Jochen Willner

Dose, volume, and tumor control prediction in primary radiotherapy of non-small-cell lung cancer.

BACKGROUND To evaluate the influence of total dose and tumor volume on local control and survival in primary radiotherapy of non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS We retrospectively analyzed the clinical course and CT-derived pre- and post-therapeutic tumor volume data of 135 patients with NSCLC undergoing primary radiotherapy at our department between 1989 and 1996. Among these, a total of 192 spatially separated tumor volumes (135 primary tumors, 1 additional intrapulmonary tumor, and 56 involved lymph nodes) were available for analysis. In all patients, treatment was planned using CT-based three-dimensional treatment planning. The dose to each tumor volume was derived from the individual dose plans. Mean total dose was 59.9 Gy (range: 30-80 Gy). All but 3 patients were followed until death. For local control analysis, each tumor was analyzed separately, and its remission status was determined in serial follow-up CT scans. A total of 784 CT scans were analyzed. Actuarial local control analysis was performed for the 192 separated tumor volumes, and survival analysis was performed for the 135 patients. Tumor control probability was calculated using a Poisson statistical model. RESULTS Overall 1- and 2-year local control rate was 50% and 37%, respectively. The 2-year local control rate for tumors <50 ccm, 50-200 ccm, and >200 ccm was 51%, 22%, and 10%, respectively (p = 0.02). The 2-year local control rate for dose levels < or = 60 Gy and >60 Gy was 28% and 43% (p < 0.001). For the subgroup of 147 tumors smaller than 100 ccm, the local control rate increased up to 70% (1 year) and 51% (2 years) with doses of more than 60 Gy. For tumors larger than 100 ccm, no dose effect was seen. Only 2 of 45 tumors >100 ccm were controlled more than 2 years. Multivariate analysis revealed tumor volume, total dose, histopathologic type, and grading as significant and independent prognostic factors for local control. The number of delay days by split course (if used) and application of chemotherapy was not found to influence local control. Overall 1- and 2-year survival rate was 42% and 13%. Total radiation dose, chemotherapy, and T and N stage---but not tumor volume---were found to be independent and significant prognostic factors for survival in multivariate analysis. CONCLUSION Tumor volume is an important predictor of local control in NSCLC. We found a clear dose effect for local control and survival in NSCLC. Long-term local control for a significant proportion of patients seems possible for small tumors only (<100 ccm, i.e., maximum diameter 6 cm) with doses of 70 Gy and more. Tumors of > or = 100 ccm are unlikely to be controlled long term by conventional doses up to 70 Gy. These results support dose escalation in patients with NSCLC.

LOCOREGIONAL RECURRENCE OF BREAST CANCER FOLLOWING MASTECTOMY: ALWAYS A FATAL EVENT? RESULTS OF UNIVARIATE AND MULTIVARIATE ANALYSIS

