Fractionated high-dose-rate brachytherapy in primary carcinoma of the nasopharynx.

PURPOSE: A growing body of data suggests that local control in nasopharyngeal cancer (NPC) is related to the radiation dose administered. We conducted a single-institution study of high-dose radiotherapy (RT), which incorporated high-dose-rate (HDR) brachytherapy (BT). These results were analyzed together with data obtained from controls who did not receive BT. PATIENTS AND METHODS: The BT group comprised 42 consecutive patients of whom 29 patients were staged according to the tumor, node, metastasis system as T1 through 3, 13 patients were T4, and 34 patients were N+ disease. BT was administered on an outpatient basis by means of a specially designed flexible nasopharyngeal applicator, and the dose distributions were optimized. Treatment for T1 through 3 tumors comprised 60 Gy of external-beam radiotherapy (ERT) followed by six fractions of 3 Gy BT (two fractions per day). Patients with parapharyngeal tumor extension and/or T4 tumors received 70 Gy ERT and four fractions of 3 Gy BT. The no-BT group consisted of all patients treated from 1965 to 1991 (n = 109), of whom 82 patients had stages T1 through 3, 27 patients had T4, and 80 patients had N+ disease. Multivariate Cox proportional hazards analyses were performed by using the end points time to local failure (TTLF), time to distant failure (TTDF), disease-free survival (DFS), cause-specific survival (CSS), and the prognostic factors age, tumor stage, node stage, and grade. Because the overall treatment time varied substantially in the no-BT group, the dependence of local failure (LF) on the physical dose as well as the biologic effective dose (BED) corrected for the overall treatment time (OTT) (BEDcor10) was studied. RESULTS: The BT group had a superior 3-year local relapse-free rate (86% v 60%; univariate analysis, P = .004). Multivariate analysis showed hazards ratios for BT versus no-BT of 0.24 for TTLF (P = .003), 0.35 for TTDF (P = .038), 0.31 for DFS (P < .001), and 0.44 for CSS (P = .01). The best prognostic group consisted of patients with T1 through 3, N0 through 2b tumors treated with BT who attained a 5-year TTLF of 94% and CSS of 91%. In contrast, the worst prognostic group, i.e., 5-year TTLF of 47% and CSS of 24%, was composed of patients with T4 and/or N2c through 3 tumors who did not receive BT. CONCLUSION: High doses of radiation (73 to 95 Gy) can be administered to patients with NPC with minimal morbidity by means of optimized HDR-BT. The use of a BT boost proved to be of significant benefit, particularly in patients with T1 through 3, N0 through 2b disease. The steep dose-effect relationship seen for the physical dose and the BEDcor10 indicates that the results are dose related. The analysis has identified a poor prognostic group in whom treatment intensification with chemotherapy (CHT) is indicated.

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.

A new applicator design for endocavitary brachytherapy of cancer in the nasopharynx.

INTRODUCTION: In attempting to improve local tumor control by higher doses of radiation, there has been a resurgence of interest in the implementation of brachytherapy in the management of primary and recurrent cancers of the nasopharynx. Brachytherapy with its steep dose fall-off is of particular interest because of the proximity of critical dose limiting structures. Recent developments in brachytherapy, such as the introduction of pulsed-dose-rate and high-dose-rate computerized afterloaders, have encouraged further evolution of brachytherapy techniques. MATERIALS AND METHODS: We have designed an inexpensive, re-usable and flexible silicone applicator, tailored to the shape of the soft tissues of the nasopharynx, which can be used with either low-dose-rate brachytherapy or high (pulsed)-dose-rate remote controlled afterloaders. RESULTS AND CONCLUSIONS: This Rotterdam nasopharynx applicator proved to be easy to introduce, patient friendly and can remain in situ for the duration of the treatment (2-6 days). The design, technique of application and the first consecutive 5 years of clinical experience in using this applicator are presented.

A clinical evaluation of implants in irradiated oral cancer patients.

