Mean Tumor Dose Research Articles

Gamma Knife surgery for brain metastases from gastrointestinal cancer

Brain metastases from gastrointestinal cancers are rare. However, the incidence is increasing because patients with gastrointestinal carcinoma tend to live longer due to earlier diagnosis and more effective treatment of systemic disease. The purpose of this study was to evaluate the efficacy of Gamma Knife surgery (GKS) for the treatment of brain metastases from gastrointestinal cancers. The authors performed a retrospective review of 40 patients (18 women and 22 men) who had undergone GKS to treat a total of 118 metastases from gastrointestinal cancers between January 1996 and December 2006. The mean patient age was 58.7 years, and the mean Karnofsky Performance Scale (KPS) score was 70. There were 7 patients with esophageal cancer, 25 with colon cancer, 5 with rectal cancer, 2 with pancreatic cancer, and 1 with gastric cancer. Nineteen patients were treated with whole-brain radiotherapy and/or local brain radiotherapy before GKS. Twenty-four patients had extracranial metastases, and 3 had an additional primary cancer. The mean metastatic brain tumor volume was 4.3 cm3, and the mean maximum tumor dose varied from 17.1 to 76.7 Gy (mean 41.8 Gy). Follow-up imaging studies were available in 25 patients with a total of 90 treated metastases. The results demonstrate a tumor control rate of 91%. The median survival time was 6.7 months, and the 6-month and 1-year survival rates were 55 and 25%, respectively. A univariate analysis revealed that the KPS score (<or=70 vs >or=80) was significant (p=0.018) for improved survival. Results in this series suggest that GKS can be an effective tool for the treatment of brain metastases from gastrointestinal cancer.

Use of Integrated SPECT/CT Imaging for Tumor Dosimetry in I-131 Radioimmunotherapy: A Pilot Patient Study

Integrated systems combining functional (single-photon emission computed tomography; SPECT) imaging with anatomic (computed tomography; CT) imaging have the potential to greatly improve the accuracy of dose estimation in radionuclide therapy. In this article, we present the methodology for highly patient-specific tumor dosimetry by utilizing such a system and apply it to a pilot study of 4 follicular lymphoma patients treated with I-131 tositumomab. SPECT quantification included three-dimensional ordered-subset expectation-maximization reconstruction and CT-defined tumor outlines at each time point. SPECT/CT images from multiple time points were coupled to a Monte Carlo algorithm to calculate a mean tumor dose that incorporated measured changes in tumor volume. The tumor shrinkage, defined as the difference between volumes drawn on the first and last CT scan (a typical time period of 15 days) was in the range 5%-49%. The therapy-delivered mean tumor-absorbed dose was in the range 146-334 cGy. For comparison, the therapy dose was also calculated by assuming a static volume from the initial CT and was found to underestimate this dose by up to 47%. The agreement between tracer-predicted and therapy-delivered tumor-absorbed dose was in the range 7%-21%. In summary, malignant lymphomas can have dramatic tumor regression within days of treatment, and advanced imaging methods allow for a highly patient-specific tumor-dosimetry calculation that accounts for this regression.

SU-FF-T-633: Impact of Tissue Heterogeneity Corrections in Stereotactic Body Radiation Therapy Treatment Plans for Non Small Cell Lung Cancer Patients

