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Following the DAHANCA 5 trial [1], which demonstrated the benefit of the hypoxic radiosensitizer Nimorazole, and the DAHANCA 6&7 trial, which demonstrated that accelerated fractionation added signi...

PURPOSE: To evaluate if correction of low hemoglobin (Hb) levels by means of darbepoetin alfa improves the outcomes of radiotherapy in patients with squamous cell carcinoma of the head and neck (HNSCC).PATIENTS AND METHODS: Patients eligible for primary radiotherapy and who had Hb values below 14.0 g/dl were randomized to receive accelerated fractionated radiotherapy with or without darbepoetin alfa. Patients also received the hypoxic radiosensitizer nimorazole. Darbepoetin alfa was given weekly during radiotherapy or until the Hb value exceeded 15.5 g/dl.RESULTS: Following a planned interim analysis which showed inferiority of the experimental treatment the trial was stopped after inclusion of 522 patients (of a planned intake of 600). Of these, 513 were eligible for analysis (254 patients treated with darbepoetin alfa and 259 patients in the control group). Overall, the patients were distributed according to the stratification parameters (gender, T and N staging, tumor site). Treatment with darbepoetin alfa increased the Hb level to the planned value in 81% of the patients. The compliance was good without excess serious adverse events. The results showed a poorer outcome with a 5-year cumulative loco-regional failure rate of 47% vs. 34%, Hazard Ratio (HR): 1.53 [1.16-2.02], for the darbepoetin alfa vs. control arm, respectively. This was also seen for the endpoints of event-free survival (HR: 1.36 [1.09-1.69]), disease-specific death (HR: 1.43 [1.08-1.90]), and overall survival (HR: 1.30 [1.02-1.64]). There was no enhanced risk of cardio-vascular events observed in the experimental arm or any significant differences in acute or late radiation related morbidity. All univariate analyses were confirmed in a multivariate setting.CONCLUSION: Correction of the Hb level with darbepoetin alfa during radiotherapy of patients with HNSCC resulted in a significantly poorer tumor control and survival.

An enzyme immunoassay (ELISA) has been developed for the detection of human autoantibodies to thyroglobulin (TgAb). The ELISA assay was compared to the previous routine method, the tanned red cell (TRC) method and a radioimmunoassay (RIA) technique for thyroglobulin autoantibodies. Sera from 163 healthy non-hospitalized persons, 31 patients with Hashimoto's thyroiditis, 13 patients with Graves disease, 136 patients with thyroid cancer and 365 sera consecutively received for thyroid autoantibody screening were examined for TgAb in the three methods. The nosological sensitivity for ELISA methods was comparable to that of RIA and higher than that of TRC. The ELISA method was accurate, precise, objective, inexpensive and well suited for quantitative routine determination of TgAb.

The aim of the study was to test the influence of thyroglobulin in vitro and in vivo on two different principles for quantification of serum antithyroglobulin antibody content. The methods employed were a previously described homogeneous phase radioassay and a newly developed enzyme-linked immunosorbent assay. Thyroglobulin inhibited the measurement of antithyroglobulin antibody content by both methods, not only by addition in vitro but also when present in vivo as a result of release from thyroid surgery. Both methods proved sufficiently sensitive as screening for presence of antithyroglobulin antibodies before measurement of thyroglobulin in serum. The study shows the importance of assessing the assay systems in each laboratory for interference before use, especially if intended for screening before quantifying serum thyroglobulin or for measurement of antithyroglobulin antibodies in other media (e.g. supernatants from lymphocyte cultures).

Background. A retrospective nationwide study of cancer of the nasal vestibule was conducted to evaluate classification systems and prognostic factors for treatment outcome. Methods. Patients treated between 1993 and 2002 at head and neck oncology centers in Denmark were included. Results. The 5-year results were locoregional control 67%, overall survival 50%, cancer-specific survival 74%. Cancer-specific survival according to Wang classification was 83%, 63%, and 39% for T1, T2, T3, respectively (p < .000). Regarding T1 tumors, 5-year locoregional control for surgery, surgery + radiotherapy (RT), or RT was 94%, 87%, or 61%, respectively (p < .000). Fifty-four Gray in 18 fractions was found comparable with 66 Gy in 33 fractions regarding T1 tumors. Conclusion. This national survey is the largest series of nasal vestibule cancer ever published. Wang classification is more prognostic and easier to use than the Union Internationale Contre le Cancer 2002. Surgery or hypofractionated RT can be used for T1 lesions, whereas larger lesions should be treated with combined approach. © 2009 Wiley Periodicals, Inc. Head Neck, 2009

BACKGROUND.: The benefit of a complementary fluorodeoxyglucose-positron emission tomography (FDG-PET) scan to standard workup for carcinoma of unknown primary (CUP) and metastatic neck lesions was prospectively studied. METHODS.: Sixty-seven patients underwent standardized diagnostic workup according to national guidelines including panendoscopies, multiple mucosal biopsies, and diagnostic CT/MRI scans. Median follow-up was 40 months (range, 2-65 months). RESULTS.: In 60 eligible patients, FDG-PET indicated a primary tumor or metastatic disease in 30 patients (50%). Additional investigations confirmed a primary tumor in 18 patients: hypopharynx in 5, oropharynx in 5, nasopharynx in 2, lung in 1, axilla in 1, bone in 1, rectum in 1, as well as multiple metastatic lesions from CUP in 2 patients. In retrospect, MRI was able to detect 1 of the PET-detected primaries, leading to an overall detection rate of PET of 29% in CUP. A therapeutic change of treatment was made in 25% as a consequence of FDG-PET. PET before panendoscopy demonstrated fewer false-positive pathological foci. CONCLUSION.: FDG-PET is a valuable tool in addition to conventional extensive workup in CUP and neck metastases. Consequently, FDG-PET is now recommended as an early diagnostic modality in the workup of these patients. (c) 2007 Wiley Periodicals, Inc. Head Neck, 2007.

In a randomized, prospective trial from 1974-1978, 73 patients with non-Hodgkin's lymphomas in clinical Stage I or II were treated with extended field radiotherapy alone (RT) or RT plus adjuvant chemotherapy with vincristine, streptonigrin, cyclophosphamide and prednisone (RT + CT). With a median follow-up time of five years, 54% have relapsed in the RT group versus only 10% in the RT + CT group (P less than 0.01). There is no statistical difference in the overall survival yet, but 13/14 deaths in the RT group versus only 3/12 in the RT + CT group were due to progressive disease. Among patients with unfavorable histology, 13/22 in the RT group have died from disease progression against 3/34 in the RT + CT group (P less than 0.01). The results are in agreement with those from two other series published in detail. Based on these results we therefore recommend to use adjuvant CT with RT in all Stage I-II patients with unfavorable histology. Further observation is necessary before a conclusion can be drawn for the lymphoma patients with more favorable histology.

