Benefit Versus Risk Assessment of Melflufen and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Analyses From Longer Follow-up of the OCEAN and HORIZON Studies

IntroductionMelphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone demonstrated superior progression-free survival (PFS) but directionally different overall survival (OS) favoring pomalidomide (hazard ratio [HR], 1.10) in OCEAN.MethodsThese analyses further investigated prognostic subgroups impacting survival in updated data from the randomized, phase 3 OCEAN study (NCT03151811; date: February 3, 2022) and the phase 2 HORIZON study (NCT02963493; date: February 2, 2022).ResultsIn OCEAN, subgroups prognostic for OS were age (P = .011; <65 years favored pomalidomide) and no previous autologous stem cell transplant (ASCT) or progression >36 months after ASCT (P = .001; favored melflufen). Overall, 245 of 495 (49%) patients randomized had received a previous ASCT, of which 202 (82%) had progressed within 36 months following their ASCT. When excluding patients who had progressed <36 months post-ASCT (melflufen group, n = 145; pomalidomide group, n = 148), median OS was 23.6 months with melflufen and 19.8 months with pomalidomide (HR, 0.83 [95% CI, 0.62-1.12]; P = .22). Among patients with triple-class refractory disease in HORIZON, patients who had progressed <36 months post-ASCT (n = 58) had a lower response rate and shorter duration of response and PFS than the remaining patients (n = 52). Safety was consistent with previous reports.ConclusionThese analyses demonstrate a consistent benefit for melflufen and dexamethasone in patients with relapsed/refractory multiple myeloma who have not received an ASCT or progressed >36 months after receiving an ASCT (ClinicalTrials.gov identifier: NCT03151811).     

An individual patient-data comparison of combined modality therapy and ABVD alone for patients with limited-stage Hodgkin lymphoma

BackgroundTreatment options for patients with nonbulky stage IA–IIA Hodgkin lymphoma include combined modality therapy (CMT) using doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) plus involved-field radiation therapy (IFRT), and chemotherapy with ABVD alone. There are no mature randomized data comparing ABVD with CMT using modern radiation techniques.Patients and methodsUsing German Hodgkin Study Group HD10/HD11 and NCIC Clinical Trials Group HD.6 databases, we identified 588 patients who met mutually inclusive eligibility criteria from the preferred arms of HD10 or 11 (n = 406) and HD.6 (n = 182). We evaluated time to progression (TTP), progression-free (PFS) and overall survival, including in three predefined exploratory subset analyses.ResultsWith median follow-up of 91 (HD10/11) and 134 (HD.6) months, respective 8-year outcomes were for TTP, 93% versus 87% [hazard ratio (HR) 0.44, 95% confidence interval (CI) 0.24–0.78]; for PFS, 89% versus 86% (HR 0.71, 95% CI 0.42–1.18) and for overall survival, 95% versus 95% (HR 1.09, 95% CI 0.49–2.40). In the exploratory subset analysis including HD10 eligible patients who achieved complete response (CR) or unconfirmed complete response (CRu) after two cycles of ABVD, 8-year PFS was 87% (HD10) versus 95% (HD.6) (HR 2.8; 95% CI 0.64–12.5) and overall survival 96% versus 100%. In contrast, among those without CR/CRu after two cycles of ABVD, 8-year PFS was 88% versus 74% (HR 0.35; 95% CI 0.16–0.79) and overall survival 95% versus 91%, respectively (HR 0.42; 95% CI 0.12–1.44).ConclusionsIn patients with nonbulky stage IA–IIA Hodgkin lymphoma, CMT provides better disease control than ABVD alone, especially among those not achieving complete response after two cycles of ABVD. Within the follow-up duration evaluated, overall survivals were similar. Longer follow-up is required to understand the implications of radiation and chemotherapy-related late effects.Clinical trialsThe trials included in this analysis were registered at ClinicalTrials.gov: HD10 - NCT00265018, HD11 - NCT00264953, HD.6 - NCT00002561.     

