in 5%. Prior transurethral resection of the prostate (p = 0.013) and bladder D(50) ≥1.19 Gy (p = 0.014) were associated with increased Grade ≥2 urinary complications; age ≥70 (p = 0.05) was associated with Grade ≥3 urinary complications. Late Grade ≥2 gastrointestinal toxicity was observed in 9% of the patients and Grade ≥3 in 1.5%. CTV size ≥35.8 cc (p = 0.007) and D(100) ≥3.05 Gy (p = 0.01) were significant for increased Grade ≥2 complications. The 5-year and 9-year biochemical relapse-free survival (nadir + 2) rates were 85.1% and 75.7%, respectively. Patients with Gleason score of 7-10 had a decreased biochemical relapse-free survival (p = 0.007). CONCLUSIONS: Intermediate-term results at the 5-year time point indicate a favorable outcome without an increase in the rate of late complications.


Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Braquiterapia/métodos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Terapia Combinada/métodos , Supervivencia sin Enfermedad , Estudios de Factibilidad , Humanos , Masculino , Clasificación del Tumor , Estadificación de Neoplasias , Órganos en Riesgo/efectos de la radiación , Estudios Prospectivos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Curva ROC , Dosificación Radioterapéutica , Recto/efectos de la radiación , Resultado del Tratamiento , Uretra/efectos de la radiación , Vejiga Urinaria/efectos de la radiación , Trastornos Urinarios/etiología
12.
Brachytherapy ; 11(2): 119-24, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-21684815

RESUMEN

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 25Gy 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.


Asunto(s)
Adenocarcinoma/radioterapia , Braquiterapia/métodos , Neoplasias Endometriales/radioterapia , Vagina , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Braquiterapia/efectos adversos , Supervivencia sin Enfermedad , Femenino , Enfermedades Urogenitales Femeninas , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias
13.
Int J Radiat Oncol Biol Phys ; 83(2): 587-93, 2012 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-22079731

RESUMEN

PURPOSE: To validate tolerance and pathological complete response rate (pCR) of a 4-week preoperative course of intensity-modulated radiation therapy (IMRT) with concurrent capecitabine and oxaliplatin (CAPOX) in patients with locally advanced rectal cancer. METHODS AND MATERIALS: Patients with T3 to T4 and/or N+ rectal cancer received preoperative IMRT (47.5 Gy in 19 fractions) with concurrent capecitabine (825 mg/m(2) b.i.d., Monday to Friday) and oxaliplatin (60 mg/m(2) on Days 1, 8, and 15). Surgery was scheduled 4 to 6 weeks after the completion of chemoradiation. Primary end points were toxicity and pathological response rate. Local control (LC), disease-free survival (DFS), and overall survival (OS) were also analyzed. RESULTS: A total of 100 patients were evaluated. Grade 1 to 2 proctitis was observed in 73 patients (73%). Grade 3 diarrhea occurred in 9% of the patients. Grade 3 proctitis in 18% of the first 50 patients led to reduction of the dose per fraction to 47.5 Gy in 20 treatments. The rate of Grade 3 proctitis decreased to 4% thereafter (odds ratio, 0.27). A total of 99 patients underwent surgery. A pCR was observed in 13% of the patients, major response (96-100% of histological response) in 48%, and pN downstaging in 78%. An R0 resection was performed in 97% of the patients. After a median follow-up of 55 months, the LC, DFS, and OS rates were 100%, 84%, and 87%, respectively. CONCLUSIONS: Preoperative CAPOX-IMRT therapy (47.5 Gy in 20 fractions) is feasible and safe, and produces major pathological responses in approximately 50% of patients.


Asunto(s)
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/métodos , Terapia Neoadyuvante/métodos , Radioterapia de Intensidad Modulada/métodos , Neoplasias del Recto/terapia , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina , Quimioradioterapia/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Diarrea/etiología , Fraccionamiento de la Dosis de Radiación , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Cooperación del Paciente , Cuidados Preoperatorios/métodos , Proctitis/etiología , Proctitis/patología , Radioterapia de Intensidad Modulada/efectos adversos , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Resultado del Tratamiento
14.
Int J Radiat Oncol Biol Phys ; 81(4): e529-39, 2011 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-21665380

