Treatment patterns and intensification within 5 year of follow-up of the first-line anti-TNFα used for the treatment of IBD: Results from the VERNE study.

BACKGROUND: Anti-TNFα represent one of the main treatment approaches for the management of inflammatory bowel diseases (IBD). Therefore,the evaluation of their treatment patterns over time provides valuable insights about the clinical value of therapies and associated costs. AIMS: To assess the treatment patterns with the first anti-TNFα in IBD. METHODS: Retrospective, observational study. RESULTS: 310 IBD patients were analyzed along a 5-year follow-up period. 56.2% of Crohn's disease (CD) patients started with adalimumab (ADA), while 43.8% started with infliximab (IFX). 12.9% of ulcerative colitis (UC) patients initiated with ADA, while 87.1% initiated with IFX. Treatment intensification was required in 28.9% of CD and 37.1% of UC patients. Median time to treatment intensification was shorter in UC than in CD (5.3 vs. 14.3 months; p = 0.028). Treatment discontinuation due to reasons other than remission were observed in 40.7% of CD and 40.5% of UC patients, although, in UC patients there was a trend to lower discontinuation rates with IFX (36.6%) than with ADA (66.7%). Loss of response accounted for approximately one-third of discontinuations, in both CD and UC. CONCLUSIONS: Around one-third of IBD biologic-naive patients treated with an anti-TNFα required treatment intensification (earlier in UC) and around 40% discontinued the anti-TNFα due to inappropriate disease control.

Treatment outcomes of induction chemotherapy combined with intensity-modulated radiotherapy and adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma in Southeast China.

ABSTRACT: Induction chemotherapy (IC) and adjuvant chemotherapy (AC) are used to enhance tumor locoregional control and support early treatment for distant metastases. However, optimum combinatorial treatment of these chemoradiotherapy regimens with radiotherapy in curing locoregionally advanced nasopharyngeal carcinoma (NPC) remains unclear. Here, we evaluate the efficacy and therapeutic outcome of a combinatorial treatment strategy involving IC, intensity-modulated radiotherapy (IMRT), and AC, by retrospectively analyzing 243 NPC patients who were treated by IC followed by IMRT and AC. The rates of 3-/5-year local-regional control rate, distant failure-free rate (DFFR), progression-free survival (PFS), and overall survival (OS) were 93.3%/90.3%, 84.2%/79.4%, 79.6%/74.4%, and 84.0%/72.6%, respectively. The 3-/5-year OS rates of patients in stage III or IVA were 91.5%/75.1% and 86.5%/56.5%, respectively. Combination cisplatin with paclitaxel showed no significance in OS as compared to cisplatin plus 5-fluorouracil (P-value = .17). Total four-cycle IC and AC was significantly beneficious versus three-cycle in DFFR (P-value = .04), as well as total 6 chemotherapy cycles compared to 4 in DFFR and PFS (P-value = .03 and P-value = .01, respectively). All survival indicators were adversely affected by T-category, while N-category could only predict DFFR and PFS. Radiation dosage represented as a second prognostic factor for local control. We propose that IC combined with IMRT and AC for locoregionally advanced NPC shows effective treatment outcomes.

Treatment patterns and outcomes of older patients with mantle cell lymphoma in an Asian population.

BACKGROUND: Significant progress has been made in the treatment outcomes of mantle cell lymphoma (MCL) since the introduction of cytarabine and rituximab in modern regimens. However, older patients may not readily tolerate these agents nor derive benefit. We investigated the impact of age on treatment patterns and clinical outcomes of MCL patients in an Asian population. METHODS: A retrospective study was conducted on patients (n = 66) diagnosed with MCL at the National Cancer Centre Singapore between 1998 and 2018. The median follow-up duration was 40 months. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. RESULTS: The median age of the cohort was 59 years (range, 26-84), with a male predominance (73%). The majority (86%) had advanced stage 3-4 disease at diagnosis. Compared with younger patients, older patients aged ≥60 years (n = 32; 48.5%) presented more frequently with B-symptoms (75% vs 38%, p = 0.0028), anaemia (75% vs 35%, p = 0.0013), and carried higher prognostic risk scores (sMIPI high risk 84% vs 56%, p = 0.016). Non-cytarabine-based induction chemotherapy was more commonly administered in older patients (76% vs 32%, p = 0.0012). The 5-year overall survival (OS) and progression-free survival (PFS) was 68 and 25% respectively. In a multivariable model, older age (HR 3.42, 95%CI 1.48-7.92, p = 0.004) and anemia (HR 2.56, 95%CI 1.10-5.96, p = 0.029) were independently associated with poorer OS while older age (HR 2.24, 95%CI 1.21-4.14, p = 0.010) and hypoalbuminemia (HR 2.20, 95%CI 1.17-4.13, p = 0.014) were independently associated with poorer PFS. In an exploratory analysis, maintenance rituximab following induction chemotherapy improved PFS in younger patients, with median PFS of 131 months and 45 months with or without maintenance therapy respectively (HR 0.39, 95%CI 0.16-0.93, p = 0.035). In contrast, no survival benefit was observed in older patients. CONCLUSIONS: We demonstrated in our analysis that older patients with MCL may harbor adverse clinical features and may not derive benefit from maintenance rituximab, highlighting the need for further research in this area of need.

