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Biomedical subjects

J M Henk

Publications and source records attributed to J M Henk.

At least 19 recordsLinked to original sources
PubMed2006

Randomized phase II study of GM-CSF to reduce mucositis caused by accelerated radiotherapy of laryngeal cancer.

Acute mucositis is dose-limiting in many accelerated radiotherapy schedules for head and neck cancer. Cytokines may be one means of reducing the severity of mucositis. A study was designed to assess the effect of subcutaneous molgramostin (granulocyte-macrophage colony stimulating factor; GM-CSF) injections on acute radiation morbidity in patients undergoing accelerated radiotherapy for laryngeal cancer. A prospective, randomized, observer-blind, controlled trial was conducted in 29 patients who were to receive radical radiotherapy over 3 weeks for early stage laryngeal cancer. Patients were randomized to receive 150 microg (approximately 2 microg kg(-1)) GM-CSF subcutaneously once daily for 14 days after the second week of radiotherapy, or no GM-CSF. Patients were assessed weekly for grade of mucositis, skin reactions and related parameters. The severity of mucositis was reduced in the GM-CSF arm (p<0.05). No other end-points reached statistical significance. Two patients failed to complete their courses of GM-CSF. Three developed influenza type symptoms and in one an allergic reaction was noted. There was no difference in tumour control rates. Subcutaneous GM-CSF reduced the severity of mucositis in patients undergoing accelerated radiotherapy. Injections were well tolerated. Further studies of cytokines are warranted, to assess the feasibility of increasing the total doses of accelerated radiotherapy given, with the aim of improving tumour cure rates.

Aged↗
PubMed2003

Mucosal malignant melanoma of the head and neck: the Marsden experience over half a century.

We reviewed patients treated at The Royal Marsden Hospital for mucosal malignant melanoma of the head and neck between 1945 and 1996. The analysis included 89 patients, and this study is the largest so far reported from a single institution in the literature. The overall 5-year survival rate for the patient population was 23% (95% confidence interval: 14-33) and the 10-year survival rate was 12%, (6-21%). The only significant predictor of survival was the tumour stage at presentation. Radical local excision was the only treatment that provided a chance of cure. Adding radiotherapy to surgery in tumours that could be radically excised did not confer any statistically significant advantage in reducing local recurrence or improving survival.

Adult↗
PubMed2003

Raynaud's phenomenon after radical radiotherapy for tumours of the head and neck.

Endothelial cell injury is implicated in the development of radiation induced tissue damage and may also be involved in the pathophysiology of secondary Raynaud's phenomenon. Two patients are presented in whom the typical symptoms and signs of Raynaud's phenomenon developed as a late complication of radical radiotherapy. One had Raynaud's of the tongue and one of the lip. Both patients had a prior history of primary Raynaud's phenomenon and in each case the symptoms were repeatedly precipitated by sudden cold exposure. The possible pathogenesis of radiation induced Raynaud's phenomenon in the head and neck region is discussed.

Aged↗
PubMed2003

Definitive radiotherapy for extramedullary plasmacytomas of the head and neck.

Extramedullary plasmacytoma of the head and neck region (EMPHN) is an uncommon malignant plasma cell neoplasm. In this study we conducted a retrospective analysis of our experience of EMPHN with particular emphasis on the role of definitive radiotherapy. From 1982 to 2001, 10 patients (6 males, 4 females) with EMPHN were treated in our institution. Of nine patients treated at initial diagnosis, all received definitive radiotherapy. One patient treated at relapse underwent surgical resection followed by post-operative radiotherapy. The median age at diagnosis was 55 years (range 35-84 years). The disease was most frequently localized in the paranasal sinuses (50%). All nine patients who received definitive radiotherapy at a dose of 40-50 Gy achieved a complete response. The median follow up period was 29 months (range 7-67 months). Four patients (40%) relapsed, three have died of their disease. Two patients (20%) with paranasal sinus disease subsequently relapsed with multiple myeloma at 10 months and 24 months, respectively. Our results indicate that treatment of EMPHN with radiotherapy achieves excellent rates of local control. The relapse rate in neck nodes of 10% does not justify elective irradiation of the uninvolved neck.