RESUMEN

PURPOSE: The present study was undertaken to determine factors predictive of toxicity, patterns of failure, and survival in 60 adult patients with soft tissue sarcomas of the extremity and superficial trunk treated with combined perioperative high-dose-rate brachytherapy and external beam radiotherapy. METHODS AND MATERIALS: The patients were treated with surgical resection and perioperative high-dose-rate brachytherapy (16 or 24 Gy) for negative and close/microscopically positive resection margins, respectively. External beam radiotherapy (45 Gy) was added postoperatively to reach a 2-Gy equivalent dose of 62.9 and 72.3 Gy, respectively. Adjuvant chemotherapy with ifosfamide and doxorubicin was given to patients with advanced high-grade tumors. RESULTS: Grade 3 toxic events were observed in 18 patients (30%) and Grade 4 events in 6 patients (10%). No Grade 5 events were observed. A location in the lower limb was significant for Grade 3 or greater toxic events on multivariate analysis (p = .013), and the tissue volume encompassed by the 150% isodose line showed a trend toward statistical significance (p = .086). The local control, locoregional control, and distant control rate at 9 years was 77.4%, 69.5%, and 63.8%, respectively. On multivariate analysis, microscopically involved margins correlated with local control (p = .036) and locoregional control (p = .007) and tumor size correlated with distant metastases (p = .004). The 9-year disease-free survival and overall survival rate was 47.0% and 61.5%, respectively. Multivariate analysis showed poorer disease-free survival rates for patients with tumors >6 cm (p = .005) and microscopically involved margins (p = .043), and overall survival rates decreased with increasing tumor size (p = .011). CONCLUSIONS: Grade 3 or greater wound complications can probably be decreased using meticulous treatment planning to decrease the tissue volume encompassed by the 150% isodose line, especially in lower limb locations. Microscopically involved margins remain a predictor of local and locoregional failure, despite radiation doses >70 Gy. Patients with tumors ≥6 cm and microscopically involved margins are at high risk of treatment failure and death from the development of distant metastases.


Asunto(s)
Extremidades , Traumatismos por Radiación/patología , Sarcoma/radioterapia , Torso , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Braquiterapia/métodos , Quimioterapia Adyuvante/métodos , Doxorrubicina/administración & dosificación , Femenino , Humanos , Ifosfamida/administración & dosificación , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasia Residual , Dosificación Radioterapéutica , Sarcoma/tratamiento farmacológico , Sarcoma/patología , Sarcoma/cirugía , Insuficiencia del Tratamiento , Carga Tumoral , Adulto Joven
15.
Int J Radiat Oncol Biol Phys ; 81(4): e245-54, 2011 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-21620582

RESUMEN

PURPOSE: To determine the impact of a set of patient, tumor, and treatment factors on toxicity and outcome in patients with head-and-neck squamous cell cancer treated with surgical resection and perioperative high-dose rate brachytherapy (PHDRB) alone (single-modality [SM] group) (n = 46) or PHDRB combined with postoperative radiation or chemoradiation (combined-modality [CM] group) (n = 57). METHODS AND MATERIALS: From 2000 to 2008, 103 patients received PHDRB after complete macroscopic resection. SM patients received 32 or 40 Gy of PHDRB in 8 or 10 twice-daily treatments for R0 and R1 resections. CM patients received 16 or 24 Gy of PHDRB in 4 or 6 twice-daily treatments for R0 and R1 resections, followed by external radiation of 45 Gy in 25 fractions with or without concomitant chemotherapy. RESULTS: Grade ≥4 complications according to the Radiation Therapy Oncology Group were more frequent in the SM group than in the CM group (p = 0.024). Grade ≥3 and ≥4 complications increased with the antecedent of prior irradiation (p = 0.032 and p = 0.006, respectively) and with TV(150) values of 13 mL or greater (p = 0.032 and p = 0.032, respectively). After a median follow-up of 34.8 and 60.8 months for SM and CM patients, respectively, patients with high-risk margins had a 9-year local control rate of 68.0% whereas patients with wider margins had a 9-year local control of 93.7% (p = 0.045). Patients with primary and recurrent tumors had 9-year actuarial locoregional control rates of 81.8% and 54.2%, respectively (p = 0.003). Patients with lymph-vascular space invasion (LVSI)-positive and LVSI-negative tumors had 9-year distant control rates of 62.8% and 81.6%, respectively (p = 0.034). Disease-free survival rates decreased in recurrent cases (p = 0.006) as well as in LVSI-positive patients (p = 0.035). CONCLUSIONS: The complications observed are largely attributable to the antecedent of prior irradiation but can possibly be minimized by meticulous mapping and exhaustive planning to reduce TV(150) values. Patients with high-risk margins, LVSI-positive status, and recurrent disease have a higher risk of treatment failure, and therefore risk-directed treatment strategies are required.


