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Background: Presence of immune cell infiltrates in tumor may influence outcome of patients with node negative breast cancer (BC) (Schmidt et al 2008). High expression of CXCL13 (B lymphocyte chemoattractant chemokine) was strongly associated with favorable survival in one recent series consisting of BC patients treated with adjuvant chemotherapy (Razis et al. 2012). Here we examined the clinical significance of breast tumor CXCL13 mRNA levels within the context of the FinHer trial, where patients were randomly assigned to receive 3 cycles of either docetaxel or vinorelbine followed by 3 cycles of FEC. Patients with HER2-positive BC had a second randomization for trastuzumab vs. control. Since intratumoral B cells are of particular importance for obtaining response to chemotherapy in triple negative BC (TNBC) and of limited value in luminal BC (Schmidt et al. 2012), and trastuzumab treatment is a confounding factor in HER2+ BC, we focused on TNBC. Methods: RNA was extracted from FFPE tumor tissue of 917 (90.8%) out of the 1010 patients who participated in the FinHer trial. CXCL13 mRNA expression was measured using RTqPCR. The molecular subtypes (luminal, HER2-enriched and triple-negative) were determined using IHC and central chromogenic in situ hybridization (CISH) testing. Prognostic significance of factors was assessed using univariate and multivariate analyses. Distant disease-free survival (DDFS) between groups was compared using the log-rank test. Results: Tumor CXCL13 mRNA expression showed a bimodal distribution and correlated negatively with tumor ESR1 mRNA levels (r = -0,31; p < 0.0001). 146 (15.9%) out of the 917cancers were classified as TNBC. High tumor CXCL13 mRNA levels above the median were strongly associated with favorable 5-yr DDFS in TNBC compared to low levels (85% vs. 60%; p < 0.0001). The prognostic value of tumor CXCL13 was evident in the subset of women with TNBC treated with vinorelbine (5-year DDFS 90% vs. 40%; p < 0.0001), whereas no significant association was found in the docetaxel arm (5-year DDFS 80% vs. 80%; p = 0.76). When only patients with TNBC and low CXCL13 mRNA levels were assessed, patients treated with docetaxel had better DDFS compared to those treated with vinorelbine (5-year DDFS 80% versus 40%; p < 0.0064). There was no DDFS difference between treatment arms in patients exhibiting high CXCL13 expression. Conclusions: Tumor CXCL13 mRNA expression is a favorable prognostic factor for women with TNBC treated with adjuvant chemotherapy providing further evidence that the host immune response may influence outcome of patients with early BC. The clinical significance of the host B cell immune response may vary substantially pending on the type of chemotherapy administered. [ABSTRACT FROM AUTHOR]

