Aberrant expression of tyrosine kinases such as c-erbB and EGFR contributes to the progression of... more Aberrant expression of tyrosine kinases such as c-erbB and EGFR contributes to the progression of head and neck squamous cell carcinomas (HNSCCs). One mechanism may be potentiation of angiogenesis, since upregulation of vascular endothelial growth factor (VEGF) expression by activation of epidermal growth factor receptor (EGFR) and/or c-erbB-2 has been described. Firstly, we demonstrated expression of all 4 members of the VEGF family in a panel of 15 HNSCC cell lines which over-express one or more c-erbB receptors. We then explored the regulatory roles of three major ligands with different selectivity of binding to c-erbB receptors (namely transforming growth factor-alpha (TGF-alpha), betacellulin (BTC) and heregulin-beta1 (HRG-beta1)) on VEGF-A, B, C and D expression in selected HNSCC lines. Using semi-quantitative reverse transcription-PCR, we showed that all three c-erbB ligands up-regulated VEGF-A mRNA (all isoforms) and VEGF-C (BTC max at 1-10 nM; TGF-alpha and HRG-beta1 max at...
Despite advances in conservative laryngeal surgery and radiotherapy, total laryngectomy still rem... more Despite advances in conservative laryngeal surgery and radiotherapy, total laryngectomy still remains the procedure of choice for advanced-stage laryngeal carcinoma around the world. The loss of natural voice is very often traumatic for the total laryngectomy patient, presenting lifelong challenges for communication in a world that relies heavily on verbal communication. Functional rehabilitation of these patients has long been one of the major challenges facing clinicians, but it is only in the last three decades that the emphasis on restoration of function and quality of life has become almost as important as cure and survival. Although voice restoration for alaryngeal speakers can be attained with any of 3 speech options - esophageal speech, electrolarynx and surgical voice restoration (SVR) using a valve the SVR technique has today become the preferred method and 'gold standard.' Successful tracheo-esophageal voice restoration in laryngectomy patients can be very rewardi...
Archives of otolaryngology--head & neck surgery, 2001
To assess the utility of a previously proposed staging system for patients with primary squamous ... more To assess the utility of a previously proposed staging system for patients with primary squamous cell carcinoma of the temporal bone. Retrospective chart review of 15 patients treated for squamous cell carcinoma of the temporal bone over a 13-year period at an academic tertiary referral center. A review of the medical and surgical records, radiographic studies, and surgical pathology reports allowed for an evaluation of the University of Pittsburgh staging system. Outcome analysis was performed on 13 patients with more than 24 months of follow-up. Radiographic and surgical pathology staging according to the University of Pittsburgh staging system correlated in 11 (73%) of 15 cases. The radiographic staging system was more accurate for larger (T3/T4) tumors than for smaller (T1/T2) tumors (83% vs 67%). When compared with patients with no evidence of disease, nonsurvivors were more likely to present with otalgia (67% vs 43%), facial nerve paralysis (33% vs 0%), and T3/T4 tumors (100% ...
Evidence suggests that there is an association between the abnormal expression of members of the ... more Evidence suggests that there is an association between the abnormal expression of members of the c-erbB receptor tyrosine kinase family and poor prognosis in head and neck squamous cell carcinomas (HNSCC). Until now, the relative contributions of different c-erbB ligands to HNSCC progression have not been clearly defined. In this paper we examined the effects of ligands with different c-erbB receptor specificities in terms of their stimulation of HNSCC proliferation, expression of matrix metalloproteinases (MMPs) and invasion. Heregulin-beta1 (HRG-beta1; selective c-erbB3/B4 ligand) was found to stimulate proliferation in the majority of cell lines, whereas epidermal growth factor (EGF; EGFR ligand) and betacellulin (BTC; EGFR/B4 ligand) induced variable responses. All three ligands up-regulated multiple MMPs including collagenases, stromelysins, matrilysin and gelatinase B (MMP-9) but had minimal or no effects on gelatinase A (MMP-2), MT1-MMP and tissue inhibitors of MMPs (TIMPs). ...