Epidemiology of acute myeloid leukemia in Virginia: Excellent survival outcomes for patients in rural Appalachia.

BACKGROUND: Acute myeloid leukemia, the most common acute leukemia in adults, has a poor overall survival. Studies have suggested that certain socioeconomic factors such as living in a rural or farming area are associated with worse outcomes. Since 42% of acute myeloid leukemia patients seen in our academic center reside in a rural area, we have a unique opportunity to study outcomes of patients in rural versus urban settings. AIM: This analysis evaluates the effect of geography and socioeconomic factors on the biology, treatment, and overall survival of patients with acute myeloid leukemia, with the goal of understanding health care disparities. METHODS AND RESULTS: Patient characteristics, cytogenetic data, treatment history, and overall survival were collected and analyzed to identify differences between urban and rural residency. This cohort included 42% of patients who resided in a rural area at the time of acute myeloid leukemia diagnosis. There was no difference in overall survival between the cohorts. The 1 year overall survival for the entire cohort was 47.9%. There was no difference detected in rates of adverse cytogenetics between the rural and urban cohorts. Similar numbers of patients received induction chemotherapy or proceeded to allogeneic stem cell transplant between the cohorts. CONCLUSIONS: This study highlights that similar outcomes can be achieved in rural and urban patients, suggesting that intensive efforts at telehealth, education, and collaboration with local oncology practices may be beneficial.

Non-maintenance intravesical Bacillus Calmette-Guérin induction therapy with eight doses in patients with high- or highest-risk non-muscle invasive bladder cancer: a retrospective non-randomized comparative study.

BACKGROUND: To explore possible solutions to overcome chronic Bacillus Calmette-Guérin (BCG) shortage affecting seriously the management of non-muscle invasive bladder cancer (NMIBC) in Europe and throughout the world, we investigated whether non-maintenance eight-dose induction BCG (iBCG) was comparable to six-dose iBCG plus maintenance BCG (mBCG). METHODS: This observational study evaluated 2669 patients with high- or highest-risk NMIBC who treated with iBCG with or without mBCG during 2000-2019. The patients were classified into five groups according to treatment pattern: 874 (33%) received non-maintenance six-dose iBCG (Group A), 405 (15%) received six-dose iBCG plus mBCG (Group B), 1189 (44%) received non-maintenance seven-/eight-dose iBCG (Group C), 60 (2.2%) received seven-/eight-dose iBCG plus mBCG, and 141 (5.3%) received only ≤5-dose iBCG. Recurrence-free survival (RFS), progression-free survival, and cancer-specific survival were estimated and compared using Kaplan-Meier analysis and the log-rank test, respectively. Propensity score-based one-to-one matching was performed using a multivariable logistic regression model based on covariates to obtain balanced groups. To eliminate possible immortal bias, 6-, 12-, 18-, and 24-month conditional landmark analyses of RFS were performed. RESULTS: RFS comparison confirmed that mBCG yielded significant benefit following six-dose iBCG (Group B) in recurrence risk reduction compared to iBCG alone (groups A and C) before (P < 0.001 and P = 0.0016, respectively) and after propensity score matching (P = 0.001 and P = 0.0074, respectively). Propensity score-matched sequential landmark analyses revealed no significant differences between groups B and C at 12, 18, and 24 months, whereas landmark analyses at 6 and 12 months showed a benefit of mBCG following six-dose iBCG compared to non-maintenance six-dose iBCG (P = 0.0055 and P = 0.032, respectively). There were no significant differences in the risks of progression and cancer-specific death in all comparisons of the matched cohorts. CONCLUSIONS: Although non-maintenance eight-dose iBCG was inferior to six-dose iBCG plus mBCG, the former might be an alternative remedy in the BCG shortage era. To overcome this challenge, further investigation is warranted to confirm the real clinical value of non-maintenance eight-dose iBCG.