Background: Biological heterogeneity of large B cell lymphomas (LBCLs) is poorly captured by current prognostic tools, hampering optimal treatment decisions., Methods: We dissected the levels of 1,463 serum proteins in a uniformly treated trial cohort of 109 patients with high-risk primary LBCL (ClinicalTrials.gov: NCT01325194) and correlated the profiles with molecular data from tumor tissue and circulating tumor DNA (ctDNA) together with clinical data., Findings: We discovered clinically and biologically relevant associations beyond established clinical estimates and ctDNA. We identified an inflamed serum protein profile, which reflected host response to lymphoma, associated with inflamed and exhausted tumor microenvironment features and high ctDNA burden, and translated to poor outcome. We composed an inflammation score based on the identified inflammatory proteins and used the score to predict survival in an independent LBCL trial cohort (ClinicalTrials.gov: NCT03293173). Furthermore, joint analyses with ctDNA uncovered multiple serum proteins that correlate with tumor burden. We found that SERPINA9, TACI, and TARC complement minimally invasive subtype profiling and that TACI and TARC can be used to evaluate treatment response in a subtype-dependent manner in the liquid biopsy., Conclusions: Altogether, we discovered distinct serum protein landscapes that dissect the heterogeneity of LBCLs and provide agile, minimally invasive tools for precision oncology., Funding: This research was funded by grants from the Research Council of Finland, Finnish Cancer Organizations, Sigrid Juselius Foundation, University of Helsinki, iCAN Digital Precision Cancer Medicine Flagship, Orion Research Foundation sr, and Helsinki University Hospital., Competing Interests: Declaration of interests H.H. (all outside of the submitted work): Genmab: honoraria, safety committee; Gilead: honoraria, advisory board; Incyte: honoraria, advisory board; Nordic Nanovector: honoraria, safety committee; Novartis: honoraria, advisory board; Takeda: honoraria, advisory board. J.J. (all outside of the submitted work): BMS: consultancy; Gilead: consultancy; Incyte: consultancy; Novartis: consultancy; Orion Pharma: consultancy; Roche: consultancy. M.B. (all outside of the submitted work): Astra Zeneca: consultancy; BMS/Celgene: consultancy; Incyte: consultancy; Janssen: consultancy; Mundipharma: consultancy; Nanexa: consultancy; Pfizer: consultancy; Roche: consultancy; Schain Research: consultancy; WntResearch: consultancy. M.J. (all outside of the submitted work): Abbvie: honoraria, research funding; Astra Zeneca: honoraria, research funding; BMS: honoraria, research funding; Genmab: honoraria; Incyte: honoraria; Janssen: honoraria, research funding; Kite/Gilead: consultancy, honoraria, research funding; Novartis: honoraria; Orion: honoraria; Roche: honoraria, research funding. S.L. (all outside of the submitted work): Genmab: consultancy, research funding; Gilead: consultancy; Incyte: consultancy; Nordic Nanovector: research funding; Novartis: consultancy, honoraria, research funding; Roche: consultancy, research funding; Merck: consultancy; Bayer: research funding; Celgene: consultancy, research funding; Orion: consultancy., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Marginal zone lymphoma (MZL) is an indolent B-cell malignancy with heterogeneous anatomical and clinical presentation. While MZLs are generally associated with long survival, some patients experience histological transformation to aggressive large B-cell lymphoma. Population-based long-term data on the transformation of MZL is limited. We conducted a nationwide population-based study to estimate the risk of transformation and relative survival in patients diagnosed with MZL in Finland from 1995-2018. We identified a total of 1454 patients with MZL from the Finnish Cancer Registry (FCR). The cumulative incidence of transformation was 4.7% (95% CI, 3.6-6.2) at 10 years. The highest incidence of transformation was observed in the patients with splenic MZL (14.0%; 95% CI, 8.6-22.7). The transformation was associated with a substantially increased risk of death (HR, 5.18; 95% CI, 3.58-7.50). Ten-year relative survival was 79% (95% CI, 73‒83%). Transformation, nodal MZL subtype, and older age at diagnosis were associated with increased excess mortality, whereas patients diagnosed at a later calendar period had a lower excess risk of death. We conclude that transformation resulted in a substantially increased mortality irrespective of MZL subtype compared with the patients without transformation. Our results also suggest a reduction in excess mortality in recent years., (© 2023. The Author(s).)

Background: Little controlled evidence exists on road traffic accident (RTA) risk among patients diagnosed with cancer, while clinicians are often requested to comment their ability to drive. The aim of this study was to evaluate RTA risk in a population-based cohort of cancer patients living in Southwest Finland., Patients: All adult patients diagnosed with cancer in 2013-2019 were included. Acute appendectomy/cholecystectomy and actinic keratosis patients without cancer were selected from the same region as the control cohort. Participants were cross-referenced to a national driving licence database, yielding 12,651 cancer and 6334 control patients with a valid licence. Due to marked differences in their clinical presentation, the cancer cohort was divided into nine cancers of interest (breast, prostate, colorectal, lung, melanoma, head & neck, primary brain tumours, gynaecological and haematological malignancies). The nationwide law-regulated motor liability insurance registry was searched for all RTAs leading to injury with claims paid to not- or at-fault participants. At-fault drivers were verified based on sex and birth year., Results: During a median follow-up of 34 months, 167 persons were at-fault drivers in RTAs leading to injury. Among the nine cancers of interest, RTA risk did not differ from the control cohort. Among cancer patients, multivariable regression suggested male sex and opioid use, but not advanced cancer stage or given systemic therapy, as the most influential risk factors for RTA., Conclusions: Cancer diagnosis itself was not associated with increased RTA risk, but other associated symptoms, medications, comorbidities or specific cancer subgroups may., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Inadequate molecular and clinical stratification of the patients with high-risk diffuse large B-cell lymphoma (DLBCL) is a clinical challenge hampering the establishment of personalized therapeutic options. We studied the translational significance of liquid biopsy in a uniformly treated trial cohort. Pretreatment circulating tumor DNA (ctDNA) revealed hidden clinical and biological heterogeneity, and high ctDNA burden determined increased risk of relapse and death independently of conventional risk factors. Genomic dissection of pretreatment ctDNA revealed translationally relevant phenotypic, molecular, and prognostic information that extended beyond diagnostic tissue biopsies. During therapy, chemorefractory lymphomas exhibited diverging ctDNA kinetics, whereas end-of-therapy negativity for minimal residual disease (MRD) characterized cured patients and resolved clinical enigmas, including false residual PET positivity. Furthermore, we discovered fragmentation disparities in the cell-free DNA that characterize lymphoma-derived ctDNA and, as a proof-of-concept for their clinical application, used machine learning to show that end-of-therapy fragmentation patterns predict outcome. Altogether, we have discovered novel molecular determinants in the liquid biopsy that can noninvasively guide treatment decisions., (© 2022 by The American Society of Hematology.)

