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Introduction: The aim of this study was to investigate phase IV efficacy, of the PD-1 inhibitor nivolumab among an unselected and unbiased national cohort of recurrent/metastatic Head and Neck Squamous Cell Carcinoma (rmHNSCC) patients. Material and Methods: Inclusion criteria included histologically confirmed rmHNSCC and nivolumab as a second-line palliative treatment. Data were collected from patient files at the five Danish head and neck cancer centers and from the DAHANCA database. The iRECIST criteria were used for treatment evaluation. Endpoints were response rate (RR), overall survival (OS), and progression-free survival (PFS), calculated from the start of treatment to the date of event/censoring by the KM-method. Descriptive statistics were used to describe patients and treatment. Analyses were two-sided, with p

BACKGROUND: Survival of medullary thyroid carcinoma (MTC) subgroups in relation to the general population is poorly described. Data on the factors predicting long-term biochemical cure in MTC patients are nonexistent at a population level. A nationwide retrospective cohort study of MTC in Denmark from 1997 to 2014 was conducted, aiming to detect subgroups with survival similar to that of the general population and to identify prognostic factors for disease-specific survival and long-term biochemical cure.METHODS: The study included 220 patients identified from the nationwide Danish MTC cohort between 1997 and 2014. As a representative sample of the general population, a reference population matched 50:1 to the MTC cohort was used.RESULTS: Patients diagnosed with hereditary MTC by screening (hazard ratio [HR] = 1.5 [confidence interval (CI) 0.5-4.3]), patients without regional metastases (HR = 1.4 [CI 0.9-2.3]), and patients with stage I (HR = 1.3 [CI 0.6-3.1]), stage II (HR = 1.1 [CI 0.6-2.3]), and III (HR = 1.3 [CI 0.4-4.2]) disease had an overall survival similar to the reference population. On multivariate analysis, the presence of distant metastases (HR = 12.3 [CI 6.0-25.0]) predicted worse disease-specific survival, while the absence of regional lymph node metastases (odds ratio = 40.1 [CI 12.0-133.7]) was the only independent prognostic factor for long-term biochemical cure.CONCLUSIONS: Patients with hereditary MTC diagnosed by screening, patients without regional metastases, and patients with stages I, II, and III disease may have similar survival as the general population. The presence of distant metastases predicted worse disease-specific survival, while the absence of regional metastases predicted long-term biochemical cure.

Treatment of squamous cell carcinoma of the supraglottic larynx (SCCSL) in Denmark has changed in several ways from the year 2000 to 2014, including the introduction of IMRT radiation technique and the addition of concurrent chemotherapy (CRT), as well as systematic reduction in waiting times until treatment initiation.Our aim is to investigate the effect of the abovementioned factors on overall survival (OS) and locoregional control (LC) for SCCSL patients.Retrospective cohort study with data from the DAHANCA database. We used the Kaplan-Meier and Cumulative Incidence plots as well as Cox regression analysis.We found a statistically significant improvement of the 5-year OS of 19.3 percentage points (pp). Cox regression found LC was not improved in patients receiving CRT compared to radiotherapy (RT) alone.Introduction of CRT treatment for head and neck cancers in general is known to improve LC. We could not demonstrate this effect for SCCSL specifically, as our results were not statistically significant on this point. OS was significantly improved.

Background The completeness of REarranged during Transfection (RET) testing in patients with medullary thyroid carcinoma (MTC) was recently reported as 60%. However, the completeness on a population level is unknown. Similarly, it is unknown if the first Danish guidelines from 2002, recommending RET testing in all MTC patients, improved completeness in Denmark. We conducted a nationwide retrospective cohort study aiming to evaluate the completeness of RET testing in the Danish MTC cohort. Additionally, we aimed to assess the completeness before and after publication of the first Danish guidelines and characterize MTC patients who had not been tested. Methods The study included 200 patients identified from the nationwide Danish MTC cohort 1997-2013. To identify RET tested MTC patients before December 31, 2014, the MTC cohort was cross-checked with the nationwide Danish RET cohort 1994-2014. To characterize MTC patients who had not been RET tested, we reviewed their medical records and compared them with MTC patients who had been tested. Results Completeness of RET testing in the overall MTC cohort was 87% (95% CI: 0.81-0.91; 173/200). In the adjusted MTC cohort, after excluding patients diagnosed with hereditary MTC by screening, completeness was 83% (95% CI: 0.76-0.88; 131/158). Completeness was 88% (95% CI: 0.75-0.95; 42/48) and 81% (95% CI: 0.72-0.88) (89/110) before and after publication of the first Danish guidelines, respectively. Patients not RET tested had a higher median age at diagnosis compared to those RET tested. Median time to death was shorter in those not tested relative to those tested. Conclusion The completeness of RET testing in MTC patients in Denmark seems to be higher than reported in other cohorts. No improvement in completeness was detected after publication of the first Danish guidelines. In addition, data indicate that advanced age and low life expectancy at MTC diagnosis may serve as prognostic indicators to identify patients having a higher likelihood of missing the compulsory RET test.