Purpose: To study the effect of tissue heterogeneity corrections on the dosimetry of stereotactic body radiation therapy treatment plans for patients with non-small cell lung cancer. Materials and Methods: Data from 15 stage I non-small cell lung patients was used. Treatment planning was done with 6 MV non-opposing coplanar beams using Varian Eclipse TPS (PBC Algorithm with Modified Batho Power Law). Prescription dose was 60 Gy in 3 fractions with tissue heterogeneity corrections. Plans were normalized to deliver prescription dose to 95% of the planning target volume (PTV) maintaining the spinal cord dose under 10 Gy. Separate plans were generated by recalculating the optimized treatment plans without heterogeneity correction while keeping identical beam arrangements, monitor units, and fluences. Results: Compared with the heterogeneity corrected plans, the uncorrected plans had lower minimum, mean, and maximum tumor doses by at least 12.5%, 7.7%, and 6.0%. The PTV receiving less than prescription dose was significantly higher (>25%) in the uncorrected plans. The percentage of uninvolved lung volume receiving minimum doses of 10 Gy, 15 Gy, 20 Gy, and 30 Gy was ⩽ 10% for both treatment plans. However, the uncorrected plans calculated slightly less dose to normal lung. The average maximum spinal cord dose was 8.56 Gy and 9.73 Gy for corrected and uncorrected plans respectively. Conclusions: Treatment plans optimized with tissue heterogeneity corrections were generated to satisfy planning goals and constraints. Re-calculating such plans without tissue heterogeneity corrections and keeping identical conditions of beam and monitor units resulted in target underdosing because the planning system assumed that more tissue attenuation was present than is actually the case. By extension, failure to use tissue heterogeneity correction to plan complex beam arrangements to treat tumors within the lung will lead to delivery of higher doses than are prescribed to less than optimum dose distributions.

SU‐FF‐J‐176: Assessing the Impact of Partial Volume Correction On Dose Painting

Purpose: Tumor heterogeneities identified by PET imaging suffer from partial volume effects (PVE) due to the scanner's limited resolution. This study establishes the necessity for including partial volume correction in dose painting prescriptions. Method and Materials: A previously reported iterative partial volume correction (PVC) method, specific to heterogeneous tumors, was applied to 15 tumors exhibiting heterogeneous uptake of [Cu‐61]Cu‐ATSM, a hypoxia surrogate marker. Dose painting prescriptions were generated from PET images using two techniques: a linear transformation converting SUV to dose, and a threshold method creating boost regions for SUVs greater than 3. All prescriptions implemented minimum tumor dose constraints of 50 Gy. Continuous prescriptions linearly redistributed dose about the mean tumor SUV, yielding a mean tumor dose of 70 Gy. Thresholding prescribed an additional 20 Gy to the boost region. Doses were optimized for each prescription using an in‐house helical tomotherapy planning system. Results: PVC images exhibited redistribution of mid‐range SUVs to higher/lower SUVs with heterogeneity uptake differences of ±25–30%. However, average dose differences for linear transformation dose painting were ±5–10%, due to the transform's ratio of base dose to boost dose. The average dose differences for threshold transformation dose painting were dependent on threshold level and the tumor SUV distribution. In cases where the mean tumor SUV was approximately equivalent to the threshold SUV, PVC increased and decreased boost volumes in equal amounts. However, with mean or max tumor SUVs below threshold values, PVC significantly increased boost volumes, creating boost regions where none previously existed. Conclusion: PVC alters the volume and magnitude of regions receiving redistributed boost doses. PVC frequently reveals tumor heterogeneities where none were previously observed due to PVE, which should be included in dose painting prescriptions. Institutions intending to implement PET‐based dose painting should understand and correct for partial volume effects prior to generating prescriptions.

Tumor control and normal tissue complications in BNCT treatment of nodular melanoma: A search for predictive quantities

A previous work concerning tumor control and skin damage in cutaneous melanoma treatments with BNCT has been extended to include doses, volumes and responses of 104 subcutaneous lesions from all patients treated in Argentina. Acute skin reactions were also scored for these patients, and cumulative dose-area histograms and dose-based figures of merit for skin were calculated. Broadening the tumor response analysis with the latest data showed that the (minimum or mean) tumor dose is not a good predictor of the observed clinical outcome by itself. However, when the tumor volume was included in the model as second explicative variable, the dose increases its significance and becomes a critical variable jointly with the volume ( p-values<0.05). A preliminary analysis to estimate control doses for two groups of tumor sizes revealed that for small tumor volumes (< 0.1 cm 3) doses greater than 20 Gy-Eq produce a high tumor control (> 80%). However, when tumor volumes are larger than 0.1 cm 3, control is moderate (< 40%) even for minimum doses up to 40 Gy-Eq. Some quantities based on skin doses, areas and complication probabilities were proposed as candidates for predicting the severity of the early skin reactions. With the current data, all the evaluated figures of merit derived similar results: ulceration is present among the cases for which these quantities take the highest values.

