Long-term outcome of biologically guided dose-escalated radiotherapy of localized prostate cancer.

BACKGROUND: Biologically created subvolumes enable non-uniform dose distributions in prostate cancer radiotherapy (RT) thus potentially improving therapeutic ratio and reducing toxicity. We present the long-term outcome of men receiving focal boosting of carbon-11 acetate (ACE) PET-CT metabolically active areas in prostate carcinoma. MATERIAL AND METHODS: Thirty men with hormone naïve localized prostate carcinoma underwent ACE PET/CT for RT planning. There were five low-, 17 intermediate-, and eight high-risk patients. Based on thresholding of the standardized uptake values (SUVs) metabolic target volumes (MTVs) corresponding to intraprostatic lesions (IPLs) were contoured. Two planning target volumes (PTVs) were applied i.e., PTVlow-risk for the whole prostate with 8-10 mm margin and PTVhigh-risk for the MTV. Pelvic nodes were not irradiated. Late toxicity of biologically guided RT was reviewed after a median of 63 months and outcome after a median follow-up of 124 months. RESULTS: Median doses to PTVlow-risk, PTVhigh-risk, prostate, and MTV were 72.9 Gy, 79.4 Gy, 76.6 Gy, and 80.4 Gy, respectively, in 38 fractions. The 10-year cancer-specific survival was 86% and the biochemical failure-free ratio 68%, respectively. The median biochemical progression-free survival (PFS) was 37, 108, and 119 months in the high, intermediate, and low-risk groups, respectively, the difference being significant between high and intermediate-risk groups (p = 0.02). One patient (3%) presented with locoregional and 5 (17%) with distant nodal metastases. Five patients (17%) had a biochemical relapse. A larger MTV was associated with shorter PFS (r = -0.41, p = 0.02), but had no influence on OS. No other statistically significant differences in the dose painting parameters were observed between recurrence-free and recurring patients. CONCLUSIONS: Biological guidance for dose-escalated prostate RT is feasible with ACE PET/CT. Since a larger MTV may be associated with a higher risk for progression, we encourage further study of dose-escalation to ACE-positive lesions considering the low toxicity of our protocol.

Epidemiological and treatment-related factors contribute to improved outcome of oropharyngeal squamous cell carcinoma in Finland.

BACKGROUND: Treatment for oropharyngeal squamous cell carcinoma (OPSCC) has changed, as the proportion of human papilloma virus (HPV)-related disease has increased. We evaluated nationwide information on its management and outcome during the treatment paradigm change period. METHODS: We included all patients diagnosed and treated for OPSCC at the five Finnish university hospitals from 2000 to 2009. Patient records and pathology registries provided the clinicopathological data. p16 staining was performed on primary tumor samples of patients who had received treatment with curative intent. RESULTS: A total of 674 patients were diagnosed and treated for OPSCC and the incidence increased along the study period. Of the evaluable tumors 58.5% were p16-positive and the number of p16-positive tumors increased along the years. The treatment was given with curative intent for 600 patients and it was completed in 564. Of them, 47.9% underwent primary surgery and 52.1% received definitive oncological treatment. Also, the treatment protocol changed towards a more oncological approach. Among patients treated with curative intent the five-year overall, disease-specific and disease-free survival rates were 60.1, 71.5 and 57.0%. In multivariate analysis, p16-positivity seemed to relate to reduced disease mortality in lateral and anterior-wall disease. Depending on primary tumor localization, also sex, classes T3-4, presence of regional metastasis and radiotherapy modality had an association with disease mortality. CONCLUSION: The incidence of p16-positive OPSCC and delivery of definitive oncological treatment increased in Finland during the study period. An improved survival outcome compared with the previous nationwide investigation was observed in this subset of patients.

Magnetic resonance-only simulation and dose calculation in external beam radiation therapy: a feasibility study for pelvic cancers.