Squamous cell carcinoma involving the oral cavity (OC) and oropharynx regions are a major cause o... more Squamous cell carcinoma involving the oral cavity (OC) and oropharynx regions are a major cause of morbidity and mortality world-wide. The recent discovery of a strong association between human papilloma virus (HPV) infection and OC and oropharyngeal (OP) cancer has prompted world-wide research into the exact etiology and pathogenesis of these cancers in relation to the HPV. HPV-positive OC/OP cancers generally present at a relatively advanced stage (by virtue of cervical nodal involvement) and are more commonly seen in younger patients without significant exposure to alcohol or tobacco. These factors are implicated in prognosis, regardless of HPV association. In this article, we review the biology and epidemiology, risk factors, association, molecular analyses, treatment response and prognosis of HPV-related cancers. Role of HPV vaccination in HPV-related OC/OP cancers has also been discussed.
Head and neck squamous cell carcinomas (HNSCCs) are characterized by a marked propensity for loca... more Head and neck squamous cell carcinomas (HNSCCs) are characterized by a marked propensity for local invasion and dissemination to cervical lymph nodes, with distant metastases developing in 30 - 40% of cases. Overexpres- sion of the epidermal growth factor receptor (EGFR/c-erbB-1) and/or its ligands and high levels of certain matrix metalloproteinases (MMPs) have been associated with poor prognosis. The aim
Francis and colleagues reported an association between blood transfusion and worsened cancer prog... more Francis and colleagues reported an association between blood transfusion and worsened cancer prognosis. Since then there has been much debate over whether there is in fact such an association. We propose a possible mechanism which could explain much of the conflicting clinical and experimental evidence, and which can be readily tested experimentally. It is suggested that the extracellular accumulation of bioactive factors in blood transfusion products can directly and indirectly cause tumour growth and hence a worsening of prognosis. This theory can be applied both in vitro and in vivo. Two separate UK studies have shown that perioperative blood transfusion is associated with worsened prognosis in head and neck squamous cell cancer patients. Furthermore, pilot experiments have shown that as blood ages, endothelial growth factors are leached from the metabolically compromised red cell. We believe that we have provided a rationale to explain the conflicting findings of research to dat...
Background Acoustic evaluation (AE) of speech is the least explored method of speech evaluation i... more Background Acoustic evaluation (AE) of speech is the least explored method of speech evaluation in oral cavity (OC) and oropharyngeal (OP) cancer patients. The aim of this study was to explore acoustic parameters of speech and their correlation with questionnaire evaluation (QE) and perceptual evaluation (PE) in OC and OP cancer patients. Methods One hundred and seventeen subjects (65 consecutive OC and OP cancer patients and 52 controls) participated. Formant frequencies (by Linear Predictive Coding), Speech Handicap Index and London Speech Evaluation scale were used for AE, QE and PE, respectively. Results Males showed significant elevation in second formant (F2) values for OC cancer patients and those who underwent surgery alone. Female patients with early T stage cancers and those who underwent surgery and chemo-radiation showed significant reduction in the mean F2 values. Importantly, however, AE parameters did not correlate with either PE or QE parameters, although there was moderate correlation between QE and PE speech parameters. Conclusions AE modalities have no clear role in the management of OC and OP cancer patients. This article is protected by copyright. All rights reserved.
Treatment of extensive recurrent cervical lymph node metastases from previously irradiated head a... more Treatment of extensive recurrent cervical lymph node metastases from previously irradiated head and neck cancer represents a difficult clinical challenge. We report the results of an approach of maximal surgical debulking and manually after-loaded intra-operative brachytherapy. Seventy-four procedures were carried out at the Royal Marsden Hospital between 1979 and 2003. All patients had previously been treated with radical radiotherapy or chemoradiation. Patients underwent maximal surgical debulking, followed by brachytherapy to the tumour bed with low-dose rate (192)Ir to a dose of 60 Gy to the reference isodose using the Paris system. Overall and disease specific survival rates were 31% and 28% at two years and 23% and 17% at five years. Corresponding Loco-regional control rates were 37% and 23%, respectively. Fifty per cent of patients developed metastatic disease within 5 years of treatment. Best results were obtained with surgical excision, brachytherapy and reconstruction of the skin defect using a vascularised myo-cutaneous flap with in-field control rates of 72% at two years and 66% at 5 years. Nine per cent of patients developed fistulae, 4% had haemorrhage and 8% wound breakdown/infection. Maximal surgical debulking, including removal of overlying skin, and brachytherapy to the surgical tumour bed provides high levels of local control, and can be achieved with acceptable morbidity. Only a minority of patients achieve long-term survival because of the high risk of systemic relapse.
