Spinal lesions in multiple myeloma: Primary bone tumors with distinct prognostic factors

PurposeAlthough prognostic factors of spinal multiple myeloma (MM) seem to differ from those of other spine metastases (SpM), the data in the literature remains scarce.MethodsA prospective population of 361 patients treated for spine MM lesions between January 2014 and 2017.ResultsOS for our series was 59.6 months (SD 6.0 months; CI 95%: 47.7–71.3). Cox multivariate proportional-hazards analysis showed that bone marrow transplant [HR: 0.390, 95% CI 0.264–0.577; p < 0.0001] and light-chain isotype [HR: 0.748, 95% CI 0.318–1.759; p = 0.005] were independent predictors of longer survival. In contrast, age >80 years [HR: 2.7, 95% CI 1.6–4.3; p < 0.0001], ISS III [HR: 2.510, 95% CI 2.01–3.124; p = 0.001], IgA isotype [HR: 1.475, 95% CI 1.031–2.11; p = 0.034] and IgD/M isotype [HR: 2.753, 95% CI 1.230–6.130; p = 0.013] were independent poor prognostic factors. However, ECOG (p = 0.486), spine surgery (p = 0.391), spine radiotherapy (p = 0.260), epidural involvement (p = 0.259), the number of vertebra lesions (p = 0.222), and synchronous/metachronous timeline (p = 0.412) were not significantly associated with improved OS.ConclusionsSpinal involvement in the context of MM does not influence OS. The main prognostic factors to consider before spinal surgery are the characteristics of the primary MM disease (ISS score, IgG isotype and systemic treatment).     

Risk factors for local recurrence and long term survival after minimally invasive intersphincteric resection for very low rectal cancer: Multivariate analysis in 161 patients

IntroductionIntersphincteric resection (ISR) is the ultimate anal-sparing technique as an alternative to abdominoperineal resection in selected patients. Oncological safety is still debated. This study analyses long-term oncological results and evaluates risk factors for local recurrence (LR) and overall survival (OS) after minimally-invasive ISR.Materials and methodsRetrospective single-center data were collected from a prospectively maintained colorectal database. A total of 161 patients underwent ISR between 2008 and 2018. OS and local recurrence-free survival (LRFS) were assessed using Kaplan-Meier analysis (log-rank test). Risk factors for OS and LRFS were assessed with Cox-regression analysis.ResultsMedian follow-up was 55 months. LR occurred in 18 patients. OS and LRFS rates at 1, 3, and 5 years were 96%, 91%, and 80% and 96%, 89%, and 87%, respectively. Tumor size (p = 0.035) and clinical T-stage (p = 0.029) were risk factors for LRFS on univariate analysis. On multivariate analysis, tumor size (HR 2.546 (95% CI: 0.976–6.637); p = 0.056) and clinical T-stage (HR 3.296 (95% CI: 0.941–11.549); p = 0.062) were not significant. Preoperative CEA (p < 0.001), pathological T-stage (p = 0.033), pathological N-stage (p = 0.016) and adjuvant treatment (p = 0.008) were prognostic factors for OS on univariate analysis. Preoperative CEA (HR 4.453 (95% CI: 2.015–9.838); p < 0.001) was a prognostic factor on multivariate analysis.ConclusionsThis study confirms the oncological safety of minimally-invasive ISR for locally advanced low-lying rectal tumors when performed in experienced centers. Despite not a risk factor for LR, tumor size and, locally advanced T-stage with anterior involvement should be carefully evaluated for optimal surgical strategy. Preoperative CEA is a prognostic factor for OS.     

Survival in breast cancer patients with spine metastases: Prognostic assessment involving molecular markers

