Predictive value of hypoxia in advanced head and neck cancer after treatment with hyperfractionated radio-chemotherapy and hypoxia modification

Purpose. Hypoxia has predictive value in head and neck cancer (HNC). It has been well described, albeit in a small number of clinical Centres. The aim of this study was to describe our experience using the polarographic probe technique to assess the predictive value of tumour oxygenation in patients with advanced HNC treated with hyperfractionated radio-chemotherapy. Hypoxia modification was induced using percutaneous spinal cord stimulation (SCS). Methods/patients. Male patients (n = 12; stage IVb n = 8; IVa n = 4; mean age 58: range 46-70 years) with advanced HNC were evaluated. Planned therapy was hyperfractionated-radiotherapy, oral tegafur (precursor of 5-fluorouracil) and hypoxia modification using SCS. Pre-treatment analyses included: haemoglobin levels and tumour oxygenation (using the Eppendorf polarographic probe device). Oxygenation was expressed as median-pO2 (in mmHg) and hypoxia as the percentage of pO2 values ≤5 mmHg (HP5) and ≤2.5 mmHg (HP2.5). Results. Lower haemoglobin levels were directly correlated with median pO2 (p = 0.017) and inversely correlated with HP5 (p = 0.020) and more advanced stages (IVb vs. IVa; p = 0.028). Patients who subsequently developed systemic metastasis had tumours that were more hypoxic, with lower median pO2 (p = 0.036) and higher HP5 (p = 0.036). The subgroup of patients with HP2.5 above the median (the most hypoxic tumours) had lower loco-regional control (p = 0.027), cause-specific survival (p = 0.008), and overall survival (p = 0.008). Conclusions. Higher tumour hypoxia showed predictive value in HNC in our study, and was significantly associated with lower overall survival, cause-specific survival, and loco-regional control. Tumour hypoxia determination could be used to select patients who would most benefit by hypoxia modification during chemo-radiotherapy of HNC (AU)

No disponible

Predictive value of hypoxia in advanced head and neck cancer after treatment with hyperfractionated radio-chemotherapy and hypoxia modification.

PURPOSE: Hypoxia has predictive value in head and neck cancer (HNC). It has been well described, albeit in a small number of clinical Centres. The aim of this study was to describe our experience using the polarographic probe technique to assess the predictive value of tumour oxygenation in patients with advanced HNC treated with hyperfractionated radio-chemotherapy. Hypoxia modification was induced using percutaneous spinal cord stimulation (SCS). METHODS/PATIENTS: Male patients (n = 12; stage IVb n = 8; IVa n = 4; mean age 58: range 46-70 years) with advanced HNC were evaluated. Planned therapy was hyperfractionated-radiotherapy, oral tegafur (precursor of 5-fluorouracil) and hypoxia modification using SCS. Pre-treatment analyses included: haemoglobin levels and tumour oxygenation (using the Eppendorf polarographic probe device). Oxygenation was expressed as median-pO2 (in mmHg) and hypoxia as the percentage of pO2 values ≤5 mmHg (HP5) and ≤2.5 mmHg (HP2.5). RESULTS: Lower haemoglobin levels were directly correlated with median pO2 (p = 0.017) and inversely correlated with HP5 (p = 0.020) and more advanced stages (IVb vs. IVa; p = 0.028). Patients who subsequently developed systemic metastasis had tumours that were more hypoxic, with lower median pO2 (p = 0.036) and higher HP5 (p = 0.036). The subgroup of patients with HP2.5 above the median (the most hypoxic tumours) had lower loco-regional control (p = 0.027), cause-specific survival (p = 0.008), and overall survival (p = 0.008). CONCLUSIONS: Higher tumour hypoxia showed predictive value in HNC in our study, and was significantly associated with lower overall survival, cause-specific survival, and loco-regional control. Tumour hypoxia determination could be used to select patients who would most benefit by hypoxia modification during chemo-radiotherapy of HNC.

Plasminogen activator inhibitor-1 (PAI-1) expression in relation to hypoxia and oncoproteins in clinical cervical tumors.

