Pretreatment Absolute Lymphocyte Count Research Articles

Risk factors for microbiological persistence after 6 months of treatment for Mycobacterium intracellulare and its impact on the drug-resistance profile.

Patients with Mycobacterium intracellulare pulmonary disease are more likely to experience poor treatment outcomes if they have been observed with microbiological persistence after 6 months of treatment. This study aims to identify the risk factors for microbiological persistence and describe the changes in the minimum inhibitory concentration (MIC) during antimycobacterial treatment. This retrospective case-control study enrolled patients diagnosed with M. intracellulare pulmonary disease between April 2017 and September 2021 at Shanghai Pulmonary Hospital. Patients with positive cultures after 6 months of treatment (positive group) were matched by age and sex in a 1:1 ratio to patients with negative conversion (negative group). Totally, 46 pairs of patients were analyzed. Risk factors for microbiological persistence at month 6 were smoking, previous tuberculosis treatment, chronic lung diseases, a positive baseline acid-fast bacilli smear, and adverse drug reactions; the risk was reduced by a regimen containing ethambutol, ≥3 effective drugs, and a higher pre-treatment absolute lymphocyte count. Regarding the drug-resistance profile, the negative group had a higher proportion of susceptibility to clarithromycin (100.0% vs 84.8%, P = 0.012). Most isolates were susceptible or intermediate to amikacin in both groups (93.5% and 84.8%, respectively). Nine patients (16.4%, 9/55) had a change in the drug-resistance profile, including four who changed from clarithromycin susceptible to clarithromycin resistant, and the other three reversed. Two pairs of isolates had a change in resistance to amikacin. In conclusion, risk factors for microbiological persistence were identified, and the change in MIC values during antimycobacterial treatment indicated the need for monitoring to enable timely adjustment of the regimen.IMPORTANCENontuberculous mycobacteria pulmonary disease (NTM-PD) has been recognized as an important public health issue because of its increasing incidence globally, low cure rate, and high recurrence rate. NTM-PD has innate resistance to many first-line anti-tuberculous drugs, which limits the treatment options. Mycobacterium intracellulare is reportedly the most important pathogenic NTM and accounts for the highest proportion of NTM-PD in China. A previous study suggested that poor microbiological response after 6 months of treatment is predictive of treatment failure. The present study investigated the risk factors associated with persistent positive sputum cultures by treatment month 6 in patients with M. intracellulare pulmonary disease and the variation in minimum inhibitory concentration patterns in clinical settings. This information might help to identify patients at higher risk of treatment failure and enable the timely provision of necessary interventions.

Drug Retention Rates of Janus Kinase Inhibitors in Rheumatoid Arthritis Patients with Therapy-Induced Lymphopenia.

To determine whether drug-induced lymphocytopenia is associated with drug retention rates of JAKi (tofacitinib or baricitinib) in rheumatoid arthritis (RA) patients. Patients with RA who were initiated with tofacitinib (n = 38) or baricitinib (n = 74) between July 2015 and July 2022 and continued for at least 4 months were enrolled in this study. Absolute lymphocyte count (ALC) value was obtained pre-treatment and monthly after initiation of JAKi (up to 4 months). Associations between ALC nadir at an early phase (up to 4 months) from JAKi initiation and drug retention rates were analysed. 112 patients (87 females; age, 71.2 ± 14.0 years; disease duration, 9.2 ± 10.5 months; DAS28-CRP, 3.60 ± 1.12; DAS28-ESR, 4.43 ± 1.29; CDAI, 17.9 ± 12.9; C-reactive protein, 3.07 ± 3.43 mg/dL; and lymphocyte count, 1361.9 ± 538.7 per μL) treated with tofacitinib or baricitinib were retrospectively analysed. Lymphocytopenia (>10% decline in lymphocyte count to pre-treatment basal levels) was observed in a quarter of RA patients treated with JAKi (tofacitinib; 16 baricitinib; 14). RA patients with lymphopenia were associated with the lower drug retention rates of tofacitinib compared to those without lymphocytopenia. The reduced drug retention rates in patients with lymphocytopenia were attributed to the discontinuation of tofacitinib due to AEs. Whereas lymphocytopenia was not associated with lower drug retention rates of baricitinib. Pre-treatment absolute lymphocyte counts did not affect the drug retention rates of JAKi in patients with RA. These findings suggest that lymphopenia during the first 4 months from the initiation of JAKi is associated with reduced drug retention rates in patients with RA due to AEs, which is exclusively associated with the use of tofacitinib.

