Oncologic and Functional Outcomes of Radical and Partial Nephrectomy in pT3a Pathologically Upstaged Renal Cell Carcinoma: A Multi-institutional Analysis

BackgroundThe efficacy of partial nephrectomy (PN) in setting of pT3a pathologic-upstaged renal cell carcinoma (RCC) is controversial. We compared oncologic and functional outcomes of radical nephrectomy (RN) and PN in patients with upstaged pT3a RCC.Patients and MethodsThis was a multicenter retrospective analysis of patients with cT1-2N0M0 RCC upstaged to pT3a postoperatively. The primary outcome was recurrence-free survival, with secondary outcomes of overall survival and de novo estimated glomular filtration rate (eGFR) < 60. Multivariable analysis was performed to identify predictive factors for oncologic outcomes. Kaplan-Meier analyses (KMA) were obtained to elucidate survival outcomes.ResultsA total of 929 patients had pT3a upstaging (686 [72.6%] RN; 243 [25.7%] PN; mean follow-up, 48 months). Tumor size was similar (RN 7.7 cm vs. PN 7.3 cm; P = .083). PN had decreased ΔeGFR (6.1 vs. RN 19.4 mL/min/1.73m²; P < .001) and de novo eGFR < 60 (9.5% vs. 21%; P = .008). Multivariable analysis for recurrence showed increasing RENAL score (hazard ratio [HR], 3.8; P < .001), clinical T stage (HR, 1.8; P < .001), positive margin (HR, 1.57; P = .009), and high grade (HR, 1.21; P = .01) to be independent predictors, whereas surgery was not (P = .076). KMA revealed 5-year recurrence-free survival for cT1-upstaged PN, cT1-upstaged RN, cT2-upstaged PN, and cT2-upstaged RN of 79%, 74%, 70%, and 51%, respectively (P < .001). KMA revealed 5-year overall survival for cT1-upstaged PN, cT1-upstaged RN, cT2-upstaged PN, and cT2-upstaged RN of 64%, 65.2%, 56.4%, and 55.2%, respectively (P = .059).ConclusionsIn pathologically upstaged pT3a RCC, PN did not adversely affect risk of recurrence and provided functional benefit. Surgical decision-making in patients at risk for T3a upstaging should be individualized and driven by tumor as well as functional risks.     

Impact of Metastasectomy on Cancer Specific and Overall Survival in Metastatic Renal Cell Carcinoma: Analysis of the REMARCC Registry

BackgroundTreatment paradigms for management of metastatic renal cell carcinoma (mRCC) are evolving. We examined impact of surgical metastasectomy on survival across in mRCC stratified by risk-group.MethodsMulticenter retrospective analysis from the Registry of Metastatic RCC database. The cohort was subdivided utilizing Motzer criteria (favorable-, intermediate-, high-risk). Primary outcome was all-cause mortality (ACM)/overall survival (OS); secondary outcome was cancer-specific mortality (CSM)/cancer-specific survival (CSS). Impact of metastasectomy was analyzed via Cox-Regression analysis adjusting for potential prognostic variables and Kaplan-Meier analysis (KMA) within each risk-group.ResultsFour hundred thirty-one patients (59 favorable-risk, 274 intermediate-risk, 98 high-risk; median follow-up 27.2 months) were analyzed. Metastasectomy was performed in 22 (37%), 66 (24%), and 32 (16%) of favorable-, intermediate- and high-risk groups (P = .012). Median number of metastases at diagnosis differed significantly (favorable-risk 2, intermediate-risk 3.4, high-risk 5.1, P < .001). On Cox-regression, high-risk (HR = 1.72, P = .002) was associated with worsened ACM, while metastasectomy was associated with improved ACM (HR = 0.56, P = .005). On KMA, median OS (months) was longer with metastasectomy in favorable- (92.7 vs. 25.8, P = .003) and intermediate-risk (26.3 vs. 20.1, P = .038), but not high-risk (P = .911) groups. Metastasectomy was associated with longer CSS in favorable- (76.1 vs. 32.8, P = .004) but not intermediate- (P = .06) and high-risk (P = .595) groups.ConclusionsMetastasectomy was independently associated with improved ACM and CSM, as well as improved CSS and OS in favorable- and intermediate-risk mRCC patients. Metastasectomy may be considered as component of multimodal management strategy in favorable and intermediate-risk subgroups. In high-risk patients, metastasectomy should be deferred except in select circumstances.     