Evaluation of ustekinumab trough levels during induction and maintenance therapy with regard to disease activity status in difficult to treat Crohn disease patients.

ABSTRACT: Ustekinumab (UST) is approved for the treatment of moderate and severe Crohn disease (CD). Therapeutic drug monitoring (TDM) can help monitor the therapeutic effects of biologics. Therefore, the aim of this study was to evaluate the clinical outcomes of UST-treated CD patients and to determine the UST trough level in clinical and corticosteroid-free remission.This retrospective study included patients with moderate and severe active disease (AD) treated intravenously with a weight-adapted induction dose of UST. The maintenance therapy consisted of 90 mg UST subcutaneously at week 8 and thereafter every 8 or 12 weeks, depending on the clinical response. Clinical and corticosteroid-free remission, Harvey-Bradshaw-Index (HBI), UST trough level, and further laboratory parameters were measured just before the injection of UST at each follow-up evaluation until week 40.37 CD patients with a median HBI of 9 at week 0 were included in the study. Starting from 24% at the beginning of the monitoring period, and 38% of patients at the end of the monitoring period were treated with an 8-week interval (P = .18). There was a significant improvement in clinical (P = .0004), corticosteroid-free remission (P = .03), and HBI (P < .0001) from week 0 until the end of the observation period. The serum UST trough level decreased significantly from 2.0 at week 8 to 0.3, in the maintenance therapy and 0.4 µg/ml at the end of the therapy (P < .0001). Neither UST trough level nor levels of C-reactive protein (CRP) or fecal calprotectin (FC) were associated with disease outcome. Concomitant immunomodulator therapy did not appear to affect the UST trough level or clinical course.UST is an effective treatment option for difficult-to-treat patients with CD. UST trough levels may not be associated with treatment efficacy or the prediction of treatment outcomes in patients with CD. Further prospective randomized trials should be conducted to evaluate whether UST trough levels are associated with treatment outcomes in patients with CD.

Outcomes for Patients With Acute Promyelocytic Leukemia in South Africa.

BACKGROUND: The characteristics and outcomes of patients with acute promyelocytic leukemia (APL) from sub-Saharan Africa have not been published. PATIENTS AND METHODS: We report retrospectively on consecutively diagnosed APL patients treated in Cape Town, South Africa, during 1998-2019. A total of 69 patients were treated, of whom 27 (39%) were classified as having high risk APL. RESULTS: Early death rates at 7 and 30 days were 7% and 13%, respectively, including 4 patients who died before any treatment could be administered. Overall survival at 3 years was 76.5% (95% confidence interval, 63.9-85.2) for the entire cohort, and 82.5% (95% confidence interval, 69.7-90.2) if patients who died within 7 days of diagnosis were excluded. For 13 patients (18.8%), there was a delay of 5 or more days from time of initial presentation at a peripheral hospital until arrival at the leukemia center and administration of all-trans retinoic acid; only 1 of these patients died within 30 days. CONCLUSION: Despite the challenges faced in the public healthcare system of a developing country, outcomes of APL patients treated at our center are similar to outcomes from developed countries.

Early predictors of renal outcome in patients with proliferative lupus nephritis: a 36-month cohort study.