PURPOSE The outcome of patients with local-regional breast cancer recurrence after mastectomy often is described as fatal. However, certain subgroups with favorable prognoses are thought to exist. To determine these favorable subgroups, we analyzed prognostic factors for their influence on postrecurrence survival by univariate and multivariate analysis. METHODS AND MATERIALS Between 1979 and 1992, 145 patients with their first isolated locoregional recurrence of breast cancer following modified radical mastectomy without evidence of distant metastases were treated at the Department of Radiation Oncology of the University of Wurzburg. Thirty-nine percent of patients (n = 67) had had postmastectomy radiotherapy, representing 7% of patients who had received routine postmastectomy irradiation at our institution. Systemic adjuvant hormonal therapy had been applied in 24% and systemic chemotherapy in 19% of patients. Several combinations were used. Treatment of recurrences consisted of surgical tumor excision in 74%, megavoltage irradiation in 83%, additional hormonal therapy in 41%, and chemotherapy in 12% of patients, employing different combinations. Local control in the recurrent site was achieved in 86%. Median follow-up for patients alive at the time of analysis was 8.9 years after recurrence. We tested different prognostic factors, including prior treatment and treatment of recurrence, for their influence on postrecurrence survival, using univariate and multivariate analysis. RESULTS Eighty-two of the 145 patients (57%) developed distant metastases within the follow-up period. Metastases-free rate was 42% at 2 years and 36% at 10 years following recurrence. With development of distant metastases, the survival rate deteriorated. Recurrences appeared within the first 2 years from primary surgery in 56% of patients, and in 89% within 5 years. Overall, 2-year and 5-year survival rates following local-regional recurrence were 67% and 42%, respectively. Univariate analysis revealed statistically significant worsening of survival rates for pT3 + 4 primary tumors, primary axillary lymph node involvement, tumor grading 3 + 4, lymphatic vessel invasion, blood vessel invasion, tumor necrosis, negative estrogen (ER) and progesterone (PR) hormonal receptor status, postmastectomy chemotherapy and hormonal therapy, short time to recurrence (< 1 year), combined recurrences and supraclavicular site of recurrence, non-scar recurrence, size of the largest recurrent nodule > 5 cm, multiple recurrent nodules, no surgical excision of recurrence, small target volume of irradiation, chemotherapy for recurrence, and no local control within the recurrence site. The 2-year and 5-year survival rates ranged from 68% to 94%, and from 33% to 65%, respectively, in the favorable subgroups compared to 2-year and 5-year survival rates ranging from 20% to 59% and 0% to 35%, respectively, in the unfavorable subgroups. Multivariate analysis showed that site of recurrence and number of recurrent nodules have the strongest influence on postrecurrence survival, but time to recurrence, age at time of recurrence, local control in recurrent site as well as primary pT and axillary status, and the presence of tumor necrosis in the primary tumor specimen showed additional independent influences on survival. Thus, we identified a highly favorable subgroup of patients with a single chest wall or axillary recurrent nodule (in a patient aged > 50 years), a disease-free interval of > or = 1 year, pT1-2N0 primary tumor, and without tumor necrosis, and whose recurrence is locally controlled. This group (12 patients) had 5- and 10-year survival rates of 100% and 69%, respectively. CONCLUSION We conclude that locoregional recurrence of breast cancer following mastectomy is not always a sign of systemic disease. Our data support previous findings, that subgroups with favorable prognosis exist and they still have a chance for cure, demanding comprehensive local treatment. (ABSTR

Simultaneous Chemoradiotherapy Compared With Radiotherapy Alone After Induction Chemotherapy in Inoperable Stage IIIA or IIIB Non–Small-Cell Lung Cancer: Study CTRT99/97 by the Bronchial Carcinoma Therapy Group

PURPOSE The aim of this study was to examine whether, after preceding induction chemotherapy, simultaneous chemoradiotherapy is superior to radiotherapy alone. PATIENTS AND METHODS Patients with non-small-cell lung cancer in inoperable stage IIIA or IIIB received induction chemotherapy with two cycles of paclitaxel 200 mg/m2 and carboplatin area under the curve 6 every 3 weeks. Patients without progression at restaging after induction chemotherapy were randomly assigned to radiotherapy (60 Gy) or chemoradiotherapy (paclitaxel 60 mg/m2 weekly). The primary end point was overall survival; secondary end points were time to progression, response, and toxicity. RESULTS Three hundred three patients entered the study, and 276 completed induction chemotherapy. Two hundred fourteen patients were randomly assigned (radiotherapy alone: n = 113; simultaneous chemoradiotherapy: n = 101). Median follow-up time of all randomly assigned patients was 13.6 months (interquartile range [IQR], 6.4 to 29.0 months), and median follow-up time of the subgroup of censored patients (n = 52) was 37.4 months (IQR, 5.9 to 57.0 months; maximum, 76.1 months). Toxicities during the induction phase were mild. During radiotherapy, overall toxicity rates were not significantly different between the two arms. Median survival times in the radiotherapy group and chemoradiotherapy group were 14.1 months (95% CI, 11.8 to 16.3 months) and 18.7 months (95% CI, 14.1 to 23.3 months; difference not statistically significant, P = .091). Median time to progression significantly favored simultaneous chemoradiotherapy (11.5 months; 95% CI, 8.3 to 14.7 months) versus radiotherapy alone (6.3 months; 95% CI, 5.0 to 7.6 months; P < .001, log-rank test). CONCLUSION Induction chemotherapy followed by chemoradiotherapy with weekly paclitaxel is feasible. Response, time to progression, and survival favor chemoradiotherapy compared with radiotherapy alone.