BACKGROUND: The clinical feasibility of using pseudo-computed tomography (pCT) images derived from magnetic resonance (MR) images for external bean radiation therapy (EBRT) planning for prostate cancer patients has been well demonstrated. This paper investigates the feasibility of applying an MR-derived, pCT planning approach to additional types of cancer in the pelvis. MATERIAL AND METHODS: Fifteen patients (five prostate cancer patients, five rectal cancer patients, and five gynecological cancer patients) receiving EBRT at Turku University Hospital (Turku, Finland) were included in the study. Images from an MRCAT (Magnetic Resonance for Calculating ATtenuation, Philips, Vantaa, Finland) pCT method were generated as a part of a clinical MR-simulation procedure. Dose calculation accuracy was assessed by comparing the pCT-based calculation with a CT-based calculation. In addition, the degree of geometric accuracy was studied. RESULTS: The median relative difference of PTV mean dose between CT and pCT images was within 0.8% for all tumor types. When assessing the tumor site-specific accuracy, the median [range] relative dose differences to the PTV mean were 0.7 [-0.11;1.05]% for the prostate cases, 0.3 [-0.25;0.57]% for the rectal cases, and 0.09 [-0.69;0.25]% for the gynecological cancer cases. System-induced geometric distortion was measured to be less than 1 mm for all PTV volumes and the effect on the PTV median dose was less than 0.1%. CONCLUSIONS: According to the comparison, using pCT for clinical EBRT planning and dose calculation in the three investigated types of pelvic cancers is feasible. Further studies are required to demonstrate the applicability to a larger cohort of patients.

[Oncologic therapy of soft tissue sarcoma]. / Pehmytkudossarkooman onkologinen hoito.

Surgery with a margin of resection is the only curative form of treatment of soft tissue sarcoma. The combination of surgery and radiotherapy can, however, be used to lower the risk of local recurrence, if wide margins are not achieved e.g. in order to preserve the function of a limb. By using combination chemotherapy, disease recurrence can in the highest-risk patients be decreased to some extent. Radiotherapy provides palliative relief from a number of the patient's symptoms. The diagnosis and treatment of soft tissue sarcoma require an early participation of a multidisciplinary team familiarized with these rare tumors.

Prognostic value of tumour blood flow, [¹8F]EF5 and [¹8F]FDG PET/CT imaging in patients with head and neck cancer treated with radiochemotherapy.

PURPOSE: In order to improve the treatment of squamous cell carcinoma of the head and neck, precise information on the treated tumour's biology is required and the prognostic importance of different biological parameters needs to be determined. The aim of our study was to determine the predictive value of pretreatment PET/CT imaging using [(18)F]FDG, a new hypoxia tracer [(18)F]EF5 and the perfusion tracer [(15)O]H2O in patients with squamous cell cancer of the head and neck treated with radiochemotherapy. METHODS: The study group comprised 22 patients with confirmed squamous cell carcinoma of the head and neck who underwent a PET/CT scan using the above tracers before any treatment. Patients were later treated with a combination of radiochemotherapy and surgery. Parametric blood flow was calculated from dynamic [(15)O]H2O PET images using a one-tissue compartment model. [(18)F]FDG images were analysed by calculating standardized uptake values (SUV) and metabolically active tumour volumes (MATV). [(18)F]EF5 images were analysed by calculating tumour-to-muscle uptake ratios (T/M ratio). A T/M ratio of 1.5 was considered a significant threshold and used to determine tumour hypoxic subvolumes (HS) and hypoxic fraction area. The findings were finally correlated with the pretreatment clinical findings (overall stage and TNM stage) as well as the outcome following radiochemotherapy in terms of local control and overall patient survival. RESULTS: Tumour stage and T-classification did not show any significant differences in comparison to the patients' metabolic and functional characteristics measured on PET. Using the Cox proportional hazards model, a shorter overall survival was associated with MATV (p = 0.008, HR = 1.108), maximum [(18)F]EF5 T/M ratio (p = 0.0145, HR = 4.084) and tumour HS (p = 0.0047, HR = 1.112). None of the PET parameters showed a significant effect on patient survival in the log-rank test, although [(18)F]EF5 maximum T/M ratio was the closest (p = 0.109). By contrast, tumour blood flow was not correlated with any of the clinical endpoints. There were no statistically significant correlations among [(18)F]FDG SUVmax, [(18)F]EF5 T/M ratio and blood flow. CONCLUSION: Our study in a limited number of patients confirmed the importance of MATV in the prognosis of locally advanced squamous cell carcinoma of the head and neck. It is of interest that high uptake of the hypoxia tracer [(18)F]EF5 showed a stronger correlation with a poor clinical outcome than [(18)F]FDG uptake. This confirms the importance of hypoxia in treatment outcome and suggests that [(18)F]EF5 may act as a surrogate marker of radioresistance.

