RESUMEN
PURPOSE: The aim of this study is to determine if a repeated hydrogel injection in a previously irradiated patient prior to salvage high-dose-rate brachytherapy (HDR-BT) is feasible. MATERIAL AND METHODS: A 61-year-old man with an organ confined (cT1c cN0 cM0, Gleason score 3 + 3 = 6, initial prostate-specific antigen [PSA] 7.9 ng/ml) prostate cancer was previously treated with HDR-BT (3 fractions of 11.5 Gy every 2nd week) after hydrogel injection to reduce the rectal dose. Ten months after, an isolated local persistence was seen on a PSMA PET-CT. Nadir PSA was 2.0 ng/ml, 3 months after treatment and was 3.95 ng/ml by the re-treatment. Salvage therapy consisted of HDR-BT (3 fractions of 9 Gy every 2nd week) with a simultaneous integrated boost to the residual region. Again, a hydrogel injection (10 ml) was applied to reduce the rectal dose prior to the treatment. RESULTS: Both hydrogel injection and salvage HDR-BT could be applied without any significant complications or toxicity. A good PSA response was observed with a nadir of 0.42 ng/ml, twelve months after salvage therapy. Acute toxicity (max grade II) resolved within 2 days after treatment. CONCLUSIONS: The use of a hydrogel prior to salvage HDR-BT in a patient previously treated with HDR-BT is feasible and could help reduce the rectal exposure in the salvage setting.
RESUMEN
PURPOSE: Concurrent chemoradiotherapy with or without surgery are options for stage IIIA(N2) non-small-cell lung cancer. Our previous phase II study had shown the efficacy of induction chemotherapy followed by chemoradiotherapy and surgery in patients with IIIA(N2) disease and with selected IIIB disease. Here, we compared surgery with definitive chemoradiotherapy in resectable stage III disease after induction. PATIENTS AND METHODS: Patients with pathologically proven IIIA(N2) and selected patients with IIIB disease that had medical/functional operability received induction chemotherapy, which consisted of three cycles of cisplatin 50 mg/m(2) on days 1 and 8 and paclitaxel 175 mg/m(2) on day 1 every 21 days, as well as concurrent chemoradiotherapy to 45 Gy given as 1.5 Gy twice daily, concurrent cisplatin 50 mg/m(2) on days 2 and 9, and concurrent vinorelbine 20 mg/m(2) on days 2 and 9. Those patients whose tumors were reevaluated and deemed resectable in the last week of radiotherapy were randomly assigned to receive a chemoradiotherapy boost that was risk adapted to between 65 and 71 Gy in arm A or to undergo surgery (arm B). The primary end point was overall survival (OS). RESULTS: After 246 of 500 planned patients were enrolled, the trial was closed after the second scheduled interim analysis because of slow accrual and the end of funding, which left the study underpowered relative to its primary study end point. Seventy-five patients had stage IIIA disease and 171 had stage IIIB disease according to the Union for International Cancer Control TNM classification, sixth edition. The median age was 59 years (range, 33 to 74 years). After induction, 161 (65.4%) of 246 patients with resectable tumors were randomly assigned; strata were tumor-node group, prophylactic cranial irradiation policy, and region. Patient characteristics were balanced between arms, in which 81 were assigned to surgery and 80 were assigned to a chemoradiotherapy boost. In arm B, 81% underwent R0 resection. With a median follow-up after random assignment of 78 months, 5-year OS and progression-free survival (PFS) did not differ between arms. Results were OS rates of 44% for arm B and 40% for arm A (log-rank P = .34) and PFS rates of 32% for arm B and 35% for arm A (log-rank P = .75). OS at 5 years was 34.1% (95% CI, 27.6% to 40.8%) in all 246 patients, and 216 patients (87.8%) received definitive local treatment. CONCLUSION: The 5-year OS and PFS rates in randomly assigned patients with resectable stage III non-small-cell lung cancer were excellent with both treatments. Both are acceptable strategies for this good-prognosis group.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia , Quimioterapia de Inducción , Neoplasias Pulmonares/terapia , Neumonectomía , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino/administración & dosificación , Fraccionamiento de la Dosis de Radiación , Esquema de Medicación , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Análisis de Supervivencia , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , VinorelbinaRESUMEN
BACKGROUND: Adjuvant radiotherapy after breast-conserving surgery (BCS) for breast cancer (BC) is a well-established indication. The risk of ischaemic heart disease after radiotherapy for BC increases linearly with the heart mean dose with no apparent threshold. Radiotherapy to the left breast in deep inspiration breath-hold (DIBH) reduces the dose to the heart. A new linac system with an integrated surface scanner (SS) for DIBH treatments was recently installed in our department. We tested it for potential benefits, safety, patients' acceptance/compliance and associated additional workload. MATERIALS AND METHODS: Twenty consecutive patients following BCS for breast carcinoma of the left side were enrolled in our institutional DIBH protocol. We compared dose to the heart and ipsilateral lung (IL) between plans in DIBH and free breathing (FB) using standard defined parameters: mean dose, maximal dose to a volume of 2 cm(3) (D2 cm (3)), volume receiving ≥ 5 Gy (V5), 10 Gy (V10), 15 Gy (V15) and 20 Gy (V20). Comparison of median calculated dose values was performed using a two-tailed Wilcoxon signed rank test. RESULTS: DIBH was associated with a statistically significant reduction (p < 0.001) in all studied parameters for the heart and the IL. In 16 of 20 patients the heart D2 cm (3) was less than 42 Gy in DIBH. In FB the heart D2 cm (3) was ≥ 42 Gy in 17 of 20 patients. The median daily treatment time was 9 min. CONCLUSION: Radiotherapy of the left breast in DIBH using a SS could easily be incorporated into daily routine and is associated with significant dose reduction to the heart and IL.
Asunto(s)
Neoplasias de la Mama/radioterapia , Contencion de la Respiración , Corazón/efectos de la radiación , Dosis de Radiación , Protección Radiológica/métodos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Factibilidad , Femenino , Humanos , Inhalación , Persona de Mediana Edad , Radiometría , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate megavoltage computed tomography (MVCT)-based image guidance with helical tomotherapy in patients with vertebral tumors by analyzing factors influencing interobserver variability, considered as quality criterion of image guidance. METHODS AND MATERIALS: Five radiation oncologists retrospectively registered 103 MVCTs in 10 patients to planning kilovoltage CTs by rigid transformations in 4 df. Interobserver variabilities were quantified using the standard deviations (SDs) of the distributions of the correction vector components about the observers' fraction mean. To assess intraobserver variabilities, registrations were repeated after ≥4 weeks. Residual deviations after setup correction due to uncorrectable rotational errors and elastic deformations were determined at 3 craniocaudal target positions. To differentiate observer-related variations in minimizing these residual deviations across the 3-dimensional MVCT from image resolution effects, 2-dimensional registrations were performed in 30 single transverse and sagittal MVCT slices. Axial and longitudinal MVCT image resolutions were quantified. For comparison, image resolution of kilovoltage cone-beam CTs (CBCTs) and interobserver variability in registrations of 43 CBCTs were determined. RESULTS: Axial MVCT image resolution is 3.9 lp/cm. Longitudinal MVCT resolution amounts to 6.3 mm, assessed as full-width at half-maximum of thin objects in MVCTs with finest pitch. Longitudinal CBCT resolution is better (full-width at half-maximum, 2.5 mm for CBCTs with 1-mm slices). In MVCT registrations, interobserver variability in the craniocaudal direction (SD 1.23 mm) is significantly larger than in the lateral and ventrodorsal directions (SD 0.84 and 0.91 mm, respectively) and significantly larger compared with CBCT alignments (SD 1.04 mm). Intraobserver variabilities are significantly smaller than corresponding interobserver variabilities (variance ratio [VR] 1.8-3.1). Compared with 3-dimensional registrations, 2-dimensional registrations have significantly smaller interobserver variability in the lateral and ventrodorsal directions (VR 3.8 and 2.8, respectively) but not in the craniocaudal direction (VR 0.75). CONCLUSION: Tomotherapy image guidance precision is affected by image resolution and residual deviations after setup correction. Eliminating the effect of residual deviations yields small interobserver variabilities with submillimeter precision in the axial plane. In contrast, interobserver variability in the craniocaudal direction is dominated by the poorer longitudinal MVCT image resolution. Residual deviations after image guidance exist and need to be considered when dose gradients ultimately achievable with image guided radiation therapy techniques are analyzed.