In this prospective study, we determined the effects of the time interval between irradiation and implant therapy, implant location, bone-resection surgery, and irradiation dose on implant survival. We analyzed the survival of 446 implants inserted after radiotherapy over a period of up to 14 years in 130 consecutive patients treated for oral cancer. The 10-year overall Kaplan-Meier implant survival percentage is 78%. The difference in survival percentages of implants inserted < 1 year and >/= 1 year after irradiation (76% and 81%, respectively) is not significant. We concluded that implant survival is significantly influenced by the location (maxilla or mandible, 59% and 85%, respectively; p = 0.001), by the incidence of bone-resection surgery in the jaw where the implant was installed (p = 0.04), and by the irradiation dose at the implant site (< 50 Gray or >/= 50 Gray, p = 0.05).

pH measurements with an ion sensitive field effect transistor in the mouth of patients with xerostomia.

A transistor pH electrode (ion sensitive field effect transistor), placed in the upper dentures of eleven xerostomia patients and five healthy volunteers, was used to register pH changes in five-, six- and seven-day-old dental plaque. A mouth rinse with a 10% sucrose solution caused a pH fall of about three decades. A significant difference in duration of critical plaque pH was observed: in xerostomia patients, a 10% longer period of pH less than 5.7 was registered during 60 min following a sucrose rinse. Normal oral functions were not influenced by the denture with an integrated electrode. This method is usable for plaque pH registration in xerostomia patients.

Diagnostic significance of salivary levels of beta 2-microglobulin in Sjögren's syndrome.

To evaluate the diagnostic significance of salivary beta 2m in Sjögren's syndrome we measured salivary beta 2m levels in 19 patients with primary sicca syndrome (PSS), 15 with secondary Sjögren's syndrome (SSS) and compared the results with 20 normal healthy persons. We showed that beta 2m is specifically excreted in the saliva, because in normal saliva the concentration of beta 2m was unrelated to IgA levels. Also in normals, there was no relationship between serum and saliva concentrations of beta 2m. The mean saliva levels of beta 2m were increased in PSS (1.13 +/- 0.58) and SSS (1.39 +/- 0.69) compared with the levels in normals (0.53 +/- 0.22). The determination of beta 2m in the saliva can therefore be used as a noninvasive measurement for the confirmation of the diagnosis Sjögren's syndrome.

Use of implants for prosthetic rehabilitation after cancer treatment: clinical experiences.

Treatment of patients with head and neck cancer may result in extensive intra- or extra-oral defects. Prosthetic rehabilitation often will be limited by insufficient retention and an atrophic mucosa or skin. In such cases, osseointegrated implants may offer substantially improved retention for the often complex prosthetic constructions. However, irradiation has a negative influence on the bone growth capacity and thus on osseointegration. Based on experimental studies, a recovery period of 6 to 12 months after irradiation is recommended. Because of the risk of failure and the lack of sufficient and sound scientific knowledge, clinical studies of titanium implants inserted in previously irradiated bone tissue have had varying results. This paper discusses the typical requirements of implant suprastructures for resection prostheses. Some of the patient histories and clinical management presented illustrate the possibilities of implants in the field of maxillofacial reconstruction.

A double-blind crossover trial of CMC- and mucin-containing saliva substitutes.

The aim of this investigation was to describe and to compare the effectiveness of a CMC- and a mucin-containing saliva substitute. 22 post-radiation patients, 17 Sjögren's Syndrome patients and 3 patients with xerostomia of unknown origin used a CMC- and a mucin-containing saliva substitute, each for 1 week in an arbitrary sequence. Neither the patient, the assistant, nor the physician were aware of the substitute being used. Each patient had to complete a questionnaire at 3 different intervals during the trial. One of the conclusions of this study is that mucin-containing substitutes are preferred by patients when compared to CMC-containing substitutes.

[Preventive oral and dental care in radiotherapy patients]. / Preventieve mond- en tandzorg bij bestralingspatiënten.