A little to a lot or a lot to a little? An analysis of pneumonitis risk from dose-volume histogram parameters of the lung in patients with lung cancer treated with 3-D conformal radiotherapy.

Purpose: To determine whether a little dose to a large normal lung volume or a high dose to a small lung volume is more critical for induction of clinical pneumonitis. The second question is if dose-volume histogram (DVH) parameters are more reliable, if the lungs are analyzed as separate organs or as a whole organ. Patients and Methods: We analyzed the clinical and DVH data from 49 patients treated for a thoracic malignancy using 3-D conformal treatment plans. 18 patients had developed a clinical pneumonitis (CTC II or III). The majority of patients (n = 48) received radiochemotherapy for non-small-cell lung cancer (NSCLC) with a combination of paclitaxel and carboplatin. Patients were generally treated 5 fx/week, single dose 2 Gy, using a two-series approach (shrinking field) up to a total dose of 60–70 Gy. For every individual patient, the overall dose distribution was recalculated in the Helax-TMS by means of adding dose plans according to the total dose applied in each series. The lungs were defined both as separate organs and as a whole organ. Low-dose volume (≤ 10 Gy, Vlow), moderate-dose volume (> 10–40 Gy, Vmod) and high-dose volume (> 40 Gy, Vhigh), as well as V10–V40 and mean lung dose (MLD) were defined from the cumulative DVH. Dose-effect relationships were fitted with a logistic regression model. Results: Manifestation of clinical pneumonitis was within 3 months from termination of irradiation in all cases. For the ipsilateral lung, the incidence of pneumonitis was closely correlated to Vhigh. The pneumonitis rate increased from 13% up to 60%. By contrast, with increasing Vlow the pneumonitis rate dropped to < 10%. A similar but less pronounced effect was seen for the total lung. The lung volumes Vlow, Vmod and Vhigh of the ipsilateral, contralateral and whole lung were significantly correlated to the corresponding MLD. The incidence of pneumonitis increased with increasing MLD for the ipsilateral lung with a D50 of 32 Gy and a γ50 of 0.98. For the whole lung, the observed increase was less steep. MLD showed a close correlation to NTCP calculated by the Kutcher model. However, NTCP calculation overestimated the pneumonitis risk for the ipsilateral lung and underestimated the risk for the whole lung due to the steeper gradient. The logistic regression curve for the DVH parameters V10–V40 showed an increase of steepness toward higher doses. From the logistic regression curves, a DVH template indicating critical borders of V10–V40 was generated for the ipsilateral as well as for the total lung. Conclusion: Our data indicate that it is reasonable to disperse the dose outside the target volume over large areas in order to reduce the volumes of lung receiving > 40 Gy. Reducing the high-dose volume reduces the pneumonitis rate more than a corresponding reduction in the low-dose regions of the DVH. Landmarks for DVH optimization as defined in this analysis may serve as a basis for DVH constraints in IMRT planning. Separate organ analysis produced more reliable results and should be preferred to whole-organ analysis, if techniques mainly involving one side of the lung are applied. Further validation of these constraints is necessary prior to general recommendation. Ziel: Klärung der Frage, ob es bei Bestrahlung im Lungenbereich günstiger ist, ein großes Lungenvolumen mit niedriger Dosis zu belasten oder umgekehrt und welche Dosis-Volumen-Histogramm-(DVH-)Parameter am besten mit dem Auftreten einer klinischen Pneumonitis korrelieren. Die zweite Frage ist, ob die DVH-Parameter verlässlicher sind, wenn beide Lungenhälften als separate Volumina oder als ein gemeinsames Volumen definiert werden. Patienten und Methodik: Wir analysierten die klinischen und DVH-Daten von 49 Patienten, die wegen eines Bronchialkarzinoms eine thorakale Bestrahlung erhielten. 