Supplementary Data containing the statistical analysis plan, Supplemental Figures 1-6 and Supplemental Tables 1 and 2

Abstract Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers. Significance: This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer. See related commentary by Letai, p. 290. This article is highlighted in the In This Issue feature, p. 275

Abstract Objectives: Changes in the integrin expression pattern have been associated with the malignant transformation of melanocytes suggesting that integrins may be potential biomarkers as well as molecular targets for individualized therapy. Since there is a lack of comprehensive qualitative and quantitative expression data, we characterized the integrin expression profile in normal and malignant human cells of the melanocytic lineage. Methods: Seven melanoma cell lines as well as normal human melanocytes were investigated in western blots including recombinant integrin subunits for quantification. Results: Expression patterns were heterogeneous. In melanoma, overexpression of α4, α6, αL, β5, and β6 was found. Integrins α7, α9, and β4 were overexpressed in a subset of the melanoma cell lines. Overexpression was defined as a lack of expression in melanocytes but expression in more than half (4) of the melanoma lines. 1.9 to 6.7 × 106 integrin molecules (about 0.3% of total cellular protein) were estimated to be expressed per cell. Expression of integrin αE at the protein level was found in melanoma and melanocytes, to the best of our knowledge, for the first time. Integrins αM and β2 were not detected. Conclusion: Integrins α4, α6, αL, β5, and β6 appear to be overexpressed in melanoma cells. These subunits may serve as biomarkers and/or therapeutic targets.

Background: Aggressive hematological malignancies in relapsed/refractory setting bear a dire prognosis with low cure rates and short survival. Matching these patients to therapies is challenged by complexity due to spatial and temporal tumor evolution and incomplete understanding of genotype to phenotype correlations. Direct functional testing could address these impediments. The EXALT trial is an interventional, one-arm study designed to assess the clinical value of next generation functional drug screening (ngFDS). An interim analysis on 17 patients suggested a clinical benefit (Snijder et al., Lancet Hematol. 2017). Methods: We applied image-based ngFDS to quantify differential ex-vivo sensitivity of primary patient tumor cells to respective non-tumor cells towards 136 small molecule drugs, including EMA approved for any indication or experimental. We screened bone marrow, peripheral blood or lymph node material from 143 patients who suffered from late stage aggressive hematological malignancies (acute leukemias, aggressive B- and T-cell lymphomas) , discussed the results in a multidisciplinary tumor board and recommended treatments to physicians (A). The primary endpoint of this study was the percentage of patients reaching a PFS-ratio (PFS(ngFDS treatment)/PFS(previous treatment)) of ≥1.3 with an H0 hypothesis < 15% patients. The secondary endpoint was overall response rate (ORR) defined as proportion of patients reaching complete remission (CR) or partial remission (PR). Additionally, we performed a post hoc analysis to evaluate the matching of ngFDS to drugs used in actual treatment (matching score of received treatment). Results: 56 (39%) patients were evaluable and treated according to ngFDS based recommendations. With 30 of 56 (54%) ngFDS guided patients experiencing a PFS ratio of ≥1.3, the primary study endpoint was reached. 11 patients (37%) had ongoing response at censoring date (B). The median follow-up was 718 days. The median number of days from sampling to treatment was 21 (range 4-77). The ngFDS treatment regimens consisted of a median of 2 drugs (range: 1-6). ORR was 55% for all evaluable ngFDS treated patients, 60% for the lymphoid subgroup and 41% for the myeloid subgroup. Patients on ngFDS guided treatment with performance status ECOG ≤ 1 had a median PFS of 207 days compared to a median PFS of 29 days for patients with higher ECOG (p < 0.001, C). 24 of 39 (62%) patients with ECOG ≤ 1 had a PFS ratio of ≥1.3 (D). In disease specific subgroup analysis median PFS of T-cell lymphoma patients was 235 days versus 60 days for B-cell lymphoma patients (p = 0.018, E). Age (≤60 vs. >60), sex, lineage (myeloid vs. lymphoid), number of previous treatment lines (≤2 vs. >2), and clinical presentation (leukemia vs. lymphoma) did not have an impact on PFS of ngFDS guided treatment. Post hoc analysis including additional 17 non-ngFDS treated patients demonstrated that only patients receiving treatment with a positive ngFDS matching score demonstrated clinical benefit (HR: 0.53, p=0.005; vs. HR: 1.4, p=0.4). ngFDS matched treatments resulted in higher PFS for patients with tumor samples that had a cancer cell fraction of 10-50% in comparison to patients with samples of lower or higher cancer cell percentage (HR:0.35, p=0.01). Conclusion: ngFDS could be integrated in the routine clinical work flow. ngFDS guided treatments led to high rates of PFS prolongation compared to previous treatments of individual patients. ngFDS guided treatment is feasible and effective in patients with late stage aggressive hematological malignancies. These results prompted a prospective randomized trial comparing treatment guidance based on ngFDS or comprehensive genomic profiling or physician's choice (EXALT-2 trial, NCT04470947). Figure Disclosures Vladimer: Allcyte GmbH: Current Employment, Current equity holder in private company, Other: Founder. Jaeger:Karyopharm: Honoraria; Amgen: Honoraria; Gilead: Honoraria, Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; True North: Honoraria, Research Funding; Miltenyi: Consultancy, Honoraria; CDR Life AG: Consultancy, Research Funding; F. Hoffmann-La Roche: Honoraria, Research Funding; Infinity: Honoraria; Takeda: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; AbbVie: Honoraria. Krall:Allcyte GmbH: Current Employment, Current equity holder in private company, Other: Founder. Valent:Allcyte GmbH: Research Funding; Cellgene: Honoraria, Research Funding; Pfizer: Honoraria. Wolf:Celgene: Honoraria, Research Funding. Zielinski:MSD: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Imugene: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Merrimack: Consultancy, Honoraria, Speakers Bureau; Merck KGaA: Consultancy, Honoraria, Speakers Bureau; Fibrogen: Consultancy, Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Tesaro: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Servier: Consultancy, Honoraria, Speakers Bureau; Shire: Consultancy, Honoraria, Speakers Bureau; Eli Lilly: Consultancy, Honoraria, Speakers Bureau; Athenex: Consultancy, Honoraria, Speakers Bureau. Superti-Furga:Allcyte GmbH: Current equity holder in private company, Other: Founder. Snijder:Allcyte GmbH: Current equity holder in private company, Other: Founder. Staber:Roche: Consultancy, Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria; Celgene/ BMS: Consultancy, Honoraria; msd: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria.