An overview is presented of the preventive measures that can be taken with regard to the various side effects of radiotherapy of the head-and-neck region. Xerostomia, mucositis, radiation caries, trismus and osteoradionecrosis are to some extent preventable.

[Orthodontic tooth extraction in a patient with idiopathic thrombocytopenia]. / Orthodontische extractie bij een patiënte met een diepe trombocytopenie.

This article describes the removal of a molar in a patient with idiopathic thrombocytopenia by means of orthodontic forces. The indications and advantages as well as the disadvantages of this alternative for surgical extraction are discussed.

A simple device to protect against osteoradionecrosis induced by interstitial irradiation.

The incidence of osteoradionecrosis has declined since the introduction of preventive oral hygiene programs and meticulous dental evaluations before and after irradiation. Nevertheless, radiation dose per se still remains an important factor in osteoradionecrosis. Interstitial radiation has received much attention in the past decade since the use of flexible afterloading systems. It has become common practice in large oncology centers to implant radiation carriers in bulky tumor in the oral cavity and/or oropharynx. For interstitial radiation, with or without external radiation, minimal tumor doses are often cited to be more than 70 Gy. Unfortunately, if the mandible receives more than 70 Gy, it is at risk for the development of osteoradionecrosis. Therefore a simple protective lead device has been designed for routine use in brachytherapy in oral cavity tumors to reduce the dose to the mandible. This device will diminish the potential risk of osteoradione-crosis development.

Behavior of calcium phosphate coatings with different chemistries in bone.

Calcium phosphate ceramic coatings with a hydroxyapatite chemistry applied on the surface of dental implants eliminate the need for initial mechanical retention and decrease the time necessary for bonding the implants to the bone. Hydroxyapatite-coated implants retrieved from patients were found to be compatible and to have bonded strongly to the bone, but the coatings showed thinning because of partial or total loss of coating material. This study compared the behavior in bone of newly developed fluorapatite and heat-treated hydroxyapatite coatings, with the clinically used hydroxyapatite coatings used as controls in experimental studies in dogs. The biologic responses to fluorapatite and heat-treated hydroxyapatite coatings were the same as those to hydroxyapatite coatings, and bone condensation around all coatings was histologically evident. However, the coating thickness of the fluorapatite and heat-treated hydroxyapatite coatings remained stable with only minor changes during the observation period of 24 months.

In vivo study on the prevention of postradiation caries.

Postradiation caries is usually prevented by the application of topical fluorides (F) at high concentrations. The aim of this study was to develop an optimal preventive program for postradiation caries by evaluating the effects of F concentration and application procedures in subjects with radiation-related xerostomia. Six ground enamel slabs were mounted on each side of the lower denture of each of 7 xerostomia patients. Four procedures were used: no F exposure (control), neutral F gel applied every 2nd day or weekly, and a daily rinse with a F mouthwash for a period of 6 weeks. The enamel slabs were analyzed at weekly intervals by scanning optical monitoring, longitudinal microradiography, and scanning electron microscopy. In addition, hardness measurements were performed on the slabs. F analyses of the enamel slabs were done prior to their insertion in the appliances and after 6 weeks of intraoral exposure. In the control experiments severe demineralization of enamel occurred within 6 weeks. Application of F gel or the use of the F mouthrinse resulted in a significant inhibition of the demineralization process. Of the procedures evaluated, F gel applied every 2nd day was the most effective in preventing the onset of postradiation caries.

A clinical comparison between commercially available mucin- and CMC-containing saliva substitutes.

In this investigation, the subjective impressions of patients, suffering from severe xerostomia, have been recorded after symptomatic treatment with different CMC- and mucin-containing artificial saliva over 3 years. A total number of 137 patients divided into 3 groups participated. Group I (40 patients) used CMC-containing artificial saliva, group II (61 patients) alternately used CMC- and mucin-containing artificial saliva and group III (36 patients) used mucin-containing artificial saliva. From this study it is concluded that artificial saliva containing mucins proved to be of benefit to patients suffering from xerostomia.