Background: Real-world data on diffuse large B-cell lymphoma (DLBCL) has remained incomplete. In Finland, health record data originally recorded in different hospital data record systems are collectively available via data lake technology, enabling efficient extraction and analysis of large data sets. The usability of Finnish data lake data in the assessment of DLBCL was evaluated. Methods: Adult DLBCL patients diagnosed between 2010 and 2019, home municipality in the Hospital District of Southwest Finland and data available in respective data lake were included. Results: The algorithmic determination of treatment lines and respective survival was successful. Patient characterization was feasible, albeit partly incomplete because of limited data content/availability and coverage. Stage, International Prognostic Index and cell of origin were available for 63.0, 68.3 and 28.4% of patients, respectively. Genetic aberrations were not structurally available or feasible to extract without a manual chart review. Conclusion: Finnish data lakes represent an efficient way to analyze large DLBCL data sets. The current study provides a tool for developing recording practices in routine care.

Background: The existing risk prediction models for chemotherapy-induced febrile neutropenia (FN) do not necessarily apply to real-life patients in different healthcare systems and the external validation of these models are often lacking. Our study evaluates whether a machine learning-based risk prediction model could outperform the previously introduced models, especially when validated against real-world patient data from another institution not used for model training., Methods: Using Turku University Hospital electronic medical records, we identified all patients who received chemotherapy for non-hematological cancer between the years 2010 and 2017 (N = 5879). An experimental surrogate endpoint was first-cycle neutropenic infection (NI), defined as grade IV neutropenia with serum C-reactive protein >10 mg/l. For predicting the risk of NI, a penalized regression model (Lasso) was developed. The model was externally validated in an independent dataset (N = 4594) from Tampere University Hospital., Results: Lasso model accurately predicted NI risk with good accuracy (AUROC 0.84). In the validation cohort, the Lasso model outperformed two previously introduced, widely approved models, with AUROC 0.75. The variables selected by Lasso included granulocyte colony-stimulating factor (G-CSF) use, cancer type, pre-treatment neutrophil and thrombocyte count, intravenous treatment regimen, and the planned dose intensity. The same model predicted also FN, with AUROC 0.77, supporting the validity of NI as an endpoint., Conclusions: Our study demonstrates that real-world NI risk prediction can be improved with machine learning and that every difference in patient or treatment characteristics can have a significant impact on model performance. Here we outline a novel, externally validated approach which may hold potential to facilitate more targeted use of G-CSFs in the future., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare B-cell malignancy associated with excellent survival. However, some patients experience histological transformation into aggressive large B-cell lymphoma. Population-based data on transformation in patients with NLPHL is limited. We conducted a nationwide population-based study to estimate the risk of transformation and relative survival in patients diagnosed with NLPHL in Finland between 1995 and 2018. We identified a total of 453 patients (median age, 48 years; 76% males) with the incident NLPHL from the Finnish Cancer Registry. The cumulative incidence of transformation was 6.3% (95% CI, 4.2-9.6) at 10 years. After adjusting for sex, age and year of diagnosis, transformation was associated with a substantially increased risk of death (HR 8.55, 95% CI 4.49-16.3). Ten-year relative survival was 94% (95% CI, 89%‒100%). The patients diagnosed at a later calendar year had lower excess risk of death (HR, 0.38 per 10-year increase; 95% CI, 0.15‒0.98). We conclude that while the 10-year relative survival for the patients with NLPHL was excellent in this large population-based cohort for the entire study period, transformation resulted in a substantially increased mortality compared with the patients without transformation. Our results also suggest a reduction in excess mortality over time., (© 2021. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Juntikka, Vaittinen, Vahlberg, Jyrkkiö and Minn.)