BackgroundTo clarify and update the prognostic assessment for heterogeneous population of patients with breast cancer and spine metastases (SpM), using molecular markers.MethodsThe patient data used in this study was obtained from a French national multi-center database of patients treated for breast cancer with SpM between 2014 and 2017. 556 SpM cases were diagnosed.ResultsMedian overall survival (OS) time for all patients following the SpM event was 43.9 months. First, we confirmed 3 previously known significant prognostic factors for survival of patients with SpM: young age [HR: 2.019, 95% CI 1.343–3.037; p = 0.001], good WHO status [ Status 0 HR: 2.823, 95% CI 1.231–3.345; p < 0.0001] or [ Status 1 HR: 1.956, 95% CI 0.768–2.874; p = 0.001] and no-ambulatory neurological status: Frankel A-C [HR: 0.438, 95% CI 0.248–0.772; p = 0.004]. Secondly, we determined the effect of gene mutations on survival in patients with SpM, and we identified that HER2+ cancer subtype [HR: 1.567, 95% CI 0.946–2.557; p = 0.008] was an independent predictor of longer survival, whereas basal cancer subtype [HR: 0.496, 95% CI 0.353–0.699; p < 0.0001] was associated with a poorer prognosis. Other factors including the number of SpM, surgery, extraspinal metastases, synchrone metastases, metastasis-free survival, and SpM recurrence were not identified as prognostically relevant to survival.ConclusionSurvival and our ability to estimate it in breast cancer patients with SpM has improved significantly. Therefore, SpM prognostic scoring algorithms should be updated and incorporate genotypic data on subtypes to make treatment more adaptive.     

Association between neutrophil-lymphocyte ratio,platelet-lymphocyte ratio,and survival in undifferentiated pleomorphic sarcoma (NLR,PLR, and overall survival in UPS)

Background and objectivesCancer-related inflammation has been shown to be a driver of tumor growth and progression, and there has been a recent focus on identifying markers of the inflammatory tumor microenvironment. Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are inflammatory indices that have been identified as prognostic biomarkers in various malignancies. However, there is limited and conflicting data regarding their prognostic value in soft tissue sarcoma (STS) and specifically in undifferentiated pleomorphic sarcoma (UPS).MethodsThis was a retrospective review of patients who underwent surgical treatment for primary UPS from 1993 to 2021. Cutoff values for NLR and PLR were determined by receiver operating curve analysis. Cox proportional hazards regression was used to determine prognostic factors on univariate and multivariate analysis.ResultsEighty-six patients were included. The optimal cutoff value was 3.3 for NLR and 190 for PLR. Both high NLR (HR 2.44; 95% CI 1.29–4.63; p = 0.005) and high PLR (HR 1.99; 95% CI 1.08–3.67, p = 0.02) were associated with worse OS on univariate analysis. On multivariate analysis, metastasis at presentation and radiotherapy were independently predictive of OS, but high NLR (HR 1.30; 95% CI 0.64–2.98; p = 0.41) and high PLR (HR 1.63; 95% CI 0.82–3.25; p = 0.17) were not predictive of survival.ConclusionsHigh pre-treatment NLR and PLR were associated with decreased overall survival but were not independent predictors of survival in patients undergoing resection for UPS. Until additional prospective studies can be done, survival outcomes are best predicted using previously established patient- and tumor-specific factors.     

Minimally invasive surgery versus percutaneous radiofrequency ablation for early-stage hepatocellular carcinoma: Results from a high-volume liver surgery center in East Asia

Background & aimsThe outcomes of minimally invasive surgery (MIS) vs. percutaneous radiofrequency ablation (RFA) in treating early-stage hepatocellular carcinoma (HCC) remain inconclusive. This study thus aimed to compare the outcomes of both treatments for early-stage HCCs.MethodsThis retrospective study consecutively enrolled patients with newly diagnosed early-stage HCCs treated with MIS or percutaneous RFA between 2011 and 2018. Outcomes were compared between the MIS and RFA groups both before and after 1:1 propensity score matching (PSM).ResultsA total of 119 and 481 patients underwent MIS and percutaneous RFA, respectively. Patients undergoing percutaneous RFA exhibited older age (p = 0.007) and higher rates of Child–Pugh class B (p < 0.001) and multifocal disease (p < 0.001). The median overall survival (OS) was 73.7 months in the MIS group, which was significantly higher than that for the RFA group of 65.1 months (p = 0.003). 50% HCC recurrence after MIS was not reached. The mean recurrence-free survival (RFS) was 49.6 months for the MIS group, which was significantly higher than the RFA group of 41.3 months (p < 0.001). On multivariate analysis, age ≥65 (HR: 1.61; 95% CI: 1.13–2.31, p = 0.009), RFA (HR: 2.21; 95% CI: 1.14–4.29, p = 0.019), and Child–Pugh class B (HR: 2.03; 95% CI: 1.29–3.21, p = 0.002) remained risk factors for OS, and RFA (HR: 2.18; 95% CI: 1.42–3.35; p < 0.001) remained a risk factor for RFS. After PSM, 103 patients were included in each group. No significant difference in OS was identified (p = 0.198), but RFS was higher in the MIS group than the RFA group (p = 0.003). Severe postoperative complications occurred at the same rate (1%) in both groups (p > 0.99).ConclusionAfter PSM, severe postoperative complication and OS rates were found to be comparable between the MIS and RFA groups, but RFS was higher in the MIS group than the RFA group, suggesting that MIS may have better outcomes for patients with early-stage HCC.     