Use of an orthovoltage X-ray treatment unit as a radiation research system in a small-animal cancer model

BackgroundWe explore the use of a clinical orthovoltage X-ray treatment unit as a small-animal radiation therapy system in a tumoral model of cervical cancer.MethodsNude mice were subcutaneously inoculated with 5 × 106 HeLa cells in both lower limbs. When tumor volume approximated 200 mm3 treatment was initiated. Animals received four 2 mg/kg intraperitoneal cycles (1/week) of cisplatin and/or 6.25 mg/kg of gemcitabine, concomitant with radiotherapy. Tumors were exposed to 2.5 Gy/day nominal surface doses (20 days) of 150 kV X-rays. Lead collimators with circular apertures (0.5 to 1.5 cm diameter) were manufactured and mounted on the applicator cone to restrict the X-ray beam onto tumors. X-ray penetration and conformality were evaluated by measuring dose at the surface and behind the tumor lobe by using HS GafChromic film. Relative changes in tumor volume (RTV) and a clonogenic assay were used to evaluate the therapeutic response of the tumor, and relative weight loss was used to assess toxicity of the treatments.ResultsNo measurable dose was delivered outside of the collimator apertures. The analysis suggests that dose inhomogeneities in the tumor reach up to ± 11.5% around the mean tumor dose value, which was estimated as 2.2 Gy/day. Evaluation of the RTV showed a significant reduction of the tumor volume as consequence of the chemoradiotherapy treatment; results also show that toxicity was well tolerated by the animals.ConclusionResults and procedures described in the present work have shown the usefulness and convenience of the orthovoltage X-ray system for animal model radiotherapy protocols.

Individual Radiosensitivity Measured With Lymphocytes May Predict the Risk of Acute Reaction After Radiotherapy

We tested whether the chromosomal radiosensitivity of in vitro irradiated lymphocytes could be used to predict the risk of acute reactions after radiotherapy. Two prospective studies were performed: study A with 51 patients included different tumor sites and study B included 87 breast cancer patients. Acute reaction was assessed using the Radiation Therapy Oncology Group score. In both studies, patients were treated with curative radiotherapy, and the mean tumor dose applied was 55 Gy (40-65) +/- boost with 11 Gy (6-31) in study A and 50.4 Gy +/- boost with 10 Gy in study B. Individual radiosensitivity was determined with lymphocytes irradiated in vitro with X-ray doses of either 3 or 6 Gy and scoring the number of chromosomal deletions. Acute reactions displayed a typical spectrum with 57% in study A and 53% in study B showing an acute reaction of Grade 2-3. Individual radiosensitivity in both studies was characterized by a substantial variation and the fraction of patients with Grade 2-3 reaction was found to increase with increasing individual radiosensitivity measured at 6 Gy (study A, p = 0.238; study B, p = 0.023). For study B, this fraction increased with breast volume, and the impact of individual radiosensitivity on acute reaction was especially pronounced (p = 0.00025) for lower breast volume. No such clear association with acute reaction was observed when individual radiosensitivity was assessed at 3 Gy. Individual radiosensitivity determined at 6 Gy seems to be a good predictor for risk of acute effects after curative radiotherapy.