Albumin-to-Alkaline Phosphatase Ratio as a Novel Prognostic Factor in Patients Undergoing Nephrectomy for Non-Metastatic Renal Cell Carcinoma: Propensity Score Matching Analysis

IntroductionTo evaluate the prognostic value of albumin-to-alkaline phosphatase ratio (AAPR) on recurrence and survival in patients with non-metastatic renal cell carcinoma (RCC) treated with radical or partial nephrectomy.Patients and MethodsBetween June 1994 and December 2018, 491 patients with RCC who underwent radical or partial nephrectomy at 2 institutions were enrolled in this study. Recurrence-free survival (RFS) and cancer-specific survival (CSS) analyses were performed to distinguish the differences in postoperative recurrence and survival between patients stratified by an optimal cut-off value of AAPR. Multivariable Cox proportional hazards regression models were established to determine the independent prognostic factors after propensity score weighting.ResultsOf the total 491 patients, 51 patients (10.4%) developed local recurrence or distant metastasis and 26 patients (5.3%) died of disease during the follow-up period. Patients with AAPR<0.41 had significantly lower rates of RFS and CSS than those of patients with AAPR≥0.41 in multivariate analysis (P < .001 and P = .027, respectively). After propensity scroe matching analyses, this difference was still remained for RFS (P < .001). However, AAPR was not an independent prognostic factor for CSS but the value was almost pregnant (HR = 2.674; 95%CI = 0.872–8.203; P = .086).ConclusionAAPR can serve as a novel and useful tool to refine prognosis in patients with non-metastatic RCC treated with partial or radical nephrectomy. These findings suggest that AAPR could be a promising prognostic factor for prediction of recurrence and survival in patients with non-metastatic RCC who undergo nephrectomy.     

Prognostic Impact of Loss of SETD2 in Clear Cell Renal Cell Carcinoma

PurposeTo evaluate the prognostic impact of immunohistochemical expression of SETD2 in patients with clear cell renal cell carcinoma (ccRCC).Patients and MethodsA total of 662 patients with primary or metastatic ccRCC were evaluated. Two genitourinary pathologist reviewed all of the cases for uniform reclassification and determined the selection of the most representative tumor areas for construction of the tissue microarray (TMA).ResultsSETD2 nuclear staining showed that 101 areas (15.3%) had negative expression, and 561 areas (84,7%) had positive expression of SETD2. The protein expression of SETD2 was associated with clinical stage (P < .001), pathological stage (P < .001), tumor size (P < .001), perinephric fat invasion (P < .001), Eastern Cooperative Oncology Group status (P = .004), surgery type (P < .001), International Society of Urologic Pathologists grade (P < .001), and tumor necrosis (P < .001). SETD2 influenced disease-specific survival (DSS) and overall survival (OS). DSS rates in patients with positive and negative expression of SETD2 were 90.2% and 58.4%, respectively (P < .001). OS rates in patients with positive and negative expression of SETD2 were 87% and 55.4%, respectively (P < .001). In a multivariate Cox analysis, low SETD2 expression was an independent predictor of DSS (hazard ratio [HR], 1.690; 95% confidence interval [CI], 1.0582.700; P = .031) and OS (HR, 1.641; 95% CI, 1.039-2.593; P = .037).ConclusionOur study showed that the negative expression of SETD2 was associated with a worse prognosis, and it was an independent predictor of survival in patients with ccRCC. We believe that the protein expression of SETD2 is an important biomarker in the management of patients with ccRCC.     

Nomograms for Predicting Overall and Recurrence-free Survival From Pathologic Stage IA and IB Lung Cancer After Lobectomy