High-dose chemotherapy with stem cell rescue in the primary treatment of metastatic and pelvic osteosarcoma: final results of the ISG/SSG II study.

BACKGROUND: Patients with metastatic osteosarcoma at diagnosis or axial primary tumors have a poor prognosis. The aim of the study was to evaluate the feasibility and efficacy of intensified treatment with high-dose chemotherapy (HDCT) and stem cell rescue in this group. METHODS: From May 1996 to August 2004, 71 patients were included in a Scandinavian-Italian single arm phase II study. Preoperative chemotherapy included methotrexate, doxorubicin, cisplatin and ifosfamide, and postoperative treatment consisted of two cycles of doxorubicin, one cycle of cyclophosphamide and etoposide and two courses of high-dose etoposide and carboplatin with stem cell rescue. RESULTS: Twenty-nine patients (43%) received two courses and 10 patients (15%) received one course of HDCT. HDCT was associated with significant toxicity, but no treatment-related deaths were recorded. Fourteen patients (20%) had disease progression before completion of the study protocol, and only 29/71 patients (41%) received the full planned treatment. Median event-free survival (EFS) was 18 months, and estimated 5-year EFS was 27%. Median overall survival (OS) was 34 months, and estimated 5-year OS was 31%. When patients who did not receive HDCT due to disease progression were excluded, there was no difference in EFS (P = 0.72) or OS (P = 0.49) between patients who did or did not receive HDCT. CONCLUSIONS: The administration of high-dose chemotherapy with stem cell rescue was feasible, but associated with significant toxicity. Patient outcome seemed comparable to previous studies using conventional chemotherapy. We conclude that HDCT with carboplatin and etoposide should not be further explored as a treatment strategy in high-risk osteosarcoma.

Isocentric integration of intensity-modulated radiotherapy with electron fields improves field junction dose uniformity in postmastectomy radiotherapy.

BACKGROUND: In postmastectomy radiotherapy (PMRT), the dose coverage of the planning target volume (PTV) with additional margins, including the chest wall, supraclavicular, interpectoral, internal mammary and axillar level I-III lymph nodes, is often compromised. Electron fields may improve the medial dose coverage while maintaining organ at risk (OAR) doses at an acceptable level, but at the cost of hot and cold spots at the electron and photon field junction. To improve PMRT dose coverage and uniformity, an isocentric technique combining tangential intensity-modulated (IM)RT fields with one medial electron field was implemented. MATERIAL AND METHODS: For 10 postmastectomy patients isocentric IMRT with electron plans were created and compared with a standard electron/photon mix and a standard tangent technique. PTV dose uniformity was evaluated based on the tolerance range (TR), i.e. the ratio of the standard deviation to the mean dose, a dice similarity coefficient (DSC) and the 90% isodose coverage and the hot spot volumes. OAR and contralateral breast doses were also recorded. RESULTS: IMRT with electrons significantly improved the PTV dose homogeneity and conformity based on the TR and DSC values when compared with the standard electron/photon and tangent technique (p < 0.02). The 90% isodose coverage improved to 86% compared with 82% and 80% for the standard techniques (p < 0.02). Compared with the standard electron/photon mix, IMRT smoothed the dose gradient in the electron and photon field junction and the volumes receiving a dose of 110% or more were reduced by a third. For all three strategies, the OAR and contralateral breast doses were within clinically tolerable limits. CONCLUSION: Based on these results two-field IMRT combined with an electron field is a suitable strategy for PMRT.