Adult↗
PubMed2001

Potential role of intensity-modulated radiotherapy in the treatment of tumors of the maxillary sinus.

PURPOSE: To assess 3-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) techniques to see whether doses to critical structures could be reduced while maintaining planning target volume (PTV) coverage in patients receiving conventional radiotherapy (RT) for carcinoma of the maxillary sinus because of the risk of radiation-induced complications, particularly visual loss. METHODS AND MATERIALS: Six patients who had recently received conventional RT for carcinoma of the maxillary sinus were studied. Conventional RT, 3D-CRT, and step-and-shoot IMRT plans were prepared using the same 2-field arrangement. The effect of reducing the number of segments in the IMRT beams was investigated. RESULTS: 3D-CRT and IMRT reduced the brain and ipsilateral parotid gland doses compared with the conventional plans. IMRT reduced doses to both optic nerves; for the contralateral optic nerve, 15-segment IMRT plans delivered an average maximal dose of 56.4 Gy (range 53.9-59.3) compared with 65.7 Gy (range 65.3-65.9) and 64.2 Gy (range 61.4-65.6) for conventional RT and 3D-CRT, respectively. IMRT also gave improved PTV homogeneity and improved coverage, with an average of 8.5% (range 7.0-11.7%) of the volume receiving <95% of the prescription dose (64 Gy) compared with 14.7% (range 14.1-15.9%) and 15.1% (range 14.4-16.1%) with conventional RT and 3D-CRT, respectively. Little difference was found between the 15 and 7-segment plans, but 5 segments resulted in a reduced minimal PTV dose. CONCLUSIONS: IMRT offers significant advantages over conventional RT and 3D-CRT techniques for treatment of maxillary sinus tumors. Good results can be obtained from 7 segments per beam without compromising the PTV coverage. This number of segments is practical for implementation in a busy RT department.

Humans↗
PubMed2001

Optimisation of radiotherapy for carcinoma of the parotid gland: a comparison of conventional, three-dimensional conformal, and intensity-modulated techniques.

BACKGROUND AND PURPOSE: To compare external beam radiotherapy techniques for parotid gland tumours using conventional radiotherapy (RT), three-dimensional conformal radiotherapy (3DCRT), and intensity-modulated radiotherapy (IMRT). To optimise the IMRT techniques, and to produce an IMRT class solution. MATERIALS AND METHODS: The planning target volume (PTV), contra-lateral parotid gland, oral cavity, brain-stem, brain and cochlea were outlined on CT planning scans of six patients with parotid gland tumours. Optimised conventional RT and 3DCRT plans were created and compared with inverse-planned IMRT dose distributions using dose-volume histograms. The aim was to reduce the radiation dose to organs at risk and improve the PTV dose distribution. A beam-direction optimisation algorithm was used to improve the dose distribution of the IMRT plans, and a class solution for parotid gland IMRT was investigated. RESULTS: 3DCRT plans produced an equivalent PTV irradiation and reduced the dose to the cochlea, oral cavity, brain, and other normal tissues compared with conventional RT. IMRT further reduced the radiation dose to the cochlea and oral cavity compared with 3DCRT. For nine- and seven-field IMRT techniques, there was an increase in low-dose radiation to non-target tissue and the contra-lateral parotid gland. IMRT plans produced using three to five optimised intensity-modulated beam directions maintained the advantages of the more complex IMRT plans, and reduced the contra-lateral parotid gland dose to acceptable levels. Three- and four-field non-coplanar beam arrangements increased the volume of brain irradiated, and increased PTV dose inhomogeneity. A four-field class solution consisting of paired ipsilateral coplanar anterior and posterior oblique beams (15, 45, 145 and 170 degrees from the anterior plane) was developed which maintained the benefits without the complexity of individual patient optimisation. CONCLUSIONS: For patients with parotid gland tumours, reduction in the radiation dose to critical normal tissues was demonstrated with 3DCRT compared with conventional RT. IMRT produced a further reduction in the dose to the cochlea and oral cavity. With nine and seven fields, the dose to the contra-lateral parotid gland was increased, but this was avoided by optimisation of the beam directions. The benefits of IMRT were maintained with three or four fields when the beam angles were optimised, but were also achieved using a four-field class solution. Clinical trials are required to confirm the clinical benefits of these improved dose distributions.