Prognostic value of absolute lymphocyte count in oral cavity squamous cell carcinoma.

Absolute lymphocyte count (ALC) has been shown to be a prognostic indicator in other solid tumors. Given this, we aimed to evaluate the prognostic value of ALC in oral cavity squamous cell carcinoma (OSCC). Using our institutional tumor registry data, we identified patients ≥18 years old who were diagnosed with OSCC between 2012 and 2018. Preoperative ALC values within 30 days of surgery were collected through retrospective chart review. American Joint Committee on Cancer, 7th-edition best stage was used to categorize cancers as early stage (stages 1 and 2) or late-stage (stages 3 and 4). Primary outcomes were likelihood of recurrence and survival rates after 3 years. Of the 412 patients identified, 262 patients had available ALC data and met inclusion criteria. Early stage cancer patients who had lymphopenia did not have any significant difference in their rate of death ([OR], 1.71, CI: 0.54-5.45, p = .36) or likelihood recurrence ([OR], 0.60, CI: 0.06-5.87, p = .66) after controlling for age, tobacco use, alcohol use, positive margins, and adjuvant therapy. Late-stage cancer patients who had lymphopenia also showed no difference in their rate of death ([OR], 2.74, CI: 0.65-11.6, p = .17) or likelihood of recurrence ([OR], 0.38, CI: 0.04-3.36, p = .38). This study evaluates the prognostic value of ALC in oral cavity cancers. Our findings demonstrate that pretreatment ALC is not significantly associated with recurrence and survival outcomes patients with OSCC. III. Absolute lymphocyte count (ALC) has been associated with prognosis in several cancers. We found that preoperative ALC was not associated with likelihood of survival or recurrence in patients with early stage or late-stage oral cavity cancer.

Pretreatment absolute lymphocyte count is an independent predictor for survival outcomes for esophageal squamous cell carcinoma patients treated with neoadjuvant chemoradiotherapy and pembrolizumab: An analysis from a prospective cohort.

The aim of the study was to analyze the relationship between pretreatment inflammatory biomarkers (IBs) and survival outcomes for patients with esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (neo-CRT) and pembrolizumab. Clinical variables and IBs (absolute monocyte count [AMC], absolute lymphocyte count [ALC], platelet count [PLT], neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR], pan-immune inflammation value [PIV], systemic immunoinflammatory index [SII], systemic immunoreactivity index [SIRI] and prognostic nutritional index [PNI]) were collected. Univariate and multivariate analysis were performed to identify the independent factors for outcomes of ESCC. A total of 51 patients were included. Of these, 35 patients achieved pathological complete response (pCR) after neo-CRT and pembrolizumab (pCR: 68.6%). With a median follow-up of 20 months, the two-year PFS and OS of the cohort was 64% and 91%, respectively. Multivariate logistic regression analysis indicated that ALC (overall response [OR] 4.4, p = 0.051) and PLT (OR 6.7, p = 0.023) were two independent predictors for achieving pCR among ESCC treated with neo-CRT and pembrolizumab. Multivariate Cox regression analysis showed that ALC (HR 0.27, p = 0.028) and SIRI (HR 3.13, p = 0.048) were two independent predictors associated with PFS. Kaplan Meier analysis demonstrated that the PFS of ESCC with high baseline ALC was significantly better than those with low ALC (2-year PFS: 77% vs. 47%, p = 0.027), but not for overall survival (2-year OS: 96% vs. 87%, p = 0.46). This retrospective analysis based on a prospective cohort for the first time demonstrates that pretreatment ALC is an independent predictor for achieving pCR and favorable outcomes of ESCC treated with neo-CRT and pembrolizumab.