Resection of isolated distant nodal metastasis in metastatic colorectal cancer

BackgroundLittle is known regarding the role of resection in patients with colorectal cancer (CRC) who present with isolated non-regional lymph node metastasis (NRLNM).MethodsUsing the Surveillance, Epidemiology and End Results database, we identified patients diagnosed with CRC and NRLNM from 2004 to 2013.ResultsA total of 849 patients presented with CRC and isolated NRLNM. Of these, 90 (10.6%) underwent resection of NRLNM. Median overall survival (OS) did not differ for patients who underwent resection of NRLNM compared to those who did not (33 versus 29 months, p = 0.68). Subgroup analysis by primary tumor site, also did not demonstrate a difference in median OS. Cox proportional hazard model revealed older age (Hazard ratio [HR] 1.34, 95% Confidence Interval [CI] 1.17–1.53, p < 0.0001), higher tumor grade (HR 1.81, 95% CI 1.52–2.16, p < 0.0001), and earlier year of diagnosis (HR 1.34, 95% CI 1.17–1.53, p < 0.0001) were associated with decreased OS. There was no survival difference between those who underwent resection of NRLNM compared to those who had not (HR 0.997, p = 0.28).ConclusionResection of NRLNM in patients with CRC is not associated with an OS benefit. Further studies are needed to determine if there is a subset of patients who could potentially benefit from this resection strategy.     

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.     

Laparoscopic versus open resection for rectal cancer: An individual patient data meta analysis of randomized controlled trials

Background and aimsThe role of laparoscopic rectal cancer resection remains controversial. Thus, we aimed to conduct a one-stage meta-analysis with reconstructed patient-level data using randomized trial data to compare long-term oncologic efficacy of laparoscopic and open surgical resection for rectal cancer.MethodsMedline, EMBASE and Scopus were searched for articles comparing laparoscopic with open surgery for rectal cancer. Primary outcome was disease free survival (DFS) while secondary outcome was overall survival (OS). One-stage meta-analysis was conducted using patient-level survival data reconstructed from Kaplan-Meier curves with Web Plot Digitizer. Shared-frailty and stratified Cox models were fitted to compare survival endpoints.ResultsSeven randomized trials involving 1767 laparoscopic and 1293 open resections for rectal cancer were included. There were no significant differences between both groups for DFS and OS with respective hazard ratio estimates of 0.91 (95% CI: 0.78–1.06, p = 0.241) and 0.86 (95% CI:0.73–1.02, p = 0.090). Sensitivity analysis for non-metastatic patients and patients with mid and lower rectal cancer showed no significant differences in OS and DFS between both surgical approaches. In the laparoscopic arm, improved DFS was noted for stage II (HR: 0.73, 95% CI:0.54–0.98, p = 0.036) and stage III rectal cancers (HR: 0.74, 95% CI:0.55–0.99, p = 0.041).ConclusionsThis meta-analysis concludes that laparoscopic rectal cancer resection does not compromise long-term oncologic outcomes compared with open surgery with potential survival benefits for a minimal access approach in patients with stage II and III rectal cancer.     

Surgery for metachronous metastasis of soft tissue sarcoma – A magnitude of benefit analysis using propensity score methods

