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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. (C) 2022 Elsevier Inc. All rights reserved.

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. Thirty men with hormone na��ve 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. 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. 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.

Teema : luukasvaimet. English summary

Background: Osteosarcomas (OS) in the craniomaxillofacial (CMF) region are typically diagnosed at later age than long-bone OS, but they are reported to have better 5-year survival. Curative treatment warrants wide surgical resection, which is often not possible in the CMF region. The purpose of this article is to present a nationwide series of CMF in Finland to discuss the role of surgery. Patients and methods: All 21 CMF OS patients managed in Finland from 1992 to 2009 were included. The mean age was 40 years (range 15e72). Data on patient and tumor characteristics, treatment modalities, and survival were recorded. All patients had a minimum follow-up of 5 years or until death. Results: OS was evenly represented in the mandible and maxillary bones, which together constituted 76% of all sites. Surgery with curative intent was carried out in 20 patients. Clear margins were achieved in only five cases. Eight (40%) of these 20 patients died due to OS, and their average survival time was 1.3 years. Seven (35%) out of the 20 patients received radiotherapy due to close/intralesional surgical margins, and four of them did not develop recurrences during the follow-up. Conclusions: The results suggest that postoperative radiotherapy may alter the prognosis in CMF OS, particularly in cases with close or intralesional margins. This may increase the survival rates achieved by prompt action in performing radical surgery. (C) 2019 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

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. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

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.

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.

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.

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 [18F]FDG, a new hypoxia tracer [18F]EF5 and the perfusion tracer [15O]H2O in patients with squamous cell cancer of the head and neck treated with radiochemotherapy.

BackgroundPatients 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. MethodsFrom 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. ResultsTwenty-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. ConclusionsThe 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. Pediatr Blood Cancer 2014;61:840-845. (c) 2013 Wiley Periodicals, Inc.

Background: The Italian Sarcoma Group and the Scandinavian Sarcoma Group designed a joint study to improve the prognosis for patients with Ewing's family tumors and synchronous metastatic disease limited to the lungs, or the pleura, or a single bone. Patients and methods: The study was opened in 1999 and closed to the enrollment in 2008. The program consisted of intensive five-drug combination chemotherapy, surgery and/or radiotherapy as local treatment, and consolidation treatment with high-dose busulfan/melphalan plus autologous stem cell rescue and total-lung irradiation. Results: During the study period, 102 consecutive patients were enrolled. The median follow-up was 62 months (range 24-124). The 5-year event-free survival probability was 0.43 [standard deviation (SD) = 0.05] and the 5-year overall survival probability was 0.52 (SD = 0.052). Unfavorable prognostic factors emerging on multivariate analysis were a poor histological/radiological response at the site of the primary tumor [relative risk (RR) = 3.4], and incomplete radiological remission of lung metastases after primary chemotherapy (RR = 2.6). One toxic death and one secondary leukemia were recorded. Conclusions: This intensive approach is feasible and long-term survival is achievable in ∼50% of patients. New treatment approaches are warranted for patients responding poorly to primary chemotherapy.

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.

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 ±3 mm 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 ±3 mm 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.

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.

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.

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.

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.All records of patients diagnosed and treated for primary laryngeal SCC during 2001 to 2005 were reviewed.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%.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.

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.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.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.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.

Positron emission tomography (PET) is a novel method in nuclear medicine to image metabolism in vivo. A wide range of physiological tracers labelled with positron emitters are available for dynamic measurements of various physiological and pathological functions of the body. PET is nowadays widely used for cardiological and neurological studies in health and disease. Oncological applications are under eager investigations. In particular, the detection of viable residual and recurrent tumour is a difficult clinical challenge which is expected to be solved by PET, while the altered metabolism related to cancer can also be studied.

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.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.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.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.

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.

