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1.
Oral Dis ; 2023 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-37466114

RESUMEN

OBJECTIVE: To map oral health-related standard of care in the context of head and neck cancer (HNC) treatment across the European Union (EU). MATERIALS AND METHODS: Six hundred and ninety centers across the European Union were contacted. The questionnaire contained questions focusing on the team/department structure, HNC treatment planning routines, and assessment and handling of dental treatment needs prior to cancer treatment. RESULTS: Eighty-seven centers across the EU responded. Department structure and number of HNC patients treated per year varied widely and dental professionals are included as part of the team in about 25% of the centers. Standard of care, in terms of dental assessment and preventive dentistry routines, such as recording an orthopantomogram, offering dental treatment, and providing a radiation protection splint and splint for fluoride application, differed significantly among the European regions. Independent of the region, these aspects are positively affected if dental professionals are part of the interdisciplinary treatment team and if dental treatment is offered within the center. CONCLUSION: Dental professionals are still only to a very limited extent included in interdisciplinary treatment planning teams of HNC patients. However, their inclusion and/or offering dental treatment within the same hospital/center appears to improve oral health-related standard of care. CLINICAL RELEVANCE: Inclusion of dental professionals in treatment planning teams of HNC patients appears to improve oral health-related standard of care within HNC treatment.

2.
Clin Otolaryngol ; 44(3): 263-272, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30615266

RESUMEN

OBJECTIVE: The objective of this study was to determine the prognostic and predictive impact of ß-catenin, TCF21 and WISP1 expression in patients with squamous cell carcinomas of the head and neck who underwent primary radiotherapy or concomitant chemoradiotherapy. STUDY DESIGN: Prospective cohort study. SETTING: University hospital. PARTICIPANTS: Protein expression profiles of ß-catenin, TCF21, WISP1 and p16 were determined by immunohistochemical analyses in tissue samples of 59 untreated patients. Expression was correlated with different outcome parameters. MAIN OUTCOME MEASURES: Impact of TNM classification, grading, sex, age, gender, type of therapy, response to therapy and p16 status on disease-specific (DSS) and disease-free survival (DFS). RESULTS: Patients with high expression of TCF21 were associated with significantly worse disease-specific survival (P = 0.005). In a multivariable analysis, TCF21 was a significant determinant of disease-specific survival. (HR 3.01; P = 0.036). Conversely, low expression of ß-catenin (P = 0.025) and WISP1 (P = 0.037) revealed a better response to radiotherapy. CONCLUSION: Since data show that TCF21 is a prognostic factor for disease-specific survival and WISP1 and ß-catenin are predictive factors for clinical outcome after definitive radiotherapy, further studies are warranted to prove these preliminary but very promising findings.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/biosíntesis , Proteínas CCN de Señalización Intercelular/biosíntesis , Neoplasias de Cabeza y Cuello/metabolismo , Estadificación de Neoplasias , Proteínas Proto-Oncogénicas/biosíntesis , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , beta Catenina/biosíntesis , Adulto , Austria/epidemiología , Biomarcadores de Tumor/biosíntesis , Quimioradioterapia , Femenino , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/terapia , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Tasa de Supervivencia/tendencias
3.
Strahlenther Onkol ; 191(3): 209-16, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25252603

RESUMEN

INTRODUCTION: In the literature, HPV infection and/or p16 positivity have been consistently demonstrated to correlate with improved response rates in oropharyngeal squamous cell carcinoma (OPSCC) patients treated with primary radiotherapy (RT) alone and in combination with chemotherapy. However, the exact role of HPV/p16 positivity in patients treated with postoperative RT is still unclear. METHODS: We analyzed tumor samples for HPV-DNA and p16 expression and correlated these variables with treatment outcome in a series of 63 consecutively treated oropharyngeal cancer patients (95% stage III/IV). HPV and p16 analysis were performed using validated test systems. Survival was estimated by the Kaplan-Meier method. Cox proportional hazard regression models were applied to compare the risk of death among patients stratified according to risk factors. RESULTS: Expression of p16 or high-risk HPV-DNA was detected in 60.3% and 39.6% of the tumors, respectively. p16 expression [overall survival (OS) at 2 years: 91%] as well as HPV infection (OS at 2 years: 95%) was associated with improved OS. Mean survival in p16-positive patients was 112 months compared to 64.6 months in case of p16 negativity. All HPV-positive tumors stained positive for p16. In a multivariable analysis, p16 positivity was associated with improved OS and with disease-free survival. CONCLUSION: p16 expression and HPV infection are strongly associated with the outcome of postoperatively irradiated OPSCC patients. HPV and p16 double-negative OPSCC patients should be regarded as a distinct "very high-risk patient group" that may benefit from intensified or novel treatment combinations.


Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirugía , Papillomavirus Humano 16 , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/cirugía , Infecciones por Papillomavirus/radioterapia , Infecciones por Papillomavirus/cirugía , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Orofaríngeas/mortalidad , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/virología , Infecciones por Papillomavirus/mortalidad , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Radioterapia Adyuvante , Tasa de Supervivencia
4.
Acta Oncol ; 54(8): 1166-74, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25850583

RESUMEN

UNLABELLED: Anatomical changes in the head-and-neck (H&N) region during the course of treatment can cause deteriorated dose distributions. Different replanning strategies were investigated for volumetric modulated arc therapy (VMAT) and intensity-modulated proton therapy (IMPT). MATERIAL AND METHODS: For six H&N patients two repeated computed tomography (CT) and magnetic resonance (MR) (CT1/MR1 at week 2 and CT2/MR2 at week 4) scans were acquired additionally to the initial planning CT/MR. Organs-at-risk (OARs) and three targets (CTV70Gy, CTV63Gy, CTV56Gy) were delineated on MRs and transferred to respective CT data set. Simultaneously integrated boost plans were created using VMAT (two arcs) and IMPT (four beams). To assess the need of replanning the initial VMAT and IMPT plans were recalculated on repeated CTs. Furthermore, VMAT and IMPT plans were replanned on the repeated CTs. A Demon algorithm was used for deformable registration of the repeated CTs with the initial CT and utilized for dose accumulation. Total dose estimations were performed to compare ART versus standard treatment strategies. RESULTS: Dosimetric evaluation of recalculated plans on CT1 and CT2 showed increasing OAR doses for both, VMAT and IMPT. The target coverage of recalculated VMAT plans was considered acceptable in three cases, while for all IMPT plans it dropped. Adaptation of the treatment reduced D2% for brainstem by 6.7 Gy for VMAT and by 8 Gy for IMPT, for particular patients. These D2% reductions were reaching 9 Gy and 14 Gy for the spinal cord. ART improved target dose homogeneity, especially for protons, i.e. D2% decreased by up to 8 Gy while D98% increased by 1.2 Gy. CONCLUSION: ART showed benefits for both modalities. However, as IMPT is more conformal, the magnitude of dosimetric changes was more pronounced compared to VMAT. Large anatomic variations had a severe impact on treatment plan quality for both VMAT and IMPT. ART is justified in those cases irrespective of treatment modalities.


Asunto(s)
Neoplasias de Cabeza y Cuello/radioterapia , Terapia de Protones/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Humanos , Imagen por Resonancia Magnética , Imagen Multimodal , Radiometría/métodos , Tomografía Computarizada por Rayos X
7.
Head Neck ; 45(8): 2087-2097, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37345576

