Epstein-Barr virus and human papillomaviruses as favorable prognostic factors in nasopharyngeal carcinoma : A nationwide study in Finland

Background Nasopharyngeal carcinoma (NPC) is related to Epstein-Barr virus (EBV) in endemic areas; however, the role of viruses in nonendemic countries is unclear. Our nationwide study investigated the prevalence and prognostic significance of EBV and human papillomaviruses (HPVs) in Finnish NPC tumors. Methods We analyzed samples from 150 patients diagnosed between 1990 and 2009. Viral status was determined using EBV and HPV RNA in situ hybridizations, and p16 immunohistochemistry. Patient and treatment characteristics were obtained from patient records. Results In our white patient cohort, 93 of 150 (62%) patients were EBV-positive and 21/150 (14%) patients were HPV-positive with no coinfections. Thirty-six (24%) tumors were negative for both viruses. The 5-year disease-specific survival for patients with EBV-positive, HPV-positive, and EBV/HPV-negative tumors was 69%, 63%, and 39%, respectively. In multivariable-adjusted analysis, overall survival was better among patients with EBV-positive (P = .005) and HPV-positive (P = .03) tumors compared to patients with EBV/HPV-negative tumors. Conclusions In our low-incidence population, EBV and HPV are important prognostic factors for NPC.Peer reviewe

PET-tutkimus syövän hoitovasteen seurannassa ja uusiutumisen toteamisessa

Teema : PET-kuvantaminen.Vertaisarvioitu. English summary.FDG-PET-TT:llä saadaan yhdellä kuvauskerralla tieto syövän aiheuttamista anatomisista ja aineenvaihdunnallisista muutoksista. Suurin osa syövistä on metabolisesti aktiivisia. Metaboliset muutokset edeltävät anatomisia, mikä mahdollistaa varhaisen hoitovastearvion tai taudin uusiutumisen aikaisen toteamisen. Jopa muutaman lääkehoitojakson jälkeen voidaan arvioida hoidon tehoa ja tarvittaessa tehdä muutokset hoitovalintoihin. Taudin uusiutumista epäiltäessä FDG-PET-TT tuo lisätietoa etenkin, jos tavanomaisilla kuvantamismenetelmillä tulokset eivät ole yksiselitteisiä. FDG-PET-TT on sisällytetty useiden syöpien osalta kansainvälisiin suosituksiin.Peer reviewe

PET-tutkimus syövän hoitovasteen seurannassa ja uusiutumisen toteamisessa

FDG-PET-TT:llä saadaan yhdellä kuvauskerralla tieto syövän aiheuttamista anatomisista ja aineenvaihdunnallisista muutoksista. Suurin osa syövistä on metabolisesti aktiivisia. Metaboliset muutokset edeltävät anatomisia, mikä mahdollistaa varhaisen hoitovastearvion tai taudin uusiutumisen aikaisen toteamisen. Jopa muutaman lääkehoitojakson jälkeen voidaan arvioida hoidon tehoa ja tarvittaessa tehdä muutokset hoitovalintoihin. Taudin uusiutumista epäiltäessä FDG-PET-TT tuo lisätietoa etenkin, jos tavanomaisilla kuvantamismenetelmillä tulokset eivät ole yksiselitteisiä. FDG-PET-TT on sisällytetty useiden syöpien osalta kansainvälisiin suosituksiin

Recurrence of head and neck squamous cell carcinoma in relation to high-risk treatment volume

Background: Locoregional recurrence remains a major cause of failure in head and neck squamous cell carcinoma (HNSCC). Human papilloma virus (HPV)-associated HNSCCs generally have a good prognosis but may recur even after standard photon radiotherapy (RT). Another incentive in observing patterns of recurrence is increased use of highly conformal techniques such as proton therapy. We therefore studied geographic distribution of recurrent tumors in relation to the high-risk treatment volume in a cohort of patients with HNSCC receiving combined modality therapy.Methods: Medical records of 508 patients diagnosed with HNSCC in 2010-2015 were reviewed. We identified a subgroup that had local and/or regional recurrence at hybrid positron emission tomography (PET)/computed tomography (CT) and/or magnetic resonance imaging (MRI). We adapted p16 as a surrogate marker for HPV-positivity and only patients with known p16 status were eligible for a detailed analysis where recurrent tumor was copied on the planning CT and the dose received by the recurrent tumor volume was determined using dose-volume histograms.Results: Twenty-five patients who had received either cisplatin (n = 23) or cetuximab-enhanced (n = 2) RT were identified. 31 locoregional recurrent tumors were detected among 18 p16 negative and 7 p16 positive patients. Of recurrent tumors 14 (45%) were classified as in-field, 5 (16%) as marginal miss, and 12 (39%) as true miss. p16 positive patients had 4 in-field, 2 marginal, and 1 true miss. By contrast, p16 negative patients had 10 in-field, 3 marginal, and 11 true miss recurrences.Conclusions: Both p16 positive and negative HNSCC recur in high-risk treatment volume despite the common view of high radiosensitivity of the former. Biomarkers predicting radioresistance should be characterized in p16 positive tumors before widely embarking on de-escalated CRT protocols. Another concern is how to decrease the number of true or marginal misses in p16 negative cases despite multimodality imaging-based target delineation.</p