Introduction: Cisplatin is used as treatment for several different malignancies and a well-known complication is irreversible kidney damage. To protect the kidneys, this treatment is often combined with mannitol infusion to promote osmotic diuresis. Earlier studies investigating the nephroprotective effect of mannitol have shown conflicting results. Objective: To investigate changes in kidney function in head and neck cancer patients treated with cisplatin with and without additional mannitol infusion. Methods: A single center, retrospective cohort study of patients with squamous cell carcinoma of the head and neck receiving radiotherapy with cisplatin. Patient data were collected from November 2013 to December 2014. Results: After exclusion, a total of 78 patients were considered evaluable. They were equally distributed between a mannitol and a non-mannitol group and anthropomorphometrically similar. 51Cr-EDTA clearance declined in the mannitol group from 99.7 (19.9) to 96.4 (20.8) mL/min and in the non-mannitol group from 102.2 (17.8) to 92.3 (23.1) mL/min. Conclusions: There was a significantly smaller decrease in 51Cr-EDTA clearance in the mannitol group indicating a nephroprotective effect of mannitol.

Background This study presents the results of an extended phase II study originally published in 2007, regarding the antitumor activity and toxicity of a non-platinum containing regimen with paclitaxel and capecitabine for the treatment of recurrent or disseminated squamous cell carcinoma of the head and neck region. Fifty patients were included in the original study. Materials and methods A total of 183 patients with recurrent or disseminated squamous cell carcinoma were eventually included in the extended study. There were 37 women and 146 men. The mean age was 56 years. Performance status (WHO) was as follows: WHO 0:31, WHO 1:107, and WHO 2:45 patients. The treatment consisted of paclitaxel 175 mg/m2, once every third week and capecitabine 825 mg/m2 p.o. b.i.d for 2 weeks. Results The overall response rate (complete response and partial response) according to the WHO criteria was: 33% (CI 26–40). The median progression-free survival was 4.8 (CI 4.2–5.4) months. The median overall survival (OS) was 8.9 (CI 7.6–9.5) months. Compliance was good. Of the 1,131 cycles, only 13% had to be administered with a reduced dose and/or postponed to a later date. Toxicity was mild and grades 3 and 4 toxicities were uncommon. Two toxic deaths were registered though. Conclusion The response rate and the OS for this low toxicity regimen makes it a feasible alternative for not cisplatin eligible patients.

Jes Sloth Mathiesen,1,2 Jens Peter Kroustrup,3 Peter Vestergaard,3,4 Kirstine Stochholm,5,6 Per Løgstrup Poulsen,5 Åse Krogh Rasmussen,7 Ulla Feldt-Rasmussen,7 Sten Schytte,8 Henrik Baymler Pedersen,9 Christoffer Holst Hahn,10 Jens Bentzen,11 Sören Möller,2,12 Mette Gaustadnes,13 Maria Rossing,14 Finn Cilius Nielsen,14 Kim Brixen,2 Anja Lisbeth Frederiksen,2,15 Christian Godballe1 1Department of ORL Head & Neck Surgery and Audiology, Odense University Hospital, Odense, Denmark; 2Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 3Department of Clinical Medicine and Endocrinology, Aalborg University Hospital, Aalborg, Denmark; 4Steno Diabetes Center North Jutland, Aalborg, Denmark; 5Department of Internal Medicine and Endocrinology, Aarhus University Hospital, DK-8000 Aarhus, Denmark; 6Center for Rare Diseases, Aarhus University Hospital, Aarhus N, Denmark; 7Department of Medical Endocrinology, Copenhagen University Hospital, Copenhagen, Denmark; 8Department of ORL Head and Neck Surgery, Aarhus University Hospital, Aarhus, Denmark; 9Department of ORL Head and Neck Surgery, Aalborg University Hospital, Aalborg, Denmark; 10Department of ORL Head and Neck Surgery, Copenhagen University Hospital, Copenhagen, Denmark; 11Department of Oncology, Herlev Hospital, Herlev, Denmark; 12Odense Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark; 13Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; 14Center for Genomic Medicine, Copenhagen University Hospital, Copenhagen, Denmark; 15Department of Clinical Genetics, Odense University Hospital, Odense, Denmark Background: The incidence and prevalence of multiple endocrine neoplasia 2A (MEN2A) have only been reported once in a nationwide setting. However, it is unclear whether the figures are representative of other populations, as the major component of the syndrome, hereditary medullary thyroid carcinoma (MTC), has been reported as rare in the same country. We conducted a nationwide retrospective cohort study of MEN2A in Denmark from 1901 to 2014, aiming to describe the incidence and prevalence. Methods: This study included 250 unique MEN2A patients born or resident in Denmark before December 31, 2014. Patients were identified through the Danish REarranged during Transfection (RET) cohort, linkage of MEN2A pedigrees, the Danish MTC cohort, a nationwide collaboration of MEN2 centers, cross-checking of other relevant cohorts, and a systematic literature search. Results: The incidence from 1971 to 2000 was 28 (95% CI: 21–37) per million live births per year. Incidence for the specific mutations or for the overall MEN2A group did not change significantly from 1901 to 2014 (P>0.05). Point prevalence at January 1, 2015, was 24 per million (95% CI: 20–28). Conclusion: The incidence and prevalence of MEN2A in Denmark seem higher than those reported in other countries. This is likely explained by the Danish C611Y founder effect. Also, our data indicate no significant change in MEN2A incidence during the last century. Keywords: multiple endocrine neoplasia 2A, incidence, prevalence, Denmark