Treatment of recurrent nasopharyngeal carcinoma is a difficult clinical problem. External beam re... more Treatment of recurrent nasopharyngeal carcinoma is a difficult clinical problem. External beam re-irradiation is associated with a long-term cure in a proportion of cases but this may be associated with severe radiation injury. Eighteen patients with post-nasal space tumours were treated between 1986 and 2001 with surgical excision and nasopharyngeal brachytherapy via a Le Fort I osteotomy approach. Low-dose rate (LDR) and high-dose rate (HDR) brachytherapy was used. Data was prospectively collected. Local control and overall survival were measured. Acute and late complications were assessed using the RTOG system. The overall survival was 67% at 2 years and 33.5% at 5 years. The corresponding local control rates were 42 and 31.5%, respectively. The T stage at relapse was a significant prognostic factor for local control (P=0.004) but not overall survival. Acute toxicity was mild. RTOG grade >/=3 late complications occurred in 40% of patients treated with the HDR, and 0% treated with LDR. The results of the Le Fort osteotomy, tumour debulking and post-operative brachytherapy gives local control rates similar to those achieved with wide-field re-irradiation. Complication rates are acceptable and are lower than that reported with other methods of radiation therapy. The surgical technique was well tolerated. HDR brachytherapy with this technique had a high complication rate. This approach is a viable option in the treatment of recurrent nasopharyngeal tumours.
Aberrant expression of tyrosine kinases such as c-erbB and EGFR contributes to the progression of... more Aberrant expression of tyrosine kinases such as c-erbB and EGFR contributes to the progression of head and neck squamous cell carcinomas (HNSCCs). One mechanism may be potentiation of angiogenesis, since upregulation of vascular endothelial growth factor (VEGF) expression by activation of epidermal growth factor receptor (EGFR) and/or c-erbB-2 has been described. Firstly, we demonstrated expression of all 4 members of the VEGF family in a panel of 15 HNSCC cell lines which over-express one or more c-erbB receptors. We then explored the regulatory roles of three major ligands with different selectivity of binding to c-erbB receptors (namely transforming growth factor-alpha (TGF-alpha), betacellulin (BTC) and heregulin-beta1 (HRG-beta1)) on VEGF-A, B, C and D expression in selected HNSCC lines. Using semi-quantitative reverse transcription-PCR, we showed that all three c-erbB ligands up-regulated VEGF-A mRNA (all isoforms) and VEGF-C (BTC max at 1-10 nM; TGF-alpha and HRG-beta1 max at...
Despite advances in conservative laryngeal surgery and radiotherapy, total laryngectomy still rem... more Despite advances in conservative laryngeal surgery and radiotherapy, total laryngectomy still remains the procedure of choice for advanced-stage laryngeal carcinoma around the world. The loss of natural voice is very often traumatic for the total laryngectomy patient, presenting lifelong challenges for communication in a world that relies heavily on verbal communication. Functional rehabilitation of these patients has long been one of the major challenges facing clinicians, but it is only in the last three decades that the emphasis on restoration of function and quality of life has become almost as important as cure and survival. Although voice restoration for alaryngeal speakers can be attained with any of 3 speech options - esophageal speech, electrolarynx and surgical voice restoration (SVR) using a valve the SVR technique has today become the preferred method and 'gold standard.' Successful tracheo-esophageal voice restoration in laryngectomy patients can be very rewardi...
