Postoperative radiotherapy for head and neck squamous cell carcinomas: Feasibility of a biphasic accelerated treatment schedule

: It has been suggested that postoperative tumor cell proliferation may influence the outcome of advanced head and neck squamous cell carcinomas treated by surgery and postoperative radiotherapy. This Phase I pilot study was undertaken to determine the feasibility of a biphasic accelerated radiotherapy regimen with early and late concomitant boost delivery for postoperative treatment of patients with advanced head and neck cancers.

: From April 1993 to April 1994, 29 patients with advanced head and neck cancers were enrolled in this study after they underwent complete surgical resection. The basic radiation course delivered a median dose of 49 Gy in 25 fractions over 5 weeks at 1.8–2 Gy/fraction. The concomitant boost was delivered to the high-risk areas as a second daily fraction during the first (1.4 Gy/fraction) and fifth weeks (1.6 Gy/fraction). The total dose to the high-risk areas was 64 Gy in 35 fractions over 5 weeks.

: Twenty-seven patients (93%) completed the treatment without interruptions. Only two patients experienced severe acute toxicity requiring treatment breaks of 6 and 8 days, respectively. All patients developed confluent mucositis; in 69% of the cases it covered >50% of the treated surface. No patient developed Grade 5 (ulceration/bleeding) mucosal reaction. Mucositis required a median time of 7 weeks for complete healing (range 3–43. Two patients developed transient bone exposure. The median weight loss was 5.5% of pretreatment body weight (range 1.2–17.1%), and four patients required nutritional with nasogastric feeding tube.

: The results of this study show that this biphasic acceleration regimen is feasible with acceptable acute toxicity.     

Three-dimensional dose distributions for radiotherapy of sinus maxillary tumours

Three-dimensional dose distributions for the radiation therapy of sinus maxillary tumours have been calculated. Irradiation techniques with 8 MV X-rays and 15 MV X-rays from a linear accelerator (Siemens Mevatron 74 and Siemens Mevatron 77) and 60Co gamma-irradiation (Siemens Gammatron S80) are compared to each other. Using an anterior and a lateral field, the three-dimensional dose distribution of high energy photons shows that the radiation burden of the lens and the skin is significantly lower than with the use of 60Co irradiation. Sufficient dose coverage and sparing of the lens and the skin can be reached using the irradiation technique with 8 MV X-rays.     

Lack of osteoradionecrosis of the mandible after intensity-modulated radiotherapy for head and neck cancer: likely contributions of both dental care and improved dose distributions

PURPOSE: To assess the prevalence and dosimetric and clinical predictors of mandibular osteoradionecrosis (ORN) in patients with head and neck cancer who underwent a pretherapy dental evaluation and prophylactic treatment according to a uniform policy and were treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Between 1996 and 2005, all patients with head-and-neck cancer treated with parotid gland-sparing IMRT in prospective studies underwent a dental examination and prophylactic treatment according to a uniform policy that included extractions of high-risk, periodontally involved, and nonrestorable teeth in parts of the mandible expected to receive high radiation doses, fluoride supplements, and the placement of guards aiming to reduce electron backscatter off metal teeth restorations. The IMRT plans included dose constraints for the maximal mandibular doses and reduced mean parotid gland and noninvolved oral cavity doses. A retrospective analysis of Grade 2 or worse (clinical) ORN was performed. RESULTS: A total of 176 patients had a minimal follow-up of 6 months. Of these, 31 (17%) had undergone teeth extractions before RT and 13 (7%) after RT. Of the 176 patients, 75% and 50% had received >or=65 Gy and >or=70 Gy to >or=1% of the mandibular volume, respectively. Falloff across the mandible characterized the dose distributions: the average gradient (in the axial plane containing the maximal mandibular dose) was 11 Gy (range, 1-27 Gy; median, 8 Gy). At a median follow-up of 34 months, no cases of ORN had developed (95% confidence interval, 0-2%). CONCLUSION: The use of a strict prophylactic dental care policy and IMRT resulted in no case of clinical ORN. In addition to the dosimetric advantages offered by IMRT, meticulous dental prophylactic care is likely an essential factor in reducing ORN risk.     