18 Patienten (37%) hatten eine klinische Pneumonitis (CTC-Grad II/III). Der größte Teil (n = 48) erhielt wegen eines nichtkleinzelligen Bronchialkarzinoms eine Radiochemotherapie mit Paclitaxel und Carboplatin. Alle Patienten wurden von Beginn an nach 3-D-konformaler Bestrahlungsplanung (Helax-TMS) normfraktioniert mit Gesamtdosen zwischen 60 und 70 Gy (50 Gy mit anschließendem Boost) bestrahlt. Für jeden Patienten wurde im Planungssystem anhand der individuellen Gesamtdosen der einzelnen Serien eine Gesamtdosisverteilung errechnet. Die Lungenhälften wurden als individuelle Organe und als Gesamtorgan definiert. Am kumulativen DVH der Gesamtverteilung wurden V10, V20, V30, V40, die mittlere Lungendosis (MLD), das Niedrigdosisvolumen (≤ 10 Gy, Vlow), Mitteldosisvolumen (> 10–40 Gy, Vmod) und das Hochdosisvolumen (> 40 Gy, Vhigh) definiert. Die Dosis-Wirkungs-Beziehung wurde unter Verwendung eines logistischen Regressionsmodells errechnet. Ergebnisse: Alle Pneumonitisfälle manifestierten sich innerhalb von 3 Monaten nach Abschluss der Radiatio. Bei Analyse der ipsilateralen Lunge zeigte sich eine enge Korrelation der Pneumonitisrate zum Vhigh mit einer Zunahme von 13% auf bis zu 60%, wohingegen mit zunehmendem Vlow die Rate auf < 10% fiel. Für die Gesamtlunge war ein ähnlicher Effekt, allerdings weniger deutlich, nachzuweisen. Die Lungenvolumina Vlow, Vmod und Vhigh der ipsilateralen, kontralateralen und Gesamtlunge zeigten eine signifikante Korrelation zu der jeweiligen MLD. Die Pneumonitisrate stieg mit zunehmender MLD (D50 = 32 Gy,γ50 = 0,98). Die Steigung der Dosis-Wirkungs-Kurve war für die Gesamtlunge flacher. Die MLD zeigte eine enge Korrelation zum NTCP-Modell nach Kutcher, jedoch überschätzte die NTCP-Berechnung das Pneumonitisrisiko für die ipsilaterale Lunge und unterschätzte das Risiko für die Gesamtlunge. Die logistische Kurve der Pneumonitisrate für V10–V40 zeigte eine Zunahme der Steilheit mit zunehmender Dosis. Aus den errechneten Kurven wurde eine „DVH-Schablone“ errechnet mit kritischen Werten für die Pneumonitisentstehung, sowohl für die ipsilaterale als auch für die Gesamtlunge. Schlussfolgerung: Unsere Daten legen nahe, dass eine Verteilung der Niedrigdosisareale außerhalb des Zielvolumens über ein möglichst großes Lungenvolumen sinnvoll ist, wenn damit das Volumen der Lunge, das > 40 Gy erhält, reduziert werden kann. Eine Volumenreduktion im Hochdosisbereich reduziert das Pneumonitisrisiko mehr als eine identische Reduktion im Niedrigdosisbereich der DVH. Vor diesem Hintergrund erscheint eine Diskussion der Ausdehnung der „traditionellen“ Zielvolumina im Hinblick auf eine anzustrebende Dosiserhöhung im Tumor zur Verbesserung der lokalen Kontrollraten notwendig. Die in dieser Arbeit präsentierten Grenzmarken für die DVH können als Basis für die Dosisgrenzwerte bei IMRT-Plänen verwendet werden, sollten jedoch noch prospektiv validiert werden. Die DVH-Analyse der separaten Lungenflügel zeigte verlässlichere Ergebnisse und sollte bevorzugt werden, wenn Techniken, die vornehmlich eine Lunge belasten, zum Einsatz kommen.

