R.B. Keus

The potential impact of CT-MRI matching on tumor volume delineation in advanced head and neck cancer

PURPOSE To study the potential impact of the combined use of CT and MRI scans on the Gross Tumor Volume (GTV) estimation and interobserver variation. METHODS AND MATERIALS Four observers outlined the GTV in six patients with advanced head and neck cancer on CT, axial MRI, and coronal or sagittal MRI. The MRI scans were subsequently matched to the CT scan. The interobserver and interscan set variation were assessed in three dimensions. RESULTS The mean CT derived volume was a factor of 1.3 larger than the mean axial MRI volume. The range in volumes was larger for the CT than for the axial MRI volumes in five of the six cases. The ratio of the scan set common (i.e., the volume common to all GTVs) and the scan set encompassing volume (i.e., the smallest volume encompassing all GTVs) was closer to one in MRI (0.3-0.6) than in CT (0.1-0.5). The rest volumes (i.e., the volume defined by one observer as GTV in one data set but not in the other data set) were never zero for CT vs. MRI nor for MRI vs. CT. In two cases the craniocaudal border was poorly recognized on the axial MRI but could be delineated with a good agreement between the observers in the coronal/sagittal MRI. CONCLUSIONS MRI-derived GTVs are smaller and have less interobserver variation than CT-derived GTVs. CT and MRI are complementary in delineating the GTV. A coronal or sagittal MRI adds to a better GTV definition in the craniocaudal direction.

The simultaneous boost technique: the concept of relative normalized total dose

The simultaneous boost technique in radiotherapy consists of delivering the boost treatment (additional doses to reduced volumes) simultaneously with the basic (large-field) treatment for all treatment sessions. Both the dose per fraction delivered by the basic-treatment fields and by the boost-treatment fields have to be reduced to end up with the same total dose in the boost volume as in the original schedule, where the basic treatment preceded the boost treatment. These dose reductions and corresponding weighting factors have been calculated using the linear-quadratic (LQ) model and the concept of Normalized Total Dose (NTD). Relative Normalized Total Dose (RNTD) distributions were computed to evaluate the dose distributions resulting for the simultaneous boost technique with respect to acute and late normal tissue damage and tumor control. For the example of the treatment of prostatic cancer the weighting factors were calculated on the basis of the NTD for late normal tissue damage. For the treatment of oropharyngeal cancer the NTD for acute normal tissue damage was used to determine the weighting factors. In this last example a theoretical sparing of late normal tissue damage can be demonstrated. A second advantage of the simultaneous boost technique is that the megavoltage images of the large basic-treatment fields facilitates the determination of the position of the patient with respect to the small boost-treatment fields.

Does the combination of radiotherapy and debulking surgery favor survival in paranasal sinus carcinoma

