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C R Leemans

Publications and source records attributed to C R Leemans.

At least 19 recordsLinked to original sources
PubMed2006

Expression profiling and prediction of distant metastases in head and neck squamous cell carcinoma.

BACKGROUND: For breast and prostate cancer, a gene expression signature of the tumour is associated with the development of distant metastases. Regarding head and neck squamous cell carcinoma (HNSCC), the only known risk factor is the presence of > or =3 tumour-positive lymph nodes. AIM: To evaluate whether a HNSCC gene expression signature can discriminate between the patients with and without distant metastases. METHODS: Patients with HNSCC with and without distant metastases had >3 tumour-positive lymph nodes, and did not differ with respect to other risk factors. Statistical analysis was carried out using Student's t test, as well as statistical analysis of microarrays (SAM), to assess the false discovery rate for each gene. These analyses were supplemented with a newly developed method that computed deviations from gaussian-order statistics (DEGOS). To validate the platform, normal mucosa of the head and neck was included as control. RESULTS: 2963 genes were differently expressed between HNSCC and normal mucosa (t test; p<0.01). More rigorous statistical analysis with SAM confirmed the differential expression of most genes. The comparison of genes in HNSCC with and without metastases showed 150 differently expressed genes (t test; p<0.01), none of which, however, could be confirmed using SAM or DEGOS. CONCLUSIONS: No evidence for a metastasis signature is found, and gene expression profiling of HNSCC has seemingly no value in determining the risk of developing distant metastases. The absence of such a signature can be understood when it is realised that, for HNSCC in contrast with breast cancer, the lymph nodes are a necessary in-between station for haematogenous spread.

Adult↗
PubMed2006

Genome-wide DNA copy number alterations in head and neck squamous cell carcinomas with or without oncogene-expressing human papillomavirus.

Oncogene-expressing human papillomavirus type 16 (HPV16) is found in a subset of head and neck squamous cell carcinomas (HNSCC). HPV16 drives carcinogenesis by inactivating p53 and pRb with the viral oncoproteins E6 and E7, paralleled by a low level of mutations in TP53 and allelic loss at 3p, 9p, and 17p, genetic changes frequently found in HNSCCs of nonviral etiology. We hypothesize that two pathways to HNSCC exist: one determined by HPV16 and the other by environmental carcinogens. To define the critical genetic events in these two pathways, we now present a detailed genome analysis of HNSCC with and without HPV16 involvement by employing high-resolution microarray comparative genomic hybridization. Four regions showed alterations in HPV-negative tumors that were absent in HPV-positive tumors: losses at 3p11.2-26.3, 5q11.2-35.2, and 9p21.1-24, and gains/amplifications at 11q12.1-13.4. Also, HPV16-negative tumors demonstrated loss at 18q12.1-23, in contrast to gain in HPV16-positive tumors. Seven regions were altered at high frequency (>33%) in both groups: gains at 3q22.2-qter, 5p15.2-pter, 8p11.2-qter, 9q22-34.1, and 20p-20q, and losses at 11q14.1-qter and 13q11-33. These data show that HNSCC arising by environmental carcinogens are characterized by genetic alterations that differ from those observed in HPV16-induced HNSCC, and most likely occur early in carcinogenesis. A number of genetic changes are shared in both tumor groups and can be considered crucial in the later stages of HNSCC progression.

Adult↗
PubMed2006

How we do it: Chemo-electroporation in the head and neck for otherwise untreatable patients.

Keypoints * Chemo-electroporation therapy with bleomycin is a locoregional treatment modality for head and neck and skin cancer, with the potential to preserve function. * In our institution, chemo-electroporation therapy is used for patients that can no longer be treated by surgery or radiotherapy, or for whom surgical treatment would be very extensive and thus declined by the patient. * This paper describes in detail the technique of bleomycin-electroporation therapy. The literature is reviewed and preliminary results of the clinical trial are presented. * The main focus of the trial is to determine the safety, effectiveness, and burden of bleomycin-electroporation therapy for the patient. * All 17 tumours responded to therapy. Local tumour control was reached in 14 of the 17 (82.4 %) tumours. * Based on the outcome of the clinical trial, bleomycin-electroporation therapy has the potential to become a valuable addition to the late-stage treatment options for patients with head and neck or skin tumours.