Objective: The aim of this study was to report our experience with malignant and borderline soft tissue tumours (STS) of the head and neck region in the period 1977–2000. Design: Retrospective case study including new evaluation of histological specimens. Setting: Tertiary centre, single centre. Participants: Review of patient's records and new evaluation of pathological specimens were made for 66 patients. After evaluation only 36 patients (26 men and 10 women) still met present criteria for a STS in head and neck in adults. Results: The original histological diagnosis was changed in 27 (41%) of the 66 patients with a primary diagnosis of sarcoma. After review the most common histological diagnoses were leiomyosarcoma (5) and rhabdomyosarcoma (5). Overall 5-year survival rate was 60%. Overall 5-year disease-free survival rate was 44%. The study showed that both tumour grade and surgical margin had a statistically significant impact on survival. No relation was found between survival and tumour size or age. Conclusion: The grave prognosis especially for high-grade tumours emphasizes the need for improved treatment strategies. Furthermore, conclusions from older studies concerning prognosis may be obsolete as approximately 40% of tumours previously diagnosed as sarcomas may be invalid by present day standards. Keypoints • Tumour grade and surgical margins are the most significant impact factors upon survival of patients with soft tissue sarcomas (STS) of the head and neck. • Based upon our re-review of histological specimens as much as 40% of tumours previously diagnosed in older studies as sarcomas of the head and neck may be faulty by present standards. Such studies may therefore be obsolete. • Improved treatment strategies on STS of the head and neck should focus on high-grade tumours.

OBJECTIVE: In 1998, the Danish Society for Head and Neck Oncology decided to conduct a nationwide survey at the five head and neck oncology centers with the aim of evaluating the surgical outcome of salvage laryngectomy after radiotherapy with special emphasis on identifying factors that could contribute to the development of pharyngocutaneous fistulae. PATIENTS: A total of 472 consecutive patients undergoing postirradiation salvage laryngectomy in the period July 1, 1987-June 30, 1997 were recorded at the five head and neck oncology centers in Denmark. Age ranged from 36 to 84 years, median 63 years, 405 men and 67 women. Primary tumor site was glottic larynx (n = 242), supraglottic larynx (n = 149), other larynx (n = 45), pharynx (n = 27), and other (n = 9). All patients had received prior radiotherapy. RESULTS: Median time between radiotherapy and laryngectomy was 10 months (range, 1-348 months). A total of 89 fistulae lasting at least 2 weeks were observed, corresponding to an overall average fistulae risk of 19%. The number of performed laryngectomies per year decreased linearly (from 58 to 37), whereas the annual number of fistulae increased slightly (from 7 to 11), which meant that the corresponding estimated fistulae risk increased significantly from 12% in 1987 to 30% in 1997. Other significant risk factors for fistulae in univariate analysis included younger patient age, primary advanced T and N stage, nonglottic primary site, resection of hyoid bone, high total radiation dose, and large radiation fields. Multiple logistic regression analysis of these parameters suggested that nonglottic tumor site, late laryngectomy period (1987-1992 vs 1993-1997), and advanced initial T stage were independent prognostic factors for fistulae risk. Surgical parameters like resection of thyroid/tongue base/trachea or radiotherapy parameters like overall treatment time or fractions per week did not influence fistulae risk. CONCLUSIONS: The risk of fistulae is especially high in patients initially treated with radiotherapy for nonglottic advanced stage tumors. A significant decrease in the number of performed salvage laryngectomies over the 10 years was seen. Over the same time period, the annual number of fistulae remained almost constant. The resulting more than doubling of fistulae rate could thus in part be explained by less surgical routine.

Objectives To demonstrate the efficacy of whole-body 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) in the detection of a carcinoma of unknown primary after conventional diagnostic workup in patients with a metastatic neck lesion and to demonstrate how the treatment policy of wide-field irradiation can be safely modified in relation to the findings from PET scanning. Study Design Prospective cohort study of consecutive patients. Methods Forty-two consecutive patients with squamous cell or undifferentiated metastatic disease in the neck from a carcinoma of unknown primary were enrolled after standard clinical workups. These patients underwent extensive clinical investigations including endoscopy under anesthesia with multiple mucosal biopsies and diagnostic imaging as well. If no primary site was indicated at this stage, a whole-body 18F-FDG PET scan was performed. Results Potential focal pathological uptake indicated a primary tumor in 20 of 42 cases (48%). After PET, this was confirmed by additional investigations in 10 patients (24%). Of these, seven primaries were found in the head and neck region (hypopharynx [three], base of tongue/vallecula [two], nasopharynx [1], floor of mouth [1]), and three primaries were found below the clavicles (lung [1], esophagus [1], and abdomen [1]. Positron emission tomography resulted in significant modifications of radiation treatment fields or fractionation prescriptions in all the patients who were diagnosed with a primary tumor after PET. Conclusion With our present strategy of wide-field irradiation in patients with neck node metastases from a carcinoma of unknown primary, whole-body 18F-FDG PET had treatment-related implications in 24% (10 of 42) of the patients.

Aims. To review all cases of esthesioneuroblastoma in Denmark from 1978 to 2000 with respect to staging, grading, histopathological and immunohistochemical evaluation, and prognostication. Methods and results. Possible cases of esthesioneuroblastoma were retrieved from Danish oncology departments. Patients were included on the basis of review of their files or pathology reports, and/or on the basis of histopathological and immunohistochemical examination. Forty-nine possible cases were retrieved. Nine cases were excluded. Esthesioneuroblastoma is a malignant neuroendocrine tumour originating in the olfactory mucosa. It is a small blue cell neoplasm with a characteristic lobular architecture. It has a neuroendocrine immunophenotype and a sustentacular S-100 staining pattern. The tumours were staged according to Kadish and graded according to Hyams. Kaplan-Meier survival analysis was used to identify prognostic factors. Conclusion. The Kadish staging system was able to group the patients into prognostically relevant groups. Intracranial involvement and metastases at the time of diagnosis were found to be poor prognostic factors. Hyams grading system is difficult to work with and it was not possible to divide patients into prognostically relevant groups. Presence of necrosis, a diffuse growth pattern and a high proliferation index proved to be equally poor prognostic factors.