Association between pretreatment lymphocyte count and efficacy of immune-enhancing therapy in acute necrotising pancreatitis: a post-hoc analysis of the multicentre, randomised, placebo-controlled TRACE trial

Immune-enhancing thymosin alpha 1 (Tα1) therapy may reduce infected pancreatic necrosis (IPN) in acute necrotising pancreatitis (ANP). However, the efficacy might be impacted by lymphocyte count due to the pharmacological action of Tα1. In this post-hoc analysis, we tested the hypothesis that pre-treatment absolute lymphocyte count (ALC) determines whether patients with ANP benefit from Tα1 therapy. A post-hoc analysis of data from a multicentre, double-blind, randomised, placebo-controlled trial testing the efficacy of Tα1 therapy in patients with predicted severe ANP was performed. Patients from 16 hospitals of China were randomised to receive a subcutaneous injection of Tα1 1.6mg every 12h for the frst 7 days and 1.6mg once a day for the following 7 days or a matching placebo during the same period. Patients who discontinued the Tα1 regimen prematurely were excluded. Three subgroup analyses were conducted using the baseline ALC (at randomisation), and the group allocation was maintained as intention-to-treat. The primary outcome was the incidence of IPN 90 days after randomisation. The fitted logistic regression model was applied to identify the range of baseline ALC where Tα1 therapy could exert a maximum effect. The original trial is registered with ClinicalTrials.gov, NCT02473406. Between March 18, 2017, and December 10, 2020, a total of 508 patients were randomised in the original trial, and 502 were involved in this analysis, with 248 in the Tα1 group and 254 in the placebo group. Across the three subgroups, there was a uniform trend toward more significant treatment effects in patients with higher baseline ALC. Within the subgroup of patients with baseline ALC≥0.8×10ˆ9/L (n=290), the Tα1 therapy significantly reduced the risk of IPN (covariate adjusted risk difference,-0.12; 95% CI,-0.21,-0.02; p=0.015). Patients with baseline ALC between 0.79 and 2.00×10ˆ9/L benefited most from the Tα1 therapy in reducing IPN (n=263). This post-hoc analysis found that the efficacy of immune-enhancing Tα1 therapy on the incidence of IPN may be associated with pretreatment lymphocyte count in patients with acute necrotising pancreatitis. National Natural Science Foundation of China.

Prognostic Value of Absolute Lymphocyte Count in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab Plus Ipilimumab

Nivolumab and ipilimumab (NIVO + IPI) is standard therapy for patients with advanced renal cell carcinoma (RCC). Absolute lymphocyte count (ALC) is a valuable prognostic factor in patients with various cancers treated with immune checkpoint inhibitors. Herein, we determined the prognostic value of pretreatment ALC in advanced RCC patients treated with NIVO + IPI as first-line therapy. Data from 46 advanced RCC patients treated with NIVO + IPI between September 2018 and August 2022 were retrospectively reviewed and analyzed. Median progression-free survival (PFS) and overall survival (OS) were significantly shorter in patients with low than high ALC (PFS: p = 0.0095; OS: p = 0.0182). Multivariate analysis suggested that prior nephrectomy [hazard ratio (HR) = 3.854, 95% confidence interval (CI) = 1.433-10.359, p = 0.0075] and pretreatment ALC (HR = 2.513, 95% CI = 1.119-5.648, p = 0.0257) were independent factors for PFS. Our new prognostic ALNx model based on ALC and prior nephrectomy suggested that the poor-risk group was a predictor of significantly worse PFS (p < 0.0001) and OS (p = 0.0016). Collectively, the developed ALNx model may be a novel predictor of response in advanced RCC patients treated with NIVO + IPI.

Neoadjuvant chemoradiotherapy induced lymphopenia in gastric cancer and associations with spleen dosimetry and survival outcomes