IntroductionMetastasectomy is hypothesised to improve OS in metastatic STS, but evidence in favour of this approach derives from non-controlled single-arm cohorts affected by selection bias. The objective was to quantify the effect of metastasectomy vs. non-surgical management on overall survival (OS) in patients with metachronous metastases from extremity- and trunk soft tissue sarcoma (STS).Materials and methodsFrom a population of 1578 STS patients, 135 patients who underwent surgery for localised STS at two European centres between 1998 and 2015 and developed metachronous STS metastases were included. Propensity score analyses with inverse-probability-of-treatment-weights (IPTW) and landmark analyses were performed to control for selection and immortal time bias, respectively.ResultsOS was significantly longer in the 68 patients undergoing metastasectomy than in the 67 patients who were treated non-invasively for their metastasis (10-year OS: 23% vs. 4%; hazard ratio (HR) = 0.34, 95% CI: 0.22–0.53, p < 0.0001). This association prevailed after IPTW-weighting of the data to control for the higher prevalence of favourable prognostic factors in the surgery group (adjusted 10-year OS: 17% vs. 3%, log-rank p < 0.0001; HR = 0.33, 95% CI: 0.20–0.52, p < 0.0001). Five-year OS estimates were 27.8% in patients who had and 14.5% in patients who had not undergone metastasectomy within the first 3 months after diagnosis of a metastasis (p < 0.0001).ConclusionIn this observational bi-centre study, metastasectomy was associated with prolonged survival in patients with metachronous STS metastases. In the absence of randomized studies, our results indicate that metastasectomy should be considered as an important treatment option for metachronous STS metastases.     

Daratumumab,Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Patients With Previously Treated Multiple Myeloma: Three-year Follow-up of CASTOR

BackgroundIn the phase III CASTOR study in relapsed or refractory multiple myeloma, daratumumab, bortezomib, and dexamethasone (D-Vd) demonstrated significant clinical benefit versus Vd alone. Outcomes after 40.0 months of median follow-up are discussed.Patients and MethodsEligible patients had received ≥ 1 line of treatment and were administered bortezomib (1.3 mg/m²) and dexamethasone (20 mg) for 8 cycles with or without daratumumab (16 mg/kg) until disease progression.ResultsOf 498 patients in the intent-to-treat (ITT) population (D-Vd, n = 251; Vd, n = 247), 47% had 1 prior line of treatment (1PL; D-Vd, n = 122; Vd, n = 113). Median progression-free survival (PFS) was significantly prolonged with D-Vd versus Vd in the ITT population (16.7 vs. 7.1 months; hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.25-0.40; P < .0001) and the 1PL subgroup (27.0 vs. 7.9 months; HR, 0.22; 95% CI, 0.15-0.32; P < .0001). In lenalidomide-refractory patients, the median PFS was 7.8 versus 4.9 months (HR, 0.44; 95% CI, 0.28-0.68; P = .0002) for D-Vd (n = 60) versus Vd (n = 81). Minimal residual disease (MRD)–negativity rates (10⁻⁵) were greater with D-Vd versus Vd (ITT: 14% vs. 2%; 1PL: 20% vs. 3%; both P < .0001). PFS2 was significantly prolonged with D-Vd versus Vd (ITT: HR, 0.48; 95% CI, 0.38-0.61; 1PL: HR, 0.35; 95% CI, 0.24-0.51; P < .0001). No new safety concerns were observed.ConclusionAfter 3 years, D-Vd maintained significant benefits in patients with relapsed or refractory multiple myeloma with a consistent safety profile. D-Vd provided the greatest benefit at first relapse and increased MRD-negativity rates.     

Synergistic effect of clinicopathological factors on mortality risk in patients with differentiated thyroid cancer: An analysis using the SEER database

ObjectivesIn this study, we analyzed the effects of histology subtypes, lymph node N-stages, and the presence of extrathyroidal extensions on cancer-specific survival (CSS) and overall survival (OS) in patients with differentiated thyroid cancer.Materials and methodsCox proportional hazards regression analyses were carried out to evaluate the correlations between clinicopathological factors and CSS/OS. The combined effects of these factors on CSS and OS were then analyzed to determine the relative excess risk, attributable proportion, and synergy index. Kaplan-Meier curves were used to evaluate the mortality rate.ResultsA total of 86033 cases were included in the analysis. Histology subtype, N-stage, and extrathyroidal extension were all found to be risk factors for CSS (hazard ratio [HR] = 1.8, 95% confidence intervals [CI]: 1.4–2.3, p < 0.001; HR = 1.9, 95% CI: 1.6–2.3, p < 0.001; HR = 1.4, 95% CI: 1.0–1.9, p = 0.035, respectively). The risk factors for OS were histology subtype and N-stage (HR = 1.3, 95% CI; 1.2–1.5, p < 0.001; HR = 1. 4, 95% CI: 1.3–1.5, p < 0.001, respectively) but not extrathyroidal extension (HR = 1.1, 95% CI: 0.9–1.3, p = 0.228). Furthermore, histology subtype and N-stage, histology subtype and extrathyroidal extension, and N stage and extrathyroidal extension (relative excess risk, attributable proportion, and synergy index: 48.8, 0.9, 7.6; 50.2, 0.7, 3.9; 7.0, 0.3, 1.6; respectively) were found to have significant synergistic effects.ConclusionPatients with follicular thyroid carcinoma (FTC) and extrathyroidal extension or lymph node metastasis are at a higher risk of mortality. Histology subtype, N-stage, and extrathyroidal extension appear to have synergistic effects on the increased risk of poor CSS in patients. This result can in the further development of treatment guidelines to improve the outcome of FTC patients.     