OBJECTIVES: Osteosarcoma of the jaw (OSAJ) is fundamentally different in clinical practice from its peripheral counterparts. Studies are difficult to conduct due to low incidence rates. The primary aim of this study was to provide for the first time a comprehensive retrospective analysis of the treatment concepts and outcome data of OSAJ patients treated at the University Hospital Vienna and to compare these with two recently published studies on OSAJ. The clinical study was accompanied by a biomarker study investigating the prognostic relevance of melanoma-associated antigen-A (MAGE-A) in OSAJ specimens. METHOD: Eighteen patients were included, and their outcomes were compared to published data. Immunohistochemistry was performed with mouse monoclonal antibodies against MAGE-A. Survival rates were estimated by the Kaplan-Meyer method. The log-rank test was used to analyze potential prognostic parameters. Fisher’s exact test was performed to define the significant differences between the survival rates of the current study and the DOESAK registry. RESULTS: Disease-specific survival was 93.8% after five and 56.3% after ten years. The development of metastases (p=0.033) or relapse (p=0.037) was associated with worsened outcomes in our group as well as in the comparative group. Despite the different treatment concepts of the study groups, survival rates were comparable. MAGE-A failed to show prognostic relevance for OSAJ patients. CONCLUSIONS: Uncertainties about the optimal treatment strategies of OSAJ patients will currently remain. Thus, prospective studies of OSAJ are needed but are only feasible in a multicenter study setting, conducted over a prolonged time period.