OBJECTIVES: To identify predictors of complete renal response (CRR) and renal flares in SLE patients with active proliferative LN. METHODS: This was a retrospective cohort study over 36 months including patients with biopsy-proven proliferative LN (class III/IV), from two European tertiary centres. CRR and renal flare were defined as proteinuria <0.5 g/day with normal renal function and proteinuria >1 g/day after CRR attainment, respectively. Demographic, clinical and analytic parameters were evaluated as early predictors of renal outcome, using survival analysis. Candidate variables were tested as predictors for CRR at time 0, 3 and 6 months after starting induction treatment. Potential predictors for renal flare were evaluated at time of reaching CRR. Variables with P < 0.10 on univariate analysis with log-rank tests were further tested with multivariate Cox proportional hazards regression models. RESULTS: We included 104 patients [81.7% female, mean (s.d.) age at baseline 32.0 (13.3) years]. Over follow-up, 91.7% reached CRR, within a median time of 6.0 months. Proteinuria <2 g/day at baseline [hazard ratio (HR) = 1.80, 95% CI 1.16, 2.79, P < 0.01] and 3 months (HR = 2.32, 95% CI 1.24, 4.32, P < 0.01) after starting induction therapy were independent predictors of CRR. Renal flares occurred in 18.4% of patients reaching CRR, after a mean time of 16.5 (8.6) months. Age up to 25 years at time of LN diagnosis (HR = 5.41, 95% CI 1.72, 16.97, P < 0.01) and positive anti-RNP (HR = 3.52, 95% CI 1.21, 10.20, P = 0.02) were independent predictors of renal flares. CONCLUSION: In patients with SLE and proliferative LN, factors assessed at baseline and 3 months from starting induction treatment can predict CRR and renal flares once CRR is achieved.

Variation in immunosuppression practices among pediatric liver transplant centers-Society of Pediatric Liver Transplantation survey results.

BACKGROUND: Variation in IS exists among pediatric liver transplant centers. While individual centers may publish their practice paradigms, current data on practices as a whole are lacking. This study sought to ascertain the IS protocols of pediatric liver transplant centers within the SPLIT to better understand variability and similarities among peer institutions. METHODS: A 27-item questionnaire was developed within the SPLIT Quality Improvement and Clinical Care Committee. The survey collected data regarding center demographics, IS practices, and treatment of acute cellular rejection. RESULTS: Twenty-eight (64%) SPLIT centers responded with 22 (79%) centers performing more than 10 transplants per year and 17 (61%) following more than 100 post-transplant recipients. All centers use a written protocol, and 25 (89%) have a dedicated transplant pharmacist/PharmD. Twenty-five (89%) centers use steroids for induction alone or in combination with thymoglobulin/interleukin-2 antibodies. All centers use tacrolimus for initial maintenance therapy. Most centers have specialized protocols for ABO-incompatible transplants, recipients with renal dysfunction, autoimmune liver diseases, and liver tumors. Treatment of rejection varied but was associated with escalation in IS. CONCLUSION: IS practices among pediatric liver transplant centers are similar including the use of written protocols, pharmacy involvement, steroids for induction, tacrolimus as initial IS, tacrolimus reduction/delay for renal dysfunction, and escalation of IS with rejection severity. However, other IS practices show wide variability including treatment for ABO-incompatible grafts and presumed rejection. This study serves as a foundation to guide prospective research linking IS practice to outcomes to determine best practice.

Decrease in treatment intensity predicts worse outcome in patients with locally advanced head and neck squamous cell carcinoma undergoing radiochemotherapy.

PURPOSE: Radiochemotherapy (RCT) is an effective standard therapy for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Nonetheless, toxicity is common, with patients often requiring dose modifications. METHODS: To investigate associations of RCT toxicities according to CTCAE version 5.0 and subsequent therapy modifications with short- and long-term treatment outcomes, we studied all 193 patients with HNSCC who received RCT (70 Gy + platinum agent) at an academic center between 03/2010 and 04/2018. RESULTS: During RCT, 77 (41%, 95% CI 34-49) patients developed at least one ≥ grade 3 toxicity, including seven grade 4 and 3 fatal grade 5 toxicities. The most frequent any-grade toxicities were xerostomia (n = 187), stomatitis (n = 181), dermatitis (n = 174), and leucopenia (n = 98). Eleven patients (6%) had their radiotherapy schedule modified (mean radiotherapy dose reduction = 12 Gy), and 120 patients (64%) had chemotherapy modifications (permanent discontinuation: n = 67, pause: n = 34, dose reduction: n = 7, change to other chemotherapy: n = 10). Objective response rates to RCT were 55% and 88% in patients with and without radiotherapy modifications (p = 0.003), and 84% and 88% in patients with and without chemotherapy modifications (p = 0.468), respectively. Five-year progression-free survival estimates were 20% and 50% in patients with and without radiotherapy modifications (p = < 0.001), and 53% and 40% in patients with and without chemotherapy modifications (p = 0.88), respectively. CONCLUSIONS: Reductions of radiotherapy dose were associated with impaired long-term outcomes, whereas reductions in chemotherapy intensity were not. This suggests that toxicities during RCT should be primarily managed by modifying chemotherapy rather than radiotherapy.