Purpose: This study focuses on the clinical characteristics of patients with osteoradionecrosis (ORN) of the jaws and on the relation between the extent of the ORN and the field of irradiation. Patients and Methods: The study group consisted of 80 patients referred for treatment of ORN. Charts of the extent of ORN, based on panoramic radiographs, were drawn by the clinical investigator and compared with charts of the field of irradiation drawn by the oncologists. Also recorded was diagnosis of the lesion, stage, location, treatment schedule, and period and dose of irradiation. Also documented were various potential initiating factors for ORN. Results: Smoking habits of ORN patients were similar to those of other patients with head and neck cancer. A new primary tumor or a recurrence was diagnosed in 10% of the patients at the time of ORN. Only 3 patients had received accumulated doses of less than 60 Gy. More than half of the cases were initiated by removal of teeth; however, one third occurred spontaneously. ORN developed within the first 3 years in 74%; but ORN can emerge on a traumatic basis for an infinite number of years after radiation therapy. Widespread ORN may be symptomless apart from a discrete dehiscense of the oral mucosa. The predilection site for ORN is the mandibular molar region. All cases of ORN but 1 were found in the field of radiation. Conclusion: Because many ORN case are symptomless, more focus on mucosal dehiscence in the follow-up after radiation therapy is advocated in an effort to detect ORN at an early stage. The consequence of practically all ORN cases being located in the field of irradiation, together with tooth removal frequently being the initiating factor, should lead to a more aggressive preirradiation approach to dental pathology located within the field of radiation. © 2000 American Association of Oral and Maxillofacial Surgeons

BACKGROUND The results and consequences of genetic testing in a family with familial medullary thyroid carcinoma (FMTC) are described. METHODS In the screening of relatives, serum calcitonin is replaced by RET mutation analysis that was performed in families suspected of hereditary medullary thyroid carcinoma (MTC). In 4 of 10 families, mutation in exon 10 was found in codon 611. RESULTS One hundred fifty persons belonging to 30 families were tested, of which 10 families were carriers of RET mutation in exon 10. In 1 of these families with MTC only, 2 brothers were gene carriers of a RET codon 611 mutation and lived without any sign of MTC. One is aged 79 years, and the other died at the age of 71 of other causes. CONCLUSIONS The results indicate that the gene carrier in families with MTC without other endocrine tumors (FMTC) exhibits a highly variable disease course. A 611 codon mutation is most often a rather mild and slow progression form of MTC. Because 2 gene carriers were still alive at age 70 years without showing any sign of the disease, it is tempting to ask if all gene carriers with a 611 codon mutation without other endocrine tumors should be operated on, and if so, at what age? In the authors' opinion, more information is needed to be able to answer these questions. The current guidelines for treatment of patients with hereditary MTC are discussed. Cancer 2000;89:863–7. © 2000 American Cancer Society.

OBJECTIVE To evaluate the value of immunostaining using the monoclonal antibody (MoAB47) against thyroperoxidase (TPO) in distinguishing between benign and malignant tumour cells in fine needle aspiration cytology (FNAC) samples obtained from a solitary cold nodule of the thyroid gland for the purpose of strengthening the indication for thyroid surgery. DESIGN A prospective, immunocytochemical study of FNACs taken from patients with solitary cold thyroid nodules who presented to Rigshospitalet, Copenhagen, Denmark, during the period April 1993 to May 1996. The first sample series was taken perioperatively in order to test the utility of the method. In the second part of the study samples were obtained preoperatively by ultrasonic guided aspiration. Tissue sections from the nodules obtained during a subsequent operation served as controls. PATIENTS One hundred and eighty-one patients, 150 women and 31 men, were studied. The age range was 14–89 years with a median age of 44 years. Fifty-seven patients were excluded from the study for various reasons leaving us with a total of 124 nodules from 124 patients for final evaluation. METHODS FNAC cells and corresponding nodular tissue were stained by immunocyto– and immuno-histochemistry using MoAb47 and by routine staining methods. Samples were considered benign if 80% or more of the epithelial-looking cells of both the FNACs and the histological tissue sections of the nodule were stained by TPO. Consequently, samples were considered malignant if more than 20% of the epithelial-looking cells failed to stain for TPO. Routinely stained tissue cells and sections served as diagnostic controls. RESULTS A pattern with negative TPO staining was found in all lesions which, by conventional histological staining, were subsequently proven to be malignant. A universal and reliable, positive TPO staining pattern was found in all subsequently proven benign lesions, with the exception of one out of 26 follicular adenomas. This gave the method a sensitivity of 1.0 (negative TPO staining = malignancy in 27 out of 27) and a specificity of 0.99 (positive TPO staining = benign lesion, in 96 out of 97). Positive and negative predictive values were 0.96 and 1.00 respectively. CONCLUSION Thyroperoxidase immunostaining of fine needle aspirates from solitary, scintigraphically cold nodules of the thyroid gland has proved to be an important and reliable diagnostic tool for distinguishing between benign and malignant nodules. Thus, patients might be spared further surgery if not otherwise indicated.

Sarcoidosis is a systemic chronic granulomatous disease of unknown etiology most commonly affecting young females. The disease was first described in the thyroid gland in 1938. Our patient, a 27-year-old male with known sarcoidosis, was referred to the National University Hospital for acute symptoms of thyrotoxicosis (weight loss of 6 kg, tremor, thyroid enlargement, and tachycardia). Laboratory findings showed suppressed serum thyrotropin (TSH,0.03 mU/L [0.5-4.20]), increased total thyroxine (T4) (223 nmol/L, [60-140]), and triiodothyronine (T3) (8.5 nmol/L, [1.5-2.7]). Furthermore, Tc-99m pertechnetate scintigraphy disclosed diffuse accumulation of the isotope confirming the diagnosis of Graves' disease. During the next 18 months of antithyroid treatment (thiamazole, Thycapzol) hyperthyroidism was difficult to control, the thyroid gland gradually enlarged, and surgery was recommended. Initially, the patient declined surgery but after an additional 18 months, he accepted surgery. During the 36-month period of antithyroid drug treatment TSH was suppressed (0.01 mU/L) and T3 often elevated despite high doses of thiamazole. Total thyroidectomy was performed, and histologic examination of the removed thyroid tissue confirmed the diagnosis of Graves' disease and also the presence of sarcoid granuloma and metastatic papillary adenocarcinoma with spread to neck lymph nodes. Four months later, a modified radical neck dissection was performed with removal of neck lymph nodes followed by external radiation therapy (2 Gy x 32 fractions to the neck). The concomitant presence of sarcoidosis, papillary carcinoma, and Graves' disease in a thyroid gland, to our knowledge, has not previously been described in the literature.