Therapy of hepatocellular carcinoma with 131I-lipiodol: patient dosimetry

Dosimetry in (131)I-lipiodol therapy for hepatocellular carcinoma (HCC) in the hitherto largest existing patient cohort. 38 courses of intra-arterial (131)I-lipiodol therapy with a total activity up to 6.7 GBq were performed in 18 patients with HCC. Liver and tumour volume were measured by computed tomography (CT) and (131)I-activity by scintigraphy on day 3, 6, 14, 28 and 42 after injection. Lipiodol deposition in tumour nodules as shown by CT rendered definite attachment to scintigraphic data possible. The radiation dose in tumour nodules, liver and lungs was calculated according to the MIRD concept and the tumour dose related to pre-therapeutic tumour volume, response and survival. Mean tumour dose was 23.6 +/- 3.6 Gy (14.2 +/- 2.1 mGy/MBq) with maximal 162 Gy (90.1 mGy/MBq) after one and 274 Gy after three courses. The dose to nontumourous liver was 1.9 +/- 0.2 Gy (1.2 +/- 0.1 mGy/MBq) and the mean dose ratio of tumour / nontumourous liver 11.1 +/- 1.7 (max. 82). The pulmonary dose was 25.9 +/- 1.8 mGy (16.3 +/- 1.2 microGy/MBq) and therefore much lower. There was a reciprocal relation between tumour dose and pretherapeutic tumour volume. Tumour dose had no effect on response or survival. High radiation doses are particularly in small tumour nodes achievable but not necessarily related to tumour response. The dose of non-tumourous liver and lungs is much lower.

Optimization of tumour control probability in hypoxic tumours by radiation dose redistribution: a modelling study

Tumour hypoxia is a known cause of clinical resistance to radiation therapy. The purpose of this work was to model the effects on tumour control probability (TCP) of selectively boosting the dose to hypoxic regions in a tumour, while keeping the mean tumour dose constant. A tumour model with a continuous oxygen distribution, incorporating pO2 histograms published for head and neck patients, was developed. Temporal and spatial variations in the oxygen distribution, non-uniform cell density and cell proliferation during treatment were included in the tumour modelling. Non-uniform dose prescriptions were made based on a segmentation of the tumours into four compartments. The main findings were: (1) Dose redistribution considerably improved TCP for all tumours. (2) The effect on TCP depended on the degree of reoxygenation during treatment, with a maximum relative increase in TCP for tumours with poor or no reoxygenation. (3) Acute hypoxia reduced TCP moderately, while underdosing chronic hypoxic cells gave large reductions in TCP. (4) Restricted dose redistribution still gave a substantial increase in TCP as compared to uniform dose boosts. In conclusion, redistributing dose according to tumour oxygenation status might increase TCP when the tumour response to radiotherapy is limited by chronic hypoxia. This could potentially improve treatment outcome in a subpopulation of patients who respond poorly to conventional radiotherapy.

Combined therapy of transcatheter arterial chemoembolisation and three-dimensional conformal radiotherapy for hepatocellular carcinoma

To evaluate the toxicity and efficacy of combined therapy of three-dimensional conformal radiotherapy (3DCRT) and transcatheter arterial chemoembolisation (TACE) for hepatocellular carcinoma (HCC). 50 HCC patients treated by combined TACE and 3DCRT were selected from a patient database. Sequence of treatments was that TACE was performed first, followed by 3DCRT with an interval of about 4 weeks between. TACE was administered by 5-Fu 500-600 mg m(-2), cis-platinum 30-40 mg m(-2), epi-adriamycin 40-60 mg m(-2) mixed with iodized oil and Gelfoam embolisation. A median of two courses of TACE was given. 3DCRT was delivered by 4-6 coplanar or non-coplanar fields. The mean tumour dose was 43.0+/-6.3 Gy by conventional fractionation (2 Gy per fraction, five fractions a week), and mean dose to normal liver, 19.1+/-6.3 Gy. Acute hepatic toxicities were notable in five patients (10%) with Common Toxicity Criteria (CTC) grade 1 in two cases and grade 3 in three patients, but all recovered eventually. Two patients developed radiation-induced liver disease (RILD) and died soon after the onset of RILD. Four patients had Radiation Therapy Oncology Group (RTOG) grade 1 acute gastrointestinal complication and one patient had acute gastrointestinal bleeding. Five patients experienced RTOG Grade 1 leukopenia and Grade 2 in five cases. Nine patients achieved have partial response, and 37 patients were in stable disease. Four patients were observed to have progressive disease. The overall survival rates at 1 year, 2 years and 3 years were 60%, 38% and 28%, respectively, with a median survival period of 17 months. Irradiation dose, T-stage and hepatic cirrhosis were identified as independent predictors for overall survival by Cox proportional regression analysis. The 1 year, 2 years and 3 years local progression-free rates were 74%, 57% and 38%, and the 1 year, 2 years and 3 years distant metastasis rates were 15%, 21% and 40%, respectively. The combined modality of TACE and 3DCRT was tolerable for the majority of HCC patients, resulted in good outcome and warrants for further prospective trial.