BackgroundStage I non–small-cell lung cancer (NSCLC) is potentially curable with surgical resection. Significant proportions of patients may still experience recurrence and death despite undergoing curative surgery. This study describes predictive nomograms for recurrence-free (RFS) and overall survival (OS) after lobectomy.Patients and MethodsA total of 301 patients with the American Joint Committee on Cancer pathologic stage IA and IB NSCLC who underwent open, thoracoscopic, or robotic lobectomy from January 2011 to April 2017 were analyzed. Multivariate Cox proportional hazards regression models were used to create nomograms for OS and RFS. Kaplan-Meier survival curves were calculated for OS and RFS comparing high-risk and low-risk cohorts based on nomogram scores.ResultsHistology (hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.10-0.56; P = .002), lymphovascular invasion (HR, 0.46; 95% CI, 0.29-0.74; P = .001), smoking status (HR, 3.46; 95% CI, 1.25-9.55: P = .02), and total lymph nodes removed (HR, 1.05; 95% CI, 1.01-1.10; P = .021) were significant predictors for OS in a multivariate model. Lymphovascular invasion (HR, 0.55; 95% CI, 0.36-0.83; P = .0040), smoking status (HR, 2.56; 95% CI, 1.16-5.62; P = .02), total lymph nodes removed (HR, 1.04; 95% CI, 1.00-1.08; P = .029), and tumor size (HR, 1.30; 95% CI, 1.30-1.68; P = .047) were significant predictors of RFS in a multivariate model.ConclusionNomograms can predict OS and RFS for pathologic stage IA and IB NSCLC after lobectomy regardless of operative approach. The risk for death and recurrence after stratification by the nomogram scores may provide guidance regarding adjuvant therapy and surveillance.     

Prognostic Factors in Patients With Advanced Renal Cell Carcinoma

BackgroundThe purpose of this study was to evaluate prognostic factors in patients with RCC.Materials and MethodsThe expression of several biomarkers were measured by immunohistochemistry (IHC), together with 2 analytic factors (thrombocytosis and neutrophilia), in 135 patients with advanced RCC treated with new targeted drugs (NTDs) (n = 67) and/or cytokines (CKs) (n = 68)—with 23 of the patients who received CKs also receiving NTDs—between July 1996 and February 2010. Relationships with overall survival (OS) and progression-free survival (PFS) were searched for.ResultsUnivariate statistical analysis revealed that high expression of hypoxia-inducible factor-1α (HIF-1α) correlated with poor prognosis in NTD treatment (PFS, 5.4 vs. 13.5, low expression months; P = .033) and CK treatment (PFS, 3.3 vs. 5.7, low expression; P = .003). Overexpression of carbonic anhydrase IX (CAIX) was associated with better prognosis with NTD treatment (OS, 32.1 vs. 7.8 months; P < .001) and CK treatment (OS, 32.9 vs. 5.9 months; P = .001). Positive PTEN was related to good prognosis with sunitinib (PFS, 15.1 vs. 6.5 months; P = .003) and CKs (OS, 13.7 vs. 7.9 months; P = .039). Increased expression of p21 was related to poor prognosis with NTD treatment (PFS, 5.9 vs. 16.8 months; P = .024) and CK treatment (PFS, 3.9 vs. 7.5 months; P < .001) Thrombocytosis was related to poor prognosis with NTDs (OS, 15.9 vs. 26.7 months; P = .007) and CKs (OS, 5.9 vs. 14.3 months; P = .010). Neutrophilia was related to poor prognosis with NTDs (OS, 17.6 vs. 25.4 months; P = .063) and CKs (OS, 5.9 vs. 12.8 months; P = .035). Multivariate analysis revealed that overexpression of CAIX was a favorable prognostic factor independent of PFS (hazard ratio [HR], 0.107; P < .001) and OS (HR, 0.055; P < .001).ConclusionsHIF-1α, PTEN, p21, thrombocytosis, neutrophilia, and CAIX in particular are useful prognostic factors in patients with advanced RCC.     

Impact of Tumor Location on Patient Outcomes in Small Bowel Cancers

BackgroundSmall bowel cancers are rare gastrointestinal malignancies and tumor location impact on outcomes is unclear.Material and MethodsA retrospective review was performed on stage I to IV small bowel cancer cases from 2000 to 2017 in British Columbia, Canada. Baseline patient characteristics, disease-free survival (DFS) and overall survival (OS) were evaluated by tumor location and systemic therapy use patterns were summarized.ResultsOf 340 patients included, primary tumor distribution was: duodenum (51.2%), ileum (19.1%), jejunum (18.5%), and unspecified (11.2%). Median DFS for stage I to III disease was 37.7, 49.1, and 26.7 months for duodenal, jejunal, and ileal tumors (P = .018). Median OS was 9.6, 35.2, and 20.1 months for duodenal, jejunal, and ileal tumors (P < .0001). Compared to duodenal primaries, both jejunal and ileal tumors were associated with significantly improved OS (HR 0.43, P < .001 for jejunal; HR 0.71, P = .035 for ileal). Adjuvant therapy was given to 21.6% of stage II and 50.6% of stage III cancers. Among patients with metastatic disease, median OS was 4.2, 11.4, and 6.9 months for duodenal, jejunal, and ileal tumors (P = .0019). Jejunal tumors had the best prognosis (HR 0.48, P = .001 vs. duodenum).ConclusionSurvival differences exist when small bowel cancers were assessed by tumor location, and jejunal tumors portended better prognosis overall.     