BACKGROUND Stereologically measured mean nuclear volume has been proven to have prognostic importance in several types of cancer, such as malignant melanoma and carcinomas of the breast, oral region, bladder, and uterine cervix. The main purpose of the current study was to investigate the possible prognostic importance of mean nuclear volume and mitotic index in carcinoma of the supraglottic larynx. METHODS The study was performed with a stratified, random sample of 113 patients from a well-defined group of 386 patients with supraglottic laryngeal carcinoma treated with radiotherapy at the Finsen Institute in Copenhagen. Histologic sections from pretreatment biopsies were used to estimate the following parameters: mean nuclear volume (Vv(|)), mitotic index (MI), number of nuclei per mm2 (QA), mean nuclear profile area (Anuc), and the area fraction of nuclei in cancer tissue (AA). The geometric means of the parameters were used as cutoff points in a single factor and in a multivariate survival analysis with relapse free survival as the primary endpoint. RESULTS The geometric means of the measured parameters were (Vv(|)) = 480 μ3, QA = 3630 nuclei/μ2 cancer tissue, MI = 0.48 mitosis/100 nuclei, AA = 0.21, and Anuc = 57.9 μ2. CONCLUSIONS None of the stereologically estimated parameters proved to have prognostic importance, whereas tumor size, and lymph node status did. The method of adaptive, stratified, random sampling used in this study can save a great deal of work and is highly recommended by the authors. Cancer 1999;86:2222–8. © 1999 American Cancer Society.

Purpose: The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery. Methods and Materials: This quantitative meta-analysis included updated individual patient data from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials. Results: With a median follow-up of 9 years, the hazard ratio (HR) of 0.89 (95% CI 0.78–1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant ( p = 0.062). No clear differences in the size of the effect by sex, age, or tumor location were apparent. Conclusion: Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients would be needed to reliably detect such an improvement (15→20%).

A retrospective study of factors of prognostic significance for clinical course and survival was performed using uni- and multivariate analyses in 251 patients with primary salivary gland carcinoma admitted during the period 1958-1992. Univariate analyses indicated that site of primary tumour, histology, clinical stage, presence of node metastases at primary diagnosis, and status of surgical margins were important prognostic factors for cause-specific survival, locoregional control and distant metastases. Multivariate analyses confirmed that histology was important for both locoregional control and cause-specific survival, whereas primary site was only of importance for locoregional control. Presence of node metastases at diagnosis was more important for locoregional control than clinical stage, whereas clinical stage was the most important factor for cause-specific survival. Status of surgical margins was of major importance for both cause-specific survival and locoregional control. Radiotherapy in addition to surgery improved locoregional control only, whereas survival was not affected.

Patients with head and neck squamous cell carcinoma (HNSCC) and a low level of hemoglobin often have a poor response to radiation that may be related to hypoxia-induced radioresistance. We have previously published the importance of hemoglobin level and the effect of transfusion by the results from the randomized DAHANCA 5 trial, including 414 patients in the analysis. Aim of the current analysis was to gain additional power by adding patients from the continued subrandomization in the DAHANCA 7 trial, now including a total of almost 1200 patients.Patients were randomized to treatment in the DAHANCA 5 and 7 study (nimorazole vs. placebo and five fx/week vs. six fx/week), and in addition, patients with "low" pre-irradiation hemoglobin values (females13 g/dl; males14.5 g/dl) were subrandomized to plus or minus transfusion. Transfusion was given with packed red blood cells with the aim to achieve a hemoglobin level in the "high" value range.A total of 1166 patients were included, 701 patients had high hemoglobin levels and 465 had low hemoglobin levels. Among the low hemoglobin patients, 235 were randomized to receive transfusion. Patient characteristics and treatment arms were well balanced. In the majority of patients, transfusion resulted in increased hemoglobin levels although this decreased slightly throughout treatment as in the non-transfused patients. Overall, the patients with low hemoglobin level had a significant reduced probability of locoregional control, disease-specific and overall survival. In the low hemoglobin group, transfusion did not improve the outcome in locoregional control, disease-specific or overall survival. In multivariate analyses, HPV/p16 status, T and N classification were significant factors for all outcome measures, whereas there was no significant influence of transfusion or hemoglobin level on endpoints.Transfusion prior to and during radiation treatment did not improve the outcome in patients with HNSCC and low hemoglobin values, but may have a negative impact on survival.

Patients with head and neck squamous cell carcinoma (HNSCC) and a low level of haemoglobin (Hb) often have a poor response to radiation which may be related to hypoxia induced radioresistance. The aim of the study was to evaluate the prognostic significance of low Hb level and its modification by transfusion in HNSCC patients treated with radiotherapy. The study was performed as a subrandomization in the DAHANCA 5 trial.Patients were randomized to treatment with the hypoxic radiosensitizer nimorazole or placebo, and in addition, patients with "low" pre-irradiation Hb values (females13 g/dL; males14.5 g/dL) were subrandomized to plus or minus transfusion. Transfusion was given with packed red blood cells with the aim to achieve a Hb level in the "high" value range.A total of 414 patients were included, 243 patients had high Hb levels and 171 patients had low Hb levels. Of the low Hb patients, 82 were randomized to receive transfusion and 89 not to receive transfusion. The treatment arms were well balanced. In the majority of patients, transfusion resulted in increased Hb levels although this tended to decline throughout treatment. Patients with high Hb levels had a significantly better probability of locoregional control, disease-specific survival and overall survival compared to 'low Hb no transfusion' patients. In the low Hb group, transfusion did not improve the outcome in locoregional control, disease-specific survival or overall survival. In multivariate analyses, T and N classifications were significant for all outcome measures, whereas there was no significant influence of transfusion or Hb level on endpoints.The univariate prognostic significance of high Hb level was demonstrated in patients with HNSCC treated with radiotherapy; however, transfusion prior to and during treatment did not improve the outcome in patients with low Hb values.

