Mucositis reduction by selective elimination of oral flora in irradiated cancers of the head and neck: a placebo-controlled double-blind randomized study.

PURPOSE: The aim of the study was to test the hypothesis that aerobic Gram-negative bacteria (AGNB) play a crucial role in the pathogenesis of radiation-induced mucositis; consequently, selective elimination of these bacteria from the oral flora should result in a reduction of the mucositis. METHODS AND MATERIALS: Head-and-neck cancer patients, when scheduled for treatment by external beam radiation therapy (EBRT), were randomized for prophylactic treatment with an oral paste containing either a placebo or a combination of the antibiotics polymyxin E, tobramycin, and amphotericin B (PTA group). Weekly, the objective and subjective mucositis scores and microbiologic counts of the oral flora were noted. The primary study endpoint was the mucositis grade after 3 weeks of EBRT. RESULTS: Seventy-seven patients were evaluable. No statistically significant difference for the objective and subjective mucositis scores was observed between the two study arms (p = 0.33). The percentage of patients with positive cultures of AGNB was significantly reduced in the PTA group (p = 0.01). However, complete eradication of AGNB was not achieved. CONCLUSIONS: Selective elimination of AGNB of the oral flora did not result in a reduction of radiation-induced mucositis and therefore does not support the hypothesis that these bacteria play a crucial role in the pathogenesis of mucositis.

Beam intensity modulation using tissue compensators or dynamic multileaf collimation in three-dimensional conformal radiotherapy of primary cancers of the oropharynx and larynx, including the elective neck.

INTRODUCTION: The treatment of midline tumors in the head and neck by conventional radiotherapy almost invariably results in xerostomia. This study analyzes whether a simple three-dimensional conformal radiotherapy (3D-CRT) technique with beam intensity modulation (BIM) (using a 10-MV beam of the MM50 Racetrack Microtron) can spare parotid and submandibular glands without compromising the dose distribution in the planning target volume (PTV). METHODS: For 15 T2 tumors of the tonsillar fossa with extension into the soft palate (To) and 15 T3 tumors of the supraglottic larynx (SgL), conventional treatment plans, consisting of lateral parallel opposed beams, were used for irradiation of both the primary tumor (70 Gy) and the elective neck regions (46 Gy). Separately, for each tumor a 3-D conformal treatment plan was developed using the 3-D computer planning system, CadPlan, and Optimize, a noncommercial program to compute optimal beam profiles. Beam angles were selected with the intention of optimal sparing of the salivary glands. The intensity of the beams was then modulated to achieve a homogeneous dose distribution in the target for the given 3D-CRT techniques. The dose distributions, dose-volume histograms (DVHs) of target and salivary glands, tumor control probabilities (TCPs), salivary gland volumes absorbing a biologically equivalent dose of greater than 40 or 50 Gy, and normal tissue complication probabilities (NTCPs) of each treatment plan were computed. The parameters of the 3D-CRT plans were compared with those of the conventional plans. RESULTS: In comparison with the conventional technique, the dose homogeneity in the target volume was improved by the conformal technique for both tumor sites. In addition, for the SgL conformal technique, the average volumes of the parotid glands absorbing a BED of greater than 40 Gy (V40) decreased by 23%, and of the submandibular glands by 7% (V40) and 6% (V50). Consequently, the average NTCPs for the parotid and submandibular glands were reduced by 7% and 6%, respectively. For the To conformal techniques, the V40 of the parotid glands was decreased on average by 31%, resulting in an average reduction of the NTCP by 49%. Both the average V50 and the NTCP of the submandibular glands were decreased by 7%. CONCLUSION: For primary tumors of the oropharynx, the parotid glands could be spared to a considerable degree with the 3D-CRT technique. However, particularly the ipsilateral submandibular gland could not be spared. For primary tumors of the larynx, the 3D-CRT technique allows sparing of all salivary glands to a considerable and probably clinically relevant degree. Moreover, the conformal techniques resulted in an increased dose homogeneity in the PTV of both tumor sites.

Treatment portals for elective radiotherapy of the neck: an inventory in The Netherlands.

PURPOSE: To assess the variation in and the three-dimensional dosimetric consequences of treatment portals for elective neck irradiation. MATERIALS AND METHODS: Radiation oncologists (n = 16) from all major Head and Neck Co-operative Groups in The Netherlands (n = 11) were asked to delineate treatment portals on a lateral and an anterior simulation film in case of elective neck irradiation for a T3N0 tumour of the supraglottic larynx and a T2N0 tumour of the mobile tongue. In addition, they had to define their target, i.e. which parts of the neck nodal regions they would choose to irradiate electively for these particular tumour sites. Subsequently, treatment portals were compared and evaluated using CT-data and a 3-dimensional (3D) treatment planning system. RESULTS: Significant variations were found in the shapes and sizes of the applied treatment techniques and portals. Also, among radiation oncologists who elected to irradiate the same lymph node regions, a significant variation in the delineated treatment portals was observed. As a consequence, substantial variations in treated volumes and in calculated normal tissue complication probabilities (NTCPs) for the parotid- and submandibular glands were observed. CONCLUSION: For the tumour sites studied there appears to be a lack of standardisation in the areas of the neck to be irradiated electively. The observed differences may have consequences for the ultimate failure rate and particularly with regard to the side effects, e.g. the degree of xerostomia. It is argued that in the near future a more precise three-dimensional definition on CT of the lymph node regions in the neck might allow for a better standardisation of the treatment portals and, in addition, for the development and application of conformal radiotherapy techniques for optimal sparing of the critical normal tissues (e.g. parotid- and submandibular glands) with maximum tumour control probability.

A simplified CT-based definition of the lymph node levels in the node negative neck.

INTRODUCTION AND PURPOSE: Using three dimensional (3D) conformal radiotherapy (CRT) techniques for elective neck irradiation (ENI) may allow for local disease control to be maintained while diminishing xerostomia by eliminating major salivary glands (or parts thereof) from the treatment portals. The standardization of CT based target volumes for the clinically negative (elective) neck is a prerequisite for 3DCRT. The aim of the present study was to substantially modify an existing ('original') CT-based protocol for the delineation of the neck target volume, into a more practical ('simplified') protocol. This will allow for rapid contouring and the implementation of conformal ENI in routine clinical procedures. MATERIAL AND METHODS: An earlier ('original') version of the CT-based definition for elective neck node regions 2-5 was re-evaluated, using 15 planning CT scans of previously treated patients. The contouring guidelines were simplified by (1) using a smaller number of easily identifiable soft tissue- and bony anatomical landmarks, which in turn had to be identified in only a limited number of CT slices, and (2) by subsequently interpolating the contoured lymph node regions. The adequacy of target coverage and the sparing using both 'original' and 'simplified' delineation protocols was evaluated by DVH analysis after contouring the primary tumor, the neck and the major salivary glands in a patient with supraglottic laryngeal (SGL) carcinoma who was treated using a 3DCRT technique. RESULTS: The BEV projections of the 'original' and the 'simplified' versions of the 3D elective neck target showed good agreement and were found to be reproducible. The DVH's of the target and parotid glands were not significantly different using both contouring protocols. CONCLUSIONS: The 'simplified' protocol for the delineation of the 3D elective neck target produced both comparable target coverage and sparing of the major salivary glands. When used together with an interpolation program, this 'simplified' protocol substantial reduced the contouring time and makes ENI with sparing of the major salivary glands a practical and achievable goal.