BackgroundFew studies concentrate on spleen dosimetry of radiotherapy for gastric cancer (GC). Although there is no consensus on the spleen dose-volume threshold for lymphopenia, several studies indicated that the higher the spleen dose, the higher the risk of lymphopenia. This study aimed to identify the appropriate spleen dosimetric parameters for predicting grade 4 + lymphopenia in patients with locally advanced GC. Material and methodsA total of 295 patients treated with nCRT and nChT from June 2013 to December 2021 at two major centers were included, of whom 220 were assigned to the training cohort and 75 to the external validation cohort. ResultsGrade 4 + lymphopenia was more common in the nCRT than in the nChT group (49.5% vs. 0, P < 0.001 in the training cohort; 25.0% vs. 0, P = 0.001 in the external validation cohort). Age ≥ 60 years (P = 0.006), lower pretreatment absolute lymphocyte count (P = 0.001), higher spleen volume (SPV) (P = 0.001), and higher V20 (P = 0.003) were significant risk factors of grade 4 + lymphopenia for patients treated with nCRT. Patients with grade 4 + lymphopenia had significantly worse PFS (P = 0.043) and showed a negative correlation trend with OS (P = 0.07). Limiting V20 to < 84.5% could decrease the incidence of grade 4 + lymphopenia by 35.7%. The predictive effectiveness of the multivariable model in the training and external validation cohorts was 0.880 and 0.737, respectively. ConclusionGrade 4 + lymphopenia during nCRT was more common than nChT, and was associated with a worse PFS in GC patients. Constraining the spleen V20 to < 84.5% may indirectly improve outcomes through lymphocyte preservation.

Role of pretreatment absolute lymphocyte count in survival outcomes for esophageal cancer treated with neoadjuvant chemoradiotherapy and pembrolizumab: An analysis from a prospective cohort.

338 Background: To analyze the relationship between pre-treatment inflammatory biomarkers (IBs) and survival outcomes for ESCC treated with neo-CRT and pembrolizumab. Methods: Clinical variables and IBs [absolute monocyte count (AMC), absolute lymphocyte count (ALC), platelet count (PLT), neutrophil lymphocyte ratio (NLR), Platelet lymphocyte ratio (PLR), Lymphocyte monocyte ratio (LMR), Pan-Immune Inflammation value (PIV), Systemic immunoinflammatory index (SII), Systemic Immunoreactivity Index (SIRI) and prognostic nutritional index (PNI)] were collected from two prospective trials. Univariate and multivariate analysis was performed. Results: A total of 51 patients were included. Of them, 35 patients achieved pathologic complete response after neo-CRT and pembrolizumab (pCR: 68.6%). With a median follow-up of 20 months, the two-year PFS and OS of the cohort was 64% and 91%, respectively. Multivariate logistic regression analysis indicated that ALC (OR 4.4, p=0.051) and PLT (OR 6.7, p=0.023) were two independent predictors for achieving pCR among ESCC treated with neo-CRT and pembrolizumab. Multivariate Cox regression analysis showed that ALC (HR 0.27, p=0.028) and SIRI (HR 3.13, p=0.048) were two independent predictors for PFS of this patient population. K-M analysis demonstrated that the PFS of ESCC with high base line ALC was significantly better than those with low ALC (2-year PFS: 77% vs. 47%, p=0.027), but not for overall survival (2-year OS: 96% vs. 87%, p=0.46). Conclusions: Our data demonstrates that pre-treatment ALC is an independent predictor for archiving pCR and favorable outcomes of ESCC treated with neo-CRT and pembrolizumab. Clinical trial information: NCT04435197 ; NCT04435197 .[Table: see text]

Predictive significance of surgery-induced lymphopenia on the survival after curative resection for locally advanced gastric cancer: a retrospective cohort analysis