Patients who have received irradiation therapy on the head and neck area are known to suffer from reduced saliva flow and may therefore use acidic candies to relieve symptoms of dry mouth. However, such acidic candies have erosive potential even among healthy individuals. Therefore, the aim of the present study was to determine if calcium-modified acidic candies have reduced erosive potential in irradiated cancer patients.Nineteen cancer patients (26 to 70 years) ipsilaterally irradiated on the head and neck area sucked control and calcium-modified acidic candies, while their whole saliva was collected into a closed system. The erosive potential of both candies was evaluated from saliva degree of saturation with respect to hydroxyapatite and by dissolution of hydroxyapatite (HAp) directly in candy-stimulated saliva. The results were compared to normative data that were previously obtained on 20 healthy test persons (21 to 29 years).No significant difference was obtained in the saliva flow rates between control and calcium-modified candy. However, the saliva became significantly less undersaturated with respect to HAp when sucking calcium-modified compared to control candy (P0.001) and more undersaturated for both candies in ipsilaterally irradiated cancer patients compared to normative data (P0.001). HAp dissolution was found to be significantly lower in patients sucking the modified candy compared to the control candy (P0.01) and, surprisingly, slightly lower in patients compared to normative data.Modified acidic candy with calcium has reduced erosive potential in patients irradiated on the head and neck area and could therefore be used as a favourable stimulant for relief of dry mouth.

In a prospective multicenter study, 186 patients with squamous cell esophageal carcinoma, who after evaluation were considered suitable for surgery, were randomized to 4 treatment groups: Group 1, surgery alone; Group 2, pre-operative chemotherapy (cisplatin and bleomycin) and surgery; Group 3, pre-operative irradiation (35 Gy) and surgery; Group 4, pre-operative chemotherapy, radiotherapy, and surgery. Three-year survival was significantly higher in the pooled groups receiving radiotherapy as compared with the pooled groups not receiving radiotherapy. Comparison of the groups having pre-operative chemotherapy with those not having chemotherapy showed no significant difference in survival. Female patients had a significantly better survival than males. The results indicate that pre-operative irradiation had a beneficial effect on intermediate term survival, whereas the chemotherapy regime used did not influence survival.

Ninety-five malignant tumors in the submandibular gland, the sublingual gland, and the minor salivary glands seen in a 25-year period were reviewed. The patients were retrospectively staged using the Union Internationale Contre le Cancer (UICC) classification. The most frequent tumor was adenoid cystic carcinoma, followed by adenocarcinoma. The submandibular gland was the most frequent location. Five-year and 10-year crude survival rates were 62% and 43%, respectively. Clinical stage was the most important prognostic factor. Survival was not correlated with location of tumor, although recurrence and metastases occurred more frequently in patients with cancer of the submandibular gland. Histologically, the 5-year and 10-year survival was significantly better for patients with adenoid cystic carcinoma compared with the other types; however, although still significant, this difference diminished at 10 years, confirming the need for a long observation time for patients with this tumor. 68:2424-2431, 1991.

Background. In the context of the Danish Head and Neck Cancer Group, nationwide material from 1992-2001 was analyzed to study the extent and nature of the disease, eval- uate treatment, compare staging systems, and examine progno- sis and survival. Methods. Review of 68 consecutive cases: 47 squamous cell carcinoma, 10 basal cell carcinoma, and 11 other histolo- gies. Moody (modified Pittsburgh) stages were T1 (26), T2 (9), T3 (8), T4 (23), Tx (2). Sixty-four patients were treated with cura- tive intent: 24 primary radiotherapy, 18 primary surgery, and 22 combined. Surgery was limited to tumor excision and mastoi- dectomy and in 1 case temporal bone excision. Results. Twenty-seven of 28 recurrences involved primary site. Kaplan-Meier analysis showed 5-year locoregional control of 48%, disease-specific survival 57%, and overall survival 44%. Conclusion. This nationwide study confirmed that local fail- ure is the main problem, and future improvements should focus on more aggressive local treatment. V C 2008 Wiley Periodicals, Inc. Head Neck 30: 1332-1338, 2008

Three hundred and four patients with squamous cell carcinomas of the oral cavity were treated at the Finsen Institute in cooperation with the ENT-surgical departments between 1978 and 1982. The primary treatment consisted of radiotherapy alone in 74%, surgery alone in 4%, and a combination of radiotherapy and surgery in 15% of the patients. Two per cent received other treatment (cryotherapy), 5% did not complete the planned radiotherapy, and 1% were not treated at all. Of 203 patients with tumour remnant or first recurrence, 45% were operated, 2% received radiotherapy, and 2% combined treatment. This treatment strategy made 38% of the patients free of disease in the follow-up period (3 1/2 to 8 years) or until the patients died from other causes. Fifty-nine per cent of the patients died from their oral carcinomas. Tumour size (T), lymph node status (N), and tumour stage were as expected important prognostic factors.

Background. The aim of this phase II study was to evaluate the antitumor activity and toxicity of a non-platin–containing regimen with paclitaxel and capecitabine. Methods. Fifty patients with recurrent or disseminated squamous cell carcinoma were included in the study. The treatment consisted of paclitaxel 175 mg/m2 once every third week and capecitabine 825 mg/m2 per oral (p.o.) twice daily (bid) for 2 weeks. Results. The overall response rate according to the World Health Organization (WHO) criteria was 42%. Two patients had a complete response (CR), 19 patients had a partial response (PR), 14 patients had no change (NC), 12 patients had progressive disease (PD), and 3 patients were not evaluable (NE). The median survival time was 8 months. Toxicity was very moderate. Only 10% of 315 delivered treatments had to be given in reduced dose or postponed for a week or more. Conclusions. The toxicity was low and manageable. The overall response rate was comparable to the commonly used cisplatin/5-fluorouracil regimen. © 2006 Wiley Periodicals, Inc. Head Neck 2007

In Denmark, a general impression of prolonged pretreatment delay for patients with head and neck cancer led to a nationwide study of time spans from symptom debut over first health care contact to start of treatment. Charts of consecutive new patients with squamous cell carcinoma of the pharynx and larynx, seen at the five Danish oncology centers in January/April 1992 and 2002, respectively, were reviewed. Of the 288 patients identified, definitive treatment was radiotherapy in 264 cases, surgery in one case. Twenty-three patients had neither surgery nor radiotherapy. Total time from first health care contact to start of definitive treatment was significantly longer in 2002 than in 1992 (median 70 versus 50 days, p B /0.001). There was no significantly difference in time used for diagnosis. Time for treatment preparation and planning was 46 days in 2002 versus 31 days in 1992 (pB /0.001). Significantly more diagnostic procedures (CT, MR, US, PET) were done in 2002. In conclusion, this nationwide study showed that waiting time before start of radiotherapy was significantly longer in 2002 compared to 1992. An increasing number of imaging procedures including CT-based dose planning was observed. The prolongation was mainly related to shortage of radiotherapy capacity. The three weeks extra pretreatment delay could theoretically lead to a 10% lower tumor control probability in 2002 compared to 1992. The clinical workup for patients with head and neck cancer is often complex. Since the options for primary treatment include surgery, radiation therapy, chemotherapy or a combination of these, multidisciplinary care over long periods of time is often required. The expression ‘continuum of care’ has been introduced to describe this ‘coordinated activities in health care linked together to achieve the best possible result for the patient’ [1]. A prolonged delay prior to treatment start may cause decrease in the local control rate as well as survival due to tumor growth [2/5]. Radiobiological studies indicate that a 4-week delay of start of