RESUMEN

OBJECTIVE: Nephrotoxicity is frequent in cisplatin-based chemoradiation of head and neck squamous cell carcinoma (HNSCC). Toxicity outcomes and achieved cisplatin-doses after change of departmental hydration policy are presented. METHODS: We performed a retrospective time-series analysis of HNSCC patients undergoing chemoradiation with conventional hydration (CH) between 01/2017 and 09/2018 versus shorter hydration with mannitol (SHM) between 09/2018 and 08/2019 to compare the rate of acute kidney injury (AKI) and cumulative cisplatin dose. RESULTS: Among 113 HNSCC patients, SHM (n = 35) in comparison to CH (n = 78) correlated with less AKI (54.3% vs. 74.4%; p = 0.034) and higher cisplatin doses (82.9% vs. 61.5% ≥200 mg/m2 ; p = 0.025). AKI ≥grade 2 was lower with SHM (2.9% vs. CH: 22.8%; p = 0.01). AKI occurred more frequently in females (92.6% vs. males: 60.5%, p = 0.002). Females received lower cumulative cisplatin doses (51.9% vs. males: 73.3%; p = 0.037). CONCLUSIONS: We observed less AKI and higher cumulative chemotherapy doses with SHM. Female patients were at higher risk of AKI.


Asunto(s)
Lesión Renal Aguda , Antineoplásicos , Neoplasias de Cabeza y Cuello , Masculino , Humanos , Femenino , Cisplatino/efectos adversos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Manitol/uso terapéutico , Antineoplásicos/efectos adversos , Estudios Retrospectivos , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Riñón
8.
J Clin Med ; 11(10)2022 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-35628813

RESUMEN

Objective: To evaluate the impact of radiotherapy (RT) on dysphagia and long-term swallowing outcome in patients with stage III and IV head and neck squamous cell carcinomas (HNSCCs). Material and Methods: Between 2005 and 2008, 189 patients with HNSCCs underwent primary or adjuvant RT in a curative setting. Long-term swallowing outcome was evaluated in 50 patients. Among them, 26 were further eligible for prospective analysis of long-term swallowing and dysphagia outcome. Medical charts were retrospectively reviewed regarding pre- and post-treatment dysphagia (3 months after last irradiation setting) as well as persisting long-term dysphagia (2019−2021). Results: Pre-treatment dysphagia was observed in 24 (48%) of 50 patients, particularly in oropharyngeal or hypopharyngeal stage III−IV tumors (OR 9.3; p = 0.003). Conversely, 46 patients (92%) complained about post-treatment dysphagic symptoms, which were more commonly seen in patients with positive neck nodes (OR 10.5; p = 0.037). The post-treatment dysphagia rate dropped from 92% to 24% (p < 0.001) during surveillance, which was significantly linked to xerostomia (OR 5.77; p = 0.019), dysgeusia (OR 9.9; p = 0.036) and free flap reconstruction (OR 6.1; p = 0.022). Conclusion: Pretreatment dysphagia is common in advanced stage HNSCCs and almost all patients complain about dysphagia at the end of RT. Importantly, applied RT protocols did not affect long-term dysphagia, which improves significantly in the majority of patients over time. Meeting Information: Preliminary results have been presented at the 65th Annual Meeting of the Austrian Society of Otorhinolaryngology, 22−26 September 2021, Austria.

9.
Wien Klin Wochenschr ; 133(21-22): 1117-1121, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34143263

RESUMEN

BACKGROUND: The aim was to assess the prognostic value of the newly proposed prognostic index (PI) in patients with p16-positive oropharyngeal squamous cell carcinoma. METHODS: Patients treated with primary surgery from 2012 to 2019 with available preoperative (0-2 days) values of C­reactive protein and white blood cell counts needed for calculation of the PI, were included. Main outcome measures were overall survival (OS) and disease-free survival (DFS). The PI was dichotomized into low (PI = 0) and high (PI ≥ 1). RESULTS: In this study 36 patients were included. Average overall (OS) and disease-free survival (DFS) were 3.3 years (range 0.2-12.3 years) and 2.8 years (0.0-9.8 years), respectively. The overall mortality was 16.7% (n = 6) and a recurrent disease was observed in 30.6% of patients (n = 11). Low PI was associated with better overall survival (mean OS 10.1 ± 1.4 years, 95% confidence interval, CI 7.3-12.9 years vs. 1.9 ± 0.4, 95% CI 1.3-2.6 years, p < 0.01; mean DFS 8.5 ± 0.7 years, 95% CI 7.1-9.6 years vs. 1.0 ± 0.3 years, 95% CI 0.5-1.5 years, p < 0.01). CONCLUSION: The PI might be an easily obtainable outcome prognosticator in p16-positive oropharyngeal squamous cell carcinoma patients. Analyzing routinely obtained blood samples can contribute to identifying high-risk patients.