Purpose The advanced lung cancer inflammation index (ALI) is a useful tool for prediction of outcome in several malignancies. However, to date, its significance in head and neck cancer patients has not been evaluated. Methods We retrospectively analyzed data from 93 patients who were diagnosed with head and neck squamous cell carcinoma (HNSCC) and treated with surgical resection and postoperative radiotherapy between 2002 and 2012. The aim of this study was to investigate whether the preoperative ALI is a prognostic indicator for disease-free survival and overall survival in HNSCC patients. Results A low ALI was significantly associated with a worse 5-year disease-free survival (47.0 vs. 83.5%, p < 0.001), and overall survival (44.4 vs. 73.6%, p = 0.008). Multivariate analysis showed that low ALI was independently associated with disease-free survival (p < 0.001) and overall survival (p = 0.02). Conclusion The ALI could serve as an easily available prognostic indicator for disease-free and overall survival prediction in patients with HNSCC.

The authors regret that the order of authors in the above mentioned abstract, were published in an incorrect order. The correct listing is shown above. PO-0994: Integrin antagonistic drugs reveal different effectiveness in 2D monolayer vs. 3D spheroid cultureRadiotherapy and OncologyVol. 123Preview Full-Text PDF Open Access

Objective : Results from publications evaluating discrepancies between clinical staging data in relation to pathological findings demonstrate that a significant number of head and neck squamous cell carcinoma (HNSCC) patients are not correctly staged. The aim of this retrospective study was to analyze potential discrepancies of radiological assessment versus pathological data of regional lymph node involvement and to compare the results with data published in the literature. Study design: In a retrospective analysis we focused on patients with HNSCC routinely treated by surgery plus PORT between 2002 and 2012. Setting: For inclusion, complete pre-operative clinical staging information with lymph node status and patho-histological information on involved lymph node regions as well as survival outcome data were mandatory. Subjects and Methods: We included 87 patients (UICC stage III-IV 90.8%) for which the aforementioned criteria obtained by CT or MRI were available.Overall survival rates were estimated by the Kaplan–Meier method. The Pearson correlation coefficient and Spearman`s rank correlation coefficient (non-linear relationship) was calculated. Results: Discrepancies at the level of overall tumor stage assessment were noticed in 27.5% of all cases. Thereof, 5.7% were assigned to patho-histological up-staging or down-staging of the primary tumor. At the lymph node level, 11.5 % of the patients were downstaged, and 10.3% were upstaged. Conclusion: Our results show that in approximately one-fifth (21.8%) of the patients, lymph node assessment by CT or MRI differs from the pathologic staging, an outcome that corresponds well with those published by several other groups in this field.

OBJECTIVES: This retrospective study performed a comprehensive analysis of the usage of intra-arterial chemotherapy (iaCh) for locally recurrent UICC stage IV oral squamous cell carcinoma (OSCC) over two decades at the Department of Cranio-Maxillofacial and Oral Surgery at the University Hospital Vienna to assess the utility of its future use.METHODS: Between 1994 and 2014, iaCh was indicated in 48 OSCC cases.In these, the two most frequent iaCh schemes, cisplatin/5-fluorouracil (Cis/5-FU) and methotrexate/bleomycin (MTX/Bleo), were chosen for further analysis.The effect on survival of two distinct intra-arterial protocols and their covariates were analyzed with the Kaplan-Meier method as well as univariate and multivariate Cox proportional hazard regression models.RESULTS: The mean follow-up period was 29.91 months.The two intra-arterial chemotherapy groups did not differ significantly in sample size, demographic data or therapeutic covariates.The Cis/5-FU iaCh regimen was associated with significantly better overall survival (median OS 2.6 years vs. 1.3 years; p=0.002) and had a beneficial effect on survival (HR=3.62,p=0.015).Side effects occurred at a frequency similar to that described in the literature for intravenous chemotherapy (ivCh).CONCLUSIONS: These results suggest a preference for administering Cis/5-FU for iaCh.Nevertheless, due to economic considerations in healthcare expenditures, there is no future for iaCh in the treatment of head and neck carcinomas because ivCh is known to be equivalent.