The treatment strategy for oral squamous cell carcinoma in Denmark has traditionally varied between the different head and neck oncology centres. A study group within the Danish Society for Head and Neck Oncology (DSHHO) was formed with the aim of optimising and standardising the treatment strategy. The approach was to use single modality treatment for stage I, stage II and some stage III and combined modality treatment for stage III and IV. Surgery was the preferred treatment when it was considered possible to perform a radical excision of the tumour and possible lymph node metastases with acceptable aesthetic and functional outcome. The implementation of a recognised national guideline facilitates prospective studies on a large well-characterised cohort. This increases the possibility of obtaining valid data on parameters such as morbidity, loco-regional control and survival. In addition the establishment of a reference program facilitates national monitoring of the treatment using defined indicators and standards.

An independent in vivo dose verification procedure for IMRT treatments of head and neck cancers was developed. Results of 177 intracavitary TLD measurements from 10 patients are presented. The study includes data from 10 patients with cancer of the rhinopharynx or the thyroid treated with dynamic IMRT. Dose verification was performed by insertion of a flexible naso-oesophageal tube containing TLD rods and markers for EPID and simulator image detection. Part of the study focussed on investigating the accuracy of the TPS calculations in the presence of inhomogeneities. Phantom measurements and Monte Carlo simulations were performed for a number of geometries involving lateral electronic disequilibrium and steep density shifts. The in vivo TLD measurements correlated well with the predictions of the treatment planning system with a measured/calculated dose ratio of 1.002+/-0.051 (1 SD, N=177). The measurements were easily performed and well tolerated by the patients. We conclude that in vivo intracavitary dosimetry with TLD is suitable and accurate for dose determination in intensity-modulated beams.

Summary Background Although head and neck cancer can be cured by radiotherapy, the optimum treatment time for locoregional control is unclear. We aimed to find out whether shortening of treatment time by use of six instead of five radiotherapy fractions per week improves the tumour response in squamous-cell carcinoma. Methods We did a multicentre, controlled, randomised trial. Between January, 1992, and December, 1999, of 1485 patients treated with primary radiotherapy alone, 1476 eligible patients were randomly assigned five (n=726) or six (n=750) fractions per week at the same total dose and fraction number (66–68 Gy in 33–34 fractions to all tumour sites except well-differentiated T1 glottic tumours, which were treated with 62 Gy). All patients, except those with glottic cancers, also received the hypoxic radiosensitiser nimorazole. Analysis was by intention to treat. Findings More than 97% of the patients received the planned total dose. Median overall treatment times were 39 days (sixfraction group) and 46 days (five-fraction group). Overall 5-year locoregional control rates were 70% and 60% for the six-fraction and five-fraction groups, respectively (p=0·0005). The whole benefit of shortening of treatment time was seen for primary tumour control (76 vs 64% for six and five fractions, p=0·0001), but was non-significant for neck-node control. Six compared with five fractions per week improved preservation of the voice among patients with laryngeal cancer (80 vs 68%, p=0·007). Disease-specific survival improved (73 vs 66% for six and five fractions, p=0·01) but not overall survival. Acute morbidity was significantly more frequent with six than with five fractions, but was transient. Interpretation The shortening of overall treatment time by increase of the weekly number of fractions is beneficial in patients with head and neck cancer. The six-fractions-weekly regimen has become the standard treatment in Denmark.

In 1998, the Danish Society for Head and Neck Oncology decided to conduct a nationwide survey at the five head and neck oncology centers with the aim of evaluating the surgical outcome of salvage laryngectomy after radiotherapy with special emphasis on identifying factors that could contribute to the development of pharyngocutaneous fistulae.A total of 472 consecutive patients undergoing postirradiation salvage laryngectomy in the period July 1, 1987-June 30, 1997 were recorded at the five head and neck oncology centers in Denmark. Age ranged from 36 to 84 years, median 63 years, 405 men and 67 women. Primary tumor site was glottic larynx (n = 242), supraglottic larynx (n = 149), other larynx (n = 45), pharynx (n = 27), and other (n = 9). All patients had received prior radiotherapy.Median time between radiotherapy and laryngectomy was 10 months (range, 1-348 months). A total of 89 fistulae lasting at least 2 weeks were observed, corresponding to an overall average fistulae risk of 19%. The number of performed laryngectomies per year decreased linearly (from 58 to 37), whereas the annual number of fistulae increased slightly (from 7 to 11), which meant that the corresponding estimated fistulae risk increased significantly from 12% in 1987 to 30% in 1997. Other significant risk factors for fistulae in univariate analysis included younger patient age, primary advanced T and N stage, nonglottic primary site, resection of hyoid bone, high total radiation dose, and large radiation fields. Multiple logistic regression analysis of these parameters suggested that nonglottic tumor site, late laryngectomy period (1987-1992 vs 1993-1997), and advanced initial T stage were independent prognostic factors for fistulae risk. Surgical parameters like resection of thyroid/tongue base/trachea or radiotherapy parameters like overall treatment time or fractions per week did not influence fistulae risk.The risk of fistulae is especially high in patients initially treated with radiotherapy for nonglottic advanced stage tumors. A significant decrease in the number of performed salvage laryngectomies over the 10 years was seen. Over the same time period, the annual number of fistulae remained almost constant. The resulting more than doubling of fistulae rate could thus in part be explained by less surgical routine.