BackgroundFollowing the establishment of the anti-cancer effect of immune checkpoint inhibitors, lymphopenia has attracted attention as a parameter of preexisting cancer-related immune tolerance. Although the pretreatment absolute lymphocyte count (ALC) has been reported as a prognostic factor in gastric cancer patients, the impact of perioperative changes in the ALC remains unknown. The aim of the present study was to explore the relationship between surgery-induced lymphopenia and outcome.MethodsDatabase entries for 584 patients who underwent curative resections for pathological Stage IB-III gastric cancer were reviewed. We retrospectively compared clinicopathological factors including pretreatment ALC (pre-ALC) and ALC at first visit after discharge (post-ALC) with the survival. The low ALC was defined as < 1000/μL.ResultsThe ALC decreased significantly at 1 and 3 days after surgery and then recovered to the baseline value. A low pre-ALC (p < 0.001) and a low post-ALC (p < 0.001) were both correlated with a poor relapse-free survival (RFS). A multivariate analysis of RFS identified a low post-ALC (hazard ratio 1.875, 95% CI 1.156–3.402, p = 0.01), age, gender, BMI, T disease, N disease, severe vessel invasion, type of gastrectomy and postoperative morbidity as independent factors. The low post-ALC group had a poor RFS among patients with Stage II (p = 0.04) and Stage III (p = 0.04) disease, but not among patients with Stage IB disease (p = 0.13). Consistently, the overall survival (OS) rate was significantly lower among patients with a low post-ALC for all stage (p < 0.001), stage II (p = 0.02) and stage III (p = 0.01) disease, not for stage IB (p = 0.09). A low post-ALC was identified as an independent factor for predicting OS by multivariate analysis (hazard ratio: 2.275, 95% CI 1.373–3.769, p = 0.01).ConclusionsA decrease in post-ALC was correlated with both of RFS and OS after curative resection in patients with locally advanced gastric cancer.HighlightsPostoperative lymphopenia was a poor prognostic factor for gastric cancer.

Hospitalized cancer patients with comorbidities and low lymphocyte counts had poor clinical outcomes to immune checkpoint inhibitors.

BackgroundImmune checkpoint inhibitor (ICI) therapy has improved survivals with a favorable toxicity profile in a variety of cancer patients. We hypothesized that hospitalized cancer patients who have acute or chronic comorbidities may have suppressed immune systems and poor clinical outcomes to ICIs. The objective of this study was to explore clinical outcomes and predictive factors of hospitalized cancer patients who received ICI therapy at an NCI-designated Comprehensive Cancer Center.MethodsA retrospective review of electronic medical records was conducted for adult cancer patients who received an FDA-approved ICI during admission from 08/2016 to 01/2022. For each patient we extracted demographics, cancer histology, comorbidities, reasons for hospitalization, ICI administered, time from treatment to discharge, time from treatment to progression or death, and complete blood counts. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using the log-rank test. The 95% confidence interval for survival was calculated using the exact binomial distribution. Statistical significance was defined as 2-sided p<0.05.ResultsOf 37 patients identified, 2 were excluded due to lack of complete blood counts on admission. Average hospital stay was 24.2 (95% CI 16.5, 31.9) days. Ten (27.0%) patients died during the same hospitalization as treatment. Of those who followed up, 22 (59.5%) died within 90 days of inpatient therapy. The median PFS was 0.86 (95% CI 0.43, 1.74) months and median OS was 1.55 (95% CI 0.76, 3.72) months. Patients with ≥3 comorbidities had poorer PFS (2.4 vs. 0.4 months; p=0.0029) and OS (5.5 vs. 0.6 months; p=0.0006). Pre-treatment absolute lymphocyte counts (ALC) <600 cells/µL were associated with poor PFS (0.33 vs. 1.35 months; p=0.0053) and poor OS (0.33 vs. 2.34 months; p=0.0236). Pre-treatment derived neutrophil to lymphocyte ratio (dNLR) <4 was associated with good median PFS (1.6 vs. 0.4 months; p=0.0157) and OS (2.8 vs. 0.9 months; p=0.0375).ConclusionsAdministration of ICI therapy was associated with poor clinical outcomes and high rates of both inpatient mortality and 90-day mortality after inpatient ICI therapy. The presence of ≥3 comorbidities, ALC <600/μL, or dNLR >4 in hospitalized patients was associated with poor survival outcomes.

Low lymphocyte-to-monocyte ratio predicts poor outcome in high-risk aggressive large B-cell lymphoma.