Asunto(s)
Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Supervivencia sin Enfermedad , Humanos , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/terapia , Pronóstico , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello
10.
Eur J Cancer ; 151: 201-210, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34022697

RESUMEN

PURPOSE: Induction chemotherapy (ICT) with cisplatin (P), 5-FU (F) and taxanes (T) is a therapeutical option in patients suffering from locally advanced or unresectable stage III or IV squamous cell carcinoma of the head and neck (SCCHN). The role of ICT is controversial, and toxicity and/or delay of radiotherapy (RT) may reduce the potential benefit of this treatment regimen. Here, we report the results of a randomised phase II trial comparing TPF with TP + cetuximab (C). PATIENTS AND METHODS: In this trial, 100 patients with locally advanced stage III or IV SCCHN were included in the analysis. Patients were randomly assigned to either TPF-ICT (N = 49) or TPC-ICT (N = 51), both followed by RT + C. The primary end-point of the study was overall response rate (ORR) three months after RT + C was finished. RESULTS: On an intention-to-treat basis, the ORR (complete remission + partial remission) was 74.5% in the TPC arm compared with 63.3% in the TPF arm (p = 0.109). OS was similar in both arms 400 days after treatment was initiated (86.1% [95% confidence interval {CI}, 73.0-93.1%] in the TPC arm and 78.5% [95% CI, 63.7-87.8%] in the TPF arm). TPC resulted in slightly less serious adverse events and in less haematological, but more skin toxicities. Two patients randomised in the TPC arm died during ICT and RT. Four patients in the TPF arm died after completion of RT. No delay from the end of ICT to RT + C was observed. A total of 83.1% of patients (80% in the TPC arm; 86% in the TPF arm) received RT without dose reduction and/or modification. CONCLUSION: TPC-containing ICT for patients with locally advanced SCCHN was found to be an effective and tolerable one-day regimen. Further prospective evidence from larger trials is warranted.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cetuximab/uso terapéutico , Cisplatino/uso terapéutico , Docetaxel/uso terapéutico , Fluorouracilo/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Austria , Cetuximab/efectos adversos , Cisplatino/efectos adversos , Docetaxel/efectos adversos , Femenino , Fluorouracilo/efectos adversos , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Quimioterapia de Inducción , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Inducción de Remisión , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Factores de Tiempo , Resultado del Tratamiento
11.
Cancer Chemother Pharmacol ; 62(5): 903-10, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18256835

RESUMEN

PURPOSE: In Her2-postive metastatic breast carcinoma, first-line trastuzumab-based therapy is well established; many centres continue antibody treatment beyond disease progression. In this trial, we evaluated the efficacy and safety of gemcitabine and trastuzumab after earlier exposure to anthracyclines, docetaxel and/or vinorelbine, and trastuzumab. METHODS: Twenty-nine consecutive patients were included as eligible. Patients received gemcitabine at a dose of 1,250 mg/m2 on day one and eight, every 21 days. Trastuzumab was administered in three-week cycles. Clinical benefit rate (CBR; CR + PR + SD > or = 6 months) was defined as primary endpoint. RESULTS: As of July 2007, all patients are evaluable for toxicity, and 26 for response. Earlier therapies consisted of trastuzumab (100%), anthracyclines (100%), vinorelbine (96.6%), docetaxel (72.4%), and capecitabine (72.4%). 19.2% of patients experienced PR, and SD > or = 6 months was observed in a further 26.9%, resulting in a CBR of 46.2%. Time to progression was median 3 months, and overall survival 17 months. Neutropenia (20.7%), thrombocytopenia (13.8%), and nausea (3.4%) were the only treatment-related adverse events that occurred with grade 3 or 4 intensity. Four patients (13.8%) developed brain metastases while on therapy. CONCLUSIONS: While CBR was low when compared to trastuzumab-based first-line therapy, it is higher than what would be expected from gemcitabine monotherapy in a similar setting. Together with the favourable toxicity profile, this regimen appears to be a safe and potentially effective salvage therapy option in a heavily pre-treated population.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Terapia Recuperativa , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Progresión de la Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Trastuzumab , Insuficiencia del Tratamiento , Gemcitabina
12.
Clin Cancer Res ; 13(15 Pt 1): 4435-9, 2007 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-17671127