Introduction: Palliative care can reduce the symptom burden and may increase the life expectancy for patients with advanced malignancies. The aim of this study was to evaluate the impact of palliative intervention on the treatment procedures for pancreatic cancer patients during their last month of life., Material and Methods: This retrospective single-centre study included adult pancreatic cancer patients who were treated in Turku University Hospital during their last month of life and died between 2011 and 2016. Data were collected from hospital database. Oncological treatments, the number of radiological examinations and procedures, surgical procedures, emergency department visits, hospitalisations, the place of death and medical costs were examined in tertiary care for patients with or without contact to the palliative care unit., Results: From 378 eligible patients, 20% ( n  = 76) had a contact to the palliative care unit. These patients had less radiological examinations ( p  < 0.0001), hospitalisations ( p  <0.0001) and emergency department visits ( p  = 0.021) during the last month of life. They did not die in the university hospital as often ( p  = 0.011) and median of their medical costs during the last month of life was approximately half ( p  <0.0001) when compared to patients with no palliative intervention ( n  = 302). They had longer overall survival ( p  <0.0001) which was the only difference detected in the characteristics of the groups., Conclusion: Fewer treatment procedures and lower tertiary care costs during the last month of life were observed for the pancreatic cancer patients who had a contact to the palliative care unit. Palliative care intervention should be an essential part of the treatment schedule for these patients.

Survival of patients with high-risk diffuse large B-cell lymphoma (DLBCL) is suboptimal, and the risk of central nervous system (CNS) progression is relatively high. We conducted a phase 2 trial in 139 patients aged 18 to 64 years who had primary DLBCL with an age-adjusted International Prognostic Index (aaIPI) score of 2 to 3 or site-specific risk factors for CNS recurrence. The goal was to assess whether a dose-dense immunochemotherapy with early systemic CNS prophylaxis improves the outcome and reduces the incidence of CNS events. Treatment consisted of 2 courses of high-dose methotrexate in combination with biweekly rituximab (R), cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP-14), followed by 4 courses of R-CHOP-14 with etoposide (R-CHOEP) and 1 course of high-dose cytarabine with R. In addition, liposomal cytarabine was administered intrathecally at courses 1, 3, and 5. Coprimary endpoints were failure-free survival and CNS progression rates. Thirty-six (26%) patients experienced treatment failure. Progression occurred in 23 (16%) patients, including three (2.2%) CNS events. At 5 years of median follow-up, failure-free survival, overall survival, and CNS progression rates were 74%, 83%, and 2.3%, respectively. Treatment reduced the risk of progression compared with our previous trial, in which systemic CNS prophylaxis was given after 6 courses of biweekly R-CHOEP (hazard ratio, 0.49; 95% CI, 0.31-0.77; P = .002) and overcame the adverse impact of an aaIPI score of 3 on survival. In addition, outcome of the patients with BCL2/MYC double-hit lymphomas was comparable to the patients without the rearrangements. The results are encouraging, with a low toxic death rate, low number of CNS events, and favorable survival rates. This trial was registered at www.clinicaltrials.gov as #NCT01325194., (© 2020 by The American Society of Hematology.)