Archives of otolaryngology--head & neck surgery, 2001
To assess the utility of a previously proposed staging system for patients with primary squamous ... more To assess the utility of a previously proposed staging system for patients with primary squamous cell carcinoma of the temporal bone. Retrospective chart review of 15 patients treated for squamous cell carcinoma of the temporal bone over a 13-year period at an academic tertiary referral center. A review of the medical and surgical records, radiographic studies, and surgical pathology reports allowed for an evaluation of the University of Pittsburgh staging system. Outcome analysis was performed on 13 patients with more than 24 months of follow-up. Radiographic and surgical pathology staging according to the University of Pittsburgh staging system correlated in 11 (73%) of 15 cases. The radiographic staging system was more accurate for larger (T3/T4) tumors than for smaller (T1/T2) tumors (83% vs 67%). When compared with patients with no evidence of disease, nonsurvivors were more likely to present with otalgia (67% vs 43%), facial nerve paralysis (33% vs 0%), and T3/T4 tumors (100% ...
Evidence suggests that there is an association between the abnormal expression of members of the ... more Evidence suggests that there is an association between the abnormal expression of members of the c-erbB receptor tyrosine kinase family and poor prognosis in head and neck squamous cell carcinomas (HNSCC). Until now, the relative contributions of different c-erbB ligands to HNSCC progression have not been clearly defined. In this paper we examined the effects of ligands with different c-erbB receptor specificities in terms of their stimulation of HNSCC proliferation, expression of matrix metalloproteinases (MMPs) and invasion. Heregulin-beta1 (HRG-beta1; selective c-erbB3/B4 ligand) was found to stimulate proliferation in the majority of cell lines, whereas epidermal growth factor (EGF; EGFR ligand) and betacellulin (BTC; EGFR/B4 ligand) induced variable responses. All three ligands up-regulated multiple MMPs including collagenases, stromelysins, matrilysin and gelatinase B (MMP-9) but had minimal or no effects on gelatinase A (MMP-2), MT1-MMP and tissue inhibitors of MMPs (TIMPs). ...
Squamous cell carcinoma involving the oral cavity (OC) and oropharynx regions are a major cause o... more Squamous cell carcinoma involving the oral cavity (OC) and oropharynx regions are a major cause of morbidity and mortality world-wide. The recent discovery of a strong association between human papilloma virus (HPV) infection and OC and oropharyngeal (OP) cancer has prompted world-wide research into the exact etiology and pathogenesis of these cancers in relation to the HPV. HPV-positive OC/OP cancers generally present at a relatively advanced stage (by virtue of cervical nodal involvement) and are more commonly seen in younger patients without significant exposure to alcohol or tobacco. These factors are implicated in prognosis, regardless of HPV association. In this article, we review the biology and epidemiology, risk factors, association, molecular analyses, treatment response and prognosis of HPV-related cancers. Role of HPV vaccination in HPV-related OC/OP cancers has also been discussed.
Head and neck squamous cell carcinomas (HNSCCs) are characterized by a marked propensity for loca... more Head and neck squamous cell carcinomas (HNSCCs) are characterized by a marked propensity for local invasion and dissemination to cervical lymph nodes, with distant metastases developing in 30 - 40% of cases. Overexpres- sion of the epidermal growth factor receptor (EGFR/c-erbB-1) and/or its ligands and high levels of certain matrix metalloproteinases (MMPs) have been associated with poor prognosis. The aim
Francis and colleagues reported an association between blood transfusion and worsened cancer prog... more Francis and colleagues reported an association between blood transfusion and worsened cancer prognosis. Since then there has been much debate over whether there is in fact such an association. We propose a possible mechanism which could explain much of the conflicting clinical and experimental evidence, and which can be readily tested experimentally. It is suggested that the extracellular accumulation of bioactive factors in blood transfusion products can directly and indirectly cause tumour growth and hence a worsening of prognosis. This theory can be applied both in vitro and in vivo. Two separate UK studies have shown that perioperative blood transfusion is associated with worsened prognosis in head and neck squamous cell cancer patients. Furthermore, pilot experiments have shown that as blood ages, endothelial growth factors are leached from the metabolically compromised red cell. We believe that we have provided a rationale to explain the conflicting findings of research to dat...