自体造血干细胞移植治疗霍奇金淋巴瘤38例临床疗效及预后影响因素分析

目的 探讨自体造血干细胞移植（ASCT）治疗霍奇金淋巴瘤（HL）的临床疗效以及影响预后的因素。方法 回顾2007年10月至2021年10月于郑州大学附属肿瘤医院经ASCT治疗的HL38例患者资料,Kaplan-Meier和Cox方法分析移植后疗效以及预后影响因素。结果 38例移植患者均获得造血重建。全组患者移植前后CR率分别为55.3%和81.6%,5年PFS和OS分别为76.1%和79.0%。单因素分析显示B症状、IPS评分、移植前缓解状态、结外受累和预处理方案（均P<0.05）是影响HL患者ASCT预后的因素,多因素分析显示B症状（P<0.05）是影响5年PFS的独立危险因素。结论 ASCT治疗高危、复发难治HL患者的疗效显著,有B症状是影响移植预后的独立危险因素。     

Role of Bone Metastases in Patients Receiving Immunotherapy for Pre-Treated Urothelial Carcinoma: The Multicentre,Retrospective Meet-URO-1 Bone Study

BackgroundConsiderable numbers of patients with metastatic urothelial carcinoma (mUC) develop bone metastases (BoM). Their impact on the efficacy of immune-checkpoint inhibitors (ICIs) is not yet investigated.MethodsBetween July 2014 and August 2020 data on pts treated with single-agent ICIs after failure of at least 1 previous line of chemotherapy for advanced disease, were retrospectively collected across 14 Italian centers. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. Cox regression analysis was performed evaluating potential prognostic factors for OS and PFS. Each factor was evaluated in univariable (UVA) and multivariable analysis (MVA).ResultsA total of 208 evaluable patients treated with ICIs were identified, including 122 (59%) without BoM (BoM-) and 86 (41%) with bone metastases (BoM+). After a median follow-up of 22.3 months, BoM+ patients showed shorter OS (median 3.9 vs 7.8 months, HR 1.59 [95%CI, 1.15-2.20], P = .005) and shorter PFS (median 2.0 vs 2.6 months, HR 1.76 [95%CI, 1.31-2.37], P < .001). Probability of being alive was 62% vs 40% after 6 months, 38% vs 23% after 1 year and 24% vs 13% after 2 years, in BoM- and BoM+ respectively. Within each Bellmunt score, OS and PFS of BoM+ patients were shorter. Both presence of BoM and higher Bellmunt risk score were significantly associated with shorter OS and PFS in UVA and MVA.ConclusionPatients treated with single-agent ICIs for BoM+ mUC have a dismal prognosis compared to BoM-. Further research is needed to understand the mechanism behind these outcomes.     

Association of Circulating Tumor Cells and Tumor Molecular Profile With Clinical Outcomes in Patients With Previously Untreated Metastatic Colorectal Cancer: A Pooled Analysis of the Phase III VISNÚ-1 and Phase II VISNÚ-2 Randomized Trials

BackgroundThe bCTC count is a well-established prognostic biomarker in mCRC, as well as in other tumor types. The aim of this analysis was to evaluate the prognostic/predictive role of the bCTC count (≥3 vs. <3) in previously untreated mCRC.Patients and MethodsThe study involved 589 untreated mCRC patients included in the intention-to-treat population of 2 randomized clinical trials (phase III VISNU-1 [NCT01640405] and phase II VISNU-2 [NCT01640444] studies).ResultsOf the 589 patients, 349 (59.2%) had bCTC≥3 and 240 (40.7%) had bCTC<3. Multivariate analysis showed that the bCTC count is an independent prognostic factor for overall survival (OS) (HR 0.59, 95% CI 0.48-0.72; P = 0.000) and potential for progression-free survival (PFS) (P = 0.0549). Median OS was 32.9 and 19.5 months in patients with bCTC<3 and bCTC≥3 (P <0.001), respectively. This effect was also observed comparing OS in RASwt patients from both studies. Other prognostic factors were: ECOG-PS, primary tumor site, number of metastatic sites and surgery of the primary tumor. Median OS was lower for patients treated with anti-VEGF versus anti-EGFR (22.3 vs. 33.3 months, P <0.0001) while there were no significant differences in PFS according to the targeted treatment received.ConclusionThis post-hoc analysis of 2 randomized studies confirms the poor prognosis of patients with bCTC≥3 but this is not associated with other adverse independent prognostic factors such as RAS/BRAF mutations.     