Asunto(s)
Braquiterapia/efectos adversos , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeza y Cuello/terapia , Recurrencia Local de Neoplasia/terapia , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Braquiterapia/métodos , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Dosificación Radioterapéutica , Carcinoma de Células Escamosas de Cabeza y Cuello , Tasa de Supervivencia , Insuficiencia del Tratamiento
16.
Int J Radiat Oncol Biol Phys ; 79(4): 1158-63, 2011 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-21353160

RESUMEN

PURPOSE: To determine patient, tumor, and treatment factors predictive of local control (LC) in a series of patients treated with either perioperative high-dose-rate brachytherapy (PHDRB) alone (Group 1) or with PHDRB combined with external-beam radiotherapy (EBRT) (Group 2). PATIENT AND METHODS: Patients (n = 312) enrolled in several PHDRB prospective Phase I-II studies conducted at the Clínica Universidad de Navarra were analyzed. Treatment with PHDRB alone, mainly because of prior irradiation, was used in 126 patients to total doses of 32 Gy/8 b.i.d. or 40 Gy/10 b.i.d. treatments after R0 or R1 resections. Treatment with PHDRB plus EBRT was used in 186 patients to total doses of 16 Gy/4 b.i.d. or 24 Gy/6 b.i.d. treatments after R0 or R1 resections along with 45 Gy of EBRT with or without concomitant chemotherapy. RESULTS: No dose-margin interaction was observed in Group 1 patients. In Group 2 patients there was a significant interaction between margin status and 2-Gy equivalent (Eq2Gy) dose (p = 0.002): (1) patients with negative margins had 9-year LC of 95.7% at Eq2Gy = 62.9Gy; (2) patients with close margins of >1 mm had 9-year LC of 92.4% at Eq2Gy = 72.2Gy, and (3) patients with positive/close <1-mm margins had 9-year LC of 68.0% at Eq2Gy = 72.2Gy. CONCLUSIONS: Two-gray equivalent doses ≥70 Gy may compensate the effect of close margins ≥1 mm but do not counterbalance the detrimental effect of unfavorable (positive/close <1 mm) resection margins. No dose-margin interaction is observed in patients treated at lower Eq2Gy doses ≤50 Gy with PHDRB alone.


Asunto(s)
Braquiterapia/métodos , Neoplasias/patología , Neoplasias/radioterapia , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Fraccionamiento de la Dosis de Radiación , Femenino , Neoplasias de los Genitales Femeninos/mortalidad , Neoplasias de los Genitales Femeninos/patología , Neoplasias de los Genitales Femeninos/radioterapia , Neoplasias de los Genitales Femeninos/cirugía , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapia , Neoplasias/mortalidad , Neoplasias/cirugía , Estudios Prospectivos , Sarcoma/mortalidad , Sarcoma/patología , Sarcoma/radioterapia , Sarcoma/cirugía , Factores Sexuales , Carga Tumoral , Adulto Joven
17.
Int J Radiat Oncol Biol Phys ; 80(3): 698-704, 2011 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-20656414

RESUMEN

PURPOSE: To analyze the rate of pathologic response in patients with locally advanced gastric cancer treated with preoperative chemotherapy with and without chemoradiation at our institution. METHODS AND MATERIALS: From 2000 to 2007 patients were retrospectively identified who received preoperative treatment for gastric cancer (cT3-4/ N+) with induction chemotherapy (Ch) or with Ch followed by concurrent chemoradiotherapy (45 Gy in 5 weeks) (ChRT). Surgery was planned 4-6 weeks after the completion of neoadjuvant treatment. Pathologic assessment was used to investigate the patterns of pathologic response after neoadjuvant treatment. RESULTS: Sixty-one patients were analyzed. Of 61 patients, 58 (95%) underwent surgery. The R0 resection rate was 87%. Pathologic complete response was achieved in 12% of the patients. A major pathologic response (<10% of residual tumor) was observed in 53% of patients, and T downstaging was observed in 75%. Median follow-up was 38.7 months. Median disease-free survival (DFS) was 36.5 months. The only patient-, tumor-, and treatment-related factor associated with pathologic response was the use of preoperative ChRT. Patients achieving major pathologic response had a 3-year actuarial DFS rate of 63%. CONCLUSIONS: The patterns of pathologic response after preoperative ChRT suggest encouraging intervals of DFS. Such a strategy may be of interest to be explored in gastric cancer.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Neoadyuvante/métodos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Estadificación de Neoplasias , Neoplasia Residual , Inducción de Remisión , Estudios Retrospectivos , Neoplasias Gástricas/radioterapia , Neoplasias Gástricas/cirugía , Resultado del Tratamiento
18.
Int J Gynecol Cancer ; 20(1): 133-40, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20130514