Background: The aim was to describe the incidence and mortality of Hodgkin lymphoma (HL) in Finland in 1996-2015 including classic Hodgkin lymphoma (cHL) subtypes and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). Material and Methods: This study included 2851 HL cases registered in the population-based Finnish Cancer Registry between 1996 and 2015. All not otherwise specified (NOS) morphology codes were manually checked and re-coded into cHL subtypes or NLPHL according to the International Classification of Diseases for Oncology 2011, if possible. Thereafter, we analyzed the incidence and mortality of HL by age, gender and time trends and by subtypes. Results: According to our registry-based study, the incidence of HL was increasing with a 5-year rate of change of 0.3% (95% confidence interval 0.2-0.5), and the mortality was decreasing with -2.8% (95%CI -3.8 to -1.8) correspondingly. The incidence of nodular sclerosis (NS) was 1.57/100 000 person years ( n  = 1529) and the incidence and mortality remained constant over 1996-2015. The incidence of mixed cellularity (MC) was 0.32/100 000 ( n  = 453) and it was decreasing with -2.2% (95%CI -3.7 to -0.5), yet the mortality was increasing with 2.7% (95%CI 1.9-3.6). The incidence of NLPHL was 0.29/100 000 accounting for 13% of all HL diagnoses ( n  = 374), and the incidence and mortality remained constant over the study period. The incidence of lymphocyte-rich (LR) subtype was 0.20/100 000 ( n  = 252) and remained constant while the mortality decreased. There were only 30 cases of lymphocyte depletion (LD) HL. In this study, 36% of all HL patients were over 50 years old. Conclusion: The incidence of HL is slightly increasing and the mortality is decreasing in Finland. NLPHL represents 13% of all HL cases in Finland. Over one third of HL patients are over 50-year-old.

Objective: To describe the trends and occupational variation in the incidence of testicular cancer in the Nordic countries utilising national cancer registries, NORDCAN (NORDCAN project/database presents the incidence, mortality, prevalence and survival from >50 cancers in the Nordic countries) and NOCCA (Nordic Occupational Cancer) databases., Patients and Methods: We obtained the incidence data of testicular cancer for 5-year periods from 1960-1964 to 2000-2014 and for 5-year age-groups from the NORDCAN database. Morphological data on incident cases of seminoma and non-seminoma were obtained from national cancer registries. Age-standardised incidence rates (ASR) were calculated per 100 000 person-years (World Standard). Regression analysis was used to evaluate the annual change in the incidence of testicular cancer in each of the Nordic countries. The risk of testicular cancer in different professions was described based on NOCCA information and expressed as standardised incidence ratios (SIRs)., Results: During 2010-2014 the ASR for testicular cancer varied from 11.3 in Norway to 5.8 in Finland. Until 1998, the incidence was highest in Denmark. There has not been an increase in Denmark and Iceland since the 1990s, whilst the incidence is still strongly increasing in Norway, Sweden, and Finland. There were no remarkable changes in the ratio of seminoma and non-seminoma incidences during the past 50 years. There was no increase in the incidences in children and those of pension age. The highest significant excess risks of testicular seminoma were found in physicians (SIR 1.48, 95% confidence interval [CI] 1.07-1.99), artistic workers (SIR 1.47, 95% CI 1.06-1.99) and religious workers etc. (SIR 1.33, 95% CI 1.14-1.56). The lowest SIRs of testicular seminoma were seen amongst cooks and stewards (SIR 0.56, 95% CI 0.29-0.98), and forestry workers (SIR 0.64, 95% CI 0.47-0.86). The occupational category of administrators was the only one with a significantly elevated SIR for testicular non-seminoma (SIR 1.21, 95% CI 1.04-1.42). The only SIRs significantly <1.0 were seen amongst engine operators (SIR 0.60, 95% CI 0.41-0.84) and public safety workers (SIR 0.67, 95% CI 0.43-0.99)., Conclusions: There have always been differences in the incidence of testicular cancer between the Nordic countries. There is also some divergence in the incidences in different age groups and in the trends of the incidence. The effect of occupation-related factors on incidence of testicular cancer is only moderate. Our study describes the differences, but provides no explanation for this variation., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Background: 68 Ga-DOTANOC PET/CT is routinely used to image neuroendocrine tumors (NETs). A case of lymphoma initially thought to be NET based on a positive 68 Ga-DOTANOC PET/CT was recently seen at our institution. This prompted us to determine prospectively somatostatin receptor (SSTR) status in patients with lymphoma by immunohistochemical analysis of SSTR subtypes 2, 3 and 5 (SSTR 2,3,5 ) and 68 Ga-DOTANOC PET/CT imaging., Material and Methods: Twenty-one patients with newly diagnosed lymphoma were referred to 68 Ga-DOTANOC and FDG PET/CT prior to any treatment. Tracer uptake was evaluated visually by two nuclear medicine specialists. Maximum standardized uptake values (SUVmax) were determined from 14 nodal and two extranodal regions with highest uptake in each patient. Lesions were then graded with Deauville score (1-5) on FDG PET/CT and modified Krenning score (0-4) on 68 Ga-DOTANOC PET/CT, respectively. SSTR 2,3,5 status was analyzed from routine biopsies of lymphomatous tissue and matched to corresponding PET/CT findings., Results: About 20/21 patients had FDG-positive lymphoma (Deauville score ≥3). Uptake of 68 Ga-DOTANOC was regarded as positive if Krenning score was ≥2 and resulted in 13/21 (62%) patients having 68 Ga-DOTANOC-positive lymphomas. The highest uptake of 68 Ga-DOTANOC was seen in Hodgkin's lymphoma of nodular sclerosis subtype and in diffuse large B-cell lymphoma (SUVmax median 9.8 and 9.7, respectively). Both cases showed strong SSTR 2 immunopositivity in tumor cells. Some patients had SSTR 2 immunopositivity predominantly in endothelial and dendritic cells and follicular centers of lymph nodes contributing to a positive PET/CT with probably low tumor-specific uptake. SSTR 3 and SSTR 5 were negative in most lymphoma subtypes., Conclusions: According to this pilot study, 68 Ga-DOTANOC PET/CT is positive in some lymphoma subtypes which express SSTRs. These tumors present a potential risk of being misinterpreted as NETs if a representative tumor sample is not available. Lymphomas with high expression of SSTRs may be amenable to treatments targeting these receptors.