Outcomes of Autologous Stem Cell Transplantation as a Consolidative Strategy for the Treatment of Primary and Isolated Secondary Central Nervous System Diffuse Large B Cell Lymphomas

IntroductionStandard consolidation for primary diffuse large B cell lymphoma (DLBCL) of the central nervous system (CNS) (PCNSL) is not established. This single center, retrospective observational study aims to define the outcomes of consolidative high dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) in patients with PCNSL and isolated secondary CNS DLBCL (SCNSL) and evaluate the prognostic factors.Patients and MethodsAll consecutive patients performed an HDC/ASCT for PCNSL or isolated SCNSLs between October 2012 and February 2022 were identified. Primary endpoints were progression-free survival (PFS) and overall survival (OS).ResultsAmong 35 patients included, 28 had PCNSL and 7 had isolated SCNSL. Median age was 51 (16-78). Males constituted 48.6%. Median follow-up after HDC/ASCT was 42.0 months. MATRIX (51.4%) and TEAM (80.0%) were the most frequent regimens of induction and conditioning, respectively. OS and PFS 1- and 2-year after HDC/ASCT were 68.0%, 57.0%, 58.0%, 48.0%, respectively. Increasing age, poor performance and comorbidities were associated with lower OS and PFS and higher non-relapse mortality (NRM). Complete response (CR) 1 at HDC/ACST was independently associated with higher OS and PFS [hazard ratio (HR): 4.67 and 6.99, respectively].ConclusionIn patients < 60 years consolidative HDC/ASCT yields promising OS and PFS. Patients ≥ 60 years may less likely benefit from consolidative HDC/ASCT and should be studied further in trials of novel agents, lower doses of consolidative radiotherapy and dose-adjusted conditioning regimens. Not only age, but also comorbidities, clinical performance and response to induction correlate with outcomes. Patients with isolated SCNSL may achieve similar outcomes.     

Potential Benefit of Involved-Field Radiotherapy for Patients With Relapsed-Refractory Hodgkin's Lymphoma With Incomplete Response Before Autologous Stem Cell Transplantation

IntroductionWe investigated for a possible role for peritransplantation involved-field radiotherapy (IFRT) by comparing patients who received IFRT before after autologous stem cell transplantation (ASCT) and patients who received salvage chemotherapy (CT) alone.Patients and MethodsWe retrospectively evaluated 73 consecutive patients with Hodgkin lymphoma treated with ASCT between 2003 and 2014. Twenty-one patients (28.8%) received peritransplantation radiotherapy. A Cox regression analysis (multivariate analysis; MVA) was performed to evaluate the prognostic role of any risk factor. Overall survival (OS) and progression-free survival (PFS) were calculated from the date of ASCT. Response to CT and ASCT were evaluated with positron emission tomography (PET) scan.ResultsMedian follow-up was 41 months (range, 1-136 months). Overall, no significant difference appeared between patients who received IFRT and patients treated with CT alone; however, patients who were treated with IFRT had worse prognostic factors. In the MVA, advanced stage at relapse and persistent disease before ASCT (evident on PET scan [PET+]) were related to worse PFS and OS. In patients with limited stage disease at relapse and PET+, peritransplantation radiotherapy showed higher 3-year OS rates (91.7% vs. 62.3%) and PFS rates (67.5% vs. 50%) compared with patients treated with CT alone, although this difference was not significant (P = .14 and P = .22, respectively).ConclusionIFRT used before or after ASCT might partially compensate for worse prognostic factors among the overall population; subgroup analysis showed a trend for survival benefit at 3 years in patients with limited stage disease at relapse and PET+ before ASCT.     

Long-term outcome of autologous stem-cell transplantation in relapsed or refractory Hodgkin's lymphoma

BackgroundThe purpose of this study was to assess prognostic factors and outcome of patients with relapsed/refractory Hodgkin's lymphoma (HL) who received high-dose chemotherapy and autologous stem-cell transplant (ASCT).Patients and methodsData on 195 patients who received ASCT between 1985 and June 2005 were reviewed. Median time from first treatment to ASCT was 2.6 years (0.4–27.3). Demography at ASCT was 61% stage IV, median age 31 years (18–69), median prior treatment (tx) regimens 3 (2–7), median Hasenclever index 3 (0–6); 150 patients had responding disease [54 complete remission (CR), 96 partial remission (PR)], and 45 patients had untested relapse/refractory disease.ResultsPost-ASCT, 61% (119/195) patients attained CR with an overall response (CR + PR) of 85%. Twelve patients had nonrelapse mortality. Of 119 patients attaining CR, 27 relapsed: 3 after attaining CR for >5 years and 1 after attaining CR for >10 years. Median overall survival (OS)/progression-free survival (PFS) from ASCT was 9 years/2.9 years. Five-year OS/PFS was 55% of 44% and 10-year OS/PFS was 49.4% of 37% for whole group. Twenty (10%) patients developed second cancer (seven secondary acute myeloid leukaemia (AML)/myelodysplastic syndrome (MDS)). Probability of developing second cancer at 10 years was 14.7% (95% confidence interval 8.9% to 23.8%) and 24.8% at 19 years.ConclusionThese data provide the longest follow-up reported for patients receiving ASCT for relapsed/refractory HL. In addition to previously described prognostic factors, our data show that Hasenclever index <3 influences outcome favorably and attaining CR at ASCT leads to a better outcome.     