Spinal metastases from thyroid cancer: Some prognostic factors

BackgroundSpinal metastases (SpMs) from thyroid cancers (TC) significantly reduce quality of life by causing pain, neurological deficits in addition to increasing mortality. Moreover, prognosis factors including surgery remain debated.MethodsData were stored in a prospective French national multicenter database of patients treated for SpM between January 2014 and 2017. Fifty-one consecutive patients affected by TC with 173 secondary SpM were included.ResultsMean overall survival (OS) time for all patients from the diagnosis of a thyroid SpM event was 9.1 years (SD 8.7 months). The 1-year, 5-year and 10-year survival estimates were 94% (SD 3.3), 83.8.0% (SD 5.2), and 74.5% (SD 9.9). The median period of time between primary thyroid tumor diagnosis and the SpM event was 31.4 months (SD 71.6). In univariate analysis, good ECOG-PS (status 0 and 1) (p < 0.0001), ambulatory status (Frankel score) (p < 0.0001) and no epidural involvement (p = 0.01), were associated with longer survival, whereas cancer subtype (p = 0.436) and spine surgery showed no association (p = 0.937). Cox multivariate proportional hazard model only identified good ECOG-PS: 0 [HR: 0.3, 95% CI 0.1–0.941; p < 0.0001], 1 [HR: 0.8, 95% CI 0.04–2.124; p = 0.001] and ambulatory neurological status: Frankel E [HR: 0.262, 95% CI 0.048–1.443; p = 0.02] to be independent predictors of better survival.ConclusionFor cases presenting SpM from TC, we highlighted that the only prognostic factors were the progression of the cancer (ECOG-PS) and the clinical neurological impact of the SpM (Frankel status). Surgery should be discussed mainly for stabilization and neurological decompression.     

Prognostic factors and outcomes of adult spermatic cord sarcoma. A study from the French Sarcoma Group

PurposeTo evaluate the outcomes of adult patients with spermatic cord sarcoma (SCS).MethodsAll consecutive patients with SCS managed by the French Sarcoma Group from 1980 to 2017 were analysed retrospectively. Multivariate analysis (MVA) was used to identify independent correlates of overall survival (OS), metastasis-free survival (MFS), and local relapse-free survival (LRFS).ResultsA total of 224 patients were recorded. The median age was 65.1 years. Forty-one (20.1%) SCSs were discovered unexpectedly during inguinal hernia surgery. The most common subtypes were liposarcoma (LPS) (73%) and leiomyosarcoma (LMS) (12.5%). The initial treatment was surgery for 218 (97.3%) patients. Forty-two patients (18.8%) received radiotherapy, 17 patients (7.6%) received chemotherapy. The median follow-up was 5.1 years. The median OS was 13.9 years. In MVA, OS decreased significantly with histology (HR, well-differentiated LPS versus others = 0.096; p = 0.0224), high grade (HR, 3 versus 1–2 = 2.7; p = 0.0111), previous cancer and metastasis at diagnosis (HR = 6.8; p = 0.0006). The five-year MFS was 85.9% [95% CI: 79.3–90.6]. In MVA, significant factors associated with MFS were LMS subtype (HR = 4.517; p < 10-4) and grade 3 (HR = 3.664; p < 10-3). The five-year LRFS survival rate was 67.9% [95% CI: 59.6–74.9]. In MVA, significant factors associated with local relapse were margins and wide reresection (WRR) after incomplete resection. OS was not significantly different between patients with initial R0/R1 resection and R2 patients who underwent WRR.ConclusionsUnplanned surgery affected 20.1% of SCSs. A nonreducible painless inguinal lump should suggest a sarcoma. WRR with R0 resection achieved similar OS to patients with correct surgery upfront.     