Metastatic castration resistant prostate cancer (mCRPC) is one of the most common cancers with a poor prognosis. To improve prognostic models of mCRPC, the Dialogue for Reverse Engineering Assessments and Methods (DREAM) Consortium organized a crowdsourced competition known as the Prostate Cancer DREAM Challenge. In the competition, data from four phase III clinical trials were utilized. A total of 1600 patients' clinical information across three of the trials was used to generate prognostic models, whereas one of the datasets (313 patients) was held out for blinded validation. The previously introduced prognostic model of overall survival of chemotherapy-naive mCRPC patients treated with docetaxel or prednisone (so called Halabi model) was used as a performance baseline. This paper presents the model developed by the team TYTDreamChallenge and its improved version to predict the prognosis of mCRPC patients within the first 30 months after starting the treatment based on available clinical features of each patient. In particular, by replacing our original larger set of eleven features with a smaller more carefully selected set of only five features the prediction performance on the independent validation cohort increased up to 5.4 percent. While the original TYTDreamChallenge model (iAUC=0.748) performed similarly as the performance-baseline model developed by Halabi et al. (iAUC=0.743), the improved post-challenge model (iAUC=0.779) showed markedly improved performance by using only PSA, ALP, AST, HB, and LESIONS as features. This highlights the importance of the selection of the clinical features when developing the predictive models., Competing Interests: No competing interests were disclosed.

The biological subtype of breast cancer influences the selection of systemic therapy. Distinction between luminal A and B cancers depends on consistent assessment of Ki-67, but substantial intra-observer and inter-observer variability exists when immunohistochemistry (IHC) is used. We compared RT-qPCR with IHC in the assessment of Ki-67 and other standard factors used in breast cancer subtyping. RNA was extracted from archival breast tumour tissue of 769 women randomly assigned to the FinHer trial. Cancer ESR1, PGR, ERBB2 and MKI67 mRNA content was quantitated with an RT-qPCR assay. Local pathologists assessed ER, PgR and Ki-67 expression using IHC. HER2 amplification was identified with chromogenic in situ hybridization (CISH) centrally. The results were correlated with distant disease-free survival (DDFS) and overall survival (OS). qPCR-based and IHC-based assessments of ER and PgR showed good concordance. Both low tumour MKI67 mRNA (RT-qPCR) and Ki-67 protein (IHC) levels were prognostic for favourable DDFS [hazard ratio (HR) 0.42, 95 % CI 0.25-0.71, P = 0.001; and HR 0.56, 0.37-0.84, P = 0.005, respectively] and OS. In multivariable analyses, cancer MKI67 mRNA content had independent influence on DDFS (adjusted HR 0.51, 95 % CI 0.29-0.89, P = 0.019) while Ki-67 protein expression had not any influence (P = 0.266) whereas both assessments influenced independently OS. Luminal B patients treated with docetaxel-FEC had more favourable DDFS and OS than those treated with vinorelbine-FEC when the subtype was defined by RT-qPCR (for DDFS, HR 0.52, 95 % CI 0.29-0.94, P = 0.031), but not when defined using IHC. Breast cancer subtypes approximated with RT-qPCR and IHC show good concordance, but cancer MKI67 mRNA content correlated slightly better with DDFS than Ki-67 expression. The findings based on MKI67 mRNA content suggest that patients with luminal B cancer benefit more from docetaxel-FEC than from vinorelbine-FEC.