Chromophobe Renal Cell Carcinoma: Results From a Large Single-Institution Series

BackgroundThe purpose of the study was to evaluate clinical features and prognostic factors in a large single institutional cohort of chromophobe renal cell carcinoma (ChRCC) patients for identification of tumors with the highest metastatic potential.Patients and MethodsClinicopathological parameters of all patients with ChRCC diagnosed and surgically treated at Memorial Sloan Kettering Cancer Center between 1990 and 2016 were identified and compared with patients treated for clear-cell renal cell carcinoma (ccRCC) in the same study period using Wilcoxon test for continuous variables and Fisher exact test for categorical variables. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan–Meier method, log rank test, and Cox proportional hazards regression.ResultsFour hundred ninety-six patients with ChRCC (10-year RFS, 91.7% and OS, 82.1%) and 3312 patients with ccRCC (10-year RFS, 79.4% and OS, 63.6%) were included in the analysis. Patients with ChRCC were younger (median 59 vs. 61 years; P = .0015), less frequently male (54.8% vs. 66.3%; P < .0001), showed more favorable T stages (T1-2 in 78% vs. 67%; P < .0001) and less frequent sarcomatoid differentiation (1.2 % vs. 4%; P = .0008) and showed lower rates of metastatic development compared with ccRCC patients. Larger tumor size, sarcomatoid differentiation, and higher T-stage are significantly associated with adverse RFS and OS in chromophobe tumors.ConclusionChRCC is more commonly diagnosed in female and younger patients and is associated with a more favorable clinical outcome and a lower propensity for metastatic development than ccRCC. Larger tumors and sarcomatoid differentiation of ChRCC might be considered as risk factors for metastatic development.     

Safety and Efficacy of Reproductive Organ-Sparing Radical Cystectomy in Women With Variant Histology and Advanced Stage

PurposeMuscle invasive bladder cancer surgical management has been historically a radical cystoprostatectomy in males and an anterior exenteration in females. Uterine, ovarian, and vaginal preservation are utilized, but raise concerns regarding risk to oncologic control, especially in variant histopathology or advanced stage.Materials and MethodsA retrospective single institutional analysis identified radical cystectomies performed in women, including those with variant histology, which were defined as reproductive organ sparing (uterine, vaginal, and ovary sparing) or nonorgan sparing. The Kaplan-Meier method was used for recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) in patients with advanced disease.ResultsFrom 2000 to 2020, 289 women were identified, 188 underwent reproductive organ-sparing cystectomy. No statistical differences were noted for clinical parameters or presence of variant histology for organ-sparing (ROS) and nonorgan-sparing (non-ROS). Positive margin rates did not differ for ROS and non-ROS; 4.3% vs. 7.9%, P = .19, respectively. Median RFS was not statistically significantly different for ROS vs. non-ROS (26.1 vs. 15.3 months) P = .937 hazard ratio (HR) 1.024. CSS was not statistically different for ROS vs. non-ROS (36.3 vs. 28.6 months), P = .755 HR 0.9. OS was not statistically different for ROS vs. non-ROS (25.8 vs. 23.8 months), P = .5 HR = 1.178. Variant histology did not change survival (HR 1.1, P = .643).ConclusionIn this analysis, ROS in women with advanced disease did not increase positive margin rates or decrease RFS, CSS, or OS compared to non-ROS. Variant histology did not decrease survival odds. Based on preoperative assessment and intraoperative findings, ROS in patients with variant histology and advanced disease should be considered.     