Carcinoma of the external auditory canal and middle ear

PURPOSE To evaluate therapeutic modalities used at our institutions regarding local control, disease-free survival and actuarial survival in carcinoma of the external auditory canal and middle ear, in an attempt to provide guidelines for therapy. METHODS AND MATERIALS A series of 27 patients with carcinoma of the external auditory canal and middle ear treated between 1978 and 1997 in our institutions were analyzed with particular reference to tumor size and its relation to surrounding tissues, patterns of neck node involvement, surgical procedures, and radiation techniques employed. Clinical endpoints were freedom from local failure, overall survival, and disease-free survival. The median follow-up was 2.7 years (range 0.1-17.9 years). RESULTS Treatment by surgery and radiotherapy resulted in an overall 5-year survival rate of 61%. According to the Pittsburgh classification, the actuarial 5-year survival rate for early disease (T1 and T2 tumors) was 86%, for T3 tumors 50%, and T4 stages 41%. Patients with tumors limited to the external auditory canal had a 5-year survival rate of 100%, patients with tumor invasion of the temporal bone 63%, and patients with tumor infiltration beyond the temporal bone 38%. The rate of freedom from local recurrence was 50% at 5 years. Unresectability by dural and cerebral infiltration, and treatment factors such as complete resection or resection with tumor beyond surgical margins are of prognostic relevance. All patients with dural invasion died within 2.2 years. The actuarial 5-year survival rate of patients with complete tumor resection was 100%, but 66% in patients with tumor beyond surgical margins. 192Iridium high-dose-rate (HDR) afterloading brachytherapy based on three-dimensional computed tomography (3D CT)-treatment planning was an effective tool in management of local recurrences following surgery and a full course of external beam radiotherapy. CONCLUSION Surgical resection followed by radiotherapy adapted to stage of disease and grade of resection is the preferred treatment of cancer of the external auditory canal and middle ear.

CT simulation in stereotactic brain radiotherapy — analysis of isocenter reproducibility with mask fixation

BACKGROUND AND PURPOSE CT verification and measurement of isocenter deviation using repeated mask fixation in linac-based stereotactic high dose radiotherapy of brain metastases were performed in this study. MATERIALS AND METHODS For stereotactic radiotherapy of brain metastases a commercial head mask fixation device based on thermoplastic materials (BrainLAB) was used. A two-step planning-treatment procedure was performed. Immediately before treatment the patient was relocated in the mask and a verification CT scan of the radiopaque marked isocenter was performed and if necessary its position was corrected. The verification procedure is described in detail. Twenty-two CT verifications in 16 patients were analyzed. Deviations were measured separately for each direction. A 3D-deviation vector was calculated. Additionally the average amount of deviation in each of the three dimensions was calculated. RESULTS The mean deviation and standard deviation (SD) of the isocenter was 0.4 mm (SD 1.5 mm) in the longitudinal direction, -0.1 mm (SD 1.8 mm) in the lateral direction and 0.1 mm (SD 1.2 mm) in the anterior-posterior direction. The mean three-dimensional distance (3D-vector) between the verified and the corrected isocenter was 2.4 mm (SD 1.3 mm). The average deviation (without consideration of direction) was 1.1 mm (SD 1.1 mm), 1.3 mm (SD 1.3 mm) and 0.8 mm (SD 0.9 mm) in the longitudinal, lateral and sagittal directions, respectively. No correlation was found between 3D-deviation and the distance of the isocenter from the reference plane nor between deviation and the position of metastases in the brain (central versus peripheral or between different lobes), or the date of treatment. CONCLUSION Reproducibility of the isocenter using the presented mask fixation is in the range of positioning reproducibility reported for other non-invasive fixation devices for stereotactic brain treatment. Our results underline the importance of CT verification as a quality assurance method in stereotactic radiotherapy. Under the condition of a preceding CT verification the mask can be used for single dose stereotactic radiotherapy. For fractionated stereotactic irradiation of small target volumes we recommend repeated CT verifications to assure reproducibility.

Tumor Volume and Local Control in Primary Radiotherapy of Nasopharyngeal Carcinoma