Nationwide variability in the use of induction immunosuppression for adult heart transplantation.

BACKGROUND: Institutional factors have been shown to impact outcomes following orthotopic heart transplantation (OHT). This study evaluated center variability in the utilization of induction therapy for OHT and its implications on clinical outcomes. METHODS: Adult OHT patients between 2010 and 2018 were identified from the United Network for Organ Sharing registry. Transplant centers were stratified based on their rates of induction therapy utilization. Mixed-effects logistic regression models were created with drug-treated rejection within 1 year as primary endpoint and individual centers as a random parameter. Risk-adjusted Cox regression was used to evaluate patient-level mortality outcomes. RESULTS: In 17,524 OHTs performed at 100 centers, induction therapy was utilized in 48.6% (n = 8411) with substantial variability between centers (interquartile range, 21.4%-79.1%). There were 36, 30, and 34 centers in the low (<29%), intermediate (29%-66%), and high (>67%) induction utilization terciles groups, respectively. Induction therapy did not account for the observed variability in the treated rejection rate at 1 year among centers after adjusting for donor and recipient factors (p = .20). No differences were observed in postoperative outcomes among induction utilization centers groups (all, p > .05). Furthermore, there was a weak correlation between the percentage of induction therapy utilization at the center-level and recipients found to have moderate (r = .03) or high (r = .04) baseline risks for acute rejection at 1 year. CONCLUSIONS: This analysis demonstrates that there is substantial variability in the use of induction therapy among OHT centers. In addition, there was a minimal correlation with baseline recipient risk or 1-year rejection rates, suggesting a need for better-standardized practices for induction therapy use in OHT.

Prognostic Factors in Childhood Acute Myeloid Leukemia; Experience from A Developing Country.

BACKGROUND: In the developed world, 5-years survival of childhood acute myeloid leukaemia (AML) has improved to 70%. However, the survival rates in the developing world are below 40%. The main contributing factors to these reduced survival rates are a late presentation, malnutrition and high treatment-related mortality. AIM: To document the factors affecting treatment outcome of childhood AML at a tertiary care facility of Pakistan. METHODS AND RESULTS: All newly registered cases of AML under 18 years of age from January 1, 2012 onwards who completed their treatment before November 30, 2019 were included. Data of 219 cases of AML containing 140 (63.9%) males and 79 (36.1%) females was analyzed. The mean age was 6.30 ± 3.66 years. Pallor was the commonest presenting features in 180 (82.2%) and M2 was the commonest French American-British (FAB) subtype in 103 (47.0%) cases. In univariate analysis, high white blood cells (WBC) count at presentation (P = .006), poor nutritional status (P = .005), unfavourable cytogenetics (P = .019), certain types of FAB AML subtype (P = .005), and use of etoposide in induction chemotherapy (P = .042) significantly adversely affected overall survival (OS). Neutropenic sepsis and bleeding were the major causes of treatment-related mortality. Response to induction chemotherapy was the most significant prognostic factor in the multivariate analysis (P = <.001). After a median follow-up of 40.96 ± 26.23 months, 5-year OS and DFS of the cohort were 40.6% and 38.3% respectively. CONCLUSIONS: In this largest cohort of childhood AML from Pakistan, high WBC count at presentation, malnutrition, unfavourable cytogenetics and use of etoposide during induction chemotherapy were associated with decreased OS and DFS rates. Response to the induction chemotherapy was the most significant prognostic factor.

Randomized phase III trial comparing switch-maintenance pemetrexed with observation followed by pemetrexed at progression in advanced NSCLC.