RESUMEN

PURPOSE: It has been hypothesized that response to endocrine therapy for breast cancer depends on Her2 and progesterone receptor status, grading, and tumor proliferation rate. In this study, we evaluated factors that are potentially predictive of response and time to progression in patients treated with fulvestrant. EXPERIMENTAL DESIGN: One hundred fifty-five patients were included and followed prospectively. Patients received fulvestrant at standard dose by i.m. injection. Response was evaluated every 3 months using International Union Against Cancer criteria. Time to progression and overall survival were estimated with the Kaplan-Meier product limit method. A multivariate analysis was done to evaluate factors potentially influencing response and time to progression. RESULTS: We observed a partial response in 19 patients (12.3%), stable disease > or =6 months in 56 patients (36.1%), stable disease >3 months but <6 months in 7 patients (4.5%), and progressive disease in 73 patients (47.1%). Median time to progression was 5 months, and median overall survival was 27 months. Probability of achieving clinical benefit was significantly associated with a low proliferation rate (P = 0.015), nonvisceral metastatic sites (P = 0.023), and first-line therapy (P = 0.023). First-line therapy was also associated with prolonged time to progression (P = 0.003). CONCLUSIONS: Response rate and time to progression are shown to be independent of Her2 status, grading, and progesterone receptor status. This is probably caused by the unique mechanism of action associated with fulvestrant: Due to receptor down-regulation, it blocks nuclear, cytoplasmatic, and membrane-bound estrogen receptor. Therefore, it seems to inhibit the cross-talk between growth factor receptor signaling and estrogen receptor in a more effective manner.


Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Estradiol/análogos & derivados , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/secundario , Carcinoma Lobular/tratamiento farmacológico , Carcinoma Lobular/metabolismo , Carcinoma Lobular/secundario , Progresión de la Enfermedad , Estradiol/uso terapéutico , Femenino , Fulvestrant , Humanos , Persona de Mediana Edad , Posmenopausia , Estudios Prospectivos , Resultado del Tratamiento
13.
BMC Clin Pharmacol ; 7: 7, 2007 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-17640356

RESUMEN

BACKGROUND: A synergistic cytotoxic effect has been hypothesized for taxanes and capecitabine, a prodrug of 5-fluorouracil. Based on preclinical studies, this synergism has been attributed to an up-regulation of the enzyme thymidine phosphorylase (TP). Beside tumour tissue, TP is highly expressed in white blood cells, possibly causing increased hematotoxicity, when taxanes are combined with capecitabine. So far, this hypothesis has not been investigated in humans. METHODS: A total of 128 consecutive blood samples were collected from eight patients with advanced breast cancer receiving paclitaxel weekly at a dose of 80 mg/m2. To assess the expression of TP in blood cells, samples were collected prior to first therapy, at the end of infusion, and up to 15 days thereafter. This procedure was repeated during the sixth application of paclitaxel. After isolation of the peripheral mononuclear blood cells, the expression of TP was assessed by ELISA. In parallel, paclitaxel level in plasma was evaluated at three selected time points as pharmacokinetic control parameter. RESULTS: Paclitaxel concentrations at the end of infusion did not change significantly from week 1 to week 6. The expression of TP in peripheral mononuclear blood cells decreased significantly after infusion below pretherapeutic values (p = 0.023; n = 8). After the nadir on day 3, the expression of TP increased moderately returning to baseline levels within one week. The overall picture in week 6 was similar to week 1. Using a trend analysis, neither a short-term nor a long-term induction of TP was observed. CONCLUSION: TP in peripheral mononuclear blood cells was hardly regulated under therapy with paclitaxel. Therefore, no increased haematotoxicity due to TP upregulation is expected from the combination of taxanes and capecitabine.