SU‐FF‐J‐110: Comparison Between Free Breathing, Slow and Respiratory Correlated CT in Radiation Treatment Planning for Lung Cancer Patients

Purpose: Radiotherapy for lung cancer requires a margin for internal movement of the tumor. Reduction of this margin and thus dose escalation may be possible by using a slow or a respiratory correlated CT (RC‐CT) during radiation treatment planning. In this study these two novel methods are compared to the use of a conventional free breathing CT (FB‐CT). Method and Materials: On a modified Siemens Sensation 10 an FB‐CT and an RC‐CT scan were acquired in nine patients. The RC‐CT scan was used to measure tumor motion and to reconstruct a CT at 10 respiratory phases (10p‐CT). One of these was termed the mid‐ventilation CT (MV‐CT) and by averaging all CTs, a slow‐CT could be reconstructed. Four treatments were planned based on the FB‐CT (with conventional internal margin); the slow CT; the 10p‐CT, and the MV‐CT (with an internal margin of (motion amplitude)/4). Mean tumor dose was calculated for these four plans for a fixed mean lung dose of 15Gy. The possibility of coldspots (&lt;95%) was investigated by determining minimum tumor dose that occurred during respiration. Results: The mean tumor dose in the FB‐CT based plan was 74Gy, for the MV‐CT 100Gy, for the 10p‐CT 95Gy, and for the slow‐CT 101Gy (p=0.0001 for FB‐CT vs. other; p=0.12 for MV‐CT vs. 10p‐CT). Coldspots occurred occurred in the patient with the largest tumor motion (15mm amplitude) in the case of a plan based on a slow‐CT scan. Conclusion: Since radiation treatment planning based on a slow‐CT can lead to underdosage in tumors moving with a large amplitude and the delineation of the 10p‐CT is rather cumbersome, we conclude that using an RC‐CT scan to reconstruct a mid‐ventilation CT and applying a margin of one quarter the tumor motion amplitude, is the most suitable method for radiation treatment planning in lung cancer patients.

Salvage high-dose-rate (HDR) brachytherapy for recurrent head-and-neck cancer

A significant portion of head-and-neck cancer patients will develop persistent or recurrent disease after definitive treatment. Radiation therapy is often used as definitive therapy or as an adjunct to surgery. Recurrent cancer of the head and neck in the previously irradiated field is, thus, a common occurrence and poses a therapeutic challenge. Some studies have evaluated low-dose-rate (LDR) brachytherapy as a therapeutic option, including a large case series with long-term follow-up by our own institution. High-dose-rate (HDR) brachytherapy offers therapeutic advantages over LDR brachytherapy. This study evaluates the local control and outcomes of patients with previously irradiated recurrent head-and-neck cancer treated with HDR interstitial brachytherapy. Between 1997 and 2002, 30 patients who received prior radiation therapy for primary tumors of the head and neck were treated for biopsy-proven recurrent disease. All patients received previous radiation as definitive therapy alone or as adjunct to surgery. All patients were inoperable, refused surgery, or had gross residual disease after salvage surgery for their recurrent disease. Thirty-six sites on the 30 patients were implanted by application of high-dose-rate interstitial brachytherapy techniques with mean tumor dose of 34 Gy (18-48 Gy) in twice daily fractions of 300 to 400 cGy per fraction. At a minimum follow-up of 12 months, local tumor control was achieved in 69% of implanted sites. Disease-specific survival at 1 and 2 years was 54% and 45%, respectively. Overall survival at 1 and 2 years was 56% and 37%, respectively. Grade 3/4 late complications occurred in 16% of the patients. No fatal complications occurred. HDR brachytherapy can play an important role in the salvage treatment of previously irradiated recurrent head-and-neck cancer. This study shows that comparable results are obtained by HDR brachytherapy with fewer late complications than were indicated by previously reported data for LDR brachytherapy.