[Mesenterial fibrosis--could it be desmoidi?]. / Fibroosia suoliliepeessä--voisiko olla desmoidi?

Desmoid tumors are rare benign fibrous tumors, which have a tendency to invade locally. A minority of desmoids are mesenterial. The symptoms of mesenterial desmoids are misleading, and diagnosis can be delayed. A complete surgical excision is the preferred treatment, but the mesenterial location of the tumor makes radical surgery complicated. Patients whose tumors are not amenable to surgical treatment, have been treated with antiestrogens, nonsteroidal anti-inflammatorics and various chemotherapeutics. Good responses have been observed with pegylated liposomal doxorubicin. In most cases, the quality of life can be maintained even in incurable situations.

Survival and Larynx Preservation in Early Glottic Cancer: A Randomized Trial Comparing Laser Surgery and Radiation Therapy.

PURPOSE: The prognosis of glottic T1a laryngeal squamous cell carcinoma (LSCC) is excellent with both transoral laser surgery (TLS) and radiation therapy (RT). Our aim was to compare TLS and RT treatment results in a randomized study. METHODS AND MATERIALS: Of 56 male patients with glottic T1a LSCC, 31 were randomized for TLS and 25 for RT. Survival and larynx preservation data were collected from medical records. RESULTS: Five-year overall survival (OS) was 87%, disease-specific survival (DSS) was 97%, and recurrence-free survival (RFS) was 81% in patients treated with TLS. Five-year OS was 92%, DSS was 100%, and RFS was 88% in patients treated with RT. The primary treatment method was not associated with OS, RFS, or DSS in a log-rank test. The larynx preservation rate was similar in both groups (TLS, 97%; RT, 92%; P = .575). CONCLUSIONS: In a prospective randomized setting oncological outcomes of both treatment modalities (TLS or RT) for T1a LSCC were similar.

[Oncological treatment modalities in head and neck cancer]. / Pään ja kaulan alueen syöpien onkologiset hoidot.

Intensity-modulated radiotherapy (IMRT) can be applied to reduce the radiation dose for healthy tissues and lessen adverse effects. It can be used to increase the efficiency of treatment, for example by applying the radiotherapy in two small daily fractions instead of the usual one fraction, or by accelerated fractionation, in which the radiotherapy is also given twice a day, but with larger daily doses. With the exception of early-stage tumors, chemoradiotherapy has become an established treatment modality for tumors. The most commonly used cytotoxic agent is cisplatin, the second being cetuximab, a monoclonal antibody targeting cancer cells via the epidermal growth factor.

Preliminary study of carbon-11 methionine PET in the evaluation of early response to therapy in advanced breast cancer.

OBJECTIVE: Breast cancer is one of the principal oncological challenges in the Western world. Currently, there are only a few reliable predictive methods for monitoring treatment. We investigated the ability of carbon-11 methionine ("11C-MET) positron emission tomography (PET) to evaluate early response to therapy in advanced breast cancer. METHODS: Thirteen patients with metastases in the lungs/pleura, lymph nodes, soft tissue, or bones entered a MET PET study both before and after the first cycle of polychemotherapy (n=4), or after the first month of therapy with hormones (n=5), or low dose weekly cytostatics (n=3). One patient underwent three PET studies: before hormonal therapy, after 1 month of hormonal therapy, and after the first cycle of polychemotherapy (total, 27 studies). MET accumulation in the metastatic sites was measured as standardized uptake values (SUVs), and the pretreatment and post-treatment SUVs were compared with each other and the clinical follow-up data. RESULTS: A total of 26 different metastatic sites were investigated in 13 patients. All metastases were visible by MET PET except one superficially spreading local skin recurrence, probably because of respiratory movements. Five new metastatic sites were detected. After therapy the SUVs decreased significantly (30-54%; P < 0.05) in all six responding metastatic sites, whereas the SUVs of nonresponding metastases decreased somewhat (11-130/%; n=4), remained stable (+/- 8%; n=10), or increased (13-23%; n=4) (P=NS). The SUVs of two nonresponding metastatic sites decreased clearly. Physiological MET uptake in the salivary glands, the myocardium, and the bone marrow did not disturb the image interpretation. CONCLUSION: MET PET may be useful in assessing the early response to therapy in advanced breast cancer.