Impact of Conditioning Regimen on Outcome of 2-Year Disease-Free Survivors of Autologous Stem Cell Transplantation for Hodgkin Lymphoma

BackgroundAutologous stem cell transplantation is the standard of care for patients with relapsed HL and the long-term outcomes for survivors 2 years after ASCT have not been well described. No prospective trials have compared the effect of different conditioning regimens on outcomes.Patients and MethodsWe searched the Nebraska Lymphoma Study Group database to identify patients with HL who received ASCT from 1984 to 2007. Patients were conditioned with either CBV (cyclophosphamide, carmustine, and etoposide) or BEAM (carmustine, etoposide, cytarabine, and melphalan).ResultsAt a median follow-up of 8 (range, 2-26) years, 225 patients were alive and disease-free 2 years after ASCT. Analysis was limited to these patients. At 5 years, the progression-free survival (PFS) was 92% for BEAM and 73% for CBV (P = .002) and the overall survival (OS) was 95% for BEAM and 87% for CBV (P = .07). At 10 years, the PFS was 79% for BEAM and 59% for CBV (P = .01) and the OS was 84% for BEAM and 66% for CBV (P = .02).ConclusionPatients with HL who are disease-free and alive 2 years after ASCT have favorable outcomes. We observed lower risk of progression and longer survival associated with use of BEAM vs. CBV. Patients in the BEAM group received a transplant in more recent years so we cannot exclude the possibility that the superior outcomes seen in the BEAM group are because of better supportive care, use of peripheral blood stem cell grafts, or improvements in salvage therapies before transplantation.     

Favorable Long-Term Outcomes with Autologous Stem Cell Transplantation for High-Risk Multiple Myeloma Patients with a Positive Result On 18F-FDG PET/CT at Baseline

Background18F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) is a useful tool for identifying high-risk features in patients with newly diagnosed multiple myeloma (NDMM). This study evaluated the role of autologous stem cell transplantation (ASCT) in patients presenting with positive results on PET/CT scans.Materials and MethodsThe medical records of 210 patients who underwent PET/CT at diagnosis were retrospectively reviewed. Eligible patients for transplantation proceeded to upfront ASCT with high-dose chemotherapy (HDT) after induction therapy with novel agents.ResultsThe presence of a number of focal lesions (FL) >3 and extramedullary disease (EMD) occurred in 111 and 35 patients, respectively. ASCT was performed in 54 patients. Among patients with FL > 3, those treated with ASCT showed a prolonged 2-year progression-free survival (PFS) and overall survival (OS) rates compared to those not treated with ASCT (PFS, 60.2% vs. 23.5%, P < 0.001; OS, 91.7% vs. 63.6%, P = 0.005). In patients with FL ≤ 3, treatment by ASCT was associated with a higher 2-year PFS rate than no treatment by ASCT (74.0% vs. 54.9%, P = 0.040). The OS of patients treated with ASCT was not significantly longer than that of patients not treated with ASCT (P = 0.115). In multivariate analysis, FL > 3, Revised International Staging System (R-ISS), and upfront ASCT were independent prognostic factors for PFS and OS.ConclusionPresenting FL > 3 on baseline PET/CT represents a high-risk feature in patients with NDMM. Frontline ASCT with HDT prolonged the survival of patients with FL > 3.     

Tumor Infiltrating Lymphocytes Predict Survival in Solid Organ Transplant Recipients With Monomorphic Post-transplant Lymphoproliferative Disorders