Glucose metabolism has been shown to be increased in neoplastic tissue. It has been suggested that high activity of glucose metabolism is associated with a high grade of malignancy of human cancer. We studied in vivo glucose metabolism in 22 patients with untreated non-Hodgkin's lymphoma with fluorine-18-fluorodeoxyglucose (FDG) and positron emission tomography (PET). FDG uptake in lymphoma deposits was measured blinded to clinical data, and compared with histologic classification and proliferative activity. Tracer uptake was measured by using two indices of FDG accumulation: the standardized uptake value (SUV) and the regional metabolic rate (rMR) for the tracer. The median SUV of the lymphomas was 8.5 (range, 3.5 to 31.0), and the median rMR 22.7 mumol/100 g/min (range, 9.0 to 124.3 mumol/100 g/min). A high FDG uptake in tumors was associated with high histologic degree of malignancy as defined by the Working Formulation (P = .005 for the SUV, and P = .04 for the rMR) or by the Kiel classification (P = .003 for the SUV, and P = .02 for the rMR). A high FDG accumulation was also associated with a high S-phase fraction (r = .786 for the SUV, P = .0002; and r = .774 for the rMR, P = .02). We conclude that in untreated non-Hodgkin's lymphomas high FDG uptake is associated with high histologic grade of malignancy and a high proliferation rate. This minimally invasive method may find application in assessing lymphoma lesions in patients who are poor candidates for surgery, and it may provide further information in cases where the grade of aggressiveness of lymphoma is not settled based on clinical or histologic data.

To evaluate positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) in detection of suspected recurrence of head and neck cancer, and to compare visual, static, and kinetic analyses of the tracer uptake.Seventeen dynamic FDG PET studies were performed in 15 patients. The images were interpreted visually, and the uptake was quantitated as the standardized uptake value (SUV) and as the regional FDG metabolic rate.Sensitivity of blinded visual interpretation of the PET images for the presence of malignancy was 88% and specificity was 86%. Malignant lesions accumulated significantly more FDG than benign lesions (P = .008 for SUVs, P = .002 for regional metabolic rates). When maximum uptake of FDG in the benign lesions was used as a threshold, the sensitivity of SUV analysis for malignancy was 75% and that of regional metabolic rates was 86%.Detection of recurrent head and neck cancer is feasible with FDG PET. Quantitation of FDG uptake assists in correct interpretation of the PET images.

Purpose: To evaluate the value of positron emission tomography and [ 11 C]methionine in imaging of malignant tumors of the head and neck region. Methods and Materials: Forty-seven tumors of the head and neck were investigated with 11 C-labeled methionine and positron emission tomography before treatment. Because of the resolution limits of the positron emission tomography scanner, all tumors selected for the study were larger than 1 cm in diameter. Results: Forty-two (91%) of the 46 malignant tumors were clearly visible in the positron emission tomography image (squamous cell carcinoma, n = 26; lymphoma, n = 9; adenocystic carcinoma, n = 2; lymphoepithelioma, n = 1; adenocarcinoma, n = 1; transitional cell carcinoma, n = 1; esthesioneuroblastoma, n = 1; plasmocytoma, n =1), while three (7%) squamous cell carcinomas were visible, but less easy to detect due to physiological accumulation of the tracer in the area under observation. Only one (2%) squamous cell carcinoma could not be delineated from the positron emission tomography image, and there was no uptake of ( 11 C]methionine in a benign pleomorphic adenoma. No correlation was found between the uptake of [ 11 C]methionine and the histological grade in the subset of squamous cell carcinoma ( n = 30). High physiological uptake of [ 11 C]methionine was observed in the salivary glands and the bone marrow. Conclusions: Malignant head and neck tumors can be effectively imaged with positron emission tomography using [ 11 C]methionine as the tracer.

PURPOSE: To determine the influence of a standardized meal on tumor uptake measured with positron emission tomography (PET) and L-(methyl-carbon-11) methionine. MATERIALS AND METHODS: Five patients with untreated squamous cell cancer of the head and neck underwent PET, first in a fasting state and then 6-7 days later after ingesting a liquid meal. RESULTS: All tumors were seen on PET scans, and image quality remained good after food ingestion. The standardized uptake values of the tumors were 3.7-11.4 in the fasting state but decreased after the meal (range, 3.3-10.0; P < .04). No substantial change was measured in tumor C-11 methionine influx constants (Ki values). CONCLUSION: Although cancer imaging with PET and C-11 methionine can be performed even in the patient has not fasted, a standardized meal may decrease tumor C-11 methionine uptake.