A retrospective review of all diagnosed cases of esthesioneuroblastoma registered in Denmark between 1978 and 2000 was carried out in order to obtain epidemiological data and optimize national treatment guidelines.Forty cases were verified histologically and included in the analysis Epidemiological and histopathological data were evaluated in relation to the clinical outcome.The 40 cases represent an incidence rate of 0.4 cases/million inhabitants per year. Eight (20%) patients were classified as Kadish stage A, 13 (32.5%) as stage B and 19 (47.5%) as stage C. The histopathological findings were classified according to the grading system of Hyams The median follow-up time was 2.3 years (range 0.3-11.1 years). The 5-year crude survival rate was 61%, with a median survival of 3.1 years (range 0.3-19.2 years). The 5-year disease-free survival rate was 50%, with a median survival of 1.7 years (range 0-19.2 years). Only 3 (7%) patients had positive cervical lymph nodes at presentation. A nationwide consensus regarding treatment was seen in patients classified as Kadish stages A and B. The longest duration before the first recurrence of esthesioneuroblastoma was 5(1/2) years.The following therapeutic guidelines are suggested: Kadish stage A patients, surgical tumour resection and radiotherapy; Kadish stage B, surgical tumour resection and radiotherapy; Kadish stage C, surgical tumour resection via a craniofacial resection and radiotherapy combined with chemotherapy. Long-term follow-up of esthesioneuroblastoma patients is mandatory.

Survival and swallowing function were studied in a randomized trial of 97 patients with inoperable, localized esophageal carcinoma. Radical radiotherapy was given to 51 patients, while 46 patients had two courses of bieomycin/cisplatin before radiotherapy. The survival was 29% after one year, and 6% after 3 years in the radiotherapy group. The survival in the combined treatment group was 18 and 0%, respectively; p = 0.1895. The number of patients who could swallow any food increased from 6% before treatment to 38% after 3 months in the radiotherapy group, and from 0% to 23% in the combined group. No benefit was found by combining bleomycin/cisplatin with radiotherapy.

The prognosis of salivary gland carcinomas is difficult to assess. Simple mucin-type carbohydrates (T and sialosyl-T antigens, Tn and sialosyl-Tn antigens) have been shown to be of value in predicting prognosis for carcinomas in other locations. We studied the prognostic significance of the expression of these structures in a retrospective study of 133 patients with salivary gland carcinomas, using immunohistochemistry and a panel of well-defined monoclonal antibodies (MAbs) on formalin-fixed paraffin-embedded tissues. Sialosyl-Tn, T and sialosyl-T antigens were not correlated with prognosis. Univariate analyses showed no overall difference in survival or locoregional control between patients with Tn-positive and patients with Tn-negative tumours, but indicated that expression of the Tn antigen was associated with early locoregional recurrences and deaths. Tn was, however, not an independent prognostic factor by multivariate regression analysis.

Purpose: A multicenter randomized and balanced double-blind trial with the objective of assessing the efficacy and tolerance of nimorazole given as a hypoxic radiosensitizer in conjunction with primary radiotherapy of invasive carcinoma of the supraglottic larynx and pharynx. Patients and treatment: Between January 1986 and September 1990, 422 patients (414 eligible) with pharynx and supraglottic larynx carcinoma were double-blind randomized to receive the hypoxic cell radiosensitizer nimorazole, or placebo, in association with conventional primary radiotherapy (62–68 Gy, 2 Gy per fraction, five fractions per week). The median observation time was 112 months. Results: Univariate analysis showed that the outcome (5-year actuarial loco-regional tumor control) was significantly related to T-classification (T1–T2 48% versus T3–T4 36%, P=0.0008), neck-nodes (N− 53% versus N+ 33%), pre-irradiation hemoglobin (Hb) concentration (high 46% versus low 37%, P=0.02) and sex (females 51% versus males 38%, P=0.03). Overall the nimorazole group showed a significantly better loco-regional control rate than the placebo group (49 versus 33%, P=0.002). A similar significant benefit of nimorazole was observed for the end-points of final loco-regional control (including surgical salvage) and cancer-related deaths (52 versus 41%, P=0.002). This trend was also found in the overall survival but to a lesser, non-significant extent (26 versus 16%, 10-year actuarial values, P=0.32). Cox multivariate regression analysis showed the most important prognostic parameters for loco-regional control to be positive neck nodes (relative risk 1.84 (1.38–2.45)), T3–T4 tumor (relative risk 1.65 (1.25–2.17)) and nimorazole (relative risk 0.69 (0.52–0.90)). The same parameters were also significantly related to the probability of dying from cancer. The compliance to radiotherapy was good and 98% of the patients received the planned dose. Late radiation-related morbidity was observed in 10% of the patients, irrespective of nimorazole treatment. Drug-related side-effects were minor and tolerable with transient nausea and vomiting being the most frequent complications. Conclusion: Nimorazole significantly improves the effect of radiotherapeutic management of supraglottic and pharynx tumors and can be given without major side-effects.

Purpose: Accelerated repopulation of tumor cells during radiotherapy has been suggested as an important cause of treatment failure in squamous cell carcinoma of the head and neck. Due to tumor heterogeneity, not all tumors may benefit from accelerated radiotherapy at the expense of a lower total dose. This analysis evaluates the impact of histological differentiation on loco-regional control in relation to treatment duration. Patients and methods : A total of 501 patients with advanced supraglottic and pharyngeal squamous cell carcinoma with known histopathological grading were treated with planned split-course (191 patients) or continuous radiotherapy (310 patients) in two consecutive randomized controlled trials. Irradiation was given 2 Gy per fraction, 5 fractions per week to a dose of 66–68 Gy in 9.5 or 6.5 weeks, respectively. Results : Overall, split-course and continuous treatment resulted in a 5-year loco-regional control of 30% and 41% ( P = 0.007), respectively. However, the detrimental effects of split-course were only found in moderately and well-differentiated tumors, where the 5-year tumor controls were 38% and 21% after continuous and split-course treatment, respectively ( P = 0.001). In contrast, in poorly differentiated tumors loco-regional control was obtained in 44% of the cases for continuous and 40% for split-course treatment ( P = 0.63). Conclusions: It is suggested that the ability to accelerate repopulation may be lost by dedifferentiation, and that prolongation of the overall treatment time only lead to reduced loco-regional control in well to moderately differentiated tumors.