PURPOSE: Explore the role of plasminogen activator inhibitor-1 (PAI-1) in cervical cancer and its relationship to hypoxia and the expression of p53, Ku70/80, and cyclin D1. MATERIAL AND METHODS: The expression of PAI-1, cyclin D1, and p53, together with tumor oxygenation, were determined in 43 consecutive patients suffering from localized cervical carcinoma. Oncoprotein expression was determined by immunohistochemistry. Tumor oxygenation was measured using a polarographic probe system, "pO2 histography." RESULTS: PAI expression was considered negative in 32.6% and overexpressed in 18.6% of cases. Cyclin D1 showed a median expression of 5.0 (range 0-70). We observed a positive association between PAI expression and altered p53 (p = 0.049) and cyclin D1 (p = 0.020). An inverse association was detected between PAI and Ku70/80 expression (p = 0.042). Cyclin D1 staining increased according to tumor volume (r = 0.314, p = 0.009). We did not observe a significant association between PAI and hypoxia or other clinicopathological parameters. CONCLUSION: The present results show that PAI-1 overexpression is associated with nonhomologous end-joining DNA repair down-regulation (low Ku70/80 expression) and with increased p53 and cyclin D1 expression, and they suggest that PAI-1 plays a role in the tumor behavior in cervical carcinoma.

Modification of loco-regional microenvironment in brain tumors by spinal cord stimulation. Implications for radio-chemotherapy.

The effectiveness of radiotherapy and chemotherapy in high grade gliomas (HGG) depends on tumor micro-environment. We summarize our experience of the influence of spinal cord stimulation (SCS) on this micro-environment. Patients with HGG (n = 26) were assessed pre- and post-SCS, using: (1) Doppler in middle cerebral arteries (MCA) and (2) in common carotid arteries (CCA); (3) tumor blood-flow using single photon emission computed tomography (SPECT); (4) tumor-pO(2) (mmHg) using polarographic probes (eight tumor areas from five patients); and (5) tumor glucose metabolism using (18)F-fluoro-2-deoxyglucose ((18)FDG) positron emission tomography ((18)FDG-PET). Pre-SCS: tumor blood-flow was lower (P < 0.001) than peri-tumor areas and healthy contra-lateral areas. Tumor-pO(2) was lower (P < 0.042) than healthy tissue. Tumor glucose metabolism was higher than peri-tumor areas (P = 0.017) and healthy contra-lateral areas (P = 0.048). Post-SCS: there were increases in: MCA blood-flow (P ≤ 0.002), CCA blood-flow (P ≤ 0.013), tumor blood-flow (P = 0.033), tumor glucose metabolism (P = 0.027) and tumor-pO(2) (P = 0.022). The percentage of hypoxic values decreased (P = 0.007). SCS can modify tumor micro-environment. The potential usefulness of SCS in improving the effectiveness of radio-chemotherapy in HGG needs to be evaluated.

Opioides en el dolor raquídeo. Relación riesgo/beneficio y estrategia apropiada para su utilización / Opioids in spinal pain. Risk/benefit ratio and an appropriate strategy for their use

En los últimos años se ha observado un incremento notable en el uso de los opioides en España, por lo que queda ampliamente superada nuestra tradicional posición en el furgón de cola de los prescriptores de opioides en Europa. Este crecimiento se ha reflejado también en el tratamiento de uno de los síndromes dolorosos de mayor prevalencia: el dolor raquídeo. Sin embargo, la eficacia de los opioides administrados de forma crónica para el tratamiento del dolor raquídeo no está clara, aunque cada vez sí son más patentes los riesgos que hemos de asumir: adicción, conductas aberrantes, probable incremento en el tiempo de incapacidad laboral y múltiples efectos secundarios, como la hiperalgesia o el estreñimiento rebelde al tratamiento. Teniendo en cuenta una relación riesgo/beneficio estrecha para este tratamiento, planteamos que estos fármacos sólo los han de prescribir facultativos que puedan realizar un seguimiento atento de los pacientes, pacientes en los que se han agotado otras opciones terapéuticas, incluidas diferentes técnicas antiálgicas y a los cuales habremos informado ampliamente de su correcta utilización y posibles efectos secundarios (AU)