A Population-Based Study of Incidence and Survival of 1588 Thymic Malignancies: Results From the California Cancer Registry

BackgroundThymic malignancies are rare and there are limited contemporary population-based epidemiological studies for this uncommon cancer.Patients and MethodsAdults aged 20 years and older diagnosed with thymic malignancies between 1988 and 2015 were identified from the California Cancer Registry (n = 1588). Trends in age-adjusted incidence rates were examined overall and according to race/ethnicity, and the proportion diagnosed according to stage was evaluated over time. Cox proportional hazards regression was used to estimate hazard ratios (HRs) for overall survival (OS), and Fine and Gray competing risks regression for cause-specific survival (CSS).ResultsAge-adjusted incidence increased on average 2.08% per year over the study period (95% confidence interval [CI], 1.30%-2.86%; P < .0001), with an incidence of 0.277 cases per 100,000 in 2015. Incidence was highest among Asian/Pacific Islander and non-Hispanic black individuals. The proportion of unknown stage at diagnosis declined as localized diagnoses increased over time. Compared with patients with thymoma, those with thymic carcinoma had significantly worse OS (HR, 1.63; 95% CI, 1.33-2.01; P < .0001) and CSS (subdistribution HR, 2.99; 95% CI, 2.29-3.91; P < .0001). Advanced stage at diagnosis was also associated with worse survival. Surgical intervention was associated with better prognosis for patients with localized (HR, 0.08; 95% CI, 0.02-0.30; P = .0002) or regional disease (HR, 0.14; 95% CI, 0.06-0.34; P < .0001).ConclusionThymic malignancy incidence is increasing in California. There was incidence variation across race/ethnicity, which warrants future study. These findings provide contemporary insight into the incidence and prognostic factors of thymic malignancies.     

Final results of the CAVE trial in RAS wild type metastatic colorectal cancer patients treated with cetuximab plus avelumab as rechallenge therapy: Neutrophil to lymphocyte ratio predicts survival

BackgroundHigh neutrophil-to-lymphocyte ratio (NLR) is a poor prognostic factor in metastatic colorectal cancer (mCRC). Here we provide final results of CAVE mCRC trial, of cetuximab plus avelumab rechallenge in chemo-refractory mCRC patients and investigated the predictive role of NLR.MethodsAll the 77 patients enrolled were included in the analysis. A cut-off of 3 was used to correlate baseline NLR with with overall survival (OS) and with progression free survival (PFS), in intention to treat (ITT) and in circulating tumor DNA (ctDNA) RAS/BRAF Wild Type (WT) patients.ResultsIn ITT population, NLR <3 (49%) group had median overall survival (mOS) of 17.8 months, vs. 8.9 months in NLR ≥ 3 group (51%) [HR 0.50, (CI 95% 0.3-0.8), P = .006]. Median progression free survival (mPFS) was 3.9 months in NLR <3 group and 3.5 months in NLR≥3 [HR 0.79, (CI 95% 0.5-1.24), P = .3]. In ctDNA RAS/BRAF WT population, mOS was 22 months in NLR <3 group (48%), vs. 8.9 months in NLR ≥3 group (52%), [HR 0.38, (CI 95% 0.19-0.75), P = .005]. A trend towards increased mPFS was observed in patients with NLR <3 versus NLR ≥3: 5.3 vs. 3.6 months [HR: 0.79, (CI 95% 0.44-1.4), P = .43]. In contrast, NLR did not correlate either with PFS or OS in ctDNA RAS/BRAF mutated patients.ConclusionIn the exploratory analysis of the CAVE mCRC trial, baseline NLR <3 significantly correlated with improved survival and may represent a potential predictive biomarker of cetuximab plus avelumab rechallenge activity in ctDNA RAS/BRAF WT patients, that must be confirmed in randomized studies.     