Review of monoisocentric split-field technique for conventional and IMRT treatment in head and neck cancers: technical limitations and approaches for optimization

The importance of treatment planning of head and neck malignancies arises from the necessity to achieve homogenous doses to localized target volume surrounded by normal structures, which can produce acute and long-term morbidity. In many radiotherapy departments, a commonly employed strategy is a 3-field technique. Bilateral parallel-opposed fields are matched to anterior lower neck field. In recent years, Intensity Modulated Radiotherapy (IMRT) is used to radiate head and neck tumors. When the target extends to the lower neck regions, abutment of upper IMRT and lower neck fields is required. Field matching represents a technical challenge for the medical physicist, medical engineer, and radiation oncologist to treat multiple fields while avoiding their overlap on the spinal cord. The monoisocentric split field technique has recently become a common technique to achieve matchline homogenous dose while respecting normal tissue tolerance. The aim of this work is to review merits, limitations, and recent approaches to optimize matchline dose in monoisocentric technique in conventional and intensity modulated radiotherapy for head and neck cancers. Although the technique has many advantages, it is subjected to some systematic and random errors due to equipment and patient setup inaccuracies. To decrease the magnitude of matchline inhomogeneities, customized penumbra generator or multileaf collimator have been used. Both methods are viable and represent alternative approaches to the problem of field matching using the asymmetric jaws.     

Metastatic lymph-node clearance from head and neck epidermoid carcinomas following radiotherapy

Although tumor clearance is a common criterion in assessing the impact of radiotherapy (RT), it is not always reliable. Patterns of tumor clearance were determined using 91 metastatic lymph nodes (LNs) from 51 patients with head and neck tumors treated by definitive RT (61-80 Gy) or preoperative RT (43-65 Gy). Clearance rate (CR) was estimated as a daily volume decrement expressed as a ratio to the pre-RT LN volume. CR was greater for the so-called radioresponsive nasopharyngeal subgroups and more poorly differentiated than those of oral cavity and well-differentiated, respectively. Histologically, LNs that were removed following RT consisted mainly of fibrous tissues, necrotic tissues, and few cancer cells. There was no difference in CR between the cancer-cell-positive group (n=21) and the cancer-cell-negative group (n=31). Although the CR may reflect inherent radiosensitivity of tumor cells, tumor persistence predicts the amount of oncologically inactive materials rather than that of remaining cancer cells.     

Altered fractionated radiotherapy in the management of head and neck carcinomas: advantages and limitations

PURPOSE OF REVIEW: This article provides an overview of randomized studies of altered fractionated radiotherapy (RT) in Head and Neck squamous cell carcinoma. RECENT FINDINGS: Both hyperfractionated RT and accelerated RT may improve tumor control probability as compared to conventional RT, along with increased but manageable toxicity and a modest improvement in survival. SUMMARY: Altered RT is a tool that can improve the results obtained with conventional RT in Head and squamous cell carcinoma.     

Cell kinetics and tumor regression during radiotherapy in head and neck squamous-cell carcinomas

Head and neck squamous-cell carcinoma (HN-SCC) patient management is mainly based on TNM classification and needs be improved by considering other potentially useful prognostic factors. We examined the pre-radiotherapy tumor potential doubling time (T_pot) evaluated after in vivo infusion of bromodeoxyuridine and flow-cytometric analysis and the early clinical tumor regression after 40 Gy (40 Gy-TR). T_pot values and clinical 40 Gy-TR classes (minor and major) were available for 82 HN-SCC patients. Radiation therapy completion was done either with I dose per day (conventional regimen) or 2 doses per day (accelerated regimen). Local control was also available for follow-up times above 4 years. We found that major 40 Gy-TR was strongly correlated with fast tumor growth, characterized by T_pot values below 5 days, and that patients with major 40 Gy-TR showed better local control than those with minor 40 Gy-TR, independently from the radiotherapy regimen type. We also found that treatment completion with accelerated radiotherapy gave better local control for patients with major 40 Gy-TR and fast tumor growth than conventional radiotherapy. Multivariate analysis, performed on all patients, assigned an independent prognostic value to T_pot, tumor classification and 40 Gy-TR. © 1996 Wiley-Liss, Inc.     