In the last few years there has been a notable increase in the use of opioids in our country, overcoming our traditional position at the end of the queue of opioid prescribers in Europe. This growth has also been reflected in the treatment of highly prevalent pain syndromes, such as spinal pain. However, the efficacy of opioids administered chronically for spinal pain is not clear, due to the risks that have to be assumed being obvious: addiction, aberrant behaviour, probable increase in time off sick and the many secondary effects, such as hyperalgesia or persistent constipation with treatment. Taking into account the narrow risk/benefit ratio for this treatment, we assume that these drugs have been prescribed only by physicians who can closely follow up the patients, patients in whom other options are exhausted, including different analgesic techniques and those who will have been amply informed on their correct use and possible side effects (AU)

Spinal cord stimulation in the treatment of post-stroke patients: current state and future directions.

A decrease in cerebral blood flow (CBF) and brain metabolic activity are well-known complications of stroke. Spinal cord stimulation (SCS) is successfully being used for the treatment of several low-perfusion syndromes. The aim of this chapter is to describe the data that support the effect of SCS on CBF and the use of SCS in the treatment of stroke and cerebral low perfusion syndromes. In addition, we present our relevant studies. Since April 1995, we have assessed 49 non-stroke patients. The following parameters were measured pre- and post-stroke: (1) CBF in healthy contralateral tissue by single photon emission computed tomography (SPECT), (2) systolic and diastolic velocity in the middle cerebral artery (MCA) by transcranial Doppler, (3) blood flow quantification in the common carotid artery (CCA) by color Doppler, and (4) glucose metabolism in healthy contralateral tissue by positron emission tomography (PET). Our results showed that during cervical SCS there was a significant (p < 0.001) increase in systolic (> or =21%) and diastolic (>26%) velocity in the MCA, and CCA blood flow (> or =51%) as well as glucose metabolism (44%). We concluded that cervical SCS (cSCS) can modify CBF and brain metabolism. Its potential role in the management of stroke and low-perfusion syndromes is further investigated by experimental studies and reports describing clinical experience. Appropriate clinical trials are warranted.

The role of spinal cord stimulation in the management of patients with brain tumors.

High grade gliomas (HGG) have decreased blood flow resulting in hypoxia, limited access by chemotherapeutic agents, and reduced radiation-sensitivity. Spinal cord stimulation (SCS) has been used successfully in the treatment of pain and ischemic syndromes. The present article summarizes our investigations into the effects of SCS in patients with HGG. Before their scheduled radio-chemotherapy, 23 patients with HGG were assessed pre- and post-SCS using several evaluation techniques: (1) transcranial Doppler (TCD) for middle cerebral artery blood flow; (2) color Doppler for common carotid artery blood flow; (3) single photon emission computed tomography (SPECT) for tumor blood flow; (4) polarographic probe technique for tumor pO2 measurement; (5) positron emission tomography (PET) for tumor glucose metabolism. Pre-SCS, the tumors were more ischemic and more hypoxic than healthy tissues. Post-SCS, there was significant: (1) increase in blood flow measured by TCD (> or =18%), color Doppler (> or =61%) and SPECT (15%), (2) increase in oxygenation and decrease (> or =45%) in percentage of hypoxic values <10 mmHg and <5 mmHg, and (3) increase (43%) in glucose metabolism. Our studies show that SCS can modify loco-regional blood flow and oxygen supply, as well as glucose-metabolism in HGG. This suggests that SCS could prove useful as an adjuvant treatment to radio-chemotherapy. These data merit further confirmatory studies.

Cerebral blood flow increase in cancer patients by applying cervical spinal cord stimulation.