Objectives: Two phase III trials show that maintenance pemetrexed therapy after platinum-doublet chemotherapy prolongs overall survival (OS) and progression free survival (PFS) in advanced non-squamous non-small-cell lung cancer (NSCLC). However, few patients in the control arms received pemetrexed at progression in these trials, performance status (PS) two patients were ineligible and few of the participants were elderly. Thus, we designed this study comparing immediate switch-maintenance pemetrexed therapy with pemetrexed at progression after platinum-doublet chemotherapy.Methods: Patients with stage IIIB/IV non-squamous NSCLC, ≥18 years, PS 0-2, and non-progression after four courses of carboplatin/vinorelbine were randomized to receive immediate maintenance pemetrexed therapy or observation followed by pemetrexed at progression. The primary endpoint was OS, secondary endpoints were PFS, toxicity and health related quality of life (HRQoL).Results: 105 patients were randomized between May 2014 and September 2017. Median age was 67 years, 36% were >70 years, 9% had PS 2, 91% stage IV and 47% were women. In the observation arm, 73% received pemetrexed at progression. Patients in the maintenance arm had a numerically longer OS (median 12.0 vs. 10.0 months; p = .10) and a statistically significant longer PFS (median 3.1 vs. 1.9 months; p < .01). In multivariable analyses adjusting for baseline characteristics, there was a trend toward improved OS (HR 0.65, 95% CI 0.42-1.01); p = .05), and a significantly improved PFS (HR 0.53, 95% CI 0.35-0.80; p < .01). There were no significant differences in toxicity or HRQoL between the treatment arms.Conclusion: There was a trend toward prolonged OS and significantly longer PFS from switch- maintenance pemetrexed therapy when 73% of patients in the control arm received pemetrexed at progression. ClinicalTrials.gov Identifier: NCT02004184.

Treatment Pathways Leading to Biologic Therapies for Ulcerative Colitis and Crohn's Disease in the United States.

OBJECTIVES: Biologic therapies have been available for inflammatory bowel disease for >20 years, but patient outcomes have not changed appreciably over this time period. To better understand medication utilization for this disease, we evaluated a novel technique for visualizing treatment pathways, including initial treatment, switching, and combination therapies. METHODS: This retrospective, observational study used administrative claims data from the Truven Health MarketScan Commercial and Medicare Database. Adult patients with ≥2 consecutive health claims and newly diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) were evaluated. Treatment pathways were visualized using Sankey diagrams representing the number of patients receiving treatment and duration of each treatment. RESULTS: In all, 28,119 patients with UC and 16,260 patients with CD were identified. The most common initial treatment for UC was 5-aminosalicylic acid monotherapy (61% of the patients), followed by corticosteroid monotherapy (25%); <1% of patients were initially treated with biologics. The most common initial treatment for CD was corticosteroid monotherapy (42%), followed by 5-aminosalicylic acid monotherapy (35%); <5% of the patients were initially treated with biologics. Significantly fewer patients followed biologic vs nonbiologic treatment pathways (UC: 6% vs 94%, CD: 19% vs 81%, both P < 0.05). DISCUSSION: Significantly fewer patients with inflammatory bowel disease followed treatment pathways that included biologic therapies compared with nonbiologic therapies, and very few patients were ever initiated on biologic therapy. Although we have made significant progress in treatment, our most effective medications are only being used in a small proportion of patients, suggesting barriers prevent optimized patient management.

Induction Chemotherapy in Patients With Anal Canal Cancer: A Pilot Study.

PURPOSE: To investigate the role of induction chemotherapy (IC) followed by definitive chemoradiotherapy in people with anal canal cancer with bulky disease at diagnosis. PATIENTS AND METHODS: We assessed patient acceptability and treatment feasibility of IC in patients with bulky anal canal malignant lesions. RESULTS: Theoretical IC advantages may include tumor downsizing and early micrometastasis eradication, without affecting compliance with subsequent standard chemoradiotherapy regimens, as a result of improvement of oxygenation and higher intramural concentration of cytotoxic drugs. CONCLUSION: The study design should be proven feasible, with a satisfactory patient acceptance rate and an optimized work flow. To our knowledge, this study is the first trial to investigate the use of IC in the population of patients with bulky anal canal cancer.

National management trends in clinical stage IIA nonseminomatous germ cell tumor (NSGCT) and opportunities to avoid dual therapy.