PURPOSE To determine the contribution of debulking surgery on local control and survival in paranasal sinus tumors. As most patients present with locally advanced disease, the possibility of radical surgery is limited. Consequently, radiotherapy is often needed as monotherapy or as an adjunct to surgery. METHODS AND MATERIALS Between 1977 and 1996, 73 patients (50 male: 23 female) with a paranasal sinus carcinoma were treated. The histology distribution was as follows: squamous cell carcinoma, 55%; adenocarcinoma, 19%; adenoid cystic carcinoma, 11%; and undifferentiated carcinoma, 15%. The clinical T classification was (UICC/TNM 1997): T2 14%, T3 27%, and T4 59%. Pathological neck nodes were found in 11% of patients. Treatment consisted of surgery only in 3, chemotherapy only in 1, radiotherapy only in 18, both surgery and radiotherapy in 50 patients. One patient did not receive any treatment at all. Three patients had concurrent chemotherapy. Median follow-up was 66 months (range, 1-213 months). RESULTS Five-year local control (LC) was 65% with combination of radiotherapy and debulking surgery in comparison with 47% with radiotherapy alone, but this difference was not statistically significant (p = 0.58). However, combination treatment gave significantly better 5-year overall survival (OS) (60% vs. 9%; p = 0.001) and 5-year disease-free survival (DFS) (53% vs. 6%; p < 0. 0001). Cox-regression analysis showed that pathologic N status (p = 0.04), palliative intention of treatment (p = 0.018), clinical orbital invasion (p = 0.003), and orbital wall invasion (p = 0.003) were parameters significantly associated with poor local control. Total radiation dose of greater than 65 Gy (p = 0.05) and treatment consisting of radiotherapy alone (p = 0.002) were associated with worse overall survival; for disease-free survival clinical orbital invasion (p = 0.0005), age of greater than 65 years (p = 0.013) and pathologic T4 classification (p = 0.002) were significant factors for an unfavorable outcome. In 19 of 73 patients, 26 serious (mainly ophthalmological) complications were reported; in the majority of these, the visual tract was (partly) included in the treatment fields because of tumor extension. To analyze on which basis patients were selected for the combination therapy, a logistic regression was performed, concluding that clinical T4 classification (p = 0.05), radiological evidence of skull base invasion (p = 0.005), age of greater than 65 years (p = 0.026), radiological evidence of nasopharynx invasion (p = 0.02), clinical suspicion of palate invasion (p = 0.02), and radiological evidence of skin invasion (p = 0.009) were associated with choosing radiotherapy alone. CONCLUSION Debulking surgery of paranasal sinus malignancies followed by high-dose radiotherapy to the involved sites was associated with better survival and (although not statistically significant) local control. Patient selection, based on clinical and radiological impression of tumor extension, was the main factor explaining these favorable results. We favor this combination regimen because the surgery gives quick relief of complaints and, at the same time, offers an excellent histologically proven staging method, enabling radiotherapy to be adjusted to the involved sites, thereby decreasing the risk of complications. This can all be achieved with a very low orbital exenteration rate.

Radiotherapy for management of extremity soft tissue sarcomas: why, when, and where?

This critical review will focus on published data on the indications for radiotherapy in patients with extremity soft tissue sarcomas and its role in local control, survival, and treatment complications. The differences between pre- and postoperative radiotherapy will be discussed and consensus recommendations on target volume delineation proposed.

Setup deviations in wedged pair irradiation of parotid gland and tonsillar tumors, measured with an electronic portal imaging device

The first aim of this study was to quantify estimated translational setup deviations of patients treated with a wedged pair of oblique beams for parotid gland and tonsillar tumors, using portal imaging. The second aim was to design an off-line setup verification procedure, to improve the setup accuracy, if necessary. Thirty-one patients were treated with two conformal fields (anterior-oblique and posterior-oblique). The patients were immobilized with a head cast. For the last 10 patients, the rigidity of the cast was improved while, in addition, wax molds with metal markers were placed into the outer ear for image correlation. Portal images were acquired about weekly. Setup deviations were analyzed, using anatomical structures and, when available, metal markers for image matching. The consistency of the deviations was determined by the correlation between deviations in the cranio-caudal direction, as measured from both beams. When the deviations were consistent, the translational setup deviation during a treatment session could be described by a three-dimensional (3D) vector. A setup verification procedure was designed using a computer simulation. The statistics of the 3D setup deviations were used as input. The output consisted of the resulting setup accuracy and workload (i.e., the number of setup corrections and portal images). Using the anatomical structures for image correlation, the deviations in the cranio-caudal direction were not correlated, either for the old or the improved cast. However, by using the metal markers, the deviations were correlated and a 3D analysis could be performed. The standard deviations, averaged over the three directions, were equal to 1.8 and 1.4 mm for the distribution of systematic and random deviations, respectively. Application of a setup verification procedure, with 0.7 corrections on the average per patient, could potentially reduce the percentage of 3D systematic deviations larger than 4 mm from 30 to 2%. It can be concluded that it was not possible to obtain consistent translational setup deviations, due to rotations. To quantify 3D translational setup deviations, it was necessary to use additional metal markers, which were visible in the portal images of both beams. A further improvement of the setup accuracy is possible by using an off-line setup verification procedure.

