The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma.

BACKGROUND: For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL. PATIENTS AND METHODS: ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study. We present an exploratory update of the ECHELON-2 study, including an analysis of 5-year PFS per investigator in the intent-to-treat analysis group. RESULTS: A total of 452 patients were randomized (1 : 1) to six or eight cycles of A+CHP (N = 226) or CHOP (N = 226). At median follow-up of 47.6 months, 5-year PFS rates were 51.4% [95% confidence interval (CI): 42.8% to 59.4%] with A+CHP versus 43.0% (95% CI: 35.8% to 50.0%) with CHOP (hazard ratio = 0.70; 95% CI: 0.53-0.91), and 5-year overall survival (OS) rates were 70.1% (95% CI: 63.3% to 75.9%) with A+CHP versus 61.0% (95% CI: 54.0% to 67.3%) with CHOP (hazard ratio = 0.72; 95% CI: 0.53-0.99). Both PFS and OS were generally consistent across key subgroups. Peripheral neuropathy was resolved or improved in 72% (84/117) of patients in the A+CHP arm and 78% (97/124) in the CHOP arm. Among patients who relapsed and subsequently received brentuximab vedotin, the objective response rate was 59% with brentuximab vedotin retreatment after A+CHP and 50% with subsequent brentuximab vedotin after CHOP. CONCLUSIONS: In this 5-year update of ECHELON-2, frontline treatment of patients with PTCL with A+CHP continues to provide clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy.

Whole-genome and transcriptome analysis enhances precision cancer treatment options.

BACKGROUND: Recent advances are enabling delivery of precision genomic medicine to cancer clinics. While the majority of approaches profile panels of selected genes or hotspot regions, comprehensive data provided by whole-genome and transcriptome sequencing and analysis (WGTA) present an opportunity to align a much larger proportion of patients to therapies. PATIENTS AND METHODS: Samples from 570 patients with advanced or metastatic cancer of diverse types enrolled in the Personalized OncoGenomics (POG) program underwent WGTA. DNA-based data, including mutations, copy number and mutation signatures, were combined with RNA-based data, including gene expression and fusions, to generate comprehensive WGTA profiles. A multidisciplinary molecular tumour board used WGTA profiles to identify and prioritize clinically actionable alterations and inform therapy. Patient responses to WGTA-informed therapies were collected. RESULTS: Clinically actionable targets were identified for 83% of patients, of which 37% of patients received WGTA-informed treatments. RNA expression data were particularly informative, contributing to 67% of WGTA-informed treatments; 25% of treatments were informed by RNA expression alone. Of a total 248 WGTA-informed treatments, 46% resulted in clinical benefit. RNA expression data were comparable to DNA-based mutation and copy number data in aligning to clinically beneficial treatments. Genome signatures also guided therapeutics including platinum, poly-ADP ribose polymerase inhibitors and immunotherapies. Patients accessed WGTA-informed treatments through clinical trials (19%), off-label use (35%) and as standard therapies (46%) including those which would not otherwise have been the next choice of therapy, demonstrating the utility of genomic information to direct use of chemotherapies as well as targeted therapies. CONCLUSIONS: Integrating RNA expression and genome data illuminated treatment options that resulted in 46% of treated patients experiencing positive clinical benefit, supporting the use of comprehensive WGTA profiling in clinical cancer care.

Publication trends in hidradenitis suppurativa from 2008 to 2018.

BACKGROUND: Increased interest in hidradenitis suppurativa (HS) research is encouraging. A critical analysis of the state of HS literature may demonstrate the strength of existing knowledge and highlight current gaps. OBJECTIVES: To analyse changes in HS literature from 2008 to 2018 with focus on quantity and quality of annual publications. METHODS: Review of all indexed publications reporting on HS on PubMed. Publications were categorized based on study design, study topic and treatment type where applicable. Publications were dichotomized into high level of evidence and low level of evidence groups. Linear regression analyses were performed to investigate the change in publication number over time. Annual average growth rate and distribution of high versus low level of evidence publications were calculated. RESULTS: Publication number increased over time overall (R2  = 0.64, P = 0.003) and for all publication types except randomized clinical trials. Case reports and case series represented the majority of HS publications (n = 479, 40.3%). Treatment was the main focus of publications (n = 445, 37.6%) with increasing interest in medical management evident in recent years. Distribution of low level of evidence studies (n = 974) compared with high level of evidence studies over time (n = 209) was significant (x2 : 11.45, P = 0.0007). High level of evidence studies had a higher average annual growth rate (49.9%) compared with low level of evidence studies (23.7%). Few randomized clinical trials were performed (n = 16), focusing equally on medical or procedural treatments. CONCLUSIONS: Hidradenitis suppurativa research is undergoing a tremendous shift, suggesting rapid maturation of the field. Current HS literature, however, remains primarily based on limited clinical observation data, with a particular lack of randomized clinical trials. Despite this, the increase in high level of evidence studies is encouraging and may herald a shift towards improved disease understanding and treatment paradigms.