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.

[18F]Fluorodeoxyglucose (FDG) uptake in noncerebral tumors is commonly reported as tissue radioactivity concentration normalized to injected dose and body weight. We studied the feasibility of this approach by imaging 68 tumors in 46 oncologic patients with dynamic FDG-PET and compared kinetic and static methods of quantitation of FDG uptake. Further, the effect of plasma glucose and insulin concentration on the obtained quantitative indexes was analyzed in all patients. The metabolic rate for FDG was strongly associated with normalized uptake value adjusted for injected dose (r = 0.92, p < 0.0001), dose and patient weight (r = 0.91, p < 0.0001), and dose and body surface area (r = 0.94, p < 0.0001). The FDG uptake was not related to plasma glucose concentration under euglycemic (< or = 6.5 mmol/L) conditions, but was low in two diabetic patients with overt hyperglycemia. Hyperinsulinemia was associated with a low to moderate FDG uptake, probably exerting its action through a metabolic shift of tracer influx to muscle and fat. Our results show that a single scan in the steady-state phase, e.g., 45-60 min from the injection, can be used for assessment of FDG uptake in tumors, making frequent blood sampling during imaging unnecessary. However, glucose concentration in blood must be monitored in patients with known or suspected abnormalities in glucose metabolism.

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 77.9Gy dose to PTV (prostate gland with a 6-mm margin) and a simultaneous integrated boost IMRT (SIB IMRT ) plan to deliver 77.9Gy, 81Gy, 84Gy, 87Gy and 90Gy to the BTV and 72Gy 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 82.1Gy 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.

The aim of this study was to evaluate 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5) labeled with 18F-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 18F-EF5 PET/CT scan. On a separate day, 18F-FDG PET/CT was performed to determine the metabolically active tumor volume. In 6 patients, dynamic 18F-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. 18F-EF5 uptake in tumors was compared with that in neck muscle, and the 18F-EF5 findings were correlated with the 18F-FDG PET/CT studies. Results: A total of 13 primary tumors and 5 lymph node metastases were evaluated for their uptake of 18F-EF5. The median tumor-to-muscle 18F-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 18F-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 18F-EF5 to detect hypoxia in HNSCC is encouraging. Further development of 18F-EF5 for eventual targeting of antihypoxia therapies is warranted.

In 1986, the Scandinavian Sarcoma Group initiated a Register of sarcoma patients who had been referred to tumor centers in Finland, Norway and Sweden. The Southern Sweden Sarcoma Register served as a model for the SSG Register (Rydholm 1983). All sarcoma centers in Norway (Bergen, Oslo, and Trondheim) and Sweden (Gothenburg, Linkoping, Lund, Stockholm, Umea) have continuously reported patients to the SSG Register. In these countries patients with sarcoma of the trunk wall and extremities are not treated outside of these referral centers except by mistake. Comparisons with the respective National Cancer Reg

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.

We evaluated positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) in the detection of recurrent head and neck cancer, and compared visual and quantitative interpretation of PET images for their accuracy in the identification of tumour recurrence. Sixty-two FDG PET studies were performed in 56 patients having a total of 81 lesions, which were clinically suspected for recurrent carcinoma of the head and neck. The PET images were interpreted visually, and tracer uptake was quantitated as the standardised uptake value adjusted to body weight (SUV). Sensitivity of visual interpretation of the PET images for the presence of malignancy ranged from 84 to 95%, and specificity from 84 to 93%, respectively, depending on the selected scheme for grading of the lesions. Malignant lesions accumulated significantly more FDG than the benign ones (the median SUVs were 6.8 and 3.3, respectively, P0.001). However, there was a wide overlap of the FDG uptake values between these two groups. Hence, the highest accuracy of quantitative analysis in correct identification of tumour recurrence (75% at Receiver Operating Curve analysis) was inferior to that of visual analysis (89%). FDG PET is feasible for the detection of recurrent head and neck cancer. Although quantitation of FDG uptake using SUV shows significantly higher tracer concentrations for malignant than benign lesions, the wide overlap of individual SUVs between these two groups is a serious concern in diagnostic evaluation. Therefore, in clinical practice it may be preferable to identify the presence of tumour recurrence within this patient group by qualitative interpretation of the PET images.