Humans↗
PubMed2000

Combined treatment of adenoid cystic carcinoma of the salivary glands.

A retrospective review of the experience of a single surgeon over a 20-year period is presented. Fifteen patients with primary adenoid cystic carcinoma of the major (6) or minor (9) salivary glands underwent combined treatment with wide local excision and radical postoperative radiotherapy. The actuarial survival is 100% at 5 years and 62% at 10 and 15 years. The disease-specific survival is 100% at 5 years and 86% at 10 and 15 years. There were no loco-regional recurrences. Wide local excision and radical postoperative radiotherapy seems to be an effective treatment for adenoid cystic carcinoma of the salivary glands.

Adult↗
PubMed1998

Pilot study of nimorazole as a hypoxic-cell sensitizer with the "chart" regimen in head and neck cancer.

PURPOSE: A potential disadvantage of accelerated fractionation in radiotherapy is the lack of time for reoxygenation, so that hypoxia becomes a more potent cause of failure. Accordingly, we have combined nimorazole, the only hypoxic radiosensitizer shown to significantly improve local control in head and neck cancer, with continuous hyperfractionated accelerated radiation therapy (CHART). METHODS AND MATERIALS: Twenty-two patients with locally advanced (stage IV) squamous cell carcinoma of the head and neck were treated with escalating doses of nimorazole given concomitantly with CHART (three fractions of 1.5 Gy per day, spaced 5 1/2 hours apart, on 12 consecutive days). All patients received 1.2 g/m2 nimorazole 90 minutes before each first daily fraction. Seventeen patients received a further 0.6 g/m2 before each second daily fraction and six of these patients received an additional dose of 0.6 g/m2 before each third fraction. RESULTS: The three times daily schedule yielded mean plasma drug concentrations at the time of irradiation of 37.7 microg/ml with the morning fractions, 31.2 microg/ml with the afternoon fractions, and 30.4 microg/ml with the evening fractions. In view of these results the midday dose was increased to 0.9 microg/m2 in an ongoing Phase II study. Drug toxicity was limited to nausea and vomiting apart from two cases of mild paraesthesia at the highest dose level. CONCLUSIONS: Comparison with a historical group of patients, treated with the CHART regimen alone and matched for irradiation volume and technique, showed that nimorazole did not increase the severity of acute normal tissue radiation effects. Encouraging tumor responses have been seen in the patients receiving nimorazole with every radiotherapy fraction.

Carcinoma, Squamous Cell↗
PubMed1998

Excision and low-dose radiotherapy for refractory laryngeal granuloma.

Laryngeal granulomas are uncommon lesions of an inflammatory origin. They are conventionally managed by simple excision with the occasional use of adjuvant treatment depending on the aetiological factors. Unfortunately, recurrences can occur, requiring repeated excision. Some lesions are refractory to this approach and alternative management approaches include excision and immediate adjuvant radiotherapy. The use of radiotherapy in the management of benign disease can be limited by the risk of induction of late malignancy and informed consent of a patient must include an assessment of this risk. We describe a case of refractory laryngeal granuloma successfully treated by excision and immediate radiotherapy in a patient occupationally dependent upon his voice.

Combined Modality Therapy↗
PubMed1997

Controlled trials of synchronous chemotherapy with radiotherapy in head and neck cancer: overview of radiation morbidity.

Recently published overviews of randomized controlled trials of simultaneous chemotherapy with radiotherapy in squamous cell carcinoma of the head and neck have demonstrated a significant survival advantage from the combined treatment compared with radiotherapy alone. However, they also showed that chemotherapy increased acute radiation morbidity, but there was no information on late effects. The 19 publications of trials of simultaneous chemotherapy contained in the overview by Munro were reviewed for morbidity data. It was found that chemotherapy significantly enhanced both acute and late effects, suggesting that the drugs may be merely dose-modifying. Future trials should be designed to determine whether or not chemotherapy improves the therapeutic ratio.

Antineoplastic Agents↗
PubMed1997

Cisplatin and 5-fluorouracil for symptom control in advanced salivary adenoid cystic carcinoma.