Lack of influence of intravenous contrast on head and neck IMRT dose distributions

Purpose. Intravenous (IV) contrast at the time of CT-Simulation facilitates radiotherapy contouring, but may introduce a discrepancy between planned and delivered dose due to density variation in blood vessels. Here, the effect of physiologic and non-physiologic extremes of IV contrast densities on intensity modulated radiotherapy (IMRT) plans for patients with head and neck cancer was investigated. Methods and materials. This planning study was conducted using IV contrast CT scans of ten patients with squamous cell cancer of the head and neck treated with IMRT. The target volumes and normal tissues, including the blood vessels of the head and neck, were contoured and IMRT plans were created according to RTOG Protocol 0022. The density within the blood vessels was then virtually altered to mimic non-contrast and extreme (bone and air) densities. The dose was then recalculated using the same IMRT plan. Plans obtained with and without density overrides were then compared. Results. The change in planning target volume (PTV) coverage for plans with and without IV contrast was minimal. The volume of the PTVs covered by the 93% and 100% isodoses changed on average by 0.57%. The minimum dose to PTVs varied by a maximum of 0.17 Gy. The maximum point dose to critical organs changed by a maximum of 0.12 Gy (brainstem). Non-physiologic extremes of density within blood vessels also resulted in minimal changes in tumor or normal tissue dosimetry. Conclusion. The use of IV contrast at time of CT-simulation does not significantly affect dose calculation in head and neck IMRT plans.     

Salivary and serum proteomics in head and neck carcinomas: before and after surgery and radiotherapy

Several body fluids have been evaluated as new sources for cancer biomarker discovery. In this context, salivary and serum proteomics seem promising diagnostic and predictive tools for head and neck diseases. In the present study, we performed a proteomic analysis of saliva and serum from patients presenting head and neck squamous cell carcinoma (HNSCC) and compared the results before and after therapy. In saliva of cancer patients, we observed an altered protein profile, including over-expression of PLUNC and zinc-alpha-2-glycoprotein. Both proteins may contribute to control tumor growth and, therefore, represent targets for new analysis. We also detected serotransferrin and a modified transthyretin form with altered levels in serum from patients. Comparing preoperative and postreatment samples, the results showed that the protein profile after treatment reverted to a pattern closer to those observed for controls. These results add information on the role of secreted proteins in the cancer process and emphasize the potential of saliva and serum analysis for diagnosis and monitoring of HNSCC.     

Development of new treatment modalities for advanced head and neck carcinomas

In most new cases of head and neck squamous cell carcinoma, especially in the pharynx and oral cavity, the tumors are advanced. Multidisciplinary treatments including chemotherapy in addition to definitive treatments, e.g., surgery and/or radiotherapy, have been applied. However, these treatments have not improved the poor prognosis for advanced head and neck carcinomas. A new curative treatment modality including chemotherapy and having a high complete response rate, e.g., a regimen consisting of taxanes, CDDP and 5-FU, is desirable. In addition, new therapeutic drugs against malignant solid tumors have been developed. The literature on thymidylate synthase inhibitor, dihydropyrimidine dehydrogenase inactivator, p-glycoprotein inhibitor, anti-epidermal growth factor receptor antibody, antiangiogenic drugs, COX-2 inhibitor and retinoids that may be applied in cases of head and neck carcinoma in the future, are reviewed.     

HIGH DOSE FRACTION RADIOTHERAPY FOR MUCOSAL MALIGNANT MELANOMA OF THE HEAD AND NECK

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The impact of dental metal artifacts on head and neck IMRT dose distributions.