IntroductionThe tumor microenvironment (TME) in post-transplant lymphoproliferative disorders (PTLDs) remains unexplored. Tumor infiltrating lymphocytes (TILs) are prognostic in other lymphomas. We assessed the prognostic impact of TILs in monomorphic B-cell PTLD.MethodsTIL density (CD3+ cells/mm²) was determined by CD3 immunohistochemistry in archived diagnostic biopsies from patients diagnosed with monomorphic B-cell PTLD.ResultsAmongst monomorphic PTLDs (N = 107), low TIL-count was associated with inferior 2-year progression-free survival (PFS) (41% versus 86%, P = .003) and 2-year overall survival (OS) (52% versus 93%, P = .003) by Kaplan-Meier analysis. Low TIL-count was significant on Cox univariate regression for inferior PFS (HR 4.5, 95% CI 2.0-9.9, P < .001) and OS (HR 4.6, 95% CI 1.8-11.8, P < .001). Multivariate analysis with clinical variables (age ≥60 years, high LDH, stage III/IV, CNS involvement) and TIL-count showed significance for PFS (HR 3.3, 95% CI 1.3-8.3, P = .010) and a non-significant trend for OS (HR 2.6, 95% CI 0.9-7.3, P = .064). A composite score including TILs and clinical variables (age ≥60 years, high LDH, stage III/IV, CNS involvement) effectively stratified monomorphic PTLD patients by PFS and OS (2-year OS: low-risk 93%, intermediate-risk 61%, high-risk 23%, P < .001).ConclusionsThe TME and TILs are prognostically relevant in monomorphic PTLD. Prognostic models including measures of the TME may improve risk stratification for patients with monomorphic PTLDs.     

Impact of risk factors on outcomes in early-stage Hodgkin's lymphoma: an analysis of international staging definitions

BackgroundIn early-stage Hodgkin's lymphoma (HL), treatment according to the early favorable or unfavorable subgroup is guided by staging definitions, which differ between various study groups worldwide. We analyzed risk factors used in different international staging systems and their impact on the outcome of early-stage HL patients.Patients and methodsIn 1173 early-stage HL patients treated homogenously within the German Hodgkin Study Group (GHSG) trials HD10 and HD11, the impact of three staging systems developed and used by the GHSG, the European Organization for Research and Treatment of Cancer (EORTC), and the National Comprehensive Cancer Network (NCCN) in discriminating risk groups for progression-free survival (PFS) and overall survival (OS) was assessed and the relevance of their single risk factors was investigated.ResultsAll the three staging systems defined an unfavorable risk group out of early-stage patients of comparable size (56%, 55%, and 57%), having a significantly poorer PFS and OS as compared with the corresponding favorable group; 5-year differences between early favorable and early unfavorable in terms of PFS were 9.4% (HR 2.61, 95% CI 1.74–3.91), 6.7% (HR 2.10, 95% CI 1.41–3.13), and 8.6% (HR 2.14, 95% CI 1.45–3.16) with the GHSG, EORTC, and NCCN definition, respectively. Sensitivity was high for all systems (84%, 79%, and 83%); however, there was a low specificity with high rates of false-positive results (1-specificity 54%, 53%, and 55%, respectively). Models of high sensitivity included risk factors associated with large tumor burden and high tumor activity. Most risk factors for tumor-specific end points were also predictive of OS.ConclusionsDifferentiating between a favorable and an unfavorable risk group has significant impact on PFS and OS in early-stage HL patients in the modern treatment era. Risk-adapted treatment strategies using new risk factors with higher specificity are needed.     

DiM: Prognostic Score for Second- or Further-line Immunotherapy in Advanced Non–Small-Cell Lung Cancer: An External Validation

BackgroundOther than the programmed cell death ligand 1 (PD-L1) value, oncologists have only the clinical characteristics of patients with advanced non–small-cell lung cancer (aNSCLC) to determine candidates for immunotherapy. A clinical prognostic score composed of the Eastern Cooperative Oncology Group performance status, sex, histologic type, stage, platinum-based first-line therapy, and response to first-line therapy has categorized 3 prognostic groups for patients undergoing second-line chemotherapy. We sought to validate the same score for patients with aNSCLC treated with second- or further-line immunotherapy.Materials and MethodsWe collected data from 2 Italian centers. A score was generated to divide patients into 3 prognostic groups: best, score < 5; intermediate, score 5 to 9; and worst, score > 9. Overall survival (OS) and progression-free survival (PFS) were the endpoints.ResultsA total of 347 patients were included for analysis. Their median age was 66 years (range, 30-88 years), most were aged < 70 years (67.5%), 70.7% were men, 79.5% were smokers, and 74.6% had had adenocarcinoma. The Eastern Cooperative Oncology Group performance status was 0 for 23%, 1 for 54.5%, and 2 for 22.5%. Of the 347 patients, 28% were in the best prognosis, 51% in the intermediate, and 21% in the worst prognosis group, respectively. The median OS was 18.0 months for the best, 8.5 months for the intermediate (hazard ratio [HR] vs. best, 1.83; 95% confidence interval [CI], 1.35-2.47; P < .001) and 2.6 months for worst (HR vs. best, 5.77; 95% CI, 3.99-8.33; P < .001) group. The median PFS was 3.4 months for the best, 3.7 months for the intermediate (HR vs. best, 1.35; 95% CI, 1.03-1.77; P = .032), and 1.9 months for the worst (HR vs. best, 2.51; 95% CI, 1.80-3.50; P < .001) group.ConclusionsThe prognostic score was able to predict the outcomes of patients with aNSCLC who had received immunotherapy. The worst category showed a dismal life expectancy and probably would not benefit from active systemic therapy. Thus, for these patients, best supportive care could be the best choice.     