18F-EF5: a new PET tracer for imaging hypoxia in head and neck cancer.

UNLABELLED: The aim of this study was to evaluate 2-(2-nitro-(1)H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5) labeled with (18)F-fluorine to image hypoxia in patients with squamous cell carcinoma of the head and neck (HNSCC). METHODS: Fifteen patients with HNSCC were studied. Measurement of tumor blood flow was followed by an (18)F-EF5 PET/CT scan. On a separate day, (18)F-FDG PET/CT was performed to determine the metabolically active tumor volume. In 6 patients, dynamic (18)F-EF5 images of the head and neck area were acquired, followed by static images acquired at 1, 2, and 3 h after injection. In the remaining 9 patients, only static images were obtained. (18)F-EF5 uptake in tumors was compared with that in neck muscle, and the (18)F-EF5 findings were correlated with the (18)F-FDG PET/CT studies. RESULTS: A total of 13 primary tumors and 5 lymph node metastases were evaluated for their uptake of (18)F-EF5. The median tumor-to-muscle (18)F-EF5 uptake ratio (T/M) increased over time and was 1.38 (range, 1.1-3.2) 3 h after tracer injection. The median blood flow in tumors was 36.7 mL/100 g/min (range, 23.3-78.6 mL/100 g/min). Voxel-by-voxel analysis of coregistered blood flow and (18)F-EF5 images revealed a distinct pattern, resulting in a T/M of 1.5 at 3 h to be chosen as a cutoff for clinically significant hypoxia. Fourteen of 18 tumors (78%) had subvolumes within the metabolically active tumor volumes with T/M greater than or equal to 1.5. CONCLUSION: On the basis of these data, the potential of (18)F-EF5 to detect hypoxia in HNSCC is encouraging. Further development of (18)F-EF5 for eventual targeting of antihypoxia therapies is warranted.

Preoperative hyperfractionated accelerated radiotherapy and radical surgery in advanced head and neck cancer: a prospective phase II study.

BACKGROUND AND PURPOSE: To evaluate whether preoperative hyperfractionated accelerated radiotherapy (RT) combined with major radical surgery is feasible and successful in the treatment of advanced primary head and neck cancer. PATIENTS AND METHODS: Ninety four patients with histologically confirmed head and neck squamous cell cancer (HNSCC) in the oral cavity (41/96; 43%), supraglottis (14/96; 15%), glottis (5/96; 5%), oropharynx (16/96; 17%), nasal cavity/paranasal sinuses (8/96; 8%), nasopharynx (3/96; 3%), hypopharynx (7/96; 7%) and two (2%) with unknown primary tumour and large cervical lymph nodes entered into the study. 21/96 patients (22%) had stage II, 17/96 (18%) stage III and 58/96 patients (60%) stage IV disease. The patients received preoperative hyperfractionated RT 1.6 Gy twice a day, 5 days a week to a median tumour dose of 63 Gy with a planned break for 11 days (median) after the median dose of 37 Gy. Then, after a median of 27 days the patients underwent major radical surgery of the primary tumour and metastatic lymph nodes including reconstructions with pedicled or microvascular free flaps when indicated as a part of the scheduled therapy. 12/96 patients had only ipsilateral or bilateral neck dissections. RESULTS: After a median follow-up time of 37.2 mos 77/96 (80.2%) patients had complete locoregional control. All but 2 patients had complete histological remission after surgery. 40/96 pts were alive without disease, two of them after salvage surgery. 32/96 patients had relapsed; 15 had locoregional and 13 distant relapses, 4 patients relapsed both locoregionally and distantly. Fifty patients have died; 29 with locoregional and/or distant relapse, eight patients died of second malignancy, and 19 had intercurrent diseases. Disease-specific and overall survival at 3 years was 67.7 and 51%, respectively. Acute grade three mucosal reactions were common, but transient and tolerable. Late grade 3-4 adverse effects were few. CONCLUSIONS: Preoperative hyperfractionated accelerated RT can be successfully combined with major radical surgery in the treatment of HNSCC. The amount of serious late adverse effects was not increased.