The Effect of Salvage Radiation Therapy on Survival,Functional Outcomes,and Quality of Life in Men with Persistent Prostate-specific Antigen After Robot-Assisted Radical Prostatectomy: Which Patient Benefits More?

PurposeThe aim of this study was to evaluate the effect of salvage radiation therapy (sRT) on survival, functional outcomes, and quality of life in men with persistent prostate-specific antigen (PSA >0.1 ng/mL) after a robot-assisted radical prostatectomy (RARP) and reveal subgroups that benefit more from sRT.Methods and MaterialsData of 3409 patients who underwent RARP was retrieved from a high-volume institute database, and 313 patients with persistent PSA were included in further analyses. Patients who received sRT and those who did not were compared after propensity score matching. Progression-free survival (PFS), metastasis-free survival (MFS), androgen deprivation therapy (ADT)-free, cancer-specific survival, and overall survival, as well as patient-reported outcomes were the endpoints. Multivariable Cox regression models were developed to reveal treatment effect sizes for the subgroups.ResultsThe overall persistent PSA rate was 9.2%, and the median follow-up time after RARP was 4.5 years (interquartile range, 2.7-7.9 years). The sRT was associated with improved PFS (hazard ratio [HR]: 0.29; P < .001), ADT-free survival (HR: 0.34; P < .001), MFS (HR: 0.39; P = .001), cancer-specific survival (HR: 0.34; P = .03), and overall survival (HR: 0.24; P = .001). Positive surgical margins (HR: 0.26; P < .001 for ADT-free survival), advanced pathological T stage (HR: 0.24; P < .001 for PFS) and positive lymph nodes (HR: 0.15; P = .001 for MFS), and lower Gleason score (HR: 0.15; P = .001 for PFS) were associated with marked survival benefits of sRT. Bowel symptoms were observed more frequently in patients who had sRT with or without ADT compared with patients with persistent PSA but no sRT (34.3% vs 19.2%; P = .01). Early sRT (<6 months after surgery) was associated with bothering incontinence (P < .001) and bowel symptoms (P = .03).ConclusionsPersistent PSA after a radical prostatectomy is still a common challenge in the robotic surgery era. sRT provides clear survival benefits for all endpoints, especially with unfavorable locoregional factors but a low Gleason score.     

Analysis of Toxicity and Clinical Outcomes in Full Versus Reduced Starting Dose Cabozantinib in Metastatic Renal Cell Carcinoma Patients

BackgroundFull dose cabozantinib for metastatic renal cell carcinoma (mRCC) is 60 mg, but adverse events (AEs) may require dose reductions. Limited data exist comparing efficacy among cabozantinib doses. We compared AEs and clinical outcomes in mRCC patients treated with full vs. reduced starting cabozantinib dose.MethodsWe performed a retrospective analysis of 87 mRCC patients treated with cabozantinib at Winship Cancer Institute from 2016 to 2019. Overall survival (OS), progression-free survival (PFS), and objective response (OR) rate measured clinical outcomes. AEs were collected from clinic notes and the most common were hypertension, mucositis/hand-foot skin reaction (HFSR), or gastrointestinal toxicity. Univariate analysis (UVA) between starting doses and AEs with clinical outcomes was performed using logistic regression model. Multivariable analysis was also performed using Cox proportional hazard model.ResultsMost patients were men (71%) with clear-cell RCC (72%). The majority were IMDC intermediate (58%) or poor (35%) risk. One third received first-line cabozantinib and 64% had ≥3 baseline metastatic sites. Most patients (68%) required dose reduction from 60 mg or started at reduced dose without escalation. Reduced dose patients were more likely to have ≥3 distant metastatic sites (70% vs. 58%) and ≥2 prior lines of systemic therapy (50% vs. 40%) compared to full dose patients. UVA revealed a trend towards shorter OS (HR: 1.78, P = .095), PFS (HR: 1.50, P = .107), and lower chance of OR (HR:0.42, P = .149) among reduced dose patients. This trend did not hold in Multivariable analysis (OS HR: 1.20, P = .636; PFS HR: 1.23, P = .4662). Mucositis/HFSR and hypertension were significantly associated with improved outcomes in UVA.ConclusionsAlthough we found a trend favoring full dose cabozantinib, this is likely due to worse baseline disease characteristics among patients starting on a reduced dose. Hypertension and mucositis/HFSR may be associated with improved outcomes. Larger studies are warranted to validate these findings.     