Target volume uncertainty and a method to visualize its effect on the target dose prescription

To consider the uncertainty in the construction of target boundaries for optimization, and to demonstrate how the principles of mathematical programming can be applied to determine and display the effect on the tumor dose of making small changes to the target boundary. The effect on the achievable target dose of making successive small shifts to the target boundary within its range of uncertainty was found by constructing a mixed-integer linear program that automated the placement of the beam angles using the initial target volume. The method was demonstrated using contours taken from a nasopharynx case, with dose limits placed on surrounding structures. In the illustrated case, enlarging the target anteriorly to provide greater assurance of disease coverage did not force a sacrifice in the minimum or mean tumor doses. However, enlarging the margin posteriorly, near a critical structure, dramatically changed the minimum, mean, and maximum tumor doses. Tradeoffs between the position of the target boundary and the minimum target dose can be developed using mixed-integer programming, and the results projected as a guide to contouring and plan selection.

Radiation absorbed dose distribution in a patient treated with yttrium-90 microspheres for hepatocellular carcinoma.

We have implemented a three-dimensional dose calculation technique accounting for dose inhomogeneity within the liver and tumor of a patient treated with 90Y microspheres. Single-photon emission computed tomography (SPECT) images were used to derive the activity distribution within liver. A Monte Carlo calculation was performed to create a voxel dose kernel for the 90Y source. The activity distribution was convolved with the voxel dose kernel to obtain the three-dimensional (3D) radiation absorbed dose distribution. An automated technique was developed to accurately register the computed tomography (CT) and SPECT scans in order to display the 3D dose distribution on the CT scans. In addition, dose-volume histograms were generated to fully analyze the tumor and liver doses. The calculated dose-volume histogram indicated that although the patient was treated to the nominal whole liver dose of 110 Gy, only 16% of the liver and 83% of the tumor received a dose higher than 110 Gy. The mean tumor and liver doses were 163 and 58 Gy, respectively.

Optimization of tumour control probability for heterogeneous tumours in fractionated radiotherapy treatment protocols

We find the dose distribution that maximizes the tumour control probability (TCP) for a fixed mean tumour dose per fraction. We consider a heterogeneous tumour volume having a radiation response characterized by the linear quadratic model with heterogeneous radiosensitivity and repopulation rate that may vary in time. Using variational calculus methods a general solution is obtained. We demonstrate the spatial dependence of the optimal dose distribution by explicitly evaluating the solution for different functional forms of the tumour properties. For homogeneous radiosensitivity and growth rate, we find that the dose distribution that maximizes TCP is homogeneous when the clonogen cell density is homogeneous, while for a heterogeneous initial tumour density we find that the first dose fraction is inhomogeneous, which homogenizes the clonogen cell density, and subsequent dose fractions are homogeneous. When the tumour properties have explicit spatial dependence, we show that the spatial variation of the optimized dose distribution is insensitive to the functional form. However, the dose distribution and tumour clonogen density are sensitive to the value of the repopulation rate. The optimized dose distribution yields a higher TCP than a typical clinical dose distribution or a homogeneous dose distribution.

Brain metastases treated with radiosurgery alone: an alternative to whole brain radiotherapy?