RESUMEN

OBJECTIVES: This study was undertaken to determine the tolerability of a 7-week schedule of external beam radiation therapy, high-dose-rate brachytherapy, and weekly cisplatin and paclitaxel in patients with locally advanced carcinoma of the cervix. METHODS: Twenty-nine patients with International Federation of Gynecology and Obstetrics stages IB2 to IVa cervical cancer were treated with 40 mg/m per week of intravenous (i.v.) cisplatin and 50 mg/m per week of i.v. paclitaxel combined with 45 Gy of pelvic external beam radiation therapy and 30 Gy of high-dose-rate brachytherapy. RESULTS: Eleven patients (37.9%) were able to complete the 6 scheduled cycles of chemotherapy. The median number of weekly chemotherapy cycles administered was 5 (range, 2-7). Thirty-five (20.1%) of 174 cycles of chemotherapy were not given because of toxicity. The median dose intensity of cisplatin was 31 mg/m per week (95% confidence interval [CI], 25.2-36.8); that of paclitaxel was 44 mg/m per week (95% CI, 39.9-48.3). Twenty-two patients (78.6%) were able to complete the planned radiation course in less than 7 weeks. Median radiation treatment length was 45 days (95% CI, 43.4-46.6). After a median follow-up of 48 months, 7 patients (24.1%) experienced severe (Radiation Therapy Oncology Group grade 3 or higher) late toxicity. No fatal events were observed. Seven patients have failed, 1 locally and 6 at distant sites. The 8-year local/pelvic control rate was 95.7%, and the 8-year freedom from systemic failure rate was 76.1%. Eight-year actuarial disease-free survival and overall survival were 63.1% and 75.9%, respectively. CONCLUSIONS: This study demonstrated unacceptable toxicity of combining the stated doses of concurrent cisplatin and paclitaxel chemotherapy with definitive radiotherapy for patients with advanced cervical cancer. Additional phase I/II trials are recommended to clearly establish the recommended phase II dose for these drugs.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Cisplatino/administración & dosificación , Paclitaxel/administración & dosificación , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/radioterapia , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/radioterapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Escamosas/patología , Cisplatino/efectos adversos , Terapia Combinada/efectos adversos , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Paclitaxel/efectos adversos , Cooperación del Paciente , Factores de Tiempo , Resultado del Tratamiento , Neoplasias del Cuello Uterino/patología
19.
Onkologie ; 32(10): 580-4, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19816075

RESUMEN

BACKGROUND: Pemetrexed is a multitargeted antifolate initially approved as a single agent for the second-line treatment of locally advanced or metastatic non-small cell lung cancer and more recently in the first-line setting combined with cisplatin. The combination of pemetrexed with carboplatin has been tested in several phase II clinical trials showing interesting antitumour activity with mild toxicity. Supplementation with folic acid and vitamin B12 during treatment with pemetrexed is recommended to reduce potential haematological and gastrointestinal adverse events. CASE REPORT: A patient experienced cutaneous lesions including widespread erythema, epidermal detachment, and skin denudation, associated with deterioration of his general condition after the second cycle of this chemotherapy combination, which was clinically and histologically compatible with toxic epidermal necrolysis (Lyell's syndrome). Treatment with systemic steroids, antihistamines, and antibiotics led to resolution of the skin lesions and improvement of his general condition. CONCLUSION: To our knowledge, this is the second case reported in the literature of this type of suspected adverse drug reaction associated with a pemetrexed-based chemotherapy combination.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/efectos adversos , Glutamatos/efectos adversos , Guanina/análogos & derivados , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Ácido Fólico/efectos adversos , Ácido Fólico/uso terapéutico , Glutamatos/uso terapéutico , Guanina/efectos adversos , Guanina/uso terapéutico , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pemetrexed , Síndrome de Stevens-Johnson/prevención & control , Vitamina B 12/efectos adversos , Vitamina B 12/uso terapéutico
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