Extract: Multiple endocrine neoplasia 2B (MEN2B) is an autosomal dominant inherited cancer syndrome associating medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), ganglioneuromatosis of the aerodigestive tract and facial, ophthalmologic and skeletal abnormalities. MEN2B is caused by the M918T and A883F mutation of the REarranged during Transfection (RET) proto-oncogene in approximately 95% and

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: Regional as well as national series show an increasing incidence of thyroid cancer largely small size papillary thyroid carcinoma (PTC). Prognostic scoring systems have been developed, but these do not take into account the rapidly changing case mix, and adjustments may be required. The purposes of this study were to evaluate treatment outcomes and to analyze the value of older prognostic scoring systems tested on a relatively new, unselected national cohort of PTC patients. Methods: This was a national prospective cohort study conducted in Denmark, which has a population of 5.5 million. Results: A total of 1350 patients were diagnosed with PTC during 1996-2008, and the median follow-up time was 7.9 years. The 10-year recurrence-free survival rate was 90.2%, and the 10-year crude and cause-specific survival (CSS) rates were 83.7% and 93.8% respectively. By multivariate Cox regression, it was possible to confirm age, metastases (distant and nodal), extrathyroidal extension, and tumor size as predictors of mortality, whereas only nodal metastases, extrathyroidal extension, and tumor size were predictors of recurrence. In analyses of older prognostic scoring systems, a significant correlation between the risk group ranks was found for survival as well as recurrence. The c-index for CSS was highest for MACIS (0.92) and lowest for AMES (0.80). In the TNM, MACIS, and EORTC systems, most patients were classified as stage 1, and for these patients, the 10-year CSS rate was approximately 99.5%, confirming the generally excellent survival. Conclusion: This national study provides further evidence that a favorable prognosis is to be expected for patients diagnosed with PTC. Also, it was possible to confirm age, metastases, extrathyroidal extension, and tumor size as predictors of mortality, whereas only nodal metastases, extrathyroidal extension, and tumor size were predictors of recurrence. All the scoring systems evaluated were able to produce a highly significant risk group stratification, showing that in spite of the changes in the case mix of PTC, these systems are still applicable, and in fact contain valuable prognostic information useable for treatment planning.

BACKGROUND: It is well known that thyroid hormone withdrawal (THW) in thyroid cancer patients can induce a decrease in quality of life (QOL). Recombinant human thyrotropin (rh-TSH) has been used to avoid this; however, no blinded studies have ever documented the effect.OBJECTIVE: To compare QOL in patients with differentiated thyroid cancer (DTC) treated with either rh-TSH or liothyronine (L-T3) THW for 10 days.STUDY DESIGN: Double-blind, randomised cross-over.PATIENTS: Fifty-six patients with DTC treated by total thyroidectomy and indication for postsurgery radioiodine (RI) ablation therapy.INTERVENTION: Randomisation to either L-T3 and rh-TSH prior to the first RI course and following this to ingest placebo tablets and receive placebo injections before a second RI uptake measurement 4-6 months later, or to receive placebo before the primary RI ablation and active therapy 4-6 months later.MAIN OUTCOME MEASURES: QOL was measured by SF-36 and 2 visual analogue scale (VAS) scores at baseline and during RI therapy or RI uptake.RESULTS: A significant difference in QOL was seen in 2 of 4 predefined SF-36 domains (7.2 and 6.6%) and 2 VAS scales (10 and 14%), favouring rh-TSH therapy.CONCLUSION: This is the first blinded randomised clinical trial describing the effect of rh-TSH compared to L-T3 THW on QOL in DTC patients. A significant difference was demonstrated, though smaller than described in previous non-blinded studies.