INTRODUCTION: For marker-negative clinical stage (CS) IIA nonseminomatous germ cell tumor (NSGCT), National Comprehensive Cancer Network and American Urological Association guidelines recommend either retroperitoneal lymph node dissection (RPLND) or induction chemotherapy. The goal is cure with one form of therapy. We evaluated national practice patterns in the management of CSIIA NSGCT and utilization of secondary therapies. METHODS: The National Cancer Data Base was used to identify 400 men diagnosed with marker negative CSIIA NSGCT between 2004 and 2014 treated with RPLND or chemotherapy. Trends in the utilization of initial and adjuvant treatment (chemotherapy only, RPLND only, RPLND with adjuvant chemotherapy, and postchemotherapy RPLND) were analyzed. RESULTS: Of the 400 cases, 233 (58%) underwent induction chemotherapy with surveillance, 51 (20%) underwent RPLND with surveillance, 89 (22%) underwent RPLND followed by adjuvant chemotherapy, and 14 (4%) underwent induction chemotherapy followed by RPLND. Thirty percent of patients received dual therapy. After RPLND with pN1 staging, 43 (61%) underwent adjuvant chemotherapy. The pN0 rate after primary RPLND was 22%. Five year overall survival ranged from 95% to 100% based on initial treatment choice. CONCLUSIONS: For marker negative CS IIA nonseminoma, dual, therapy, and treatment with chemotherapy is common. With low volume retroperitoneal disease resected at RPLND, adjuvant chemotherapy was frequently administered but has debatable therapeutic value. These data highlight opportunities to decrease treatment burden in patients with CS IIA nonseminoma.

Deep learning pathological microscopic features in endemic nasopharyngeal cancer: Prognostic value and protentional role for individual induction chemotherapy.

BACKGROUND: To explore the prognostic value and the role for treatment decision of pathological microscopic features in patients with nasopharyngeal carcinoma (NPC) using the method of deep learning. METHODS: The pathological microscopic features were extracted using the software QuPath (version 0.1.3. Queen's University) in the training cohort (Guangzhou training cohort, n = 843). We used the neural network DeepSurv to analyze the pathological microscopic features (DSPMF) and then classified patients into high-risk and low-risk groups through the time-dependent receiver operating characteristic (ROC). The prognosis accuracy of the pathological feature was validated in a validation cohort (n = 212). The primary endpoint was progression-free survival (PFS). RESULTS: We found 429 pathological microscopic features in the H&E image. Patients with high-risk scores in the training cohort had shorter 5-year PFS (HR 10.03, 6.06-16.61; P < .0001). The DSPMF (C-index: 0.723) had the higher C-index than the EBV DNA (C-index: 0.612) copies and the N stage (C-index: 0.593). Furthermore, induction chemotherapy (ICT) plus concomitant chemoradiotherapy (CCRT) had better 5-year PFS to those received CCRT (P < .0001) in the high-risk group. CONCLUSION: The DSPMF is a reliable prognostic tool for survival risk in patients with NPC and might be able to guide the treatment decision.

Prevalence of endoscopic improvement and remission according to patient-reported outcomes in ulcerative colitis.

BACKGROUND: Treatment targets for ulcerative colitis are evolving towards achievement of endoscopic improvement and remission in addition to symptom resolution. It remains to be accurately quantified what proportion of patients with symptom resolution have residual endoscopic activity that might warrant treatment modification. AIM: To quantify the prevalence of endoscopic improvement and remission amongst ulcerative colitis patients with various permutations of patient-reported outcomes. METHODS: Individual participant data from active intervention and placebo arms of clinical trials of infliximab, golimumab, vedolizumab and tofacitinib were pooled to estimate the prevalence of endoscopic improvement (Mayo endoscopic sub-score [MES] 0 or 1) and remission (MES 0) scores with various permutations of the rectal bleeding sub-score (RBS) and stool frequency sub-score (SFS) of the Mayo score, following induction (6-8 weeks) and maintenance (30-54 weeks) therapy. Subgroup analyses were performed by year of publication and centrally read endoscopy scoring. RESULTS: Data from 2586 trial participants were analysed. Using locally scored endoscopy, the prevalence of endoscopic improvement and remission was highest among participants with a RBS 0 + SFS 0 post-induction (MES 0/1:81%, [95% CI 78-84]; MES 0:29% [26-33]) and during maintenance (MES 0/1:91% [87-93]; MES 0:57% [52-62]). Prevalence estimates were lower for more recently performed trials (P < .01). In comparison to locally scored endoscopy, when using central endoscopy scoring, the prevalence of endoscopic improvement and remission was lower post-induction (MES 0/1 57% [50-64], P < .001; MES 0 15% [11-21], P = .09) and during maintenance (MES 0/1 74% [67-81], P = .001; MES 0 31% [24-38], P = .001) for participants achieving a RBS 0 + SFS 0. CONCLUSIONS: Approximately 8 of 10 patients with normalisation of rectal bleeding and stool frequency have improvement in endoscopic disease activity, whereas approximately only half of these patients have endoscopic remission.