Low lymphocyte‐to‐monocyte‐ratio (LMR) has been associated with unfavorable survival in patients with diffuse large B‐cell lymphoma (DLBCL). To date, however, the impact of LMR on survival has not been examined in a uniformly treated cohort of patients with high‐risk aggressive large B‐cell lymphoma. We collected peripheral blood absolute lymphocyte counts (ALCs) and absolute monocyte counts (AMC) prior to treatment and calculated LMR from 112 adult patients, who were less than 65 years of age, had age‐adjusted International Prognostic Index 2–3, or site‐specific risk factors for central nervous system (CNS) recurrence, and were treated in a Nordic Lymphoma Group LBC‐05 trial with dose‐dense immunochemotherapy and early systemic CNS prophylaxis (www.ClinicalTrials.gov, number NCT01325194). Median pretreatment ALC was 1.40 × 109/l (range, 0.20–4.95), AMC 0.68 × 109/l (range, 0.10–2.62), and LMR 2.08 (range, 0.10–12.00). ALC did not correlate with tumor‐infiltrating lymphocytes, AMC did not correlate with tumor‐associated macrophages, and neither ALC nor AMC correlated with survival. However, low LMR (<1.72) translated to unfavourable progression‐free survival (PFS) (5‐year PFS 70% vs. 92%, p = 0.002) and overall survival (OS) (5‐year OS, 77% vs. 92%, p = 0.020). In the patients with low LMR, relative risk of progression was 4.4‐fold (95% confidence interval [CI] 1.60–12.14, p = 0.004), and relative risk of death was 3.3‐fold (95% CI 1.18–9.50, p = 0.024) in comparison to the patients with high LMR. We conclude that low LMR is an adverse prognostic factor in uniformly treated young patients with high‐risk aggressive large B‐cell lymphoma.

Low lymphocyte counts and association with clinical outcomes in hospitalized patients with cancer receiving immune checkpoint inhibitor therapy.

e14600 Background: Immune checkpoint inhibitors (ICIs) improve survivals in a variety of cancer patients by harnessing the immune system. Pre-treatment lymphopenia as measured by absolute lymphocyte counts (ALC) was associated with decreased progression-free survival (PFS) and overall survival (OS) in patients receiving ICIs. During hospitalization ICI treatment is often deferred and efficacy in this population is unclear. Our study explores outcomes and predictive factors for hospitalized patients who received ICI therapy. Methods: Cancer patients who received inpatient ICI were identified in the institutional pharmacy database from 08/2016 to 07/2021. Data were abstracted from electronic medical records. Data were summarized according to frequency and percentage for qualitative variables, and by mean ± standard deviation, median, and range for quantitative variables. The 95% confidence interval for survival was calculated using the exact binomial distribution. PFS and OS were estimated using the Kaplan–Meier method and compared using the log-rank test between groups. Receiver-operating characteristic (ROC) analysis was used to evaluate the discrimination ability of ALC for prognosis. Statistical significance was defined as 2-sided P &lt; 0.05. Results: Of 37 identified patients, 2 were excluded from the ALC analysis due to lack of blood counts. The most common cancer type treated was lung cancer (13, 35.1%). The majority of subjects were men (29, 78.4%) and the median age was 57 (21-79) years. Average hospital stay was 24.2 (95% CI 16.5, 31.9) days, and the most common reasons for admission were initiation of therapy (14, 37.8%) and infection (5, 13.5%). Reasons for inpatient treatment included convenience (6, 16.2%), disposition delays (6, 16.2%), initiation of therapy (13, 35.1%), and emergent or last resort measures (10, 27.0%). Most patients died during the study period, and 5 were alive at the time of data analysis. 10 patients died during the same hospitalization as treatment. Of those who followed up, 22 died within 90 days of inpatient therapy. The median PFS was 0.86 (95% CI 0.43, 1.74) months and median OS was 1.55 (95% CI 0.76, 3.72) months. Pre-treatment ALC &lt; 600 cells/µL were associated with poor PFS (0.33 vs. 1.35 months; HR 6.9, 95% CI 10.8-25.9, P = 0.0053) and poor OS (0.33 vs. 2.34 months; HR 4.66, 95% CI 1.2-17.5, P = 0.0236), respectively. Furthermore, patients with ALC &lt; 600 were less likely to receive a subsequent ICI dose than their counterparts. Conclusions: Administration of inpatient ICI therapy is associated with poor clinical outcomes and high rates of both inpatient mortality and death within 3 months of discharge. The presence of ALC &lt; 600/µL in hospitalized patients was associated with poor clinical outcomes.

Pretreatment Lymphocyte Count Predicts Benefit From Concurrent Chemotherapy With Radiotherapy in Oropharyngeal Cancer.