Evidence for early and persistent impairment of salivary gland excretion after irradiation of head and neck tumours

Salivary gland scintigraphy with technetium-99m pertechnetate was used to follow changes in the excretion and uptake function of the major salivary glands until 1 year after irradiation. Twenty-five patients who received radiotherapy for head and neck tumours were included in the study. Seventy-nine salivary glands (39 parotid and 40 submandibular) were evaluated in relation to the average received radiation dose. Salivary gland scintigraphy was performed before and 1, 6 and 12 months after radiotherapy. For each gland the excretion response to carbachol, evaluated by calculation of the salivary excretion fraction (SEF), the cumulative gland uptake (CGU) and the absolute excreted activity (AEA) at various intervals after radiotherapy were compared with the baseline values. The excretion response decreased in 20 of 25 patients at 1 month after radiotherapy. One month after radiotherapy both SEF and AEA decreased significantly in relation to the radiation dose. These decreases in excretion parameters persisted during the follow-up period. Parotid excretion was affected significantly more than submandibular excretion. CGU values did not change significantly until 6 months after radiotherapy, but at 12 months a significant decrease related to radiation dose was observed. Xerostomia was assessed during radiotherapy and on the days of the scintigraphic tests. The incidence of xerostomia did not correspond to the effects observed in the scintigraphy studies. It is concluded that radiotherapy induces early and persistent impairment of salivary gland excretion, related to the radiation dose. This impairment is stronger in parotid glands than in submandibular glands.

Limb-sparing therapy of extremity soft tissue sarcomas: treatment outcome and long-term functional results

The purpose of this study is to assess the long-term success rate and functional results of limb-sparing therapy in a group of 156 patients with soft tissue sarcomas of the extremities in the Netherlands Cancer Institute, treated according to a standard protocol of surgery and radiotherapy, if indicated. The patients (79 females and 77 males) were treated between 1977 and 1983 by an intended wide local excision with a margin of at least 2 cm. Postoperative radiotherapy was applied in 117 patients; 26 patients had surgery only, including 13 patients who had to be treated by amputation. The total dose was 60 Gy, with 40 Gy to a large volume and a boost of 20 Gy to the tumour bed at 2 Gy per fraction, five fractions per week. Most sarcomas were located in the proximal part of the lower extremity (51%). The group comprised 50 liposarcomas, 47 malignant fibrous hystiocystoma (MFH) and 59 other histologies; 69 (44%) had high-grade tumours. Three treatment groups with limb-sparing treatment were defined: group I (n = 26) patients who had a complete excision receiving no further treatment, group II (n = 64) with narrow surgical margins and radiotherapy and group III (n = 53) with incomplete resection and radiotherapy. The 10-year actuarial overall survival and local control rate for all patients was 63 and 81%, respectively. Multivariate analysis showed that histological grade (P < 0.0001), age (P = 0.0005) and location deep to the fascia (P = 0.0008) were independent prognostic factors for survival, while local control was predicted by grade (P = 0.0014) and treatment group (p = 0.028). Patients with surgery only (group I) had 81% 5-year local control as compared to 92% with radiotherapy after narrow surgery (group II) and 74% with incomplete surgery and radiotherapy (group III). Limb preservation when attempted was achieved in 90% of the patients. After limb-sparing treatment, 7% had severe impairment of mobility, 3% had lymph oedema and 16% marked fibrosis. Fractures in the irradiated bone occurred in 6% of the patients. The combination of limited surgery followed by radiotherapy resulted in a high local control rate with good functional results. Ultimately limb sparing treatment was successful in 83% of all patients with extremity sarcomas.