Onko nenänielusta löytynyt parillinen sylkirauhanen - päivittyykö ihmisen makroskooppinen anatomia?

Sylkirauhasilla on keskeinen merkitys fysiologisissa toiminnoissa, jotka liittyvät nielemiseen, purentaan, puheen tuottamiseen ja ruuansulatukseen. Ihmisen suurista sylkirauhasista korvasylkirauhanen on kuvattu ajanlaskumme alun aikoihin. Nykyään kolmen suuren parillisen ja lukuisten pienten sylkirauhasten tehtävät, rakenteet ja sijainti tiedetään täsmällisesti. Pieniä sylkirauhasia tai syljentuotantoa nenänielussa ei kuitenkaan yleensä kuvata, vaikka alueelta lähtöisin olevat sylkirauhaskasvaimet tunnetaan. Hollantilainen tutkimusryhmä havaitsi nenänielussa korvatorven aukon läheisyydessä suurena sylkirauhasena pitämänsä parillisen rakenteen potilailla, joita oli molekyylikuvannettu urologisen syövän takia. Nenänielun sylkirauhasiin viittaavat löydökset havaittiin sylkirauhaskudokseen aktiivisesti hakeutuvalla radioaktiivisella lääkeaineella positroniemissiotomografiassa ({PET}). Löydöstä selvitettiin makroskooppisesti ja mikroskooppisesti vainajatutkimuksessa. Siinä ilmeni, että kuvatulla rauhasella on rakenteellisia yhtäläisyyksiä kielenalus- ja pieniin sylkirauhasiin

Ablaatiohoidot - sädehoidon jälkeen paikallisesti uusiutuneen eturauhassyövän hoitovaihtoehto

Uusien kuvantamismenetelmien myötä eturauhassyövän paikantaminen ja riskiluokitus ovat tarkentuneet. Magneettikuvauksella pystytään usein luotettavasti visualisoimaan ennusteen kannalta merkittävin syöpäkasvain. Modernit kuvantamisohjatut ablatiiviset eli kudosta tuhoavat hoitomenetelmät kohdistuvat hoidettavaan elimeen niin, että pyritään välttämään ympäröivien kudosten vaurioita. Koko rauhasen käsittäviin ablaatiohoitoihin vaikuttaa liittyvän suotuisampi haittavaikutusprofiili kuin leikkaukseen ja sädehoitoon. Primaarikasvaimeen kohdistuvassa hoidossa eli rauhasen osan hoitostrategiassa (fokaaliterapia) elämänlaadulliset haitat näyttävät edelleen vähentyvän ilman, että tehossa olisi merkittävästi eroa koko rauhasen hoitoihin verrattuna. Tieteellinen näyttö koko rauhasen ja rauhasen osan ablaatiohoitojen pitkäaikaistehosta paikallisen eturauhassyövän hoidossa on toistaiseksi niukkaa, ja ablaatio- ja standardihoitoja vertailevat tutkimukset puuttuvat. Sen sijaan sädehoidon jälkeen paikallisesti uusiutuneen eturauhassyövän ablatiiviset hoitomenetelmät tuovat uuden tehokkaan hoidon tähän vaativaan kliiniseen ongelmaan

Evaluation of prognostic biomarkers in a population-validated Finnish HNSCC patient cohort