Whole brain radiotherapy (WBRT) provides benefit for patients with brain metastases but may result in neurological toxicity for patients with extended survival times. Stereotactic radiosurgery in combination with WBRT has become an important approach, but the value of WBRT has been questioned. As an alternative to WBRT, we managed patients with stereotactic radiosurgery alone, evaluated patients' outcomes, and assessed prognostic factors for survival and tumor control. One hundred seventy-two patients with brain metastases were managed with radiosurgery alone. One hundred twenty-one patients were evaluable with follow-up imaging after radiosurgery. The median patient age was 60.5 years (age range, 16-86 yr). The mean marginal tumor dose and volume were 18.5 Gy (range, 11-22 Gy) and 4.4 ml (range, 0.1-24.9 ml). Eighty percent of patients had solitary tumors. The overall median survival time was 8 months. The median survival time in patients with no evidence of primary tumor disease or stable disease was 13 and 11 months. The local tumor control rate was 87%. At 2 years, the rate of local control, remote brain control, and total intracranial control were 75, 41, and 27%, respectively. In multivariate analysis, advanced primary tumor status (P = 0.0003), older age (P = 0.008), lower Karnofsky Performance Scale score (P = 0.01), and malignant melanoma (P = 0.005) were significant for poorer survival. The median survival time was 28 months for patients younger than 60 years of age, with Karnofsky Performance Scale score of at least 90, and whose primary tumor status showed either no evidence of disease or stable disease. Tumor volume (P = 0.02) alone was significant for local tumor control, whereas no factor affected remote or intracranial tumor control. Eleven patients developed complications, six of which were persistent. Nineteen (16.5%) of 116 patients in whom the cause of death was obtained died as a result of causes related to brain metastasis. Brain metastases were controlled well with radiosurgery alone as initial therapy. We advocate that WBRT should not be part of the initial treatment protocol for selected patients with one or two tumors with good control of their primary cancer, better Karnofsky Performance Scale score, and younger age, all of which are predictors of longer survival.

Neodymium YAG Contact Laser in the Treatment of Cancer of the Mobile Tongue

The aim of this study was to evaluate the usefulness of a contact neodymium YAG laser for the treatment of squamous cell carcinoma (SCC) of the mobile tongue in 35 patients. The TNM stage and histologic grade were as follows: T1, n = 20; T2, n = 11; T3, n = 4; and N0, n = 33; N1, n = 2; G1, n = 20; G2, n = 10; and G3, n = 5. The surgical treatment consisted of a hemiglossectomy or resection with adequate margins in 28 cases, and an ipsilateral neck dissection was also performed in 7 patients. Radiotherapy to a mean tumor dose of 62-64 Gy and an elective dose of 50 Gy to the cervical lymph nodes was given to 14 patients. The radiotherapy was preoperative in 12 patients and postoperative in 2. Tongue resection was easily performed using the contact neodymium YAG laser, with a mean operation time of 31 min and intraoperative bleeding varying from negligible to 100 cm 3 . During postoperative follow-up no major complications occurred: cases with minor hemorrhage were easily controlled on the ward and 1 patient had a bleed on the 14th postoperative day necessitating hospitalization. The resection was histologically radical in all cases. During follow-up one patient had a local recurrence (T2N0, G3) and four failed in the neck (T1N0 G2, T1N0 G2, T1N0 G2, T2N0 G2), three of whom were successfully salvaged with a neck dissection and radiotherapy. One patient with osteoradionecrosis was diagnosed and treated curatively. Two patients died of their tongue cancer (T2N0 G3, T2N0 G2), 1 died from a second primary tumor (T2N0 G1) and 2 of intercurrent disease with no evidence of cancer; 30 patients (86%) are still alive with no evidence of disease. The function of the tongue in all patients in this sample was good to satisfactory. The major complaint was xerostomia in the irradiated patients. In conclusion, the contact neodymium YAG laser appears to be suitable for resection of T1-T2 SCCs of the oral tongue. In this limited patient sample T stage or grade did not predict failures in the neck. Biologic predictive markers need to be evaluated.