An investigation of the effect of tumor volume and total dose on local control following primary radiotherapy for nasopharyngeal carcinoma was carried out in order to estimate the radiation dose necessary to control a specific tumor volume. Between 1983 and 1996 a total of 104 patients underwent radiation therapy for nasopharyngeal carcinoma at the Department of Radiation Oncology of the University of Wuerzburg. Total doses of between 8 and 80 Gy (5 fractions per week) were administered. Complete CT-data on primary tumor size, total tumor dose (calculated by 3D- or quasi 3D-CT-based radiation planning computer) and on local control status in the follow-up period were available for 63 patients. Lymph node metastases were present in 38 of these patients and they were also entered into the study. Thus this study is based on a total of 101 tumor regions. A Poisson probability-based model was used for calculating the dose-response relationship. Assuming a correlation between tumor volume and the total dose necessary to obtain local control, the individual tumor volumes were rescaled to a 1 ml volume by introducing a volume-dependent modification factor for the applied dose, in order to eliminate the influence of different individual tumor volumes. All dose values given are based on a fractionation scheme of 2 Gy single dose, 5 fractions per week. Nineteen tumors and 11 lymph nodes were considered locally uncontrolled or recurrent. Without dose-volume modification, a weak dose-response correlation was found and a typical shallow dose-response curve was calculated with a 50% response dose (RD50) of 60.2 Gy and a normalized dose-response gradient (gamma50) of 3.2+/-0.62. After dose-volume modification and rescaling to a 1 ml tumor volume, a steep dose-response curve with an RD50 of 40.9 Gy and gamma50 of 8.2. was found. Tumor volume is a very important factor influencing local control in nasopharyngeal carcinoma. The rescaling procedure to a reference volume of 1 ml used in this study revealed a very steep dose-response relationship. This result suggests that the clinically observed smooth dose-response relationships may be explained by interindividual tumor volume heterogeneity. The additional dose necessary to control a tumor of the double volume is close to 5 Gy. With a total dose of 72 Gy (5x2 Gy/week), tumor volumes larger than 64 ml are unlikely to be controlled.

The prognostic significance of the supraclavicular lymph node metastases in breast cancer patients

PURPOSE To define the patterns of failure and outcome of patients presenting supraclavicular lymph node involvement and the prognostic significance of supraclavicular lymph node involvement. METHODS AND MATERIALS We reviewed the history of 795 breast cancer patients treated at the Department of Radiation Therapy, University of Würzburg between 1978 and 1988. The clinical and pathologic features of 21 patients who had ipsilateral supraclavicular lymph node metastases at primary diagnosis and 38 patients who presented supraclavicular lymph node recurrence during the course of disease were reviewed. These were compared with the features of 20 patients who initially had M1 status at primary diagnosis and 278 patients who had developed distant metastases in the follow-up period. Survival rates were calculated starting from the time of diagnosis of supraclavicular involvement respective of distant metastases. RESULTS Survival from appearance of supraclavicular lymph node metastases at primary diagnosis or as a recurrence is not different from survival of patients presenting with a primary M1 stage or presenting distant metastases during the course of disease. Two and 5-year survival rates of patients with supraclavicular lymph node involvement at primary diagnosis were 52% and 34% compared to 50% and 16% 2- and 5-year survival rate of patients with supraclavicular lymph node involvement as a recurrence. Patients who presented a primary M1-status had 2- and 5-year survival rates of 56% and 24%. Survival of patients with distant metastases calculated from the onset of metastatic disease was similar to that of the other three groups with a 46% and 16% survival rate at 2 and 5 years. There was no difference in survival rates between the four groups. CONCLUSION The prognostic significance of supraclavicular lymph node involvement at primary diagnosis or as a relapse is similar, both have the same significance as the first distant relapse and are characterized by a poor prognosis.

Three dimensional variability in patient positioning using bite block immobilization in 3D-conformal radiation treatment for ENT-tumors