BACKGROUND AND PURPOSES: To quantify the cold or hot spot induced in IMRT treatment plans due to the presence of metal artifact in CT image data sets stemming from dental work. PATIENTS AND METHODS: Metal artifact corrected image data sets of five patients have been analyzed. IMRT plans were generated using five different planning image data sets: (a) uncorrected (UC) (b) homogeneous uncorrected (HUC), (c) sinogram completion corrected (SCC), (d) minimum value corrected (MVC), and (e) image set (d) subsequently corrected with a streak artifacts reduction algorithm (SAR-MVC). The SAR-MVC data set is assumed to be the closest approximation to the absence of metal artifacts and has therefore been taken as the reference image data set. An IMRT plan was generated for each of the image datasets (a)-(e). The resulting IMRT treatment plans for data sets (a)-(d) were then projected onto the reference data set (e) and recalculated. The reference dose distribution (e) was then subtracted from these recalculated dose distributions. Using dose difference analysis, the cold and hot spots in organs at risk (OARs) and the target volumes (TVs) were quantified. RESULTS: When compared to the reference dose distribution, the UC, HUC, and SCC plans exhibited hot spots showing on average more than 1.0 Gy hot dose in the left and right parotids. For the UC, HUC, and SCC recalculated plans, subvolumes of the clinical target volumes (CTV) were under dosed on average by more than 0.9 Gy. On the other hand, the MVC plan showed less than 0.3 Gy hot dose in both parotids, and the cold dose in the CTVs were reduced by up to 0.8 Gy. CONCLUSIONS: The presence of dental metal artifacts in head and neck planning CT data sets can lead to relative hot spots in OARs and relative cold spots in regions of the TVs when compared to the reference data set that more closely approximates the patient anatomy. This effect can be reduced if a simple minimum value correction (MVC) method for the dental metal artifacts is employed.     

Radioresistant tumor cells are present in head and neck carcinomas that recur after radiotherapy

We determined the in vitro survival parameters of 14 human head and neck squamous cell carcinoma tumor cell lines cultured from patients who suffered local failure after a curative course of radiotherapy. The radiobiological parameters determined included D, D0, n, and surviving fractions at 100, 200, and 300 cGy. When compared to in vitro radiobiological parameters of tumor cells cultured from head and neck cancer patients prior to radiotherapy, human sarcoma cell lines derived from patients not receiving therapeutic radiation, normal human diploid fibroblasts or other human tumor cell lines reported in the literature, the human tumor cells derived from radiotherapy failures are radioresistant.     

Epidemiology of head and neck carcinomas]

Head and neck carcinomas, i.e. oral cavity, pharynx and larynx cancers, are frequent among men in France. They are mostly squamous-cell carcinomas. The main risk factors are alcohol and tobacco, and their effects are multiplicative. In France, alcohol and tobacco consumptions are decreasing in the male population leading to decrease in head and neck carcinoma incidence and mortality. The best way to prevent head and neck carcinoma is the reduction of alcohol and tobacco consumption.     

Combined concomitant boost radiotherapy and chemotherapy in stage III-IV head and neck carcinomas: A comparison of toxicity and treatment results with those observed after radiotherapy alone

Background: Alteration of radiation therapy (RT) fractionation and thecombination of chemotherapy (CT) with RT represent two predominant fields ofcurrent research in the treatment of head and neck carcinomas. To assess thepotential integration of these two fields, a retrospective comparison oftoxicity and treatment outcome was carried out in stage III–IV patientstreated with a concomitant boost RT schedule with or without CT.Patients and methods: Fifty-two patients were treated by RT alone and 35by RT and CT. In the RT group, there were significantly fewer T3–4tumors(56% vs. 88%, P = 0.002) and higher proportion of planned neckdissections (35% vs. 14%, P = 0.047). The planned total dose was69.9 Gy delivered over 5.5 weeks. In 10 cases CT was given before RT and in25 concomitantly with RT, either alone or with neoadjuvant and/or adjuvant CT.All patients but two had cisplatin-based (CDDP, 100mg/m²) CT, associated in 28 patients with 5-fluorouracil(5-FU, 1000 mg/m²/24 h × 5). The median follow-upfor the surviving patients was 21 and 31 months for the RT and RT–CTgroupsrespectively.Results: Grade 3–4 acute toxicity (RTOG) was observed in 73%and86% of patients, and grade 3 dysphagia in 31% and 57% (P=0.02) respectively in the RT and RT–CT groups. The rates of grade3–4 late complications were similar in the two groups (5% vs.12%). At three years, actuarial loco-regional control (LRC) was57% and 66% (P = 0.66) and overall survival was 56% and47% (P = 0.99) in the RT and RT–CT groups respectively.Conclusions: While acute toxicity was higher compared with RT alone, thisaccelerated RT schedule was feasible in association with 5-FU/CDDP, evenadministered concomitantly. Despite the significant proportion of moreadvanced disease in the RT–CT group, LRC was similar to that obtainedby RTalone. Combinations of concomitant boost RT and chemotherapy merit furtherinvestigation in prospective trials.