Introduction Prognostic biomarkers and novel therapeutic approaches have been slow to emerge in the treatment of head and neck squamous cell carcinoma (HNSCC). In this study, an HNSCC patient cohort is created and performance of putative prognostic biomarkers investigated in a population-validated setting. The overall goal is to develop a novel way to combine biomarker analyses with population-level clinical data on HNSCC patients and thus to improve the carryover of biomarkers into clinical practice. Materials and methods To avoid selection biases in retrospective study design, all HNSCC patients were identified and corresponding clinical data were collected from the Southwest Finland geographical area. A particular emphasis was laid on avoiding potential biases in sample selection for immunohistochemical staining analyses. Staining results were evaluated for potential prognostic resolution. Results After comprehensive evaluation, the patient cohort was found to be representative of the background population in terms of clinical characteristics such as patient age and TNM stage distribution. A negligible drop-out of 1.3% (6/476) was observed during the first follow-up year. By immunohistochemical analysis, the role of previously implicated HNSCC biomarkers (p53, EGFR, p16, CIP2A, Oct4, MET, and NDFIP1) was investigated.Discussion ​​​​​​​Our exceptionally representative patient material supports the use of population validation to improve the applicability of results to real-life situations. The failure of the putative prognostic biomarkers emphasizes the need for controlling bias in retrospective studies, especially in the heterogenous tumor environment of HNSCC. The resolution of simple prognostic examination is unlikely to be sufficient to identify biomarkers for clinical practice of HNSCC.</p

Somatostatin Receptors and Chemokine Receptor CXCR4 in Lymphomas: A Histopathological Review of Six Lymphoma Subtypes

Background Somatostatin receptors (SSTR) and chemokine receptor CXCR4 are expressed in lymphomas, while the abundance is known to be heterogeneous in different subtypes of lymphomas. Targeting tumor cells expressing these receptors might add to therapeutic opportunities while radiolabeled ligands for both imaging and therapy have been developed. The aim of this study was to establish SSTR subtype 2, 3 and 5 and also CXCR4 status immunohistochemically in six different lymphoma subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), mucosa-associated marginal B-cell lymphoma (MALT), Hodgkin lymphoma (HL) and peripheral T-cell lymphoma (PTCL). Material and Methods This study included a total of 103 lymphoma patients (24 DLBCL, 22 FL, 18 HL, 9 MALT, 20 MCL and 10 PTCL) diagnosed in the Southwest hospital district of Finland during 2010-2019. SSTR 2, 3 and 5 and CXCR4 expression was analyzed immunohistochemically (IHC) in lymphoma samples obtained from local archival Biobank tissue repository. Immunopositivity of each receptor was scored on a four-point scale accounting for staining intensity and proportion of positively stained tumor cells. Results Of different SSTR subtypes SSTR2 immunopositivity was most common and seen predominantly at the cell membrane of the malignant cells in 46-56% of DLBCL, HL and FL. CXCR4 co-expression was frequently present in these cases. SSTR3 and SSTR5 IHC were negative in DLBCL and FL but in HL SSTR expression was more heterogenous and SSTR3 and SSTR5 positivity was found in cytoplasm in 35% and 25% of cases. 2/4 blastoid MCL variants and one pleomorphic MCL variant had positive CXCR4 IHC whilst all other MCL cases (85%) were negative for all receptors. 30% (n=3) of the PTCL patients had positive SSTR5 IHC and CXCR4. MALT lymphomas were negative for all receptors. Conclusion SSTR2 and CXCR4 are found in DLBCL, FL and HL and co-expression of these receptors is common. Although in general expression of SSTRs and CXCR4 is heterogenous and very low in some subtypes such as MCL and MALT there are also patients with abundant expression. The latter are candidates for trials studying SSTR2 and/or CXCR4 based treatments in the future.</p

Epstein-Barr virus and human papillomaviruses as favorable prognostic factors in nasopharyngeal carcinoma: A nationwide study in Finland

Background: Nasopharyngeal carcinoma (NPC) is related to Epstein‐Barr virus (EBV) in endemic areas; however, the role of viruses in nonendemic countries is unclear. Our nationwide study investigated the prevalence and prognostic significance of EBV and human papillomaviruses (HPVs) in Finnish NPC tumors.Methods: We analyzed samples from 150 patients diagnosed between 1990 and 2009. Viral status was determined using EBV and HPV RNA in situ hybridizations, and p16 immunohistochemistry. Patient and treatment characteristics were obtained from patient records.Results: In our white patient cohort, 93 of 150 (62%) patients were EBV‐positive and 21/150 (14%) patients were HPV‐positive with no coinfections. Thirty‐six (24%) tumors were negative for both viruses. The 5‐year disease‐specific survival for patients with EBV‐positive, HPV‐positive, and EBV/HPV‐negative tumors was 69%, 63%, and 39%, respectively. In multivariable‐adjusted analysis, overall survival was better among patients with EBV‐positive (P = .005) and HPV‐positive (P = .03) tumors compared to patients with EBV/HPV‐negative tumors.Conclusions: In our low‐incidence population, EBV and HPV are important prognostic factors for NPC.</p