Incorporation of the SUVmax Measured From FDG PET and Neutrophil-to-lymphocyte Ratio Improves Prediction of Clinical Outcomes in Patients With Locally Advanced Non–small-cell Lung Cancer

IntroductionThe aim of the present study was to investigate the value of incorporation 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) maximum standardized uptake value (SUVmax) and neutrophil-to-lymphocyte ratio (NLR) for improving prediction of clinical outcomes of patients with locally advanced non–small-cell lung cancer (LA NSCLC).Materials and MethodsWe retrospectively enrolled 138 patients with unresectable LA NSCLC at our institution from July 2010 to August 2017. Spearman correlation analyses were used to estimate the correlations between SUVmax and NLR level. The univariate and multivariate Cox survival analyses were used to evaluate the prognostic indicators, including the incorporation of SUVmax and NLR. We defined the SUVmax and NLR grade (SNG = 0, 1, or 2) score as the number of risk factors among (1) SUVmax > 11.95 and (2) NLR > 3.82. The SNG score prognostic value was evaluated for overall survival (OS) and progression-free survival (PFS).ResultsUnivariate analysis showed that tumor stage, SUVmax, SUVmean, NLR, and SNG score were significantly associated with OS and PFS in patients with LA NSCLC. Kaplan-Meier analysis and log-rank test demonstrated significant differences in both OS and PFS among patients in SNG score (OS, P < .001; PFS, P < .001). Spearman correlation analyses showed that SUVmax had a correlation with the NLR (r = 0.237; P = .005). In subgroup analyses for patients with tumor pathologic stage IIIA/IIIB, we found that the SNG score was significantly associated with OS and PFS in each subgroup (P < .001, P < .001 for OS and P = .027, P < .001 for PFS, respectively). Multivariate analysis showed that the SNG score was a significantly independent prognostic factor for OS (hazard ratio, 1.612; 95% confidence interval, 1.157-2.246; P = .005) and PFS (hazard ratio, 2.241; 95% confidence interval, 1.486-3.379; P < .001).ConclusionIncorporation of the SUVmax and NLR improves prediction of clinical outcomes in patients with LA NSCLC.     

Clinical features,neurologic recovery,and risk factors of postoperative posterior fossa syndrome and delayed recovery: a prospective study

BackgroundPosterior fossa syndrome (PFS) is a known consequence of medulloblastoma resection. Our aim was to clinically define PFS, its evolution over time, and ascertain risk factors for its development and poor recovery.MethodsChildren with medulloblastoma treated at St Jude Children’s Research Hospital from 6/2013 to 7/2019 received standardized neurological examinations, before and periodically after radiation therapy. Most (98.3%) were enrolled on the ongoing multi-institutional protocol (SJMB12; {"type":"clinical-trial","attrs":{"text":"NCT 01878617","term_id":"NCT01878617"}}NCT 01878617).ResultsSixty (34%) of 178 evaluated children had PFS. Forty (23%) had complete mutism (PFS1) and 20 (11%) had diminished speech (PFS2). All children with PFS had severe ataxia and 42.5% of PFS1 had movement disorders. By multivariable analysis, younger age (P = .0005) and surgery in a low-volume surgery center (P = .0146) increased PFS risk, while Sonic Hedgehog tumors had reduced risk (P = .0025). Speech and gait returned in PFS1/PFS2 children at a median of 2.3/0.7 and 2.1/1.5 months, respectively, however, 12 (44.4%) of 27 PFS1 children with 12 months of follow-up were nonambulatory at 1 year. Movement disorder (P = .037) and high ataxia score (P < .0001) were associated with delayed speech recovery. Older age (P = .0147) and high ataxia score (P < .0001) were associated with delayed gait return. Symptoms improved in all children but no child with PFS had normal neurologic examination at a median of 23 months after surgery.ConclusionsCategorizing PFS into types 1 and 2 has prognostic relevance. Almost half of the children with PFS1 with 12-month follow-up were nonambulatory. Surgical experience was a major modifiable contributor to the development of PFS.     