Adenoid cystic carcinoma is a relatively rare tumour which arises in the parotid and submandibular salivary glands. Initial management is surgical, often with post-operative radiotherapy, but local relapse is common and distant metastasis not infrequent. Chemotherapy is generally reserved for cases where symptoms are not controlled by other means, since the tumour is slow growing and the response rate frequently disappointing. Cisplatin and 5-fluorouracil (5-FU) both show single agent activity in this disease but had not been previously investigated in combination. All patients referred for palliative chemotherapy of metastatic, symptomatic, histologically confirmed adenoid cystic carcinoma between November 1990 and February 1994 were considered for this study. The drugs were administered as follows: cisplatin 100 mg/m2 with appropriate pre- and post-hydration and 5-FU on a 4-day schedule of 1 g/m2/day. A total of 11 patients (7 male, 4 female) with median age 53 years (range 34-69) received 46 courses of chemotherapy (median four, range one to six). All patients had prior surgery and 8 had previously received radiotherapy. There were no objective responses of > 50% reduction in tumour size. 3 patients had a minor response and two progressed on treatment. The symptomatic response rate, however, was 64%, which compares favourably with other previously reported regimens. Toxicity was manageable. The median time to tumour progression was 9 months (range 0-38) and median survival was 12 months (range 1-65). This cisplatin/5-FU regimen would appear to produce a low rate of objective response but useful palliative benefits in advanced symptomatic adenoid cystic carcinoma. Prior series suggest that a higher objective response rate may be possible with a platinum/anthracycline/fluorouracil combination, and investigation of such a regimen is warranted.

Adult↗
PubMed1997

Chemotherapy for symptom control in recurrent squamous cell carcinoma of the head and neck.

BACKGROUND: The role of chemotherapy in patients with recurrent squamous cell carcinomas of the head and neck (SCCHN) is unclear. The aim of this study was to assess the ability of combination chemotherapy to control symptoms in this setting. PATIENTS AND METHODS: Using a prospectively accrued database all patients referred for chemotherapy with symptomatic relapse following surgery were identified. Objective response was recorded using standard criteria and maximum symptom response was assessed retrospectively from case notes using a published scoring scale. RESULTS: A total of 57 (median age 56, range 37-85) patients were studied who had received mainly cisplatin/5-fluorouracil combinations. Thirty-seven had previously received radiotherapy. Fifty-two patients had evaluable disease; 18 (35%) had objective responses (14 PRs and 4 CRs). There were a total of 103 symptoms recorded with eight different individual symptoms. Forty-four (43%) symptoms improved on treatment, 52 (50%) were unchanged and 7 (7%) worsened. The number of patients with improvement in the most frequently recorded symptoms were as follows: pain 11/28 (39%), swelling 12/23 (52%) and dysphagia 6/18 (33%). Sixty-seven percent of patients with objective response also had an improvement in their symptoms but a significant proportion (33%) of non-responders had a symptomatic response. Lack of objective response was not correlated with worsening symptoms. Grade 3/4 toxicity was uncommon (6%-17%) and there were no toxic deaths. A majority of patients (82%) experienced either no change or an improvement in performance status. CONCLUSION: These results demonstrate that chemotherapy improves many of the symptoms associated with recurrent SCCHN, without deterioration in performance status. Symptomatic improvement is more likely if there is evidence of significant tumour shrinkage, but even non-responding patients can benefit.

Adult↗
PubMed1996

Salvage treatment for inoperable neck nodes in head and neck cancer using combined iridium-192 brachytherapy and surgical reconstruction.

The results of debulking surgery and re-irradiation with radioactive implants (brachytherapy) are reported for 39 patients with inoperable metastatic neck nodes from primary head and neck cancers. For 13 patients conventional salvage by partial debulking surgery and brachytherapy proved effective, with 68 per cent control at 1 year, but six patients suffered severe radiation fibrosis, necrosis and contractures. Some 26 patients were treated by combined tumour debulking, skin resurfacing and brachytherapy implant. Initial tumour control and freedom from serious toxicity was achieved in 24 patients. Local control was achieved in 63 per cent of patients at 1 year, with a serious morbidity rate of 12 per cent.

Adult↗