The De Ritis (Aspartate Transaminase/Alanine Transaminase) Ratio as a Prognosticator in Patients With End-stage Renal Disease–associated Renal Cell Carcinoma

BackgroundThe aspartate transaminase (AST)/alanine transaminase (ALT) ratio (ie, the De Ritis ratio) is associated with prognosis in some types of cancers including renal cell carcinoma (RCC). Meanwhile, an effective prognosticator for end-stage renal disease (ESRD)–associated RCC remains unknown. Thus, we investigated the prognostic impact of the AST/ALT ratio in patients with ESRD-associated RCC.Patients and MethodsWe retrospectively evaluated 243 patients receiving radical nephrectomy for nonmetastatic ESRD-associated RCC. The patients were divided according to the cutoff value of preoperative AST/ALT ratio. Prognostic factors associated with cancer-specific survival (CSS) after radical nephrectomy were analyzed.ResultsThe maximum Youden index showed that the cutoff value of the AST/ALT ratio was 1.42. The high AST/ALT ratio group (≥ 1.42; n = 88) had a significantly shorter 10-year CSS than the low AST/ALT ratio group (64.3% vs. 87.2%; P = .0027). Multivariate analysis revealed that the AST/ALT ratio was an independent prognostic factor of CSS (hazard ratio [HR], 3.03; P = .0020), together with serum C-reactive protein level (HR, 4.84; P < .0001), pathologic stage (HR, 2.79; P = .0030), and tumor grade (HR, 7.08; P = .0087). Based on these independent factors, the patients were further classified into 3 groups: low (0-1 factor), intermediate (2 factors), and high risk (3-4 factors). The 10-year CSS in the high-risk group was significantly shorter than that of the other groups (68.9% vs. 70.9% vs. 94.4%; P < .0001).ConclusionThe AST/ALT ratio can aid in the risk classification of patients with ESRD-associated RCC.     

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.     

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.     

Up-front Therapy With CHOP Plus Etoposide in Brazilian nodal PTCL Patients: Increased Toxicity and No Survival Benefit Compared to CHOP Regimen–Results of a Real-Life Study From a Middle-Income Country

BackgroundNodal peripheral T-cell lymphoma (nPTCL) constitute a heterogeneous group of neoplasms with aggressive behavior and poor-survival. They are more prevalent in Latin America and Asia, although data from Brazil are scarce. Its primary therapy is still controversial and ineffective. Therefore, we aim to describe clinical-epidemiological characteristics, outcomes, predictors factors for survival and compare the results of patients treated with CHOP and CHOEP regimens.MethodsRetrospective, observational and single-center study involving 124 nPTCL patients from Brazil treated from 2000 to 2019.ResultsWith a median follow-up of 23.7 months, the estimated 2-year overall survival (OS) and progression-free survival (PFS) were 59.2% and 37.3%, respectively. The median age was 48.5 years and 57.3% (71/124) were male, 81.5% (101/124) had B-symptoms, 88.7% (110/124) had advanced disease (stage III/IV) and 58.1% (72/124) presented International Prognostic Index (IPI) score ≥3, reflecting a real-life cohort. ORR to first-line therapy was 58.9%, 37.9% (N = 47) received CHOP-21 and 35.5% (N = 44) were treated with CHOEP-21; 30.1% (37/124) underwent to consolidation with involved field radiotherapy (IF-RT) and 32.3% (40/124) were consolidated with autologous hematopoietic stem cell transplantation (ASCT). The overall response rate (ORR) was similar for CHOP-21 (76.6%) and CHOEP-21 (65.9%), P = .259. Refractory disease was less frequent in the CHOEP-21 group (4.5% vs. 21.2%, P = .018). However, few patients were able to complete 6-cycles of CHOEP-21 (31.8%) than to CHOP-21 (61.7%), P = .003. Delays ≥2 weeks among the cycles of chemotherapy were more frequent for patients receiving CHOEP-21 (43.1% vs. 10.6%), P = .0004, as well as the toxicities, including G3-4 neutropenia (88% vs. 57%, P = .001), febrile neutropenia (70% vs. 38%, P = .003) and G3-4 thrombocytopenia (63% vs. 27%, P = .0007). The 2-year OS was higher for CHOP (78.7%) than CHOEP group (61.4%), P = .05, as well as 2-year PFS (69.7% vs. 25.0%, P < .0001). In multivariate analysis, high LDH (HR 3.38, P = .007) was associated with decreased OS. CR at first line (HR: 0.09, P < .001) and consolidation with ASCT (HR: 0.08, P = .015) were predictors of increased OS.ConclusionIn the largest cohort of nPTCL from Latin America, patients had poor survival and high rate of chemo-resistance. In our cohort, the addition of etoposide to the CHOP-21 backbone showed no survival benefit and was associated with high-toxicity and frequent treatment interruptions. Normal LDH values, obtaintion of CR and consolidation with ASCT were independent factors associated with better outcomes.     