Adenocarcinoma↗
PubMed2005

Screening for distant metastases in patients with head and neck cancer: what is the current clinical practice?

OBJECTIVES: The detection of distant metastases during screening influences the choice of treatment in patients with head and neck squamous cell carcinoma (HNSCC). There is no consensus on the diagnostic technique that has to be used nor on the subgroup of HNSCC patients that may benefit from screening. DESIGN: Questionnaire on current practice concerning the diagnostic work-up in HNSCC patients for screening for distant metastases. PARTICIPANTS: Investigators in the 12 otolaryngology / head and neck and seven oromaxillofacial departments treating head and neck cancer in the Netherlands. RESULTS: The response rate was 100%. Indications for screening were cervical lymph node metastases (63%), mutilating surgery (58%), locoregional recurrence (47%), advanced T-stage (32%), second primary tumour (21%). Diagnostic techniques routinely used for screening besides chest X-ray were chest CT (84%), liver ultrasound (53%), liver CT (16%) and bone scintigraphy (42%). Forty-two per cent of the clinicians were not satisfied with the current methods of screening. CONCLUSION: This survey shows a substantial variation in indications and diagnostic techniques used for screening for distant metastases between the major institutions treating head and neck cancer in the Netherlands. There is a need for guidelines for screening for distant metastases in patients with head and neck cancer.

Bone and Bones↗
PubMed2005

Infrahyoid myocutaneous flap reconstruction after wide local excision of a Merkel cell carcinoma.

The case is presented of an 8 1-year-old female coming to our observation after two non radical local excisions of a Merkel cell carcinoma of the sub-mental skin region. After a wide local excision, with en bloc elective bilateral neck dissection, simultaneous reconstruction with an infra-hyoid myocutaneous flap was performed. A brief overview concerning this rare tumour is presented and the surgical technique of the reconstructive procedure is described in detail. The infra-hyoid myocutaneous flap represents a reliable flap, easy and quick to prepare, limiting the time of surgery. The donor site can be primary closed avoiding skin grafting or scars beyond the head and neck area with no significant cosmetic or functional sequelae in the donor area. In this elderly patient, reconstruction with an infra-hyoid myocutaneous flap appears to have been the best option for closing the surgical defect.

Aged↗
PubMed2004

A review on re-irradiation for recurrent and second primary head and neck cancer.

The purpose of this paper is to review the results of studies regarding radiation as primary or adjuvant treatment modality for head and neck recurrences or second primary tumours (SPT) in previously irradiated areas, with emphasis on acute and late radiation induced morbidity, locoregional control and survival. The criteria for the studies to be included in this review were: (1) re-irradiation for locoregional recurrent disease or SPT in the head and neck region, (2) squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx and larynx, and (3) a minimum of 10 patients included in the study. Studies were divided in four categories, including (1) external beam re-irradiation, (2) re-irradiation with brachytherapy, (3) re-irradiation in combination with chemotherapy and (4) postoperative re-irradiation. Most studies were retrospective using heterogeneous treatment regimens and including heterogeneous groups of patients. A total number of 27 studies were included. Overall survival, locoregional control and acute and late radiation-induced morbidity are reported. High dose reirradiation as salvage treatment in case of recurrent or second primary head and neck cancer should be considered, particularly when salvage surgery is not feasible. Although long term survivors are reported is some studies, the relatively high incidence of treatment-related morbidity emphasize the need for further optimisation in order to improve locoregional control and reduce the risk on late morbidity.

Brachytherapy↗
PubMed2004

The additional value of chemotherapy to radiotherapy in locally advanced nasopharyngeal carcinoma: a meta-analysis of the published literature.