Asunto(s)
Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Guiada por Imagen/métodos , Radioterapia de Intensidad Modulada/métodos , Neoplasias de la Columna Vertebral/radioterapia , Adulto , Anciano , Neoplasias de la Mama , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/radioterapia , Variaciones Dependientes del Observador , Oncología por Radiación , Errores de Configuración en Radioterapia , Estudios Retrospectivos , Sarcoma/diagnóstico por imagen , Sarcoma/radioterapia , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Neoplasias de la Columna Vertebral/secundario , Tomografía Computarizada EspiralRESUMEN
BACKGROUND: Pemetrexed-based chemotherapy represents the standard of care in first-line treatment of advanced malignant pleural mesothelioma (MPM). However, there are no established predictors of clinical benefit. Pemetrexed inhibits multiple enzymes involved in pyrimidine and purine synthesis, but the main target is thymidylate synthase (TS). After cellular uptake pemetrexed is converted into more effective polyglutamated forms by folylpoly-γ-glutamate synthetase (FPGS). We hypothesized that FPGS and TS protein expressions are associated with clinical outcome after pemetrexed-based chemotherapy. METHODS: Pretreatment tumor samples from 84 patients with histologically confirmed MPM, who received pemetrexed combined with platinum (79 of 84) or single-agent pemetrexed (5 of 84) as first-line treatment, were retrospectively analyzed. FPGS and TS protein expressions were semiquantitatively assessed by using the Hybrid (H)-scoring system (range, 0-300). H-scores were correlated with radiological response according to modified Response Evaluation Criteria in Solid Tumors, progression-free survival (PFS) and overall survival (OS). RESULTS: Median H-score of the entire cohort was 230 for FPGS (range, 100-300), and 210 for TS (range, 100-300). High FPGS protein expression was significantly associated with longer PFS (pCOX = 0.0337), better objective tumor response (partial response versus stable disease + progressive disease; pKW = 0.003), and improved disease-control rate (partial response + stable disease versus progressive disease; pKW = 0.0208), but not with OS. In addition, high TS protein expression was associated with progressive disease under pemetrexed-based therapy (p = 0.0383), and shorter OS (pCOX = 0.0071), but no association with PFS was observed. CONCLUSION: FPGS and TS expressions were associated with clinical response and outcome to pemetrexed-based first-line chemotherapy in MPM. Prospective evaluation of FPGS and TS expressions and their prognostic/predictive power in MPM patients is warranted.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mesotelioma/tratamiento farmacológico , Péptido Sintasas/metabolismo , Neoplasias Pleurales/tratamiento farmacológico , Timidilato Sintasa/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Carboplatino/administración & dosificación , Cisplatino/administración & dosificación , Femenino , Estudios de Seguimiento , Glutamatos/administración & dosificación , Guanina/administración & dosificación , Guanina/análogos & derivados , Humanos , Masculino , Mesotelioma/enzimología , Mesotelioma/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Pemetrexed , Neoplasias Pleurales/enzimología , Neoplasias Pleurales/patología , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Terapia Combinada , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/radioterapia , Recurrencia Local de Neoplasia/etiología , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
For most patients who have stage III non-small cell lung cancer (NSCLC), a combination of chemotherapy and radiation represents the current treatment of choice. Recent developments include the use of adjuvant chemotherapy after up-front surgery in subgroups of patients who have stage III disease, as well as innovative ways to deliver concurrent chemoradiotherapy or combinations of chemotherapy with higher-dose conformal radiotherapy techniques. This article focuses on patients who have stage IIIA NSCLC and reviews the different possibilities for their treatment. Special emphasis is given to the inclusion of surgery into the different approaches to this disease stage. The current literature on this topic is reviewed, and the different aspects of surgical treatment in the management of stage IIIA NSCLC are discussed.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/patología , Estadificación de NeoplasiasRESUMEN
PURPOSE: To reexamine the use of adjuvant radiotherapy in optimally debulked patients. METHODS AND MATERIALS: Between January 1985 and April 1998, 60 patients were treated with adjuvant whole abdominal radiotherapy (A-WART). The stage distribution was Stage IC in 17 patients, Stage II in 9, and Stage III in 34. The grade distribution was Grade 1 in 9 patients, Grade 2 in 27, and Grade 3 in 24; thus, 60% of the patients had Stage III disease and 40% had Grade 3 tumors. After surgery, no residuum was left in 42 (70%),