BACKGROUND: With an observed general rise in papillary thyroid carcinoma incidence, papillary microcarcinoma (PMC) is accordingly found more frequently and often incidentally by histological examination of surgical specimens from presumed benign thyroid disease. Only a few studies have specifically addressed the prognosis of incidentally found PMC, and they have been limited to retrospective single-center studies.METHODS: This was a national, unselected, prospective cohort study of 406 papillary thyroid microcarcinoma patients diagnosed in Denmark from 1996 to 2008. Objective: The aim of this study was to evaluate incidence, outcome, and extent of necessary treatment, with special attention given to incidentally detected PMC.RESULTS: Age-standardized ratios were found to increase from 0.35 per 100,000 per year in 1996 to 0.74 per 100,000 per year in 2008. A total of 240 out of 406 cases were found incidentally, and a significant rise in incidence was only found for the incidental cases. Median follow-up was 7.6 years for the incidental cases, and in this time span, five cases of recurrence and no deaths from thyroid cancer occurred. The five-year recurrence-free survival was 98.1%, and only occurrence of lymph-node metastasis was found to affect the recurrence rate. A total of 160 incidental cases were initially treated with lobectomy, and the incidence of recurrence was not significantly different in the cases receiving completion thyroidectomy.CONCLUSION: The rising incidence of PMC in Denmark is explained by incidental cases. When the carcinoma is not the index tumor for surgery, this study implies that completion thyroidectomy does not improve prognosis.

Phonosurgical excision biopsies are gradually replacing traditional punch biopsies during direct lar-yngoscopy. As excision aims at removing all pathologic tissue, some malignant lesions may be completely removed. We present our experience with phonosurgical excision biopsies of T1a glottic cancers without primary radiotherapy. From 2001 till 2010, 24 patients with T1a glottic squamous cell carcinoma did not receive primary radiotherapy as tumours could not be observed at the post-operative control or because of concurrent malignancy or the presence of other co-morbidity. All lesions were excised by instrumental ("cold steel") phonosurgery in which only the epithelial layer above the vocal ligament was removed (type 1 cordectomy). All patients were closely followed by an ear-nose-throat (ENT) surgeon in collaboration with a radiation oncologist. Relapse was observed in nine of the 24 patients (37.5 %), all within 12 months. The per-operative evaluation of resectability and the results of margin biopsies were insufficient for prediction of recurrence risk. Neither tumour size, primary or secondary excision nor differentiation of the carcinoma influenced the relapse rate. T1a glottic cancers may be removed by "cold steel" phonosurgical excision biopsies, but this is inferior to treatment with radiotherapy or laser-assisted phonosurgery. As more than half of the patients did not need radiotherapy, phonosurgery may be considered as sole treatment in selected cases, provided close follow-up with videostroboscopy for the first year after surgery is performed. not relevant.not relevant.

Background : A rise in the incidence of thyroid cancer has been reported in several countries, and the increase is only seen in the papillary type. Increased detection due to higher resolution ultrasound and fine needle aspiration has been proposed as the explanation, recent registry studies however question this assumption. Methods : National, unselected, prospective cohort study of 1350 papillary thyroid cancer patients in Denmark from 1996 to 2008. Objective : To analyze changes in incidence by time and to identify factors which might influence detection rate. Results : A rise in incidence is seen with age standardized ratios increasing from 1.43 per 100.000 per year in 1996 to 2.16 per 100.000 per year in 2008. The median age at presentation was 46 years and median tumor size was 18mm. Male/female ratio was 1/2.9. By dichotomizing the material in a time period before and after the 30th of June 2001, no significant change in the proportion of diagnosed tumors smaller than 1 or 2cm was found, and 42.8% of the rise in incidence was explained by tumors larger than 2cm. No significant change in diagnostic use of ultrasound or fine needle aspiration was found, and a significant change toward more extensive thyroid surgery could not be confirmed. Conclusion : This study shows a significant rise in incidence of papillary thyroid carcinoma in Denmark from 1996 to 2008, which is not explained by increased use of preoperative diagnostic modalities. Other reasons need to be considered.