Desmoid tumors: need for an individualized approach.

Desmoid tumor, also known as aggressive fibromatosis or desmoid-type fibromatosis, is a rare monoclonal, fibroblastic proliferation arising in musculoaponeurotic structures. Although histologically benign, desmoids are often locally invasive and associated with a high local recurrence rate after resection. Since it is a heterogeneous disease, in particular regarding clinical presentation, anatomic location and biological behavior, treatment should be individualized to reduce local tumor control failure with concurrently acceptable morbidity and preservation of quality of life. Many issues regarding optimal treatment of desmoids remain controversial. However, wide surgical excision remains the treatment of choice, except when surgery is mutilating and is associated with considerable function loss or major morbidity. Involvement of surgical margins is probably associated with an increased risk of local recurrence. Postoperative radiotherapy results in a significant reduction of the local recurrence rate, but only in the case of involved surgical margins. Radiotherapy for gross disease is considerably effective, but is associated with a relatively high rate of complications, which are usually mild or moderate and radiation dose dependent. Radiotherapy should only be applied where anatomic constraints preclude complete resection and radiotherapy is not too toxic. Risk factors for local tumor control failure include young age, large size, presentation as recurrent disease, limb/girdle or intra-abdominal location, involved surgical margins, omission of radiotherapy, radiation dose less than 50 Gy and insufficient radiation field size. Increased comprehension of the pathogenesis and biological behavior of desmoids resulted in the emerging applicability of systemic therapies and a wait-and-see policy. Systemic treatment may be indicated in patients that have anatomic barriers to effective surgery or radiotherapy. Considering the significant morbidity of surgery and/or radiotherapy for certain locations, especially mutilation and loss of function, and the tumor’s natural history, which is often characterized by prolonged periods of stability or even regression, a period of watchful waiting may compose the most appropriate management in selected asymptomatic patients. Attempts to complete eradication of the disease may be worse than the disease itself.

High-dose superselective intra-arterial cisplatin and concomitant radiation (RADPLAT) for advanced head and neck cancer.

The purpose of this study was to study the effect of intensive targeted chemoradiation in a group of patients with head and neck cancer with stage IV inoperable disease.

Multidimensional assessment of voice characteristics after radiotherapy for early glottic cancer

Objectives/Hypothesis: To assess voice characteristics of patients following radiotherapy for early glottic cancer through a multidimensional analysis protocol including vocal function and voice quality measures. Methods: Voice analyses were performed for 60 patients treated with radiotherapy (66 Gy/33 fractions, 60 Gy/30 fractions, or 60 Gy/25 fractions) for early T1 glottic cancer and 20 matched control speakers. There was a longitudinal group of 10 patients for whom data were collected before as well as 6 months and 2 years after radiation. Furthermore, data were collected for five separate groups of 10 patients each, before, 6 months after, 2 years after, 3 to 7 years after, and 7 to 10 years after radiation. Vocal function was investigated by means of videolaryngostroboscopy, phonetography, maximum phonation time, and phonation quotient measures. Voice quality was assessed by means of objective acoustical analysis and subjective perceptual ratings by trained raters. Results: Voice characteristics of patients were decreased before radiotherapy, improved after treatment, and became comparable to the voice characteristics of control speakers in at least 55% of the patients. Following radiotherapy, deviant voice quality was mainly negatively affected by increased age and stripping the vocal cord for initial diagnosis. Stroboscopy revealed that next to increasing age and stripping the vocal cord, continued smoking after treatment decreased vocal function following radio‐therapy. Conclusion: Voices of patients diagnosed with early glottic cancer improved but did not normalize fully after radiotherapy. Stripping the vocal cord for initial diagnosis and continued smoking after treatment decreased voice characteristics. A multidimensional analysis protocol including perceptual and acoustical analysis of voice quality and stroboscopic analysis of vocal function is recommended to investigate voice characteristics following treatment for early glottic cancer.