Māori and Pacific Peoples With Multiple Myeloma in New Zealand are Younger and Have Inferior Survival Compared to Other Ethnicities: A Study From the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR)

Background: Māori and Pacific peoples (MPP) in New Zealand (NZ) have poorer health outcomes than other ethnicities. However, this has not been clinically investigated in multiple myeloma (MM). Using data from the Australian and NZ Myeloma and Related Diseases Registry for all participating centers in NZ, we compared MPP demographics, clinical characteristics, diagnostics, treatment, and outcomes to non-MPP.Patients and Methods: MPP were defined as having ≥1 grandparent of this heritage. We tested ethnicity as a predictor of overall survival (OS) with multivariable Cox regression.Results: Of 568 NZ patients with MM (September 2012 to April 2021) and ethnicity data, 138 were MPP. They were diagnosed younger than non-MPP (median age 63 [IQR: 57-72] vs. 70y [62-77], P < .001). Obesity (53 vs. 27%, P < .001), diabetes (24 vs. 8%, P < .001), renal insufficiency (28 vs. 17%, P = .005), pulmonary disease (10 vs. 5%, P = .02) and FISH abnormalities (54 vs. 42%, P = .04) were more common in MPP, and a lower proportion received first-line drug therapy (88 vs. 94%, P = .03) and autologous stem cell transplant (ASCT) (age <70y: 56 vs. 70%, P = .03). OS for MPP was shorter than non-MPP even after adjusting for age, comorbidities, disease stage, performance status, FISH abnormalities and treatment (HR 1.58 [1.04-2.39], P = .03).Conclusion: MPP with MM in NZ were younger, a greater proportion had comorbidities and FISH abnormalities at diagnosis, fewer received first-line treatment and/or ASCT, and they had poorer OS than non-MPP. Investigation of modifiable factors to improve outcomes and discern why MM occurs at a younger age in MPP is needed.     

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.     

Transarterial chemoembolization plus immune checkpoint inhibitor as postoperative adjuvant therapy for hepatocellular carcinoma with portal vein tumor thrombus: A multicenter cohort study

PurposeThis study aimed to assess the efficacy and safety of postoperative adjuvant transarterial chemoembolization (PA-TACE) plus immune checkpoint inhibitor (ICI) for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).Patients and methodsThis study was conducted on three centers from June 2018 to December 2020. Patients were divided into the PA-TACE (n = 48) and PA-TACE plus ICI groups (n = 42). The recurrence-free survival (RFS) and overall survival (OS) curves were depicted by Kaplan-Meier method, and the differences between the two groups were compared using log-rank test. Univariate and multivariate Cox analyses were performed to identify independent risk factors for RFS and OS. Adverse events (AEs) were assessed according to the Common Terminology Criteria for AEs (CTCAE) version 5.0.ResultsThe median RFS of the PA-TACE plus ICI group was significantly longer than the PA-TACE group (12.76 months vs. 8.11 months; P = 0.038). The median OS of the PA-TACE plus ICI group was also significanfly better than the PA-TACE group (24.5 months vs. 19.1 months; P = 0.032). PA-TACE plus ICI treatment was an independent prognostic factor for RFS (HR: 0.54, 95% CI: 0.32–0.9, P = 0.019) and OS (HR: 0.47, 95% CI: 0.26–0.86, P = 0.014). Only one patient experienced grade ≥3 immune-related AEs in the PA-TACE plus ICI group.ConclusionsPA-TACE plus ICI treatment had better efficacy in preventing recurrence and prolonging survival than PA-TACE alone for HCC patients with PVTT after R0 resection. This novel treatment modality may be an appropriate option for HCC with PVTT.     