We evaluated the predictive value of interim positon emission tomography (I-PET) after one course of chemoimmunotherapy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). One hundred and twelve patients with DLBCL were enrolled. All patients had PET/computed tomography (CT) scans performed after one course of chemotherapy (PET-1). I-PET scans were categorized according to International Harmonization Project criteria (IHP), Deauville 5-point scale (D 5PS) with scores 1-3 considered negative (D 5PS > 3) and D 5PS with scores 1-4 considered negative (D 5PS = 5). Ratios of tumor maximum standardized uptake value (SUVmax) to liver SUVmax were also analyzed. We found no difference in progression-free survival (PFS) between PET-negative and PET-positive patients according to IHP and D 5PS > 3. The 2-year PFS using D 5PS = 5 was 50.9% in the PET-positive group and 84.8% in the PET-negative group (p = 0.002). A tumor/liver SUVmax cut-off of 3.1 to distinguish D 5PS scores of 4 and 5 provided the best prognostic value. PET after one course of chemotherapy was not able to safely discriminate PET-positive and PET-negative patients in different prognostic groups.

Cancers in pregnant women are rare and similar to those in women of similar, reproductive age. Diffuse large B-cell lymphoma differs in its course in pregnant women. Cancer treatment according to the guidelines is modified only according to what is necessary in the overall situation. The goal of the treatment is to secure the well-being of the mother and the fetus. Cancer surgery is successful on almost the same principles as in other patients. Drug therapies required by a severe cancer diagnosed in early pregnancy may jeopardize the health of both the mother and the fetus. Radiation therapy during pregnancy is generally not recommended.

The number of long-term survivors after cancer therapy in childhood and young adulthood is increasing. Accordingly, life-long follow-up of significant health problems related to the given cancer therapy is needed as only one third of the survivors will remain free of any physical or psychosocial late effects. At present, national activity is needed to establish a uniform follow-up clinic service to support education, diagnostics, therapy and rehabilitation of these long-term adverse effects after cancer therapy at young age.

There is no consensus on treatment strategies for elderly patients with mantle cell lymphoma (MCL). In this prospective phase II study we investigated whether the poor outcome could be improved, with reasonable toxicity, by prolonging the immunochemotherapy. Ten cycles of alternating cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP)/cytarabine (AraC) with eight doses of rituximab (R) were given as induction. The potential synergism of intermediate-dose AraC and fludarabine was tested in cycles 6-8. Induction was followed by bimonthly rituximab maintenance for 2 years. The median age of the 60 included patients was 74 years, and the Mantle Cell Lymphoma International Prognostic Index (MIPI) was intermediate or high risk in 98% of the patients. The overall response rate was 95% (complete response/complete response unconfirmed 87%). The response of 11 patients improved with cycles 6-8 (R-fludarabine-AraC). Progression-free survival was 70% and overall survival 72% at 4 years, respectively. Treatment related mortality was 2%. Severe infections were rare, with only one grade 4 infection. More dose reductions were needed during fludarabine-containing courses as compared to R-AraC. In 20 patients a transient grade 4 neutropenia without severe infections was recorded during maintenance. In conclusion, elderly patients with MCL can be treated relatively intensively with acceptable toxicity.