Asunto(s)
Neoplasias de la Mama/enzimología , Regulación Enzimológica de la Expresión Génica/fisiología , Leucocitos Mononucleares/enzimología , Paclitaxel/uso terapéutico , Timidina Fosforilasa/biosíntesis , Anciano , Neoplasias de la Mama/sangre , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Persona de Mediana Edad , Paclitaxel/farmacología , Timidina Fosforilasa/sangre
14.
Acta Otolaryngol ; 137(3): 320-325, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27739348

RESUMEN

CONCLUSION: On the one hand, AZD5582, an inhibitor of inhibitor of apoptosis family proteins (IAP), leads to cellular growth arrest and induction of apoptosis in head and neck squamous cell carcinoma (HNSCC) cell lines. On the other hand, it is a viable candidate for combination therapy with irradiation. OBJECTIVES: The aim and purpose of this study was to evaluate the effects of AZD5582 on HNSCC cell lines. METHODS: HNSCC cell lines SCC25, Cal27, and FaDu were used for all cell culture experiments. Proliferation assays were used to assess a potential inhibitory effect of AZD5582 and a combination therapy of the IAP inhibitor and irradiation. Colony forming assays were used to determine long-term effects of a combined treatment. Apoptosis was measured via flow cytometry and wound-healing assays were performed. RESULTS: All three cell lines showed a dose-dependent cytotoxic effect after treatment with AZD5582. It was possible to observe a synergistic and additive effect after short-term treatment of AZD5582 and irradiation in Ca27 and FaDu cells, respectively. All test cell lines showed a significant inhibition of colony formation after combined treatment. Treatment of AZD5582 resulted in apoptosis in SCC25, Cal27, and FaDu cells.


Asunto(s)
Alquinos/uso terapéutico , Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeza y Cuello/terapia , Oligopéptidos/uso terapéutico , Alquinos/farmacología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Quimioradioterapia , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Oligopéptidos/farmacología
15.
Head Neck ; 39(7): 1421-1427, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28452184

RESUMEN

BACKGROUND: Sinonasal carcinomas are rare. The purpose of this study was for us to present our assessment of the effects of retropharyngeal lymph node involvement at diagnosis on patient outcomes. METHODS: Retropharyngeal lymph node involvement in 36 patients with sinonasal carcinoma was determined by radiology at initial presentation. Clinical outcome, in particular, overall survival (OS) and locoregional control, was assessed by Kaplan-Meier analysis and log-rank testing. RESULTS: Retropharyngeal lymph node involvement was associated with statistically significant decreased OS (P = .0066) in the patient collective. In the squamous cell carcinoma (SCC) subgroup (n = 23), decreased OS (P = .0046) and worse locoregional control (P = .0065) were observed. In these patients, decreased OS (P = .0423) and worse locoregional control (P = .0315) were also seen in the advanced tumor subgroup. CONCLUSION: Retropharyngeal lymph node involvement at diagnosis is a significant prognostic factor for decreased OS and locoregional control in sinonasal carcinoma.


Asunto(s)
Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Ganglios Linfáticos/patología , Neoplasias de los Senos Paranasales/mortalidad , Neoplasias de los Senos Paranasales/patología , Faringe/patología , Adulto , Anciano , Anciano de 80 o más Años , Austria , Carcinoma de Células Escamosas/cirugía , Estudios de Cohortes , Supervivencia sin Enfermedad , Hospitales Universitarios , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática/patología , Persona de Mediana Edad , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Neoplasias de los Senos Paranasales/cirugía , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Tasa de Supervivencia
16.
BMC Cancer ; 6: 63, 2006 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-16539726

