Background Patients with esophageal cancer commonly suffer from dysphagia, leading to nutritional problems and impaired quality of life. Self-expanding metallic stents (SEMS) is frequently used in the palliative setting providing a rapid but short-term relief. In this phase II study we assessed a novel first-line treatment schedule with short-course radiotherapy followed by chemotherapy with the primary aim to achieve a long-term improvement of dysphagia. Methods Patients with dysphagia due to adenocarcinoma of the esophagus or esophagogastric junction, not eligible for curative treatment, were recruited. Treatment consisted of radiotherapy (5 x 4 Gy) followed by 4 cycles of chemotherapy (FOLFOX regimen). Dysphagia was assessed using a 5-grade scale and a response was defined as an improvement from baseline with at least one step in dysphagia score during the study treatment period or within 4 weeks after end of study treatment. Response of the primary tumour was assessed using endoscopy and PET imaging. Results From October 2014 to May 2018 a total of 29 patients were enrolled. Median age was 68 years. WHO PS (0/1/2); 10/12/7, female/male; 6/23, stage III/IV; 3/26, dysphagia score (0/1/2/3/4); 0/15/6/7/1. In the per-protocol (PP) population of 23 patients (treated with at least 4 fractions of radiotherapy and 2 cycles of chemotherapy) the rate of dysphagia improvement was 91%, the median time to improvement was 2.0 months (95% CI: 1.5, 2.5) and the median duration of improvement was 12.2 months (95% CI: 6.2, 18.2). 5 patients received SEMS during follow-up. In the PP population the endoscopic response rate was 78% with 22% complete responders, the metabolic response rate of the primary tumor was 61% with 30% complete responders. Median overall survival was 16.0 months (95% CI: 9.6, 22.5). In the safety population (28 patients who started treatment) the most frequent grade 3-4 adverse events were neutropenia (32%), infection (25%), pain (14%), esophagitis (11%) and anorexia (11%). Conclusions Palliative short-course radiotherapy followed by chemotherapy is a promising treatment strategy that can provide long-lasting relief of dysphagia in patients with esophageal adenocarcinoma. Clinical trial identification 2014-002362-74. Legal entity responsible for the study Skane University Hospital, Department of Oncology. Funding Lund University Faculty of Medicine and Skane University Hospital Funds and Donations. Disclosure All authors have declared no conflicts of interest.

A. M€akitie , M. Ruuskanen , J. Bentzen, E. Brun, M. Gebre-Medhin, S. Friesland, E. Marsk, L. Hammarstedt-Nordenvall, E. Gille, J. Reizenstein, G. Adell, L. Farnebo , J. Rzepecki, H. Haugen, K. S€ oderstr€ om, B. Zackrisson, S. Bergstr€ om, B. L€ od en, L. Cederblad, G. Laurell , E. Smeland, J. Folkvard Evensen, J. Å. Lund, H. Tøndel, Å. Karlsdottir, J. J ohannsson, J. Johansen, C. A. Kristensen, K. Jensen, L. J. Andersen, P. Koivunen, M. Korpela, L. Voutilainen, T. Wigren, H. Minn, H. Joensuu, J. Overgaard and K. Saarilahti Department of Otorhinolaryngology – Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; Department of Otorhinolaryngology – Head and Neck Surgery, Turku University Hospital, Turku, Finland; Department of Oncology, Herlev University Hospital, Copenhagen, Denmark; Department of Oncology, Skane University Hospital, Lund University, Sweden; Department of Oncology, Karolinska University Hospital, Stockholm, Sweden; Department of Oncology, € Orebro University Hospital, € Orebro, Sweden; Department of Oncology, Link€oping University Hospital, Link€oping, Sweden; Department of Otorhinolaryngology – Head and Neck Surgery, Link€oping University Hospital, Link€oping, Sweden; Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Radiation Sciences, Umeå University, Umeå, Sweden; Department of Oncology, G€avle Hospital, G€avle, Sweden; Department of Oncology, Karlstad Hospital, Karlstad, Sweden; Department of Oncology, Uppsala University Hospital, Uppsala, Sweden; Department of Otorhinolaryngology – Head and Neck Surgery, Uppsala University Hospital, Uppsala, Sweden; Department of Oncology, University Hospital North Norway, Tromsoe, Norway; Department of Oncology, Oslo University Hospital, Oslo, Norway; Department of Oncology, Trondheim University Hospital, Trondheim, Norway; Department of Oncology, Haukeland University Hospital, Bergen, Norway; Department of Oncology, Landspitali University Hospital, Reykjavik, Iceland; Department of Oncology, Odense University Hospital, Odense, Denmark; Department of Oncology, The Finsen Centre, Rigshospitalet, Copenhagen, Denmark; Department of Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Oncology, Aalborg Hospital, Aalborg, Denmark; Department of Otorhinolaryngology – Head and Neck Surgery, Oulu University Hospital, Oulu, Finland; Department of Oncology, Oulu University Hospital, Oulu, Finland; Department of Oncology, Kuopio University Hospital, Kuopio, Finland; Department of Oncology, Tampere University Hospital, Tampere, Finland; Department of Oncology, Turku University Hospital, Turku, Finland; Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark

e18519 Background: In a phase II study for patients with DLBCL aged 18-65 and high-risk disease (aaIPI 2-3), we evaluated end-therapy FDG PET analysis performed at five of the centres and a score using internal standards Methods: Patients were given 6 courses of R-CHOEP14 with G-CSF-support, 1 high dose cytarabine and 1high dose methotrexate. 18FDG PET / CT were scored as negative, indeterminate or positive. Retrospectively, PET intensity was scored as follows (Barrington protocol): 1: no uptake, 2: uptake ≤ mediastinum, 3: uptake > mediastinum, but ≤ liver, 4: moderately- and 5: markedly increased uptake compared to liver. Results: PET scan was performed in 53 patients who all received the planned therapy out of a total of 156 eligible patients from all centres. Median observation time for live patients: 30 months. OS and FFS at 30 months: 91.3% (95% CI 82.7-99.9%) and 88.4% (95% CI 78.0-98.8%), respectively. Nine patients were given consolidating radiotherapy. 18FDG PET / CT were originally considered negative in 39 cases (1 relapse), indeterminate in 6 cases (1 relapse) and positive in 8 cases (2 relapses, 1 secondary cancer). Only 1 of 17 cases had a positive biopsy, 3 were undetermined with fully necrotic cells. Forty-eight of the cases were scored according to the Barrington protocol: 1: 14 cases, 2: 17 cases, 3: 8 cases, 4: 3 cases, 5: 6 cases. For 1-3 scored as negative and 4-5 as positive, there were 2 out of 39 and 2 out of 9 relapses, respectively. Four of the 17 cases with PET score 3 or higher were given radiotherapy, all these patients are in CR1. The original and the Barrington score dichotomising for neg. and pos. cases between 3 and 4 were equally effective in predicting FFS (p < 0.03). Conclusions: Patients with a negative FDG PET / CT have an excellent prognosis while PET positive ones have a low positive predictive value. For a few patients, a relapse may have been avoided by the use of radiotherapy. The Barrington score seems useful for multicenter analysis. Positive lesions should be documented with a biopsy or with a follow-up PET before further chemotherapy is initiated.

Objectives The main purpose of this study was to investigate the feasibility of fine needle aspiration (FNA) of neck node metastases in head and neck squamous cell carcinoma (HNSCC) for evaluating changes in DNA ploidy and S-phase fraction (SPF) during cytotoxic treatment. The results of flow cytometric (FCM) and image cytometric (ICM) analyses of ploidy were compared. Secondly, the association of SPF and ploidy with the metabolic rate (MR) of 2-18F-fluoro-deoxy-2-D-glucose (FDG) in positron emission tomography (PET) was studied. Material and Methods Between 1993 and 1999, 47 patients with locally advanced, non-resectable HNSCC underwent FDG PET prior to (PET1) and early during (PET2) cytotoxic radical treatment. The MR of FDG was calculated separately in primary tumours and lymph node metastases. Immediately after both PET scans, FNA of node metastases was done in 29 patients at PET1 and in 27 at PET2. DNA ploidy was evaluated using FCM and manually using ICM. The SPF was evaluated using FCM only. Results At PET1 it was possible to evaluate the SPF using FCM in only 13/29 aspirations due to a poor cell yield or large amounts of debris. Ploidy was obtained in 23/29 aspirates using FCM and in 27/29 using ICM. A discordance in ploidy findings was apparent, with more non-diploid clones being detected by ICM than FCM. Eradication of non-diploid clones during therapy was observed in six cases using FCM, of which only one was confirmed by ICM. Neither SPF nor ploidy status showed any strong correlation with the MR of FDG. Conclusion FNA of HNSCC metastases demands a high and qualitatively good cell yield for FCM examinations. ICM is laborious but feasible and offers more accurate detection of non-diploid cell clones. Ploidy and SPF were not strongly associated with FDG metabolism.