Outcomes Following SBRT vs. IMRT and 3DCRT for Older Patients with Stage IIA Node-Negative Non-Small Cell Lung Cancer > 5 cm

BackgroundTo describe outcomes and compare the effectiveness of stereotactic body radiotherapy (SBRT) versus 3-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) in patients with stage IIA lymph node-negative (N0) non-small cell lung cancer (NSCLC) tumors > 5 cm.MethodsWe used the SEER-Medicare database (2005-2015) to identify patients > 65 years with stage IIA (AJCC TNM7) N0 NSCLC > 5 cm tumors who were treated with SBRT, IMRT, and 3DCRT. We used propensity score methods with inverse probability weighting to compare lung cancer-specific survival (LCSS), overall survival (OS), and toxicity.ResultsOf 584 patients, 88 (15%), 140 (24%), and 356 (61%) underwent SBRT, IMRT, and 3DCRT, respectively. The SBRT group was older (P = .004), had more comorbidities (P = .02), smaller tumors (P = .03), and more adenocarcinomas (P < .0001). We found a trend towards higher median unadjusted OS with SBRT compared to IMRT and 3DCRT (19 vs. 13 and 14 months, respectively, P = .37). In our propensity score-adjusted analyses, SBRT was significantly associated with better OS and LCSS compared to IMRT (HR_OS: 0.78, 95% CI: 0.68-0.89, HR_LCSS: 0.70, 95% CI: 0.60-0.81) and 3DCRT (HR_OS: 0.81, 95% CI: 0.72-0.93, HR_LCSS: 0.80, 95% CI: 0.68-0.93). SBRT-treated patients also had lower overall adjusted complication rates compared to IMRT (OR: 0.74, 95% CI: 0.55-0.99) and 3DCRT (OR: 0.53, 95% CI: 0.40-0.71).ConclusionFor patients with NSCLC tumors > 5 cm, SBRT trends towards fewer toxicities and improved survival compared to other forms of radiotherapy. Our findings support SBRT as an appropriate treatment strategy for older patients with larger inoperable NSCLC tumors.     

Clinical utility of lymphocyte to C-reactive protein ratio in predicting survival and postoperative complication for esophago-gastric junction cancer

BackgroundThere are still no useful predictive biomarkers for esophago-gastric junction (EGJ) cancer. We compared 15 candidate inflammation-based markers and investigated the clinical impact of the selected biomarker.MethodsOne hundred three patients with EGJ cancer between 2002 and 2020 were enrolled, and associations between clinicopathological data and inflammatory biomarkers were retrospectively analyzed. Area under the curve (AUC) values of 15 candidate biomarkers were compared in receiver operating characteristic (ROC) curves regarding overall survival (OS). Clinical impacts of the selected marker were further investigated regarding long-term prognosis, postoperative complications, and preoperative chemotherapy effects.ResultsLymphocyte/CRP ratio (LCR) demonstrated the highest AUC (0.68552) and was chosen as a candidate biomarker. The high LCR group (LCR >4610) demonstrated significantly better OS (p < 0.0001) and relapse-free survival (RFS) (p < 0.0001) compared with the low LCR group (LCR ≤4610), and preoperative LCR was an independent prognostic factor for both OS (HR 4.97, 95% CI:2.24–11.58; p < 0.0001) and RFS (HR 2.84, 95% CI:1.33–6.14, p = 0.007) in EGJ cancer patients. Another cut-off value was established for postoperative complications, and the incidence rates were significantly higher in the low LCR group (LCR ≤12000) than in the high LCR group (LCR >12000) for all postoperative complications, infectious complications, and surgical site infection (p = 0.013, p = 0.016, and p = 0.030, respectively). Furthermore, patients with decreased LCR after preoperative chemotherapy demonstrated significantly worse RFS compared with patients with increased LCR (p = 0.043).ConclusionsLCR is a potential biomarker to predict long-term prognosis as well as occurrence of postoperative complications in patients with EGJ cancer.     

A systematic review and meta-analysis on the impact of pre-operative neutrophil lymphocyte ratio on long term outcomes after curative intent resection of solid tumours