PURPOSE: The purpose of this meta-analysis was to determine the additional value of neoadjuvant, concurrent, and/or adjuvant chemotherapy to radiation in the treatment of locally advanced nasopharyngeal carcinoma (NPC) with regard to the overall survival (OS) and the incidence of local-regional recurrences (LRR) and distant metastases (DM). PATIENTS AND METHODS: To be eligible, full published studies had to deal with biopsy-proven NPC and have patients randomly assigned to receive conventional radiotherapy (66 to 70 Gy in 7 weeks) or radiotherapy combined with chemotherapy. RESULTS: Ten randomized clinical studies were identified, including 2,450 patients. The pooled hazard ratio (HR) of death for all studies was 0.82 (95% CI, 0.71 to 0.95; P = .01) corresponding to an absolute survival benefit of 4% after 5 years. Three categories of trials were defined according to the sequence of chemotherapy, including neoadjuvant chemotherapy, at least concomitant chemoradiotherapy, and adjuvant chemotherapy. A significant interaction term (P = .02) was found among these three categories. The largest effect was found for concomitant chemotherapy, with a pooled HR of 0.48 (95% CI, 0.32 to 0.72), which corresponds to a survival benefit of 20% after 5 years. Comparable results were found for the incidence of LRR and DM. CONCLUSION: The results of this study indicate that concomitant chemotherapy in addition to radiation is probably the most effective way to improve OS in NPC.

Carcinoma↗
PubMed2003

Postoperative radiotherapy in squamous cell carcinoma of the oral cavity: the importance of the overall treatment time.

PURPOSE: To test the hypothesis that (1) the distinction between intermediate- and high-risk patients by clustering different prognostic factors results in a significant difference in treatment outcome and (2) a shorter interval between surgery and radiotherapy and shorter overall treatment times of radiation (OTTRT) result in higher rates of locoregional control (LRC). METHODS AND MATERIALS: Included were patients (n = 217) with previously untreated squamous cell carcinoma of the oral cavity treated with radical surgery and postoperative radiotherapy. Patients with extranodal spread or microscopic residual disease and patients with two or more other risk factors (i.e., N2b-N3, >1 nodal level involved, perineural growth, or stage T3-T4) were classified as high-risk patients. Patients with only one other risk factor were classified as intermediate risk. RESULTS: In the intermediate-risk group, the 3-year LRC was 87% as compared with 66% in the high-risk group (p = 0.0005). No association was found between interval and LRC. However, the OTTRT was significantly associated with LRC. The 3-year LRC was 87%, 75%, 69%, and 51% when the OTT was <6 weeks, 6-7 weeks, 7-8 weeks, and >8 weeks, respectively (p = 0.0004). The 3-year overall survival (OS) in the intermediate risk patients was 74% compared with 50% in the high-risk group (p = 0.0014). A significant association was also found between the OS and OTTRT. The OS increased from 50% when the OTTRT was >8 weeks to 74% when the OTT was <6 weeks (p = 0.006). Similar results were found with regard to the disease-free survival (DFS). In the multivariate analysis, both risk group and OTT were significantly associated with LRC, DFS, and OS. No significant interaction term was present between these two factors, which means that the OTT was of importance both for the high-risk and the intermediate-risk patients. CONCLUSION: In the subset of patients with carcinoma of the oral cavity, the classification of high- and intermediate-risk patients by clustering a number of prognostic factors provides important prognostic information regarding LRC, DFS, and OS. The OTT was the most important prognostic factor both in the high-risk and intermediate-risk patients. Reducing the OTT to 6 weeks or less is a rather simple measure to achieve a considerable improvement of the outcome of treatment in this category of patients.

Adult↗
PubMed2003

[CO2-laser decortication: an efficient alternative to radiotherapy in the treatment of T1a carcinomas of the glottis].

OBJECTIVE: Given that CO2-laser decortication and radiotherapy are equally effective in the treatment of T1a glottic carcinomas, to determine which of the two is most efficient with respect to treatment costs. DESIGN: Retrospective analysis. METHOD: The costs of both treatment modalities from the first visit to the Free University Medical Centre, Amsterdam, the Netherlands, until two years after the start of the treatment were calculated, based on the medical consumption of 89 patients who were treated with curative intent for a T1a glottic carcinoma in the years 1995-1999. RESULTS: The total costs from diagnosis until two years after the start of treatment were [symbol: see text] 7,253,- for radiotherapy and [symbol: see text] 3,864,- for CO2-laser decortication. These amounts included the costs of diagnosis and treatment of any recurrence or benign laryngeal disorders occurring within the two-year interval. The difference was statistically significant. CONCLUSION: Radiotherapy was significantly more expensive than CO2-laser decortication. Therefore CO2-laser decortication is an efficient alternative to radiotherapy in the treatment of eligible patients with T1a glottic carcinoma.