Using Scipion for stream image processing at Cryo-EM facilities.

Three dimensional electron microscopy is becoming a very data-intensive field in which vast amounts of experimental images are acquired at high speed. To manage such large-scale projects, we had previously developed a modular workflow system called Scipion (de la Rosa-Trevín et al., 2016). We present here a major extension of Scipion that allows processing of EM images while the data is being acquired. This approach helps to detect problems at early stages, saves computing time and provides users with a detailed evaluation of the data quality before the acquisition is finished. At present, Scipion has been deployed and is in production mode in seven Cryo-EM facilities throughout the world.

ABVD chemotherapy with reduced radiation therapy rates in children, adolescents and young adults with all stages of Hodgkin lymphoma.

Background: We adopted ABVD chemotherapy with risk-adapted radiation therapy (RT) as first-line therapy for children, adolescents and young adults with Hodgkin lymphoma (HL) in British Columbia in 2004. Patients and methods: Patients ≤ 25 years diagnosed from 2004 to 2013 with all stages of HL who received ABVD as initial therapy were included. Results: Among 55 children (age < 18 year) and 154 young adults (18-25 year), there were no significant differences among age groups for sex, histologic subtype, tumour bulk, B symptoms, prognostic risk groups or treatment received. The rates of complete response, partial response and progressive disease were 84%, 7% and 10% for children and 95%, 4% and 1% for young adults (P=0.01), respectively. Treatment failures in children all occurred within one year of completion, while 8/21 (38%) relapses in young adults occurred later (P=0.04). With a median follow-up of 66 months the 5-year progression-free (PFS) and overall survival (OS) were 85 ± 3% and 97 ± 1%, respectively. For limited stage disease, PFS was 90 ± 7% for children and 93 ± 3% for young adults (P=0.65); OS was 100% for both. For advanced stage patients, PFS and OS were also similar for the children and young adults (77 ± 7% versus 81 ± 4%; P=0.38 and OS 90 ± 6% versus 97 ± 2%; P=0.17). The rate of consolidative RT was low (21%) and did not differ between age groups. Conclusion: ABVD is an effective treatment in children, adolescents and young adults with HL. Children were less likely to achieve complete response and demonstrated earlier relapses compared to young adults. RT may be omitted for the majority of patients while maintaining excellent 5-year OS.

Observation as the initial management strategy in patients with mantle cell lymphoma.

BACKGROUND: Patients with mantle cell lymphoma (MCL) follow a heterogeneous clinical course. While they generally require treatment initiation shortly after diagnosis, it is unclear whether deferring treatment in selected patients with an indolent clinical behavior affects their overall outcome. PATIENTS AND METHODS: In this population-based study, all patients diagnosed with MCL during 1998-2014 were identified in the British Columbia Cancer Agency Lymphoid Cancer Database. The associations between clinico-pathologic characteristics, including the expression of Ki67, SOX11, and TP53, and time to treatment (TtT) and OS were analyzed. RESULTS: A total of 440 patients with MCL were evaluated: 365 (83%) received early treatment and 75 (17%) were observed ≥3 months. In the observation group, 54 (72%) patients had a nodal presentation, 16 (21%) a non-nodal presentation, and 5 (7%) had only gastrointestinal involvement. Characteristics associated with deferred treatment included good performance status, no B symptoms, low LDH, non-bulky disease, non-blastoid morphology, and lower Ki67 values. The median TtT in the observation group was 35 months (range 5-79), and 60 (80%) patients were observed beyond 12 months. The median OS was significantly longer in the observation group than in the early treatment group (72 versus 52.5 months, respectively, P = 0.041). In multivariable analysis, treatment decision was not associated with OS [HR 0.804 (95% CI 0.529-1.221), P = 0.306]. CONCLUSIONS: A subgroup of patients with MCL may be safely observed from diagnosis without negatively impacting their outcomes, including patients with non-nodal presentation as well as asymptomatic patients with low burden nodal presentation and a low proliferative rate.