INTRODUCTION: Generally, high-grade gliomas and head and neck tumors have decreased loco-regional blood flow resulting in reduced delivery of chemotherapy and oxygen, as well as an increases in radiation resistance to radiotherapy. The aim of this study was to analyze the effect of cervical spinal cord electrical stimulation (cSCS) on cerebral blood flow in patients with those tumors. PATIENTS AND METHODS: We have evaluated 27 cancer patients with 12 with high grade gliomas and 15 with advanced head and neck tumors, who had cSCS devices placed after tumor diagnoses and before the commencement initiating of radio-chemotherapy. They were 12 high grade gliomas and 15 advanced head and neck tumors. Before and after cSCS, cerebral blood flow was assessed bilaterally by transcranial Doppler. RESULTS: During cSCS there was a significant (p<0.001) increase in systolic (mean > 22%) and diastolic (> 29%) blood-flow velocities in both, healthy and tumor middle cerebral arteries. The analyses by subgroup of tumors showed similarly significant outcomes findings. CONCLUSIONS: The results suggest that neuro-stimulation spinal cord electrical stimulation can increase cerebral blood flow in cancer patients. The implication is that this technique could be useful in modifying locoregional ischemia in brain tumors thus improving the outcomes of after radio-chemotherapy. Further research is in progress to confirm the advantages of the technique.

Cerebral blood flow increase in cancer patients by applying cervical spinal cord stimulation

Introducción. Los gliomas de alto grado y los tumores avanzados de cabeza y cuello generalmente tienen un flujo sanguíneo disminuido. Esto produce una disminución de la llegada de quimioterapia agentes quimioterápicos y oxígeno, lo que lleva a un aumento de la resistencia a la radioterapia y a la quimioterapia. El objetivo de este estudio fue analizar el efecto de la electroestimulación epidural de la médula espinal cervical(EME) sobre el flujo cerebral en pacientes con esos tumores. Material y métodos. Hemos evaluado 27 pacientes oncológicos portando dispositivos de EME, que fueron colocados después del diagnóstico y antes de empezar el tratamiento con radio-quimioterapia. Se trata de 12 pacientes con gliomas de alto grado y 15 pacientes con tumores avanzados de cabeza y cuello. Antes y después de la EME se determinó bilateralmente el flujo sanguíneo en las arterias cerebrales medias mediante Doppler transcraneal. Resultados. Durante la EME se produjo un aumento significativo (p<0.001) de la velocidad sistólica (mean media >=22%) y diastólica (>=29%) del flujo en la arteria cerebral media, tanto del hemisferio ipsilateral al tumor como del hemisferio sano. El análisis por subgrupos de tumores mostró también resultados semejantes. Discusión. Los resultados sugieren que la EME es capaz de aumentar el flujo sanguíneo cerebral en pacientes oncológicos. La principal implicación de este hallazgo sería su potencial utilidad para modificar la isquemia local y regional de los tumores cerebrales, y así intentar mejorar el efecto de la radioterapia y quimioterapia. Están en marcha estudios adicionales para confirmarlos potenciales efectos beneficiosos de la técnica

Introduction. Generally, high-grade gliomas and head and neck tumors have decreased loco-regional blood flow resulting in reduced delivery of chemotherapy and oxygen, as well as an increases in radiation resistance to radiotherapy. The aim of this study was to analyze the effect of cervical spinal cord electrical stimulation (cSCS) on cerebral blood flow in patients with those tumors. Patients and methods. We have evaluated 27 cancer patients with 12 with high grade gliomas and 15 with advanced head and neck tumors, who had cSCS devices placed after tumor diagnoses and before the commencement initiating of radio-chemotherapy. They were 12high grade gliomas and 15 advanced head and neck tumors. Before and after cSCS, cerebral blood flow was assessed bilaterally by transcranial Doppler. Results. During cSCS there was a significant(p<0.001) increase in systolic (mean >22%) and diastolic(>29%) blood-flow velocities in both, healthy and tumor middle cerebral arteries. The analyses by subgroup of tumors showed similarly significant outcomes findings. Conclusions. The results suggest that neuro-stimulation spinal cord electrical stimulation can increase cerebral blood flow in cancer patients. The implication is that this technique could be useful in modifying locoregional ischemia in brain tumors thus improveing the outcomes of after radio-chemotherapy. Further research is in progress to confirm the advantages of the technique

Radioterapia y anemia: nuevas bases / No disponible

No disponible

Effect of cervical spinal cord stimulation on regional blood flow and oxygenation in advanced head and neck tumours.