Positron emission tomography (PET) is a unique noninvasive method of measuring regional biochemical and physiological processes in vivo. High-contrast spatial and temporal resolution, sensitivity and quantification make PET superior to conventional isotope imaging methods. Advanced morphological imaging modalities reveal changes in macrostructures, while PET may give information about the characteristics of cancer tissue and assist in distinguishing malignant from benign or theraphy-induced changes. Modern PET devices have a spatial resolution of 5 mm or less, a 15-cm-wide field of view (FOV) and a three-dimensional (3-D) imaging capability (DeGrado et al. 1994), they and can produce whole-body images. Computed tomography (CT) or magnetic resonance (MR) scancs can be digitally fused with PET for co-registration of morphological and metabolic images (Wahl et al. 1993), which will further improve the efficacy of PET in cancer detection.

The aim of this study was to investigate whether uptake of carbon-11 methionine (MET) is associated with histological grade of malignancy and survival in patients with newly diagnosed or recurrent lymphoma. Thirty-two patients with histologically confirmed lymphoma participated in the study. Twenty-six (81%) were studied before any therapy and six before treatment for recurrent disease. Twenty-eight patients had non-Hodgkin’s lymphoma and four had Hodgkin’s disease. An ECAT 931/08-12 positron emission tomography (PET) scanner was used for PET imaging. After the transmission scan, a median dose of 293 MBq of MET was injected intravenously and dynamic images were acquired for 40 min. The uptake of MET in tumour was measured as the standardized uptake value (SUV) and influx constant (K i). The SUV formula was also adjusted to the predicted value of lean body mass (SUVlean) and body surface area (SUVBSA). The PET results were correlated with the clinical follow-up data. The median SUV in 32 malignant lesions was 6.6 (range, 1.9–12.4) and the median K i was 0.116 min−1 (range, 0.025–0.201, n=23). The median SUV was 7.0 (range, 5.4–12.4, n=9) in high, 6.2 (range, 1.9–10.4, n=11) in intermediate and 5.7 (range, 3.8–8.3, n=8) in low grade lymphomas. One intermediate grade lymphoma of the skin was visually negative (SUV 1.9). In Hodgkin’s disease the median SUV was 7.0 (range, 3.2–7.9, n=4). The median K i value was 0.162 min−1 (range, 0.147–0.197, n=7) in high, 0.099 (range, 0.025–0.152, n=10) in intermediate, and 0.078 (range, 0.056–0.152, n=4) in low grade lymphomas and 0.149 (range, 0.096–0.201, n=2) in Hodgkin’s disease. The difference between high and other grade non-Hodgkin’s lymphomas was significant when using K i (P

Purpose : To evaluate the usefulness of positron emission tomography (PET) and L-[methyl- ll c]methionine in assessing treatment response to radiotherapy in head and neck cancer. Methods and Materials : Fifteen patients with head and neck cancer (13 with squamous cell carcinoma, 1 with adenocystic carcinoma, and 1 with paranasal plasmocytoma) underwent a PET study with [ 11 C]-methionine both before and after preoperative radiotherapy to the total tumor dose of 61-73 Gy. Twelve primary and 12 metastatic tumor sites were within the field of view. Nineteen of the 24 tumor sites were surgically explored after radiotherapy, and the tumor standardized uptake values (SUVs) of [ 11 C]methionine were compared with histological findings. Results : All 24 malignant lesions were detectable in the pretreatment study. In all but one case, the tumor SUV decreased after radiotherapy. The median SUV of the tumor site was smaller (1.9, range, 1.3-3.1, n = 7) in cases with histologically verified complete response than in cases with persistent cancer (median 4.1, range, 2.8-7.6, n = 12, p = 0.0008). A complete histological response was verified in none of the 9 cases with a postirradiation SUV larger than the median (3.1), whereas 7 of the 10 cases with a SUV of 3.1 or smaller had complete response (p = 0.003). The preirradiation uptake of [ 11 C]methionine in tumors did not have significant association with histological response (p = 0.45). The PET findings correlated well with follow-up data in five cases with unoperated tumor sites. The [ 11 C]methionine uptake of the submandibular salivary glands decreased after radiotherapy (p = 0.04). Conclusion : PET with [ 11 C]methionine as a tracer may be useful in assessing response to radiotherapy in head and neck cancer. High uptake of [ 11 C]methionine in the postirradiation scan suggests the presence of persistent disease.