Effect of nivolumab on health-related quality of life in patients with treatment-naïve advanced melanoma: results from the phase III CheckMate 066 study.

BACKGROUND: Nivolumab has shown significant survival benefit and a favorable safety profile compared with dacarbazine chemotherapy among treatment-naïve patients with metastatic melanoma in the CheckMate 066 phase III study. Results from the health-related quality of life (HRQoL) analyses from CheckMate 066 are presented. PATIENTS AND METHODS: HRQoL was evaluated at baseline and every 6 weeks while on treatment using the European Organisation for Research and Treatment of Care (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and the EuroQoL Five Dimensions Questionnaire (EQ-5D). Via a multi-step statistical plan, data were analyzed descriptively, cross-sectionally, and longitudinally, adjusting for baseline covariates, in patients having baseline plus ≥1 post-baseline assessment. RESULTS: Baseline-adjusted completion rates for all HRQoL questionnaires across treatment arms were 65% and 70% for dacarbazine and nivolumab, respectively, and remained similar throughout treatment. The mean baseline HRQoL scores were similar for patients treated with nivolumab and dacarbazine. Baseline HRQoL levels with nivolumab were maintained over time. This exploratory analysis showed a between-arm difference in favor of nivolumab on the EQ-5D utility index and clinically meaningful EQ-5D improvements from baseline at several time points for patients receiving nivolumab. Patients treated with nivolumab did not show increased symptom burden as assessed by the EORTC QLQ-C30. No HRQoL change was noted with dacarbazine patients up to week 43, although the high attrition rate after week 13 did not allow any meaningful analyses. Patients receiving nivolumab deteriorated significantly later than those receiving dacarbazine on several EORTC QLQ-C30 scales and the EQ-5D utility index. CONCLUSIONS: In addition to prolonged survival, these exploratory HRQoL results show that nivolumab maintains baseline HRQoL levels to provide long-term quality of survival benefit, compared with dacarbazine in patients with advanced melanoma.

The value of routine bone marrow biopsy in patients with diffuse large B-cell lymphoma staged with PET/CT: a Danish-Canadian study.

BACKGROUND: The added diagnostic and prognostic value of routine bone marrow biopsy (BMB) in patients with diffuse large B-cell lymphoma (DLBCL) undergoing positron emission tomography combined with computed tomography (PET/CT) staging is controversial. PATIENTS AND METHODS: Patients with newly diagnosed DLBCL who underwent both staging PET/CT and BMB were retrospectively identified in British Columbia, Aalborg, and Copenhagen. Original written PET/CT and pathology reports were retrospectively reviewed to determine Ann Arbor stage and outcomes, with and without the contribution of BMB. RESULTS: A total of 530 patients were identified: 146 (28%) had focal bone marrow (BM) lesions on PET/CT and 87 (16%) had positive BMB. Fifty-two of 146 patients (36%) with positive PET/CT had a positive BMB [39 DLBCL, 13 indolent non-Hodgkin lymphoma (iNHL)], while 35 of 384 patients (9%) with negative PET/CT had positive BMB (12 DLBCL, 23 iNHL). BMB upstaged 12/209 (6%) of stage I/II patients to stage IV, although this was the case for only 3 (1%) patients with DLBCL in the BMB. PET/CT identified BM involvement by BMB with sensitivity 60%, specificity 79%, positive predictive value 36%, and negative predictive value 91%. Concordant histological involvement of the BM by DLBCL was associated with worse overall survival and progression-free survival than discordant or no involvement in univariate and multivariate analyses. CONCLUSIONS: In patients with DLBCL, staging PET/CT can miss BM involvement with concordant DLBCL (less common) or discordant iNHL (more common). Routine BMB does not add relevant diagnostic or prognostic value over PET/CT alone in the majority of patients with DLBCL.