RESUMEN

BACKGROUND: Combining trastuzumab and chemotherapy is standard in her2/neu overexpressing advanced breast cancer. It is not established however, whether trastuzumab treatment should continue after the failure of one earlier combination. In this trial, we report our experience with continued treatment beyond disease progression. METHODS: Fifty-four patients, median age 46 years, range 25-73 years, were included. We analysed for time to tumour progression (TTP) for first, second and beyond second line treatment, response rates and overall survival. RESULTS: Median time of observation was 24 months, range 7-51. Response rates for first line treatment were 7.4% complete remission (CR), 35.2% partial remissions (PR), 42.6% stable disease > 6 months (SD) and 14.8% of patients experienced disease progression despite treatment (PD). Corresponding numbers for second line were 3.7% CR, 22.2% PR, 42.6% SD and 31.5% PD; numbers for treatment beyond second line (60 therapies, 33 pts 3rd line, 18 pts 4th line, 6 pts 5th line, 2 pts 6th line and 1 patient 7th line) were 1.7% CR, 28.3% PR, 28.3% SD and 41.6% PD respectively. Median TTP was 6 months (m) in the first line setting, and also 6 m for second line and beyond second line. An asymptomatic drop of left ventricular ejection fraction below 50% was observed in one patient. No case of symptomatic congestive heart failure was observed. CONCLUSION: The data presented clearly strengthen evidence that patients do profit from continued trastuzumab treatment. The fact that TTP did not decrease significantly from first line to beyond second line treatment is especially noteworthy. Still, randomized trials are warranted.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/mortalidad , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Trastuzumab , Insuficiencia del Tratamiento , Resultado del Tratamiento
17.
BMC Cancer ; 6: 81, 2006 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-16563172

RESUMEN

BACKGROUND: At many centres tumour markers are used to detect disease recurrence and to monitor response to therapy in patients with advanced disease, although the real value of serial observation of marker levels remains disputed. In this study, we evaluated the prognostic value of tumour markers for predicting response (partial response [PR], stable disease [SD] > or = 6 months), de novo disease progression (PD) and secondary PD in patients receiving fulvestrant ('Faslodex') 250 mg/month for the treatment of metastatic breast cancer (MBC). METHODS: Changes in cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) were prospectively monitored (monthly) and were also evaluated for the 3 months preceding secondary PD. Data from 67 patients with previously treated MBC participating in a Compassionate Use Programme were analysed. RESULTS: In patients with a PR (n = 7 [10.4%]), a non-significant increase in CA 15-3 occurred during the first 6 months of treatment; CEA was significantly reduced (P = 0.0165). In patients with SD >/= 6 months (n = 28 [41.8%]), both CA 15-3 (P < 0.0001) and CEA (P = 0.0399) levels increased significantly after 6 months treatment. In those experiencing de novo PD (n = 32 [47.8%]), CA 15-3 increased significantly (P < 0.0001) after 4 months; CEA also increased significantly (P = 0.0002) during the same time period. Both CA 15-3 (P < 0.0001) and CEA (P < 0.0001) increased significantly in the 3 months preceding secondary PD. CONCLUSION: CA 15-3 increases in patients progressing on fulvestrant but may also increase in those experiencing clinical benefit; this should not be taken as a sign of PD without verification. Overall, both CA 15-3 and CEA appear to be poor prognostic markers for determining progression in patients receiving fulvestrant.


Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Antígeno Carcinoembrionario/sangre , Estradiol/análogos & derivados , Mucina-1/sangre , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Estradiol/uso terapéutico , Femenino , Fulvestrant , Humanos , Inyecciones Intramusculares , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Sensibilidad y Especificidad , Resultado del Tratamiento
19.
Int J Radiat Oncol Biol Phys ; 82(2): e265-72, 2012 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-21620581