IntroductionThere is increasing evidence to suggest that cancer-associated inflammation is associated with poorer long-term outcomes. Various markers have been studied over the past decade in an attempt to improve selection of patients for surgery. This meta-analysis explored the association between the neutrophil-lymphocyte ratio and prognosis following curative-intent surgery for solid tumours.MethodsStudies were identified from US National Library of Medicine (Medline) and the Exerpta Medica database (EBASE) performed in March 2013. A systematic review and meta-analysis were performed to generate combined hazard ratios for overall survival (OS) and disease-free survival (DFS).ResultsForty-nine studies containing 14282 patients were included. Elevated NLR was associated with poorer overall survival [HR: 1.92, 95% CI (1.64–2.24)] (p < 0.001) and disease-free survival [HR: 1.99, 95% CI (1.80–2.20)] (p < 0.001). Significant heterogeneity was found with an I² of 77% and 97% for OS and DFS respectively. Subgroup analyses demonstrated that gastro-intestinal malignancies; mainly gastric [HR: 1.97, 95% CI (1.41–2.76)], colorectal [HR: 1.65, 95% CI (1.21–2.26)] and oesophageal [HR: 1.48, 95% CI (0.91–2.42)] cancers were predictive of OS (I² = 54.3%). A separate analysis for studies using an NLR cutoff of 5 demonstrated significantly poorer outcomes [HR: 2.18, 95% CI (1.74–2.73)] (p = 0.002) with less heterogeneity (I² = 58%).ConclusionElevated NLR correlates with poorer prognosis. It potentially represents a simple, robust and reliable measure that may be useful in identifying high-risk groups who could benefit from adjuvant therapy.     

Relevance of sentinel lymph node biopsy for thick melanoma in the era of immunotherapy

BackgroundSentinel lymph node biopsy provides prognostic information in patients with thick melanoma but is often underutilized. We examine regional lymph node evaluation (RLNE) in patients with thick melanoma and the effect on treatment and overall survival (OS).MethodsPatients with clinical T4N0M0 melanoma were selected from the National Cancer Database (2004–2015). Binary logistic regression analysis was used to identify factors associated with RLNE and treatment. Overall survival analysis was performed.ResultsA total of 14 286 patients with clinical T4N0M0 melanoma were identified; RLNE was performed in 70.2% of patients, and positive LNs were identified in 27.1%. RLNE was more likely in males (OR:1.44, 95%CI: 1.32–1.56, p < .001), and patients treated at academic centers (OR:1.58, 95%CI:1.46–1.71, p < .001). Immunotherapy was more commonly used in patients with RLNE (13.9% vs 3.4%, p < .001) and was associated with positive LNs (OR:2.50, 95%CI:2.19–2.86, p < .001). The 5-year OS for RLNE was 56.9% and for no RLNE was 32.7%. Independent factors associated with better OS were treatment at an academic center (HR:0.88, 95%CI:0.84–0.93, p < .001), and immunotherapy use (HR:0.86, 95%CI:0.76–0.96, p < .001).ConclusionThe use of RLNE in patients with thick melanoma is important for prognosis and to risk stratify patients for selection of adjuvant therapies and clinical trials.     

Effect of Breast Conservation Therapy vs Mastectomy on Overall Survival and Breast Cancer-Specific Survival Among Men With Stage I-II Breast Cancer: Analysis of SEER, 2000-2018

BackgroundMale breast cancer is a rare malignant tumor, and outcomes of breast conservation therapy (BCT) are currently lacking.MethodThe retrospective, population-based cohort study included 1369 stage I-II (T1–2 N0–1 M0) male breast cancer patients from the SEER database (2000-2018). The patients were grouped in two groups: BCT group and mastectomy group, according to surgical and radiation therapy. Kaplan-Meier method and univariable Cox proportional hazard analysis were used to compare overall survival (OS) and breast cancer-specific survival (BCSS) between two treatment groups. Propensity score matching (PSM) was performed to balance the confounding factors.ResultsOf the 1369 men, 97 (7%) patients received BCT, 1272 (93%) received mastectomy alone. The 5- and 10-year OS rates were 92.3% and 80.7% for BCT group compared with 80.4% and 61.4% for mastectomy group. The 5- and 10-year BCSS rates were 96.5% and 93.9% for patients undergoing BCT, as compared with 93.1% and 84.4% for patients undergoing mastectomy. Compared with mastectomy group, BCT group showed improved OS (hazard ratio [HR], 0.294; 95% CI 0.138-0.623, P = .002) and BCSS (hazard ratio [HR], 0.182; 95% CI 0.040-0.820, P = .027). Of the 791 patients with T1 stage, BCT showed insignificant association with OS (hazard ratio [HR], 0.555; 95% CI 0.207-1.488, P = .242) and BCSS (hazard ratio [HR], 1.217; 95% CI 0.171-8.675, P = .844).ConclusionThe results of this cohort study suggest that BCT is at least equivalent to mastectomy in male breast cancer patients. The underlying mechanism of this association needs further research.