PURPOSEThere is a need to refine the selection of patients with oropharyngeal squamous cell carcinoma (OPSCC) for treatment de-escalation. We investigated whether pretreatment absolute lymphocyte count (ALC) predicted overall survival (OS) benefit from the addition of concurrent chemotherapy to radical radiotherapy.PATIENTS AND METHODSThis was an observational study of consecutive OPSCCs treated by curative-intent radiotherapy, with or without concurrent chemotherapy (n = 791) with external, independent validation from a separate institution (n = 609). The primary end point was OS at 5 years. Locoregional control (LRC) was assessed using competing risk regression as a secondary end point. Previously determined prognostic factors were used in a multivariable Cox proportional hazards model to assess the prognostic importance of ALC and the interaction between ALC and cisplatin chemotherapy use.RESULTSPretreatment ALC was prognostic for 5-year OS on multivariable analysis (hazard ratio [HR] 0.64; 95% CI, 0.42 to 0.98; P = .04). It also predicted benefit from the use of concurrent cisplatin chemotherapy, with a significant interaction between cisplatin chemotherapy and pretreatment ALC (likelihood ratio test, P = .04): higher ALC count reduced the 5-year OS benefit compared with radiotherapy alone (HR 2.53; 95% CI, 1.03 to 6.19; P = .043). This was likely driven by an effect on LRC up to 5 years (interaction subdistribution HR 2.29; 95% CI, 0.68 to 7.71; P = .094). An independent validation cohort replicated the OS (HR 2.53; 95% CI, 0.98 to 6.52; P = .055) and LRC findings (interaction subdistribution HR 3.43; 95% CI, 1.23 to 9.52; P = .018).CONCLUSIONFor OPSCC, the pretreatment ALC is prognostic for OS and also predicts benefit from the addition of cisplatin chemotherapy to radiotherapy. These findings require prospective evaluation, and could inform the selection of good prognosis patients for a de-escalation trial.

Pre-treatment neutrophil to lymphocyte ratio as a biomarker of frailty and predictor of survival among older adults with multiple myeloma

IntroductionNeutrophil to Lymphocyte Ratio (NLR) combines a marker of inflammation and reduced cell turnover to reflect age related alterations in the immune system. Whether NLR can serve as a biomarker of frailty and predict survival among older adults with Multiple Myeloma (MM) is unknown. Materials and methodsWe used an electronic health record-derived database to identify older adults (age ≥ 60y) with incident MM diagnosed between 1/2011 and 2/2020, with known pre-treatment absolute neutrophil and lymphocyte count up to 90 days before the start of therapy. The calculated NLR values were stratified into quartiles (Q1-Q4). We constructed a previously validated, simplified frailty index combining age, comorbidity and ECOG performance status. We measured the association between NLR quartiles and this frailty index using a logistic regression, adjusted for age, sex and race/ethnicity. We used Kaplan Meier methods and multivariable Cox regression to assess the impact of NLR on overall survival adjusting for potential confounders. ResultsWe identified 1729 older adults with newly diagnosed MM, at a median age of 73y (IQR: 67-78y). The median NLR was 2.13 (IQR: 1.44 to 3.31). Of the 1135 evaluable patients, 55% met criteria for frailty. Multivariable analysis revealed a 2.1-fold higher odds of frailty (95%CI = 1.42–3.10, p < 0.001) for patients in the NLR Q4 group vs. NLR Q1 group. In a multivariable analysis, adjusting for age, sex, race/ethnicity, M-protein type, stage, high risk cytogenetics, baseline creatinine, LDH and type of first line therapy, patients in NLR Q4 group had a 1.51 times increased hazards of death (95%CI = 1.15–1.98, p 0.002) when compared to those in NLR Q1 group. ConclusionNLR, a readily available laboratory biomarker, is associated with frailty measured using a simplified frailty index as well as inferior overall survival among older adults with MM. Future studies should explore its value as a screening tool to identify frail older adults with MM.

Correlations between peripheral blood biomarkers and clinical outcomes in advanced non-small cell lung cancer patients who received immunotherapy-based treatments.