OBJECTIVES:Survival after preoperative radiotherapy in locally advanced head and neck squamous cell cancer is associated with pathological response. The prognostic importance of p16 expression in these patients has not been established yet.MATERIALS AND METHODS:Ninety-seven patients with oral squamous cell carcinoma, treated preoperatively with radiotherapy in combination with chemotherapy or cetuximab, were included in this retrospective analysis. Survival rates were estimated by the Kaplan-Meyer method. Pathological response was evaluated by histological analysis and p16 expression by immunohistochemistry.RESULTS:Overall survival after 2 years was 66% for the entire group, 92% in the p16-positive and 62% in the p16-negative group, respectively. 12.4% of the tumours were p16-positive. P16 expression (HR 6.98, p = .05) and regression grade (HR 2.94, p = .001) had a statistically significant impact on prognosis. 83.3% of p16-expressing tumours were pathological responders. All p16-positive patients with pathological response were alive within the observation period.CONCLUSION:P16 expression is associated with prognosis in preoperatively irradiated OSCC patients. The association between p16 positivity, regression grade and improved survival provides a rationale for de-intensification strategies in patients with head and neck cancer who respond well to neoadjuvant therapy, a concept that is being tested in prospective clinical trials.

AIMS:Expression profiles and clinical impact of programmed cell death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) expressing tumour infiltrating lymphocytes (TILs) in head and neck squamous cell carcinoma (HNSCC) are not elucidated fully. This study evaluates expression patterns in primary HNSCC and related lymph node metastasis and the impact on patients' clinical outcome.METHODS AND RESULTS:Immunohistochemical staining patterns of PD-L1 and PD-1 were evaluated in 129 specimens of primary HNSCC and 77 lymph node metastases. Results were correlated with patients' clinical data. PD-L1 expression was observed in 36% of primary carcinoma and 33% of lymph node metastasis, and correlates significantly with decreased overall survival (OS) (P = 0.01) and disease-free survival (DFS) (P = 0.001) in oral cavity squamous cell carcinoma patients. PD-L1 expression was associated with presence of lymph node metastasis (P = 0.0223). Infiltration of PD-1-expressing lymphocytes correlates significantly with favourable OS (P = 0.001) and DFS (P = 0.001) in oropharyngeal cancer and hypopharyngeal cancer patients OS (P = 0.007) and DFS (P = 0.001). Presence of PD-1 TILs also correlates significantly with better OS (P = 0.005) and DFS (P = 0) in the human papilloma virus (HPV)-negative cohort. Cox regression multivariate analysis revealed PD-1 TIL expression as an independent prognostic marker for OS (P = 0.004) and DFS (P = 0.001) and T stage was validated as negative prognostic marker for OS (P = 0.011). PD-1-expressing lymphocytes (P = 0.0412) and PD-L1 expression (P = 0.0022) patterns correlate significantly in primary cancers and matched lymph node metastases.CONCLUSIONS:Our results characterise the expression profiles of PD-1 axis proteins in HNSCC which might serve as possible clinical prognostic markers.

PurposeTherapy response to neoadjuvant radiochemotherapy (nRCT) of locally advanced rectal cancer varies widely so that markers predicting response are urgently needed. Fibroblast growth factor (FGF) and FGF receptor (FGFR) signaling is involved in pro-survival signaling and thereby may result in radiation resistance.MethodsIn a cohort of 43 rectal cancer patients, who received nRCT, we analyzed protein levels of FGF 8 and its downstream target Survivin by immunohistochemistry to assess their impact on nRCT response. In vitro resistance models were created by exposing colorectal cancer cell lines to fractionated irradiation and selecting long-term survivors.ResultsOur findings revealed significantly higher FGF8 and Survivin staining scores in pre-treatment biopsies as well as in surgical specimens of non-responsive compared to responsive patients. Functional studies demonstrated dose-dependent induction of FGF8 mRNA expression in mismatch-incompetent DLD1 cells already after one dose of irradiation. Surviving clones after one or two series of radiation were more resistant to an additional radiation fraction than non-irradiated controls and showed a significant increase in expression of the FGF8 receptor FGFR3 and of Survivin on both the RNA and the protein levels.ConclusionThe results of this study suggest that FGF8 and Survivin contribute to radiation resistance in rectal cancer and may serve as markers to select patients who may not benefit from neoadjuvant radiotherapy.