Effectiveness and safety of Ustekinumab for the treatment of Crohn's disease in real-life experiences: a meta-analysis of observational studies.

Background: The aim of this meta-analysis was to estimate the effectiveness and safety of Ustekinumab in Crohn's disease (CD) reported by observational studies.Research design and methods: PubMed/Medline and Embase were systematically searched through September 2019. Only real-life observational studies were included.Results: Thirteen studies comprising 1450 patients met the inclusion criteria. Ustekinumab was administered subcutaneously at induction among 7 studies, while in 6 studies the intravenous formulation was used. At induction (8-16 weeks), the pooled estimate rates of clinical response and remission were 56% (95% CI: 43-68%; range: 16-94%; I2 = 94%) and 34% (95% CI: 25-45%; range: 15-58%; I2 = 90%), respectively. The rate of clinical response was higher among studies which employed the subcutaneous compared with the intravenous induction (68% vs. 38%, p = 0.01). At maintenance, the pooled estimate rates of clinical response, clinical remission, endoscopic response, and endoscopic remission were 62% (95% CI: 50-73%; range: 42-89%; I2 = 89%), 40% (95% CI: 28-54%; range: 26-73%; I2 = 90%), 56% (95% CI: 37-73%; range: 20-77%; I2 = 87%), and 19% (95% CI: 11-30%; range: 7-31%; I2 = 67%), respectively.Conclusions: Ustekinumab is an effective treatment in patients with CD with a reassuring safety profile. The subcutaneous induction seems to be superior to the intravenous one.

Development and validation of a novel MR imaging predictor of response to induction chemotherapy in locoregionally advanced nasopharyngeal cancer: a randomized controlled trial substudy (NCT01245959).

BACKGROUND: In locoregionally advanced nasopharyngeal carcinoma (LANPC) patients, variance of tumor response to induction chemotherapy (ICT) was observed. We developed and validated a novel imaging biomarker to predict which patients will benefit most from additional ICT compared with chemoradiotherapy (CCRT) alone. METHODS: All patients, including retrospective training (n = 254) and prospective randomized controlled validation cohorts (a substudy of NCT01245959, n = 248), received ICT+CCRT or CCRT alone. Primary endpoint was failure-free survival (FFS). From the multi-parameter magnetic resonance images of the primary tumor at baseline, 819 quantitative 2D imaging features were extracted. Selected key features (according to their interaction effect between the two treatments) were combined into an Induction Chemotherapy Outcome Score (ICTOS) with a multivariable Cox proportional hazards model using modified covariate method. Kaplan-Meier curves and significance test for treatment interaction were used to evaluate ICTOS, in both cohorts. RESULTS: Three imaging features were selected and combined into ICTOS to predict treatment outcome for additional ICT. In the matched training cohort, patients with a high ICTOS had higher 3-year and 5-year FFS in ICT+CCRT than CCRT subgroup (69.3% vs. 45.6% for 3-year FFS, and 64.0% vs. 36.5% for 5-year FFS; HR = 0.43, 95% CI = 0.25-0.74, p = 0.002), whereas patients with a low ICTOS had no significant difference in FFS between the subgroups (p = 0.063), with a significant treatment interaction (pinteraction <  0.001). This trend was also found in the validation cohort with high (n = 73, ICT+CCRT 89.7% and 89.7% vs. CCRT 61.8% and 52.8% at 3-year and 5-year; HR = 0.17, 95% CI = 0.06-0.51, p <  0.001) and low ICTOS (n = 175, p = 0.31), with a significant treatment interaction (pinteraction = 0.019). Compared with 12.5% and 16.6% absolute benefit in the validation cohort (3-year FFS from 69.9 to 82.4% and 5-year FFS from 63.4 to 80.0% from additional ICT), high ICTOS group in this cohort had 27.9% and 36.9% absolute benefit. Furthermore, no significant survival improvement was found from additional ICT in both groups after stratifying low ICTOS patients into low-risk and high-risks groups, by clinical risk factors. CONCLUSION: An imaging biomarker, ICTOS, as proposed, identified patients who were more likely to gain additional survival benefit from ICT+CCRT (high ICTOS), which could influence clinical decisions, such as the indication for ICT treatment. TRIAL REGISTRATION: ClinicalTrials.gov , NCT01245959 . Registered 23 November 2010.