RESUMEN

PURPOSE: It is generally agreed that the safe implementation of stereotactic body radiotherapy requires image guidance. The aim of this work was to assess interobserver variability in the delineation of lung lesions on cone-beam CT (CBCT) images compared with CT-based contouring for adaptive stereotactic body radiotherapy. The influence of target size was also evaluated. METHODS AND MATERIALS: Eight radiation oncologists delineated gross tumor volumes in 12 patient cases (non-small cell lung cancer I-II or solitary metastasis) on planning CTs and on CBCTs. Cases were divided into two groups with tumor diameters of less than (Group A) or more than 2 cm (Group B). Comparison of mean volumes delineated by all observers and range and coefficient of variation were reported for each case and image modality. Interobserver variability was assessed by means of standard error of measurement, conformity index (CI), and its generalized observer-independent approach. The variance between single observers on CT and CBCT images was measured via interobserver reliability coefficient. RESULTS: Interobserver variability on CT images was 17% with 0.79 reliability, compared with 21% variability on CBCT and 0.76 reliability. On both image modalities, values of the intraobserver reliability coefficient (0.99 for CT and 0.97 for CBCT) indicated high reproducibility of results. In general, lower interobserver agreement was observed for small lesions (CI(genA) = 0.62 ± 0.06 vs. CI(genB) = 0.70 ± 0.03, p < 0.05). The analysis of single patient cases revealed that presence of spicules, diffuse infiltrations, proximity of the tumors to the vessels and thoracic wall, and respiration motion artifacts presented the main sources of the variability. CONCLUSION: Interobserver variability for Stage I-II non-small cell lung cancer and lung metastasis was slightly higher on CBCT compared with CT. Absence of significant differences in interobserver variability suggests that CBCT imaging provides an effective tool for tumor localization, and image data could be also used for target volume delineation purposes.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Tomografía Computarizada de Haz Cónico , Neoplasias Pulmonares/diagnóstico por imagen , Radiocirugia , Carga Tumoral , Análisis de Varianza , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Humanos , Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Variaciones Dependientes del Observador , Oncología por Radiación , Planificación de la Radioterapia Asistida por Computador/métodos , Reproducibilidad de los Resultados , Estadísticas no Paramétricas , Tomografía Computarizada por Rayos X/métodos
20.
J Clin Oncol ; 25(25): 3853-8, 2007 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-17679724

RESUMEN

PURPOSE: In human epidermal growth factor 2 (HER-2)-positive advanced breast cancer, taxanes or vinorelbine plus trastuzumab are among the most widely applied options in the first-line setting. We evaluated the efficacy and tolerability of capecitabine plus trastuzumab after anthracycline and docetaxel or vinorelbine failure and prior trastuzumab exposure. PATIENTS AND METHODS: Forty consecutive patients were included. Capecitabine was administered at a dose of 1,250 mg/m(2) bid for 14 consecutive days in 3-week cycles, with dose modifications if necessary. Trastuzumab was administered every 3 weeks. Time to progression (TTP) was defined as primary end point. Response was evaluated every 3 months using International Union Against Cancer criteria. RESULTS: TTP was a median of 8 months, and overall survival was 24 months. No significant difference was found for second-line and beyond second-line treatment. A complete response (CR) was observed in 2.5%, partial response (PR) in 17.5%, stable disease lasting at least 6 months (SD) in 50%, resulting in a clinical benefit rate (CR + PR + SD > or = 6 months) of 70%. Diarrhea (5%) and hand-foot syndrome (15%) were the only treatment-related adverse events that occurred with grade 3 or 4 intensity. Three patients (7.5%) developed brain metastases while receiving therapy. CONCLUSION: Capecitabine plus trastuzumab appears to be an effective and safe option in a heavily pretreated population. Therefore, a direct comparison of this regimen with capecitabine monotherapy in this setting is warranted.


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Fluorouracilo/análogos & derivados , Adulto , Anciano , Antraciclinas/administración & dosificación , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Encefálicas/secundario , Capecitabina , Desoxicitidina/administración & dosificación , Diarrea/inducido químicamente , Progresión de la Enfermedad , Docetaxel , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Enfermedades Hematológicas/inducido químicamente , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Tasa de Supervivencia , Taxoides/administración & dosificación , Trastuzumab , Insuficiencia del Tratamiento , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , Vinorelbina
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