BACKGROUND AND PURPOSE The aim of this prospective study was to analyze the three-dimensional (3D) reproducibility of the isocenter position and of patient positioning with the use of bite block immobilization by means of a simple verification procedure for a complex beam arrangement applied for ENT-tumors. MATERIALS AND METHODS We analyzed the positioning data of 29 consecutive patients treated for ENT-tumors at the Department of Radiotherapy and Oncology of the University of Wurzburg. A total of 136 treatment sessions were analyzed. Patients were positioned and immobilized using an individualized bite block system and a head and neck support. A complex beam arrangement was applied combining two offset rotational and two oblique wedge fields on a 5 MV linear accelerator. Orthogonal verification films were taken once weekly. Four to six film pairs per patient were obtained (during 4-6 weeks) with a mean number of 4.7 film pairs per patient. These were compared to the corresponding orthogonal simulator films taken during primary simulation. Deviations of the verified isocenter from the isocenter on the simulator film were measured and analyzed in three dimensions in terms of overall, systematic and random categories. A 3D-deviation vector was calculated from these 3D data as well as a 2D-deviation vector (for comparison with literature data) from the lateral verification films. RESULTS The overall setup deviation showed standard deviations (SD) of 2.5, 2.7 and 3.1 mm along the cranio-caudal, anterior-posterior and medio-lateral axes, respectively. The random component ranged from SD 1.9 to 2.1 mm and the systematic component ranged from SD 1.8 to 2.2 mm. The mean length of the 3D-vector was 3.1 mm for the systematic as well as the random component. Ninety percent of 3D systematic and random deviations were less than 5 mm. The mean length of the 2D-vector was 2.4 mm for the random component and 2.2 mm for the systematic component. Ninety percent of 2D-random and systematic variations were less than 4 mm. CONCLUSIONS The presented individualized bite block immobilization device provides an accurate and reproducible patient positioning for 3D-conformal radiation therapy in the head and neck. Random and systematic deviations in each of the three directions are in the range of +/-4 mm (2 SD, comprising 95% of the deviations) and are within the range or even less than deviations described for most thermoplastic or PVC-mask fixation devices. These deviations should be taken into account during definition of planning target volume in head and neck tumors.

The influence of the radicality of resection and dose of postoperative radiation therapy on local control and survival in carcinomas of the upper aerodigestive tract

PURPOSE To evaluate dose concepts in postoperative irradiation of carcinomas of the upper aerodigestive tract according to the radicality of resection. PATIENTS AND METHODS In a retrospective analysis, the charts of 257 patients with histologically-proven carcinoma of the upper aerodigestive tract (40 T1, 80 T2, 53 T3, 84 T4 tumors, with nodal involvement in 181 cases) were reviewed according to the radicality of resection and dose of irradiation administered. Sixty-four patients had tumor-free resection margins (> 3 mm), 66 patients had close resection margins (< 3 mm), and 101 patients had R1 resections, and 26 patients had R2 resections. A median dose of 56 Gy was applied to the primary tumor bed and the cervical lymphatics (2 Gy/fraction, 5 fractions/week). In cases of R1 or R2 resection, or of close margins (< 3 mm), the tumor bed or, respectively, tumor residuals were boosted with doses up to a median of 66 Gy. Locoregional tumor control and survival was investigated by uni- and multivariate analyses according to T-, N-stage, grade of resection, total dose of radiation, and presence or absence of extracapsular tumor spread and lymphangiosis carcinomatosa. RESULTS An overall 3- and 5-year survival rate of 60% and 45%, respectively, was achieved. Rates for freedom from locoregional recurrence were 77% and 72% at 3 and 5 years, respectively. The survival rates according to the grade of resection at 5 years were 67% for patients resected with tumor-free margins, 59% for patients resected with close margins, 26% for patients with R1 resection, and 27% for patients with R2 resection. Within a median follow-up period of 4.7 years for living patients, a total of 67 recurrences (26%) were observed (in 9% of patients resected with tumor-free margins, in 27% with close margins, in 37% of R1 resected, and in 19% of R2 resected patients). Freedom from locoregional recurrence at 3 years was achieved in 100% of the patients resected with tumor-free margins, in 92% of patients resected with close surgical margins, in 87% of R1 and 69% of R2 resected patients. In multivariate Cox-regression analysis, the variables grade of resection (p = 0.00031) and total dose of irradiation (p = 0.0046) were found as factors influencing locoregional control. Variables influencing survival according to multivariate analysis are T-stage (p = 0.0057), N-stage (p = 0.024), grade of resection (p = 0.000015), total dose of irradiation (p < 0. 000000). Extracapsular tumor spread and lymphangiosis carcinomatosa are factors of borderline significance (p = 0.055, p = 0.066). CONCLUSION In postoperative radiotherapy of head and neck carcinomas, doses adapted to the risk of locoregional recurrent disease should be applied. Patients with R1 and R2 resections should be treated with doses of more than 68 Gy (2 Gy/fraction, 5 fractions/week) (with close margins [< 3 mm] more than 66 Gy) to achieve an improvement in locoregional control and survival.