BACKGROUND:Results from publications evaluating discrepancies between clinical staging data in relation to pathological findings demonstrate that a significant number of head and neck squamous cell carcinoma (HNSCC) patients are not correctly staged. The aim of this retrospective study was to analyze potential discrepancies of radiological assessment versus pathological data of regional lymph node involvement and to compare the results with data published in the literature. PATIENTS AND METHODS:In a retrospective analysis we focused on patients with HNSCC routinely treated by surgery plus postoperative radiotherapy between 2002 and 2012. For inclusion, complete pre-operative clinical staging information with lymph node status and patho-histological information on involved lymph node regions as well as survival outcome data were mandatory. We included 87 patients (UICC stage III-IV 90.8%) for which the aforementioned data obtained by CT or MRI were available. Overall survival rates were estimated by the Kaplan-Meier method. The Pearson correlation coefficient and Spearman's rank correlation coefficient (non-linear relationship) was calculated. RESULTS:Discrepancies at the level of overall tumour stage assessment were noticed in 27.5% of all cases. Thereof, 5.7% were assigned to patho-histological up-staging or down-staging of the primary tumour. At the lymph node level, 11.5% of the patients were downstaged, and 10.3% were upstaged. CONCLUSIONS:The study showed that in approximately one-fifth (21.8%) of the patients, lymph node assessment by CT or MRI differs from the pathologic staging, an outcome that corresponds well with those published by several other groups in this field.

A comprehensive evaluation of the current national and regional radiotherapy capacity in Austria with an estimation of demands for 2020 and 2030 was performed by the Austrian Society for Radiation Oncology, Radiobiology and Medical Radiophysics (ÖGRO).

In 2008 the Ludwig Boltzmann Cluster Oncology (LBC ONC) was established on the basis of two previous Ludwig Boltzmann Institutes working in the field of hematology and cancer research. The general aim of the LBC ONC is to improve treatment of hematopoietic neoplasms by eradicating cancer-initiating and disease-propagating cells, also known as leukemic stem cells (LSC) in the context of leukemia. In a first phase, the LBC ONC characterized the phenotype and molecular aberration profiles of LSC in various malignancies. The LSC phenotypes were established in acute and chronic myeloid leukemia, in acute lymphoblastic leukemia and in chronic lymphocytic leukemia. In addition, the concept of preleukemic (premalignant) neoplastic stem cells (pre-L-NSC) was coined by the LBC ONC and was tested in myelodysplastic syndromes and myeloproliferative neoplasms. Phenotypic characterization of LSC provided a solid basis for their purification and for the characterization of specific target expression profiles. In a second phase, molecular markers and targets were validated. This second phase is ongoing and should result in the development of new diagnostics parameters and novel, more effective, LSC-eradicating, treatment strategies; however, many issues still remain to be solved, such as sub-clonal evolution, LSC niche interactions, immunologic control of LSC, and LSC resistance. In the forthcoming years, the LBC ONC will concentrate on developing LSC-eradicating strategies, with special focus on LSC resistance, precision medicine and translation of LSC-eradicating concepts into clinical application.

After publishing promising results for the treatment of patients with human papilloma virus (HPV) positive oropharyngeal cancer with radiochemotherapy regarding 2‑year survival, we present an update of the disease-specific and disease-free survival after 5 years.