Background and purpose : In 1986 a prospective, randomized, multi-centre trial for evaluation of neoadjuvant chemotherapy with cisplatin and 5-fluorouracil in the treatment of advanced squamous cell carcinoma of the head and neck was initiated. As survival in this group of patients is poor the purpose was to find a possible survival benefit of the chemotherapy in addition to radiotherapy compared to radiotherapy only. Methods . Four-hundred sixty-one patients from Denmark, Norway and Sweden with tumors in oral cavity, oropharynx, hypopharynx and larynx were randomized to receive either standard treatment (radiotherapy or radiotherapy followed by surgery) or neoadjuvant chemotherapy followed by standard treatment. Chemotherapy included three courses of cisplatin 100 mg/m 2 i.v. infusion on day 1 followed by 5-fluorouracil 1000 mg/m 2 per day continuous i.v. infusion for 120 hours. Radiotherapy 64–70 Gy in 2 Gy per fraction, 5 times/week, was given to patients in both treatment arms. Results : Response rate was 71% for patients randomized to chemotherapy-radiotherapy and 66% for patients randomized to standard treatment (not statistically significant). Residual tumors were excised if possible. After surgery 62% of the patients randomized to chemotherapy-radiotherapy and 60% of the patients in the standard treatment group were clinically tumor free. Conclusions : No statistically significant benefit in survival was observed for patients treated with neoadjuvant chemotherapy followed by radiotherapy. Nor was there any impact of chemotherapy on the number of patients achieving loco-regional tumor control after primary treatment.

Purpose/Objectives: In cancer of the uterine cervix, lymph node (LN) metastases are associated with poor prognosis. The purpose of this study was to evaluate the efficacy of PET/CT to guide and verify laparoscopic diagnostic lymph node excision in cervical cancer patients. Materials/Methods: A single institution retrospective analysis of procedure efficacy and survival in cervical cancer patients with PET/ CT positive LN as well as identifying possible sources of error. Patient inclusion criteria: Histopathological diagnosis of cervical cancer, LN metastases at PET/CT prior to staging, laparoscopic diagnostic lymph node excision, control PET/CT after surgery. Missed Lesion (ML) was a lesion seen on the staging PET/CT with no sign of tumor tissue at histological analysis and a subsequent planning PET/CT revealing the same lesion as before laparoscopy. False Positive Lesion (FPL) was a lesion seen on the staging PET/CT with no sign of tumor tissue at histological analysis and verified by the planning PET/CT. Kaplan Meier plots and log-rank tests were performed. Histopathology of removed LN number of FPL over time was registered. Results: Sixty-five patients were included. Laparoscopy confirmed metastatic spread to LN in 39 patients. In 4 of 26 patients with negative laparoscopic results, post-operative PET/CT showed ML. Of these, three patients were re-operated of which two had LN metastases confirmed, and one continued having no evidence of metastatic disease. Of the total 23 patients with twice verified negative LN pathology, one patient died of metastatic breast cancer. Of the 42 patients with metastatic disease, 15 died. For the entire staging procedure sensitivity and specificity were calculated to 0.98 and 1.00 respectively. Positive and negative predictive values were 1.00 and 0.96. Of the 23 patients with FPL, histopathology of removed LN showed nonspecific changes of reactive originin65%(C.I.43-84%),fibrosisin17%(5-39%),calcificationsin13% (3-34%), histiocytosis in 35% (16-57%), follicular hyperplasia in 9% (128%) and necrosis in 4% (0-21%) (some showed more than one type). Completely normal architecture was observed in 17% (5-39%) of the patients. No change in frequency of FPL was observed over time. Conclusions: PET/CT as control of laparoscopic diagnostic lymph node excision provides high sensitivity and specificity as well as high positive and negative predictive values, for lymph node staging in cervical cancer patients. However, a high number of FPL was observed at PET/CT, mainly due to inflammation. Although no change in frequency

The purpose of the study was to examine the value of a commercial immunoradiometric (IRMA) method for measuring serum thyroglobulin as a tumor marker after treatment for differentiated thyroid carcinoma. A prospective analysis of consecutive serum samples from 53 patients was performed using the IRMA method and a traditional double antibody radioimmunoassay (RIA). The results were compared with those of 100 healthy control subjects and furthermore the method was validated by investigating sera from 24 patients with Hashimoto's thyroiditis positive for thyroglobulin autoantibodies. Finally, in vitro studies of the influence of thyroglobulin autoantibodies on the method were done. The IRMA method had an acceptable analytical precision and was more sensitive than the RIA. It was furthermore less sensitive to the presence of thyroglobulin autoantibodies but it was affected by them, and it showed less unspecific serum effect. Both methods had limitations as tumor marker when the patients had a thyroid remnant, when serum thyrotropin was not suppressed, and in cases of local recurrence. The highest predictive value was found in patients with distant metastases. Thus, in cases of only slightly elevated serum thyroglobulin, the strongest indication for recurrence is still an increasing serum thyroglobulin level within the same patient rather than a single value.

The prognostic significance of lymph node metastases was evaluated in an unselected material of 427 oropharyngeal cancer patients treated primarily with radiotherapy. At first referral, palpable lymph node metastases were present in 60% of the patients. After irradiation, 60% of all palpable nodes had disappeared. As many as 50% of the nodes initially palpable in N3 patients vanished after irradiation. Recurrences were significantly increased in patients primarily with lymph node metastases (N1–3) compared with No. patients; recurrences in the primary tumour site were (56% vs. 43%) in neck lymph nodes (40% vs. 9%) and in distant metastases (14% vs. 5%). Surgery was performed in 98 of 256 patients (38%) with recurrent or metastatic disease. The 5-year disease-free survival rate after radiotherapy for NO patients was an improvement (44%) on that of Nl-3 patients (23%). The N-stage is an important prognostic factor for oropharyngeal canter patients.

Purpose/Objective: In cancer of the uterine cervix, lymph node metastasis (LN) has been associated with a poor prognosis. The purpose of the current study was to evaluate the effect of the introduction of PET/CT-planned Intensity Modulated Radiotherapy (IMRT) on survival in patients with cervical cancer with LN Materials and Methods: A single institution retrospective analysis of survival and characteristics in cervical cancer patients with LN Inclusion criteria: Histopatological diagnose of cervical cancer, approved curative intended IMRT plan for patients with pelvic and/or para aortic fields, lymph node metastasis verified by CT, PET/CT and/or lymph node biopsy. Cisplatin based chemotherapy concomitant to IMRT. Consecutive patients from 1. January 2000 to 15. September 2011 with primary pelvicor para aortic LN, or recurrence of para aortic LN after primary treatment were included. IMRT was given as a sliding window technique and PET/CT planed on an Eclipse (Varian) doseplanning system. Doses to CTV: 50 Gy and a concomitant boost to LN: 60-64 Gy. Furthermore, patients with primary tumors received PDR brachytherapy 17.5 Gy x 2 Survival statistics and Kaplan Meier plots were calculated using SPSS. The distribution of patient characteristics was also tested. Results: Eighty-three patients were included. Patient characteristics are listed in Table 1. The statistical analysis indicated significant differences in the distributions of histopathology between the three groups. For both age and stage, no significant differences was found.