Laryngeal cancer in Finland: A 5-year follow-up study of 366 patients.

BACKGROUND: The purpose of this study was to acquire nationwide data on the management and outcome of laryngeal squamous cell carcinoma (SCC) in Finnish university hospitals over a 5-year posttreatment follow-up. METHODS: All records of patients diagnosed and treated for primary laryngeal SCC during 2001 to 2005 were reviewed. RESULTS: Three hundred sixty-six patients with laryngeal cancer were identified, 360 of whom had laryngeal SCC. Three hundred forty-two patients with laryngeal SCC (95%) were treated with curative intent. Five-year disease-specific survival (DSS) for T1a, T1b, T2, T3, and T4 glottic SCC was 100%, 95%, 78%, 79%, and 53%, respectively. The corresponding figures for T1 to T4 supraglottic SCC were 68%, 54%, 72%, and 59%. CONCLUSION: Results of this nationwide study give a general overview of the outcome of unselected patients treated with unified guidelines. Patients with T2 tumors, usually treated with radiotherapy (RT), had a worse prognosis than expected. This patient group warrants further investigation and possibly treatment intensification.

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 cm3. 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.

Voice quality after treatment of early vocal cord cancer: a randomized trial comparing laser surgery with radiation therapy.

OBJECTIVE: Early laryngeal cancer is usually treated with either transoral laser surgery or radiation therapy. The quality of voice achieved with these treatments has not been compared in a randomized trial. METHODS AND MATERIALS: Male patients with carcinoma limited to 1 mobile vocal cord (T1aN0M0) were randomly assigned to receive either laser surgery (n=32) or external beam radiation therapy (n=28). Surgery consisted of tumor excision with a CO2 laser with the patient under general anaesthesia. External beam radiation therapy to the larynx was delivered to a cumulative dose of 66 Gy in 2-Gy daily fractions over 6.5 weeks. Voice quality was assessed at baseline and 6 and 24 months after treatment. The main outcome measures were expert-rated voice quality on a grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, videolaryngostroboscopic findings, and the patients' self-rated voice quality and its impact on activities of daily living. RESULTS: Overall voice quality between the groups was rated similar, but voice was more breathy and the glottal gap was wider in patients treated with laser surgery than in those who received radiation therapy. Patients treated with radiation therapy reported less hoarseness-related inconvenience in daily living 2 years after treatment. Three patients in each group had local cancer recurrence within 2 years from randomization. CONCLUSIONS: Radiation therapy may be the treatment of choice for patients whose requirements for voice quality are demanding. Overall voice quality was similar in both treatment groups, however, indicating a need for careful consideration of patient-related factors in the choice of a treatment option.

PET imaging of blood flow and glucose metabolism in localized musculoskeletal tumors of the extremities.

INTRODUCTION: Little is known about blood flow in sarcomas. Our purpose was to study glucose metabolism and blood flow in untreated localized musculoskeletal tumors of the extremities using [(18)F]fluorodeoxyglucose (FDG), oxygen-15 labeled water ([15O]H(2)O) and positron emission tomography (PET). METHODS: Six patients with high-grade osteosarcoma (OS), two with soft-tissue sarcoma (STS) and one with aneurysmal bone cyst had PET studies with [15O]H(2)O and FDG. Arterial blood sampling and autoradiography calculation method were used to define blood flow as milliliters per 100 g times minutes. Tumor FDG uptake was measured as standardized uptake values (SUVs) and regional metabolic rates for FDG (rMRFDG). Two patients also had FDG PET studies during (one patient) and after (two patients) preoperative chemotherapy. All patients underwent dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The PET findings were compared with the clinical follow-up data and results of DCE-MRI. RESULTS: Blood flow in bone tumors was 31.7-75.2 ml/(100 g×min) and in STS 9.0-45.9 ml/(100 g×min). [(18)F]-Fluorodeoxyglucose uptake and rMRFDG in untreated bone tumors were 5.4-18.4 and 10.9-57.4 µmol/100 g/min, respectively. [(18)F]-Fluorodeoxyglucose uptake and rMRFDG in STS were 2.6-11.5 and 5.6-32.2 µmol/100 g/min, respectively. Four of five sarcomas with SUV>9.0 have already relapsed. High blood flow in untreated OS was related to long overall survival, while the predictive power of glucose metabolism was less apparent. Good histopathological response to therapy was not associated with long survival. CONCLUSIONS: Measurement of blood flow in musculoskeletal tumors appears to be feasible by PET and [(15)O]H(2)O. The influence of tumor blood flow and glucose metabolism on the final outcome in sarcoma is variable and needs further research.