Clinical OtolaryngologyVolume 43, Issue 2 p. 742-745 CORRESPONDENCE: OUR EXPERIENCE The effect of adjuvant radiotherapy on radial forearm free flap volume after soft palate reconstruction in 13 patients G. Haymerle, G. Haymerle orcid.org/0000-0002-2464-6856 Department of Otolaryngology Head and Neck Surgery, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorE. Enzenhofer, E. Enzenhofer orcid.org/0000-0002-0502-4250 Department of Otolaryngology Head and Neck Surgery, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorW. Lechner, W. Lechner Department of Radiation Oncology, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorM. Stock, M. Stock Department of Radiation Oncology, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorA. Schratter-Sehn, A. Schratter-Sehn Institute for Radiooncology, Kaiser-Franz-Josef-Hospital, Vienna, AustriaSearch for more papers by this authorE. Vyskocil, E. Vyskocil orcid.org/0000-0003-1458-9824 Department of Otolaryngology Head and Neck Surgery, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorB. Bachtiary, B. Bachtiary Rinecker Proton Therapy Center, Munich, GermanySearch for more papers by this authorE. Selzer, E. Selzer Department of Radiation Oncology, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorB.M. Erovic, Corresponding Author B.M. Erovic boban.erovic@meduniwien.ac.at Department of Otolaryngology Head and Neck Surgery, Medical University of Vienna, Vienna, Austria Correspondence B.M. Erovic, Department of Otolaryngology Head and Neck Surgery, Medical University of Vienna, Vienna, Austria. Email: boban.erovic@meduniwien.ac.atSearch for more papers by this author G. Haymerle, G. Haymerle orcid.org/0000-0002-2464-6856 Department of Otolaryngology Head and Neck Surgery, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorE. Enzenhofer, E. Enzenhofer orcid.org/0000-0002-0502-4250 Department of Otolaryngology Head and Neck Surgery, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorW. Lechner, W. Lechner Department of Radiation Oncology, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorM. Stock, M. Stock Department of Radiation Oncology, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorA. Schratter-Sehn, A. Schratter-Sehn Institute for Radiooncology, Kaiser-Franz-Josef-Hospital, Vienna, AustriaSearch for more papers by this authorE. Vyskocil, E. Vyskocil orcid.org/0000-0003-1458-9824 Department of Otolaryngology Head and Neck Surgery, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorB. Bachtiary, B. Bachtiary Rinecker Proton Therapy Center, Munich, GermanySearch for more papers by this authorE. Selzer, E. Selzer Department of Radiation Oncology, Medical University of Vienna, Vienna, AustriaSearch for more papers by this authorB.M. Erovic, Corresponding Author B.M. Erovic boban.erovic@meduniwien.ac.at Department of Otolaryngology Head and Neck Surgery, Medical University of Vienna, Vienna, Austria Correspondence B.M. Erovic, Department of Otolaryngology Head and Neck Surgery, Medical University of Vienna, Vienna, Austria. Email: boban.erovic@meduniwien.ac.atSearch for more papers by this author First published: 01 December 2017 https://doi.org/10.1111/coa.13042Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume43, Issue2April 2018Pages 742-745 RelatedInformation

Objectives: Preoperative radiotherapy followed by surgery is an effective treatment option for solid tumors including locally advanced squamous cell cancers of the head and neck region. Histopathologic response to radiation has been shown to be associated with survival. However, the relative prognostic importance of regression grade compared to other potential biomarkers has not been established yet.Materials and methods: One-hundred forty-four oral squamous cell carcinoma patients with stage III/IV disease were included in this analysis. Patients had received preoperative radiotherapy (RT) up to 50 Gy total dose in combination with 5-Fluorouracil (5-FU)/Mitomycin C (MMC) or with Cetuximab, followed by radical surgery six to eight weeks later. Outcome data were obtained from the patient's files. Survival rates were estimated by the Kaplan-Meyer method. Cox-proportional-hazard regression models were used to compare the risk of death among patients stratified according to risk factors.Results: Five-year overall survival (OS) was 58% in the presented collective. Regression grade 4 (HR 3.58; p < 0.001) was most significantly associated with reduced survival, followed by elevated neutrophils (HR 2.22; p = 0.01), the combination of elevated neutrophils plus elevated CRP (HR 2.40; p = 0.01), and elevated CRP alone (HR 1.74; p = 0.03). In a multivariate analysis, the regression grade remained the most influential predictor of outcome (HR 4.23; p < 0.001).Conclusion: In a comparative analysis, tumor response to pre-operative radiotherapy remains the strongest prognostic factor for treatment outcome, while elevated CRP, as well as neutrophils, were also found to be of significance. (C) 2016 Elsevier Ltd. All rights reserved.