Local radiotherapy for unresectable hepatocellular carcinoma patients who failed with transcatheter arterial chemoembolization

Purpose: The purpose of this study was to investigate the efficacy of local radiotherapy (RT) as a salvage treatment for unresectable hepatocellular carcinoma (HCC) patients who failed with transcatheter arterial chemoembolization (TACE). Methods and Materials: Patients with unresectable HCC who had been treated with and eventually failed with TACE were eligible. The judgment of TACE failure was based on incomplete tumor filling of lipiodol-adriamycin mixture on either angiography or computed tomography (CT) scan. From January 1993 to December 1997, 27 patients were entered into this study. They had UICC Stage III (17) or IVA (10) disease, with a mean tumor size of 7.2 ± 2.9 cm. Local RT was done, with a mean tumor dose of 51.8 ± 7.9 Gy, in daily 1.8-Gy fractions using a 10- or 6-MV linear accelerator. Survival was calculated from both the diagnosis and the start of RT using the Kaplan-Meier method. Results: An objective response was observed in 16 of 24 patients (66.7%) including 1 CR. Intrahepatic metastasis was noted outside the RT field in 10 patients (37.0%). Extrahepatic distant metastasis occurred in 4 patients. Survival rates at 1, 2, and 3 years were 85.2%, 58.1%, and 33.2%, respectively, from the diagnosis and 55.9%, 35.7%, and 21.4%, respectively, from the start of RT. The median survivals were 26 months from the diagnosis and 14 months from the start of RT. Acute toxicity involved alteration in liver function test (13 patients) and thrombocytopenia (2 patients). Subacute and chronic toxicity involved gastroduodenal ulcer (3 patients) and duodenitis (2 patients). There was no treatment-related death. Conclusion: In unresectable HCC patients who failed with TACE, local RT induced a substantial tumor response of 66.7%, with a 3-year survival rate of 21.4% and a median survival time of 14 months. Toxicity was significant but manageable. Although we do not know if there is survival benefit through this treatment, local RT in these patients seems to be valuable as a salvage for TACE-failed HCC.

Gamma Knife Radiosurgery for Functioning Pituitary Microadenoma

Transsphenoidal microsurgery remains the treatment of choice for pituitary microadenomas One hundred and six patients were treated with Gamma Knife radiosurgery (GKRS) for pituitary adenomas, and of these, 23 patients (1 male, 22 female) had microadenomas. Twenty-two of these patients were followed up and endocrinological tests were available for 15 of these 22. Thirteen of these 15 had prolactinomas, while the remaining 2 had acromegaly. The follow-up period was from 3 to 26 months (median 12 months). The mean age was 33.6 years (range 21 to 60 years). The mean maximum tumor dose was 35.7 Gy and the mean margin dose was 22 Gy. Serum prolactin (PRL) was normalized in three patients, decreased in eight and unchanged in two. The growth hormone (GH) secretion in the acromegalic patients has remained unchanged through the follow-up period. Thus, GKRS is a valuable adjuvant to transsphenoidal microsurgery for patients with pituitary microadenomas.

Radiotherapy in the management of giant pituitary adenomas

Background and purpose: The description of giant pituitary adenoma is not clear yet. In this study we tried to identify which adenomas can be defined as giant pituitary adenomas when tumor control and progression free survival (PFS) are taken as end points and we also tried to evaluate prognostic factors other than tumor size. Materials and methods: Between January 1981 and December 1997, 74 patients with pituitary macroadenomas more than 2 cm in size were treated. Of these 30 had tumors of more than 4 cm, while 44 patients were with tumors of 2–4 cm. Two patients received primary radiotherapy, while 72 were treated postoperatively. In the postoperative group, 52 patients underwent immediate radiotherapy after surgery and 20 were treated with irradiation after regrowth or progression of the tumor after initial surgery. The mean and median tumor doses were 5518 and 5425 cGy, respectively. Results: Overall primary tumor control rate was 84%. The local control rates among patients with tumors more than 4 cm and among patients with tumors 2–4 cm after radiotherapy were 73 and 91%, respectively. PFS was 65% for patients who had a tumor size of more than 4 cm and 87% for the patients with tumor size of 2–4 cm ( P=0.09). Young age (<20) and tumors of unclassified histology were the bad prognostic factors. Six months after radiotherapy normalisation or improvement in hormonal hypersecretion and visual field and acuity deficits were 82 and 63%, respectively. Conclusion: Tumors more than 4 cm in size may be more convenient for the definition of ‘giant pituitary adenoma’ when tumor control and PFS are taken as the end points.