Background. The anabolic properties of insulin have been suggested for use to reverse malnutrition associated with cancer. The host and tumor sensitivities to insulin are critical for such treatments, which aim to improve patient nutrition. The authors studied insulin effects on tumor and skeletal muscle metabolism with 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET). Methods, Six patients with lymphoma twice underwent [18F]FDG-PET imaging: once after fasting overnight and once during euglycemic hyperinsulinemic clamp. The dynamic uptake of the glucose analogue [18F]FDG was measured in diseased nodes and upper arm skeletal muscle in both metabolic states. The [18F]FDG uptake in muscle and the whole body glucose use during euglycemic hyperinsulinemic clamp were compared with those of weight-matched healthy subjects studied under similar circumstances. Results. In lymphomatous tissue, [18F]FDG uptake rates were similar in overnight fasting and euglycemic hyperinsulinemic clamp (38 ± 10 versus 41 ± 9 μmol/100 g/minute, not significant), whereas glucose uptake in skeletal muscle was increased by insulin (1.7 ± 0.2 versus 3.8 ± 0.5 μmol/100 g/minute, P = 0.012). Both basal (2.3 ± 0.2 μmol/100 g/minute, P = 0.061) and insulin-stimulated (8.5 ± 1.9 μmol/100 g/minute, P = 0.055) skeletal arm muscle glucose uptake rates were higher in control subjects than in patients. Whole body glucose use was 55% lower in patients than in control subjects (17 ± 3 μmol/kg/minute versus 38 ± 3 μmol/kg/minute, P = 0.002), consistent with insulin resistance in cancer. Conclusions. We found that insulin does not induce major changes in glucose uptake of lymphomatous tissue. Although insulin sensitivity of skeletal muscle was also reduced in patients with lymphoma, the net insulin effect may counteract imbalance between glucose uptake of tumor and muscle, offering a potential means to circumvent at least some metabolic abnormalities found in cancer. Cancer 1994; 73:1490–8.

Positron emission tomography (PET) and 11C-methionine (MET) are used for imaging amino acid metabolism in cancer. The aim was to study the potential of MET PET in assessing response to radiotherapy (RT) in primary squamous cell cancer (SCC) of the head and neck cancer. Seven patients had altogether 13 evaluable tumor sites. Six patients with SCC in the oral cavity and one with laryngeal SCC entered a MET PET study before and after preoperative RT (total tumor dose 62–73 Gy). All except one were operated, and the standardized uptake values (SUVs) of the tumor sites were compared with histology. The median SUV was significantly smaller (2.3; range 1.6–3.1; N = 4) in cases with complete response to RT than in those with persistent cancer (median 4.5; range 3.1–7.0, N = 7, P = 0.01). MET PET may distinguish persistent cancer from benign therapy-induced changes. High MET uptake in the tumor site after RT suggests the presence of persistent cancer.

Glucose metabolism has been demonstrated to be increased in neoplastic tissue, and to reflect the grade of malignancy of human cancer. We studied in vivo glucose metabolism in 22 pts with untreated non-Hodgkin's lymphoma with fluorine-18-fluorodeoxyglucose (FDG) and positron emission tomography (PET). FDG uptake in lymphoma deposits was measured as standardized uptake values (SUVs) of the tracer, and compared with histological classification and proliferative activity. Results The median SUV of the lymphomas was 8.5. A high FDG uptake in tumors was associated with high histological degree of malignancy by the Working Formulation (P = 0.005) or by the Kiel classification (P = 0.003). A high FDG accumulation was also associated with a high S-phase fraction (r = 0.786, P = 0.002). Conclusion FDG PET may find application in assessing the grade of aggressiveness of lymphoma in clinically problematic cases.