BACKGROUND: Tumour ischaemia leads to decreased delivery of oxygen, chemotherapy and radiosensitisers. Hypoxia in head and neck (H&N) tumours is an important adverse prognostic factor. Spinal cord stimulation (SCS) is a well-established neurosurgical technique in the treatment of several ischaemic syndromes. This prospective study evaluated the effect of cervical-SCS on common carotid artery (CCA) blood flow and tumour oxygenation in patients with advanced H&N cancer. PATIENTS AND METHODS: Sixteen patients with advanced H&N tumours were enrolled. Cervical-SCS devices were inserted subcutaneously prior to commencement of scheduled chemoradiotherapy. Pre- and post-SCS measurements were as follows: (i) tumour oxygenation (mmHg) using polarographic probes; (ii) blood flow quantification (ml/min) and diastolic and systolic velocimetry (cm/s) in the CCA using colour Doppler. RESULTS: After SCS, median tumour oxygenation increased in two-thirds of patients (34%; P = 0.023), all patients had improved CCA blood flow (50%; P <0.001) and almost all patients showed an increased CCA diastolic velocity (26%; P = 0.003) and systolic velocity (20%; P = 0.011). CONCLUSIONS: Cervical-SCS increased tumour oxygenation and CCA blood flow, and could enhance the loco-regional delivery of oxygen, radiosensitising and chemotherapeutic drugs. Cervical-SCS as adjuvant in chemoradiotherapy of these tumours warrants further investigation.

Carcinoma epidermoide de cérvix tratado con radioterapia radical: factores clásicos de pronóstico y resultados / Epidermoid carcinoma of the cervic treated with radical radiotherapy: classical prognostic factors and results

Objetivo: El estudio en una serie homogénea de pacientes, de la influencia de factores clásicos de pronóstico (edad, estadio clínico, tamaño tumoral, grado histológico, afectación ganglionar) en relación con la respuesta, control local y supervivencia, nos permitirá la identificación de factores que deberían ser controlados en el diseño de futuros estudios.Sujetos y métodos: Se han incluido entre diciembre de 1977 y abril de 1999 204 pacientes diagnosticadas de carcinoma epidermoide de cérvix y tratadas con RT radical. Cincuenta y cuatro pacientes (26 por ciento) eran estadio Ib, 112 (55 por ciento) estadio II y 38 (19 por ciento) estadio III. El tamaño medio tumoral fue 4,11 cm (1-9). La mayoría presentaban tumores grado II (43 por ciento) o III (45 por ciento). En 152 pacientes se evaluó la afectación ganglionar mediante TAC, que estuvo presente en 20 casos (13 por ciento). Resultados: El tamaño tumoral se relacionó directamente con el estadio (p < 0,015), y de forma inversa con la edad (p < 0,0001). Se observó diferencia significativa en la afectación ganglionar entre los estadios I vs II-III (p < 0,02). Ciento cincuenta y tres pacientes tuvieron respuesta completa (75 por ciento). El control local fue del 74, 67 y 65 por ciento a 1, 5 y 10 años, respectivamente. Tanto la respuesta como el control local se relacionaron estrechamente con el estadio y el tamaño tumoral en el análisis multivariante (AM). La supervivencia causa-específica fue del 85, 67 y 62 por ciento a 1, 5 y 10 años, respectivamente. La respuesta fue el principal factor predictivo de supervivencia en el AM seguida del estadio.Conclusiones: La extensión de la enfermedad (estadio clínico, tamaño tumoral) es el factor predictivo más relevante de respuesta completa, y ésta a su vez es el principal factor pronóstico de supervivencia por su impacto en la esfera local del proceso. Sin embargo, pacientes con idéntica extensión y volumen de la enfermedad muestran evoluciones diferentes, por lo que la importancia de otras características biológicas tumorales en la respuesta a RT y en la supervivencia será motivo de estudios posteriores (AU)