Sociodemographic Disparities in Access to Chemotherapy for Bladder Cancer

BackgroundWe sought to evaluate sociodemographic disparities in access to neoadjuvant (NAC) and adjuvant (AC) chemotherapy in the United States and their effect on survival.MethodsThe National Cancer Database was used to identify all patients from 2004 to 2016 eligible for NAC and AC. Univariate and multivariate logistic regression was performed to identify sociodemographic predictors associated with receipt of NAC and AC. Kaplan-Meier and Cox proportional hazard models were used for survival analysis.ResultsA total of 17,121 patients were eligible for NAC, and 18,962 for AC. Older (OR 0.94, P < .001), Medicare (OR 0.88, P = .047), Medicaid (OR 0.66, P = .001), uninsured (OR 0.47, P < .001), rural (OR 0.70, P = .042), and community hospital patients (OR 0.72, P < .001) were less likely to receive NAC. Older, (OR 0.95, P < .001), female (OR 0.79, P < .001), Medicaid (OR 0.71, P = .003), uninsured (OR 0.60, P = .001), and lower income patients (OR 0.86, P = .017) were less likely to receive AC. In NAC-eligible patients, older (HR 1.02, P < .001), Medicare (HR 1.11, P = .024), Medicaid (HR 1.25, P = .012), and community hospital patients (HR 1.09, P = .021) were at an increased risk of death. In AC-eligible patients, older (HR 1.01, P < .001), Black (HR 1.15, P = .011), Medicaid (HR 1.14, P = .042), lower income (HR 1.07, P = .038) and community hospital patients (HR 1.07, P = .021) were at an increased risk of death.ConclusionsSignificant sociodemographic disparities currently exist in the United States in access to neoadjuvant and adjuvant chemotherapy for bladder cancer. Uninsured and Medicaid insurance status are the strongest predictors of not receiving chemotherapy. Efforts must be made to deliver this critical standard-of-care treatment to these patients.     

Predictive Impact of Early Changes in Serum C-Reactive Protein Levels in Nivolumab Plus Ipilimumab Therapy for Metastatic Renal Cell Carcinoma

BackgroundSerum C-reactive protein (CRP) is reportedly associated with metastatic renal cell carcinoma (mRCC) activity. However, in the era of immune checkpoint inhibitors, the predictive value of CRP is unclear. In this study, we investigated the predictive impact of pretreatment CRP levels and early changes in CRP levels for the treatment of mRCC with nivolumab plus ipilimumab (NIVO-IPI) therapy.MethodsForty-eight patients with mRCC treated with NIVO-IPI as a first-line therapy were retrospectively analyzed. First, patients were divided into 2 groups: initial CRP ≥ 1.0 mg/dL and < 1.0 mg/dL. Progression-free survival (PFS) was compared between the 2 groups. Second, based on the CRP change within the first 3 months of NIVO-IPI, patients were placed in the normal group (CRP remains < 1.0 mg/dL), normalized group (CRP decreased < 1.0 mg/dL), and non–normalized group (CRP remained or increased to ≥ 1.0 mg/dL). The predictive association between CRP change and PFS was evaluated.ResultsPFS was significantly lower in the high initial CRP group (n = 24, 50%) compared to the normal CRP group (n = 24, 50%) (median: 4.3 vs. 28.1 months, P = .03). As for the early CRP change, the normal (2.7 vs. 28.1, P = .0002) and normalized (2.7 vs. 11.0, P = .0094) groups showed significantly higher PFS, compared to the non–normalized group. Meanwhile, there was no significant difference between normal, and normalized groups (P = .51). The objective response rate was higher in the normal (57.1% vs. 18.7%, P = .015) and normalized (81.8 vs. 18.7%, P = .0008) groups, compared to the non–normalized group. Multivariate Cox regression analysis showed that normal [Hazard ratio (HR) = 0.15, 95% Confidence interval (CI) = 0.02-0.70, P = .026] and normalized (HR 0.21, 95% CI = 0.05-0.73, P = .015) CRP showed significant association with PFS.ConclusionIn the NIVO-IPI therapy for mRCC, early changes in CRP could predict PFS. This data may be useful for the early detection of ineffective NIVO-IPI therapy and conversion to subsequent therapies.