Smoking is the major cause of lung, laryngeal and bladder cancer. The exact mechanisms of carcinogenic substances in tobacco smoke are not known, but signaling pathways mediated via cyclooxygenase and its derivatives are considered the most important mechanisms. Cessation of smoking lowers the risk of disease at all ages. Besides increasing the risk of developing cancer, smoking also worsens the prognosis of a cancer patient and increases adverse effects of cancer treatments. Cessation of smoking is an essential part of appropriate cancer therapy resulting in positive effect on the prognosis and quality of life of the patient.

Purpose: To study the CYP3A activity before and after docetaxel administration. Furthermore, it was investigated whether peroral midazolam could predict docetaxel exposure and adverse events., Methods: Twenty patients with primary high risk breast cancer were given docetaxel as a 1-h infusion 80 mg/m(2) in a 21-day cycle in 3 cycles followed by 3 cycles of cyclophosphamide, epirubicin and fluorouracil. CYP3A activity was assessed a day before and a day after docetaxel by 7.5 mg oral midazolam. All patients were given peroral dexamethasone a total dose of 45 mg, of which 15 mg was given before docetaxel infusion and 30 mg before the latter assessment of CYP3A activity. All except one patient were given 11-19 mg of intravenous dexamethasone before docetaxel infusion., Results: CYP3A activity was clearly induced when assessed a day after docetaxel administration as shown by lower midazolam AUC (P < 0.0001) and higher AUC ratio (1-OH-midazolam/midazolam, P = 0.018). The mean docetaxel AUC was about a half of that previously reported in the literature. Incidence of febrile neutropenia was smaller (15%) than reported in literature with comparable docetaxel doses and seemed to associate with slower metabolism. No correlation between pharmacokinetics of midazolam and docetaxel was found at baseline., Conclusions: We show here a markedly reduced docetaxel exposure followed by CYP3A induction by, most likely, dexamethasone. Peroral midazolam seemed not to predict docetaxel exposure. Slow CYP3A-mediated metabolism might predispose patients to adverse events of docetaxel.

The disease recurs in a significant proportion of lymphoma patients after the first-line treatment. Intensive treatment supported by the patient's own cells (autologic stem cell transplantation) has long been utilized in selected cases, but restrictions of this form of therapy are well known. Allogenic transplantation with another person's stem cells provides a possibility to treat lymphoma having a poor prognosis even in cases where other methods of treatments have failed. Allogeneic stem cell transplantation is, however, associated with a significant risk of death.

When a pregnant woman develops cancer, death and life are competing in her body and in her mind. In this article, two cases of pregnant cancer patients are described. The pregnant women were accompanied through their journey toward delivery and during the first months with their newborn. The process of being in intensive cancer treatment during pregnancy, of giving birth, and of building an early relationship with the infant is explored., (Copyright © 2010 Michigan Association for Infant Mental Health.)

Objective: Breast cancer is one of the principal oncological challenges in the Western world. Currently, there are only a few reliable predictive methods for monitoring treatment. We investigated the ability of carbon-11 methionine ("11C-MET) positron emission tomography (PET) to evaluate early response to therapy in advanced breast cancer., Methods: Thirteen patients with metastases in the lungs/pleura, lymph nodes, soft tissue, or bones entered a MET PET study both before and after the first cycle of polychemotherapy (n=4), or after the first month of therapy with hormones (n=5), or low dose weekly cytostatics (n=3). One patient underwent three PET studies: before hormonal therapy, after 1 month of hormonal therapy, and after the first cycle of polychemotherapy (total, 27 studies). MET accumulation in the metastatic sites was measured as standardized uptake values (SUVs), and the pretreatment and post-treatment SUVs were compared with each other and the clinical follow-up data., Results: A total of 26 different metastatic sites were investigated in 13 patients. All metastases were visible by MET PET except one superficially spreading local skin recurrence, probably because of respiratory movements. Five new metastatic sites were detected. After therapy the SUVs decreased significantly (30-54%; P < 0.05) in all six responding metastatic sites, whereas the SUVs of nonresponding metastases decreased somewhat (11-130/%; n=4), remained stable (+/- 8%; n=10), or increased (13-23%; n=4) (P=NS). The SUVs of two nonresponding metastatic sites decreased clearly. Physiological MET uptake in the salivary glands, the myocardium, and the bone marrow did not disturb the image interpretation., Conclusion: MET PET may be useful in assessing the early response to therapy in advanced breast cancer.