Background Acoustic evaluation (AE) of speech is the least explored method of speech evaluation i... more Background Acoustic evaluation (AE) of speech is the least explored method of speech evaluation in oral cavity (OC) and oropharyngeal (OP) cancer patients. The aim of this study was to explore acoustic parameters of speech and their correlation with questionnaire evaluation (QE) and perceptual evaluation (PE) in OC and OP cancer patients. Methods One hundred and seventeen subjects (65 consecutive OC and OP cancer patients and 52 controls) participated. Formant frequencies (by Linear Predictive Coding), Speech Handicap Index and London Speech Evaluation scale were used for AE, QE and PE, respectively. Results Males showed significant elevation in second formant (F2) values for OC cancer patients and those who underwent surgery alone. Female patients with early T stage cancers and those who underwent surgery and chemo-radiation showed significant reduction in the mean F2 values. Importantly, however, AE parameters did not correlate with either PE or QE parameters, although there was moderate correlation between QE and PE speech parameters. Conclusions AE modalities have no clear role in the management of OC and OP cancer patients. This article is protected by copyright. All rights reserved.
Treatment of extensive recurrent cervical lymph node metastases from previously irradiated head a... more Treatment of extensive recurrent cervical lymph node metastases from previously irradiated head and neck cancer represents a difficult clinical challenge. We report the results of an approach of maximal surgical debulking and manually after-loaded intra-operative brachytherapy. Seventy-four procedures were carried out at the Royal Marsden Hospital between 1979 and 2003. All patients had previously been treated with radical radiotherapy or chemoradiation. Patients underwent maximal surgical debulking, followed by brachytherapy to the tumour bed with low-dose rate (192)Ir to a dose of 60 Gy to the reference isodose using the Paris system. Overall and disease specific survival rates were 31% and 28% at two years and 23% and 17% at five years. Corresponding Loco-regional control rates were 37% and 23%, respectively. Fifty per cent of patients developed metastatic disease within 5 years of treatment. Best results were obtained with surgical excision, brachytherapy and reconstruction of the skin defect using a vascularised myo-cutaneous flap with in-field control rates of 72% at two years and 66% at 5 years. Nine per cent of patients developed fistulae, 4% had haemorrhage and 8% wound breakdown/infection. Maximal surgical debulking, including removal of overlying skin, and brachytherapy to the surgical tumour bed provides high levels of local control, and can be achieved with acceptable morbidity. Only a minority of patients achieve long-term survival because of the high risk of systemic relapse.
Treatment of recurrent nasopharyngeal carcinoma is a difficult clinical problem. External beam re... more Treatment of recurrent nasopharyngeal carcinoma is a difficult clinical problem. External beam re-irradiation is associated with a long-term cure in a proportion of cases but this may be associated with severe radiation injury. Eighteen patients with post-nasal space tumours were treated between 1986 and 2001 with surgical excision and nasopharyngeal brachytherapy via a Le Fort I osteotomy approach. Low-dose rate (LDR) and high-dose rate (HDR) brachytherapy was used. Data was prospectively collected. Local control and overall survival were measured. Acute and late complications were assessed using the RTOG system. The overall survival was 67% at 2 years and 33.5% at 5 years. The corresponding local control rates were 42 and 31.5%, respectively. The T stage at relapse was a significant prognostic factor for local control (P=0.004) but not overall survival. Acute toxicity was mild. RTOG grade >/=3 late complications occurred in 40% of patients treated with the HDR, and 0% treated with LDR. The results of the Le Fort osteotomy, tumour debulking and post-operative brachytherapy gives local control rates similar to those achieved with wide-field re-irradiation. Complication rates are acceptable and are lower than that reported with other methods of radiation therapy. The surgical technique was well tolerated. HDR brachytherapy with this technique had a high complication rate. This approach is a viable option in the treatment of recurrent nasopharyngeal tumours.
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Papers by Peter Rhys-Evans