UNLABELLED: During follow-up on patients treated for differentiated thyroid cancer, thyroglobulin (Tg) antibodies can interfere with the Tg assay, making the use of Tg less reliable as a tumor marker.PURPOSE: To compare Tg and Tg autoantibodies (Tg-Ab) methods used in Denmark, regarding the number of patient samples being accepted for evaluating the result of a serum thyroglobulin (s-Tg) measurement.DESIGN: 95 consecutive blood samples drawn from patients in 2006 in one center were selected according to the following criteria: s-Tg RESULTS: The number of patient samples that was not accepted for Tg evaluation varied from 2 to 26% when the reference values suggested by the manufacturers of the assay were used. When using the detection limit to the cutoff seen in epidemiological studies the number increased to 40%.CONCLUSION: We found large discrepancies in acceptance of patient samples for s-Tg evaluation, thus illustrating a diagnostic dilemma.

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.

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

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.

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.

Introduction More than fifty percent of patients with esophageal cancer have metastatic disease at presentation, the 5-year survival being less than five percent. Very few studies have compared chemotherapy with best supportive care for metastatic esophageal cancer. No survival benefit has been shown for chemotherapy in randomized controlled trials. The efficacy of triplet combinations including platinum and fluoropyrimidines was demonstrated in gastroesophageal cancer in 2008, and doublet and triplet combinations are now considered standard for patients with esophageal adenocarcinoma. Methods Patients between 18 and 75 years of age, PS 0-2 and histological proven metastatic or non-resectable esophageal or gastroesophageal junction cancer were included. Patients received first-line treatment with oxaliplatin 130 mg/m2 given as iv-infusion day 1 every three weeks and tegafur-uracil 300 mg/m2 orally day 1-14 with a folic acid (rescuvorin/leucovorin/isovorin) supplementation 60 mg day 1-14 every three weeks, for a maximum of nine cycles. Toxicity was registered according to CTCAE 3.0, and response evaluation was performed according to RECIST criteria. The primary end-point was response rate; secondary objectives were overall survival (OS), progression-free survival (PFS) and toxicity in the intention-to-treat population. Results From November 2004 to March 2008, a total of 111 patients with locally advanced or non-resectable squamous cell (SCC) or adenocarcinoma (AC) of the esophagus or gastroesophageal junction were included. Fifty-three patients presented with AC and 58 had SCC. A total of 105 patients (94%) had metastatic disease and six patients (6%) had unresectable localized disease. Seventy-eight percent of the patients had ECOG performance status 0 or 1, whereas 15% had PS 2. Twenty-one percent had body mass index below 20. Median age was 59 years (range 40-75). Median number of series given was 3 (1-9), 109 patients were evaluable for response. Two patients were excluded from response evaluation due to nonmeasurable disease. No patients had complete response, twenty-four of 109 patients (22%) showed a partial response (PR), 27.5% had stable disease (SD) and 38.5% had progressive disease (PD), thirteen patients went off-study due to toxicity before response-evaluation. Median progression-free survival (PFS) was 4.7 months (95% CI 3.4-5.9) and median OS was 5.5 months (95% CI 4.7-6.3). Most common grade 3/4 adverse events included diarrhoea (12%), nausea and vomiting (12%), fatigue (8%) and neuropathy (4%). No cases of grade 3/4 hand-foot syndrome (PPE) or febrile neutropenia was noted. Four suspected treatment-related deaths were seen, all due to diarrhoea CTCAE grade 5. Conclusion The oxaliplatin/UFT regimen demonstrated both a modest response rate (22%) and survival benefit (OS 5.5 months) as first-line treatment of patients with metastatic or unresectable esophageal cancer. The regimen showed considerable toxicity, particularly gastrointestinal toxicity, including four treatment-related deaths, and is not attractive for further evaluation.

Clinical data from 218 patients consecutively treated for nasopharyngeal carcinoma at the Finsen Institute in Copenhagen during the period 1965 through 1985 have been analyzed for factors of prognostic importance. Of the 218 patients, 47 were Greenland Inuit eskimos and 169 were white Danish. The 5-year crude survival for the entire group of patients was 30%. The two groups of patients differed with respect to the importance of different prognostic factors. Keratinizing tumors were only present in the Danish population. These patients had a highly significant worse outcome than the rest of the Danish (P less than 0.00001). Age, stage, and T classification were important prognostic factors in the Danish population, but not in the Inuit population.