Aged↗
PubMed2002

Shoulder function and patient well-being after various types of neck dissections.

Preserving the accessory nerve results in a better outcome of the shoulder function after neck dissection. However, little is known about the impact of preserving a cervical contribution to the accessory nerve. This study describes the shoulder function after different types of neck dissections, with the emphasis on the significance of the cervical contribution to the accessory nerve. Fifty-nine patients who underwent neck dissections of various types were included. Thirty-eight patients underwent unilateral radical or modified radical neck dissections, and 21 patients underwent bilateral neck dissections. All the patients were assessed subjectively and objectively, using a questionnaire and an inclinometer. Radical neck dissections inflicted significantly more morbidity than modified radical neck dissections. Preserving a cervical contribution to the accessory nerve did not decrease pain complaints or functional impairment. However, there might be some improvement in range of motion, especially exorotation and anteflexion. Preserving the accessory nerve has a positive influence on shoulder function and complaints. Preserving a cervical contribution does not decrease morbidity significantly.

Accessory Nerve↗
PubMed2001

The costs of head and neck oncology: primary tumours, recurrent tumours and long-term follow-up.

We retrospectively calculated the costs of head and neck oncology for reimbursement purposes. This analysis was based on 854 head and neck cancer patients treated between 1994 and 1996 in two major Dutch university hospitals. To anticipate future care costs, costs of required improvements in the quality of care were added. Costs of diagnosis, treatment and 2 years of follow-up of patients with a primary tumour were (euro) 21 858. For patients with a recurrent tumour, this amount was (euro) 27 629. The costs of 10 years of follow-up were (euro) 423 after discounting and correction for survival. In total, average costs per new patient were (euro) 31 829, which covered discounted costs of treating the primary tumour, costs of treating recurrent tumours in 40% of all patients and the costs of 10 years of follow-up. Costs of improving the quality of care were estimated to be (euro) 1598 per new patient.

Continuity of Patient Care↗
PubMed2001

The hinged-door composite septal flap as structural support and lining of nasal reconstruction by a forehead flap.

In this paper we describe four patients who underwent extensive nasal surgery for carcinoma in the nasal vestibule. Two patients underwent salvage surgery after radiotherapy, whereas the other two patients were treated with primary surgery. In all cases the nasal defect was reconstructed using a composite hinged-door septal flap for structural support and internal lining combined with a paramedian forehead flap which supplied the skin coverage. All patients had a pleasing aesthetic and good functional result. The combination of a paramedian forehead flap with a composite hinged-door septal flap is an excellent reconstruction procedure for defects of the lateral nasal wall and alar region.

Aged↗
PubMed2001

Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications.

In 1953, Slaughter et al. [D. P. Slaughter et al., Cancer (Phila.), 6: 963-968, 1953] proposed the concept of field cancerization in patients with squamous cell carcinoma of the head and neck (HNSCC) and discussed its clinical significance for the development of second primary tumors and local recurrences. To define the process of field cancerization and its putative clinical implications, we analyzed genetic aberrations in HNSCC and the accompanying macroscopically normal mucosa. In 28 HNSCC patients, loss of heterozygosity was determined in tumor and five noncontiguous mucosal biopsies using eight microsatellite markers at 9p, 3p, and 17p. For patients who showed loss of heterozygosity in their mucosal biopsies, all margins of the surgical specimen were subsequently analyzed to determine the extension of the field. In these cases, additional markers at 8p, 13q, and 18q as well as p53 mutations were included to determine subclonal differences between field and tumor. Genetically altered fields were detected in 36% (10 of 28) of the HNSCC patients. The field varied in size between patients and consisted of genetically different subclones. In 7 of 10 cases, the field extended into the surgical margins. One particular patient with a genetically altered field in a surgical margin developed a local recurrence after 28 months of follow-up. Microsatellite analysis showed that this recurrence had more molecular markers in common with the nonresected premalignant field than with the original tumor, suggesting that this persistent field has progressed further into a new malignancy. Our data show that genetically altered mucosa remains after treatment in a significant proportion of HNSCC patients, which may explain in part the high frequency of local recurrences and second primary tumors. Adequate identification and risk assessment of these genetically altered fields may have profound implications for future patient management.

Biopsy↗