Prognostic significance of neutrophil-to lymphocyte ratio and platelet-to lymphocyte ratio in older patients with metastatic colorectal cancer

Aging is associated with a higher risk of cancer, >70% of cancer-related deaths occur in aged patients; however, this population is underrepresented in clinical trials, therefore, clinical information regarding this age group is rather limited.ObjectivesNeutrophil-to lymphocyte ratio (NLR) and platelet-to lymphocyte ratio (PLR) have been described as biomarkers in cancer, thus, we have assessed their impact in an aged cohort of patients with metastatic colorectal cancer (mCRC).Patients and Methods110 patients with a mean age of 72.2 years at diagnosis were retrospectively reviewed; NLR and PLR were calculated and dichotomized using a cutoff point estimated by a ROC curve. Survival curves and Cox regression analysis were performed to assess the prognostic potential of ratios in terms of progression free survival (PFS) and overall survival (OS).ResultsHigh NLR was associated to worse outcome in terms of PFS (ten vs sixteen months; Log rank <0.001) (HR 2.00 95%CI 1. 29–3.11; p = .002) and OS (20 vs 26 months; Log rank 0.002) (HR 2.28 95%CI 1.40–3.71; p = .001). Similarly it occurs with high PLR and PFS (nine vs fifteen months; Log rank 0.04) (HR 1.55 95%CI 1.01–2.40; p = .04) and OS (nineteen vs 25 months; Log rank <0.001) (HR 2.35 95%CI 1.45–3.80; p < .001).ConclusionThis study confirms the role of NLR and PLR as accessible and noninvasive biomarkers that could be use as a routine tool in the clinical practice in geriatric patients with mCRC.     

A novel pretherapeutic gene expression-based risk score for treatment guidance in gastric cancer

BackgroundPerioperative chemotherapy is an established treatment of advanced gastric cancer patients. Treatment selection is based on clinical staging (cT). We aimed to establish and validate a prognostic score including clinical and molecular factors, to optimize treatment decisions for these patients.Patients and methodsWe analyzed 626 carcinomas of the stomach and of the gastro-esophageal junction from two academic centers including primarily resected and pre-/perioperatively treated patients. Patients were divided into a training (N = 269) and validation (N = 357) set. Expression of 11 target genes was measured by quantitative PCR in resected tumors. A risk score to predict overall survival (OS) was generated and validated. Intra-tumoral heterogeneity was assessed by analyzing 50 tumor areas from 10 patients.ResultsA risk score including the expression of CCL5, CTNNB1, EXOSC3 and LZTR1 and the clinical parameters cT, tumor localization and histopathologic type suggested two groups with a significant difference in OS [hazard ratio (HR) 0.30; 95% confidence interval (CI) 0.17–0.52]. The risk score was successfully validated in an independent cohort (HR 0.32; 95% CI 0.21–0.51; P < 0.001) as well as in subgroups of primarily resected (HR 0.30; 95% CI 0.17–0.54; P < 0.001) and pre-/perioperatively treated patients (HR 0.37; 95% CI 0.17–0.81; P = 0.009). A significant difference in OS of high- and low-risk patients was also found in primarily resected patients with intestinal (HR 0.45; 95% CI 0.23–0.90; P = 0.020) and nonintestinal-type carcinomas (HR 0.1; 95% CI 0.02–0.42; P < 0.001). Intra-tumor heterogeneity analysis indicated a classification reliability of 95% for a supposed analysis of three biopsies.ConclusionThe identified risk score could substantially contribute to an improved management of gastric cancer patients in the context of perioperative chemotherapy.     

Increased Bone Marrow Plasma-Cell Percentage Predicts Outcomes in Newly Diagnosed Multiple Myeloma Patients