Comparative periodontal status of human immunodeficiency virus-positive patients and controls in a dedicated human immunodeficiency virus clinic in Nigeria.

BACKGROUND: There are diverse reports on the prevalence and severity of chronic periodontitis in human immunodeficiency virus (HIV) positive persons. Few studies have been carried out in developing countries in Sub-Saharan Africa. This study was aimed at comparing the prevalence and severity of chronic periodontitis of HIV-seropositive patients with that of HIV-seronegative persons using the community periodontal index (CPI). METHODOLOGY: This was a comparative study of the periodontal status of 110 HIV-positive subjects and 110 age and gender-matched HIV-negative controls attending a dedicated HIV Clinic in a Teaching Hospital in Lagos, Nigeria. The CPI and simplified oral hygiene index score were used in the periodontal examination. Highest CPI scores and percentages of CPI sextants assessed the prevalence and severity of chronic periodontitis respectively. Logistic regression was used in adjusting demographic differences in the study population. P ≤ 0.05 was considered as significant. RESULTS: A significant proportion of the HIV-positive patients 61 (55.5%) and the HIV-negative controls 53 (48.7%) had shallow pockets (4-5 mm) (CPI code 3). The prevalence of deep pockets (≥ 6mm) (CPI code 4) was higher among HIV-positive patients 9 (8.2%) than the controls 4 (3.5%) (P = 0.079). HIV-positive patients had a greater percentage of CPI codes 3, 4 and fewer CPI code 0 sextants than controls (P = 0.000). Both groups had comparable oral hygiene status (P = 0.209). Using a logistic regression analysis, HIV-positive status and lower education accounted for the greater severity of chronic periodontitis. CONCLUSION: HIV-seropositive patients had more severe chronic periodontitis than the HIV-seronegative controls, which was independent of lower education.

Outcome of patients with primary refractory diffuse large B cell lymphoma after R-CHOP treatment.

Primary refractory diffuse large B cell lymphoma (DLBCL) following R-CHOP chemotherapy is a major concern. We identified 1126 patients with DLBCL treated with R-CHOP from 2000 to 2009, of whom 166 (15 %) had primary refractory disease. Of the 75/166 (45 %) who were age <70 years and had been planned for stage-directed curative therapy, 43 (57 %) were primary nonresponders and 32 (43 %) relapsed within 3 months of completing R-CHOP. Thirty of 75 (40 %) patients had serious comorbidity and organ dysfunction precluding intensive treatment and had palliative treatment only. Twelve of 45 (27 %) patients responded to second-line treatment and underwent ASCT. The median overall survival for the 75 patients was 10 months with only seven patients alive without evidence of disease at follow-up ranging from 14 to 106 months. Primary refractory DLBCL after R-CHOP has a very poor outcome with only anecdotal survivors independent of the intended treatment approach.

Association between periodontal disease and pregnancy outcomes.

OBJECTIVE: To evaluate the association between periodontal disease and pregnancy outcomes like preterm birth and low birth weight. PATIENTS AND METHOD: Interviewer-administered questionnaires were completed by the subjects who attended the antenatal clinic of the Lagos University Teaching Hospital, Lagos. Information obtained included; maternal age, gestational age, marital status, educational status, occupation and expected date of delivery. After delivery, the questionnaire was completed with baby's weight at birth and the actual date of delivery. Clinical assessment of the periodontium was done using Oral Hygiene Index (OHI) and Community Periodontal Index of Treatment Needs (CPITN). Participants were divided into three groups: Test, Control I and Control II groups. Scaling and polishing were done for all patients with periodontal disease before (Test group) and after delivery (Control I). All Control II participants (those without periodontal disease) were given Oral hygiene instructions. Descriptive and comparative analyses were done using Epi info version 2008. RESULTS: Four hundred and fifty women received the questionnaire but the response rate was 94%, giving an actual sample size of 423 participants. Maternal age range was between 18 and 34 years with mean age of 29.67 (± 3.37). Gestational age at the point of recruitment was between 10 weeks and 26 weeks with mean of 23.34 (± 4.05). The prevalence of periodontal disease among the study group was 33.38%. About 71% of the participants attained tertiary level of education; only 0.7% had no formal education. There was 9.9% use of alcohol among the participants. The mean oral hygiene score for the participants was 1.94 (± 1.31). The prevalences for preterm deliveries, low birth weight and spontaneous abortion were 12.5%, 12.1% and 1.42% respectively. CONCLUSION: This study confirms periodontal disease as a probable risk for adverse pregnancy outcomes such as preterm delivery and low birth weight. Therefore, health workers should be encouraged to promote good oral health among women.