Positron emission tomography (PET) provides metabolic information of tissues in vivo. The purpose of this study was to assess the value of PET with 2‐[18 F] fluoro‐2‐deoxy‐D‐glucose (FDG) in prediction of therapy outcome (tumor response, survival, and locoregional control) in locally advanced HNSCC.

The prognostic value of histopathological response to preoperative radiotherapy (50 Gy) in radically resected oral carcinomas was studied in 39 consecutive patients. Microvessel density (MVD) was evaluated for relation to radioresponse and outcome. Resected tumour tissue was examined histopathologically and response to radiotherapy was scored according to induced morphological changes. Pretreatment biopsies were stained with antibodies to von Willebrand factor to evaluate MVD in hot-spot regions, in stromal tissue and in tumour epithelial tissue. Histopathological response to radiotherapy was highly prognostic of local failures and survival (p = 0.002), though microscopic surgical radicality was obtained. In good responders to preoperative radiotherapy, the 5-year survival rate was 68% compared with 24% in poor responders. In 12 patients with local recurrence after radical surgery, 11 had poor histopathological radiotherapy responses. In univariate analysis, a high MVD score in tumour epithelium was associated with poor clinical outcome but MVD did not correlate with histopathological radiotherapy response.

The development of alternative treatment regimens in clinical oncology has increased the need for early prediction of cancer therapy outcome. The aim of this study was, early in the treatment phase, to identify patients with advanced head and neck cancer, responding or not responding to initiated therapy. The tumour metabolic rate of glucose (MRgl) examined by 2-18FDG-PET was determined in 17 patients before and after the first weeks of either radiotherapy (16-35 Gy) or one course of combination chemotherapy. Metabolic values uptake values normalized to plasma activity integrals--were correlated to loco-regional outcome, as evaluated 5-6 weeks after completion of treatment. Initial low tumour MRgl (<20 micromol/min/100 g tissue), in primary lesions or regional metastases, predicted a local complete response. When a high initial tumour MRgl was found, the magnitude of the reduction of MRgl in the second PET examination might be an adjunct in predicting local tumour response.

The feasibility of administering metoclopramide (MCA) as a radiosensitizer has been evaluated in 23 patients with a pathological or cytological diagnosis of a squamous cell carcinoma of the lung, clinically evaluated as inoperable. All patients received 40-60 Gy radiotherapy fractionated into 1.8 Gy fractions 5 times per week (Monday-Friday). Two MCA treatment regimens were used: (i) MCA at 2 mg/kg administered by intravenous infusion 1-2 h prior to radiotherapy 3 times per week (Monday, Wednesday, Friday); and (ii) MCA at 1 mg/kg administered by intravenous infusion 1-2 h prior to radiotherapy 5 times per week (Monday-Friday). 11 of the 23 patients treated with radiotherapy and MCA had none to mild pneumonitis or fibrosis and another 8 of the 23 had moderate levels. No patient had their therapy interrupted due to radiation-related side-effects. The MCA-related side-effects were as expected, i.e. 78% of the patients experienced sedation/tiredness and 48% expressed restlessness/anxiety symptoms. Both the total dose and serum levels of MCA were significantly associated to the MCA side-effect profile. Tumour response, duration of tumour response and survival were significantly positively correlated to the total and weekly doses of MCA administered to the patients during their radiotherapy treatment. These favourable phase II data have justified the initiation of a phase II/III randomised multicentred trial being carried out in Europe to evaluate MCA as a radiosensitiser.

Prognostic factors and treatment results were analysed in 72 consecutive patients with primary gastric lymphoma treated between 1970 and 1985. There were 37 patients in stage IE, 17 in IIE, 3 in IIES and 15 in stage IV. Histopathological re-evaluation and classification according to the TNM system were performed. We found that disseminated disease (stage IV), serosal penetration (T3), involvement of adjacent organs (T4) and extensive abdominal lymph node involvement (N3) were poor prognostic factors. Neither histological malignancy grading, nor the appearance of lympho-epithelial lesions were significantly associated with relapse-free survival. Forty-six patients with 'limited localized' disease (stage IE, IIE, N3 excluded) received potentially curative treatment (surgery, radiotherapy, chemotherapy or combinations thereof), of whom 85% remained relapse-free. Thirty-four patients did only get local treatment (surgery and/or radiotherapy) with curative potential, the relapse-free survival rate was 85%. We conclude that primary gastric lymphoma stage IE and IIE (N3 excluded) is often a truly localized disease that can be cured with local therapy.