BackgroundPrevious reports have suggested that a higher bone marrow plasma-cell percentage (BMPC%) is associated with worse outcomes. However, it is unknown whether BMPC% is an independent predictor because genetic information was not available at that time. Currently the impact of BMPC% at diagnosis of multiple myeloma (MM) is not well described.Patients and MethodsWe evaluated the prognostic impact of BMPC% ≥ 60% versus < 60% in 1426 newly diagnosed MM patients. All patients had an estimation of their BMPC% at diagnosis, and the highest percentage was used. Progression-free survival (PFS) and overall survival (OS) analyses were performed by the Kaplan-Meier method. Univariate and multivariate analyses for PFS and OS using the Cox proportional hazards model were performed for age, Revised International Staging System (R-ISS) score, creatinine level, and BMPC%.ResultsBMPC% ≥ 60% was found in 562 patients (39%), and the median PFS was shorter for these patients compared to BMPC% < 60% (22.6 vs. 32.1 months; P < .0001). Also, for OS, the median was shorter for the higher BMPC% group (53.4 vs. 75.4 months; P < .0001). On the multivariate analysis for PFS, age ≥ 65 years (hazard ratio [HR], 1.46; P < .0001), R-ISS (1-2 vs. 3) (HR, 0.49; P < .0001), and BMPC% ≥ 60% (HR, 1.23; P = .015) were predictive. On the multivariate analysis for OS, age ≥ 65 years (HR, 2.23; P < .001), R-ISS (1-2 vs. 3) (HR, 0.41; P < .0001), and BMPC% ≥ 60% (HR, 1.24; P = .02) were also predictive.ConclusionBMPC% ≥ 60% at diagnosis is predictive for PFS and OS, even in a multivariate analysis that included known prognostic factors for MM.     

Geriatric assessment measures are predictive of outcomes in chronic lymphocytic leukemia

IntroductionChronic lymphocytic leukemia (CLL) commonly affects older adults. However, few studies have examined the relationship between baseline geriatric domains and clinical outcomes in this population. Here, we aim to evaluate the use of a comprehensive geriatric assessment in older (>65 years) untreated patients with CLL to predict outcomes.Materials and MethodsWe conducted a planned analysis of 369 patients with CLL age 65 or older treated in a phase 3 randomized trial of bendamustine plus rituximab versus ibrutinib plus rituximab versus ibrutinib alone (A041202). Patients underwent evaluations of geriatric domains including functional status, psychological status, social activity, cognition, social support, and nutritional status. We examined associations among baseline geriatric domains with grade 3+ adverse events using multivariable logistic regression and overall survival (OS) and progression-free survival (PFS) using multivariable Cox regression models.ResultsIn this study, the median age was 71 years (range: 65–87). In the combined multivariable model, the following geriatric domains were significantly associated with PFS: Medical Outcomes Study (MOS) - social activities survey score (hazard ratio [HR] [95% confidence interval (CI)] 0.974(0.961, 0.988), p = 0.0002) and nutritional status (≥5% weight loss in the preceding six months: (HR [95% CI] 2.717[1.696, 4.354], p < 0.001). MOS - social activities score [HR (95% CI) 0.978(0.958, 0.999), p = 0.038] was associated with OS. No geriatric domains were significantly associated with toxicity. There were no statistically significant interactions between geriatric domains and treatment.DiscussionGeriatric domains of social activity and nutritional status were associated with OS and/or PFS in older adults with CLL. These findings highlight the importance of assessing geriatric domains to identify high-risk patients with CLL who may benefit from additional support during treatment.     

18F-FDG PET/CT for assessing heterogeneous metabolic response between primary tumor and metastases and prognosis in non-small cell lung cancer

IntroductionThis study aimed to use ¹⁸F-fluorodeoxyglucose positron emission tomography and/or computed tomography (¹⁸FDG-PET/CT) imaging to evaluate the heterogeneous metabolic response between primary tumor and metastases in NSCLC after therapy and explored its correlation with prognosis.MethodsThe data of patients with NSCLC who underwent ¹⁸FDG-PET/CT before and after treatment were retrospectively analyzed. Heterogeneous metabolic response (HR), defined as the difference in metabolic response between any metastases and primary lesion, was evaluated using ¹⁸FDG-PET/CT. And the correlation between HR and clinical prognosis was also analyzed.ResultsA total of 56 patients with NSCLC including 56 primary lesions and 491 metastases were enrolled in the study. 46.4% (26/56) of patients had HR, especially in patients with stage IV disease and whose metastases with high metabolic burden. HR was significantly correlated with poorer overall survival (OS) and progression-free survival (PFS) (P < .001 and P = .045, respectively). The multivariate analysis suggested that HR was an unfavorable independent prognostic factor for OS (HR = 4.36; 95% CI, 2.00–9.49; P < .001) but not for PFS (P = .469). HR between lymph node metastases was correlated with shorter OS (P < .001) but not with PFS (P = .370).ConclusionHR was observed between primary and metastatic lesions in NSCLC after treatment using PET/CT. HR is significantly associated with poor prognosis and is an independent prognostic factor for OS.