Chemoresistance can be overcome with high-dose chemotherapy and autologous stem-cell transplantation for relapsed and refractory Hodgkin lymphoma.

BACKGROUND: High-dose therapy and autologous stem-cell transplant (HDT/ASCT) is the preferred treatment of chemosensitive relapsed/refractory Hodgkin lymphoma (HL). The role for HDT/ASCT in chemoresistant HL is less well defined. We evaluated long-term outcomes of relapsed/refractory HL patients whose disease was refractory to secondary chemotherapy preceding HDT/ASCT. PATIENTS AND METHODS: All HL patients who underwent HDT/ASCT in British Columbia for primary progression (PP, defined as progression within 3 months of initial therapy completion) or first relapse (REL1) were reviewed. Patients were grouped based on response to secondary chemotherapy as sensitive (S), resistant (R), and untested/unknown (U). RESULTS: A total of 256 patients underwent HDT/ASCT for PP (35%) or REL1 (65%) between 1985 and 2011. At median follow-up of 11.7 years, 58% were alive without HL, 36% relapsed; 6% died of transplant-related mortality, 3% secondary malignancies, and 3% unrelated causes. For PP/S, PP/R, and PP/U groups, 10-year FFS were 47%, 31%, and 38%; 10-year OS were 52%, 29%, and 37%, respectively. For REL1/S, REL1/R, and REL1/U groups, 10-year FFS were 64%, 51%, and 81%; 10-year OS were 71%, 59%, and 79%, respectively. In multivariate analysis, resistance to secondary chemotherapy predicted for post-transplant mortality in the PP (P = 0.04) but not REL1 (P = 0.16) groups. CONCLUSION: In this large uniformly treated cohort of HL patients with long-term follow-up, chemoresistance preceding HDT/ASCT was identified as a poor prognostic factor; however, this factor can be partially overcome by HDT/ASCT, resulting in cure in 30%-50% of patients. HDT/ASCT should therefore be considered in all transplant eligible patients, regardless of responsiveness to salvage chemotherapy.

Self-Reported Medical Conditions and Oral Health Status of Patients seen in a Nigerian Dental Clinic.

OBJECTIVE: To assess the prevalence of self-reported medical conditions among patients attending a dental clinic in Nigeria. SUBJECTS AND METHODS: This was a cross-sectional study conducted at the Oral Diagnosis Clinic of the Lagos University Teaching Hospital. A self-administered questionnaire was used to collect bio-data and history of medical conditions. Oral examination was carried out on all the patients. Teeth present, carious teeth, mobile teeth and the oral hygiene status were recorded. Data entry and analysis was done using SPSS statistical software. RESULTS: The prevalence of self-reported medical conditions in this study was 22.1%. Hypertension was the most prevalent (10.3%), followed by allergies (4.4%), diabetes mellitus (4%) and gastrointestinal disorders (3%). Hypertension (p=0.000) and diabetes (p=0.000) had a statistically significant association with increasing age. The prevalence of medical conditions increased significantly with the increased number of mobile teeth (p=0.033). There was no statistically significant association between the self-reported medical conditions and the number of carious teeth (p=0.619), the oral hygiene status (p=0.765) and the educational level (p=0.712). CONCLUSION: The prevalence of medical conditions among the dental patients was moderate.

Hyperspectral imaging of gel pen inks: an emerging tool in document analysis.

Hyperspectral imaging (HSI) is a useful technique in the examination of writing inks, including gel pen inks, which combines digital imaging with % reflectance spectroscopy. This facilitates the detection of subtle differences between chemically similar inks. This study analysed a variety of blue, red and black gel inks on white office paper using HSI. The potential of the technique for ink discrimination compared to other analytical methods of examination is highlighted. Discriminating powers of 1.00, 0.90 and 0.40 were achieved using HSI for red, blue and black gel inks respectively. The overall discriminating power of 0.76 for the technique combined with its non-destructive nature and minimal sampling requirements demonstrates promise for this type of application.