A method to improve target dose homogeneity of craniospinal irradiation using dynamic split field IMRT.

PURPOSE: Craniospinal irradiation (CSI) is technically very challenging and field edge matching is needed because of the mechanical limitations of standard linear accelerators. We assessed the feasibility of intensity-modulated radiotherapy (IMRT) in CSI to overcome the standard feathering and dose inhomogeneities associated with the standard feathering technique in the junction areas. MATERIALS AND METHODS: The use of IMRT in CSI was studied with five patients CT scanned in the supine position. Isocentric treatment plans of three dimensional conventional radiotherapy (3D-CRT) and split field IMRT (sfIMRT) with dynamic intrafractional feathering were created with the same field setup and the resulted dose distributions were compared. The effect of treatment inaccuracy was simulated with an intentional shift of +/-3mm with both treatment plans. Dosimetric verification of the sfIMRT treatment plan was performed with radiographic films placed in a phantom. RESULTS: The sfIMRT treatment plans resulted in a better dose coverage and uniformity in the target volume. The +/-3mm shift had only a minor effect on the dose distribution of the sfIMRT treatment plan whereas with the 3D-CRT the shift resulted in an error of +/-38% of the calculated dose in the spinal cord. The measured dose distribution of the sfIMRT treatment plan correlated well with the calculations. CONCLUSIONS: Improved dose homogeneity in the target volume was achieved with the sfIMRT compared to the conventional 3D-CRT treatment plan. With the sfIMRT technique only a single treatment plan is required to deliver the total treatment dose and the resulting dose distribution is also less volatile for technical uncertainties of the treatment.

Carbon-11 acetate PET/CT based dose escalated IMRT in prostate cancer.

PURPOSE: To demonstrate the theoretical feasibility of [(11)C]acetate PET/CT in delineating the malignant intraprostatic lesions (IPL's) in prostate cancer and to use the data in external beam radiotherapy to boost the biologically defined target volume (BTV). METHODS AND MATERIALS: Twelve men with intracapsular prostate carcinoma were imaged with [(11)C]acetate PET/CT and the data were used to delineate the BTV. Six dynamic IMRT plans were generated to each patient: a standard IMRT (sIMRT) plan with a 77.9 Gy dose to PTV (prostate gland with a 6-mm margin) and a simultaneous integrated boost IMRT (SIB(IMRT)) plan to deliver 77.9 Gy, 81 Gy, 84 Gy, 87 Gy and 90 Gy to the BTV and 72 Gy to the rest of PTV. To study the theoretical dose escalation based on the delineation of BTV, tumor control probabilities (TCPs) and normal tissue complication probabilities (NTCPs) of bladder and rectum were calculated and compared between the treatment plans. RESULTS: [(11)C]Acetate was used to delineate the IPL's of all 12 patients. With every patient the TCP was increased with SIB(IMRT) without increasing the NTCP of the bladder or rectum. The probability of uncomplicated control (PUC) was increased on average by 28% with the SIB(IMRT) treatment plans. The highest PUC was achieved with an average dose of 82.1 Gy to the BTV. CONCLUSIONS: Our study indicates that [(11)C]acetate can be used to define the IPL's and in combination with SIB(IMRT) the defined areas can theoretically be treated to ultra high doses without increasing the treatment toxicity. These results motivate the formal validation of [(11)C]acetate PET for biological dose planning in prostate cancer.