BackgroundPeripheral blood-based biomarkers (PBB) predicting response, survival and immune-related adverse events (irAEs) in patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are still a matter of debate. Thus, we investigated the associations between PBB, the efficacy of ICIs and the incidence of irAEs.MethodsPatients with advanced NSCLC, who had been treated at Peking Union Medical College Hospital and received ICIs or chemoimmunotherapy from January 2015 to December 2020, were retrospectively identified. PBBs results were retrieved from medical records. Associations with overall response rate, survival, and incidence of irAEs were assessed using Kruskal-Wallis, Kaplan-Meier analysis, Pearson’s chi-squared and Student’s t-tests as required. Cox proportional hazards and logistic regression models were used to determine independent risk factors. Analyses were performed on the whole population (n=103), patients receiving ICIs only (n=32), and patients receiving chemoimmunotherapy (n=71). Changes in pretreatment and on-treatment PBB were also analyzed.ResultsAmong 103 patients, 38 (36.9%) developed irAEs. Pretreatment absolute lymphocyte count (ALC) was related to an increased risk of irAEs in the whole population [odds ratio (OR), 2.165; 95% confidence interval (CI): 1.040 to 4.509, P=0.039] and patients receiving ICIs only (OR, 6.461; 95% CI: 1.067 to 39.112; P=0.042). A low prognostic nutritional index (PNI ≤45) was associated with worse progression-free survival (PFS) and overall survival (OS) in the whole population, in patients receiving ICIs only, and in patients receiving chemoimmunotherapy. High pretreatment interleukin (IL)-6 was associated with both worse PFS and OS in the whole population (IL-6 >13.80 pg/mL), in patients receiving ICIs only (IL-6 >11.30 pg/mL), and in patients receiving chemoimmunotherapy (IL-6 >11.85 pg/mL). Increase of IL-6 during treatment was associated with inferior OS in the whole population (P<0.001).ConclusionsPretreatment ALC has the potential to predict irAEs in patients with advanced NSCLC treated with ICIs. Additionally, a low level of pretreatment PNI and high level of IL-6 may be associated with shorter survival.

Predictors of Severe Chemoradiation-Related Lymphopenia in Patients With Anal Squamous Cell Carcinoma

Treatment-related lymphopenia may be prognostic for poorer survival in anal squamous cell carcinoma (ASCC). With current randomized trials evaluating the potential role of immunotherapy in localized ASCC, the contribution of host immunity will become increasingly important. We sought to identify clinical, tumor, and dosimetric predictors for severe lymphopenia during chemoradiation (CRT) for ASCC.Patients who underwent CRT for ASCC from 2008-2020 at two Comprehensive Cancer Centers were identified and charts were reviewed. Only those who received 5-fluorouracil and mitomycin C concurrent with IMRT to 50.4-59.4 Gy were included. Lymphopenia was graded per CTCAE v5.0 with absolute lymphocyte count (ALC) nadir < 0.2×109/L indicating grade 4 toxicity. Logistic regression was used to distinguish the effects directly attributable to radiation exposure from contextual covariates. The outcome was presence of grade 4 lymphopenia. The primary predictors of interest were iliac crest V40 and total prescription dose (TPD). It was hypothesized that higher iliac crest V40 and higher TPD would be positively associated with severe lymphopenia. PTV total volume (PTVtv) and GTVp volume were also included and interactions with dose were examined for each. Lastly, covariates included history of malignancy, age, and pre-treatment ALC. These variables were selected because literature has identified them as relevant to lymphopenia in other samples.A total of 119 patients were identified with a median age of 59 years. Forty-seven patients (39%) had T3/4 disease and 57 patients (49%) had node positive disease. Fifty-eight patients (49%) developed grade 4 lymphopenia during CRT or within 1 month of completing treatment. On multivariate analysis pre-treatment ALC (P = 0.006, OR = 0.31), GTVp volume (P = 0.010, OR = 1.23), and iliac crest V40 (P = 0.013, OR = 1.08) were predictive of grade 4 lymphopenia. History of previous malignancy was associated with reduced risk of grade 4 lymphopenia (P = 0.030, OR = 0.04). TPD and PTVtv were not independently predictive of grade 4 lymphopenia, though patients with a higher TPD and smaller PTVtv were significantly more likely to develop grade 4 lymphopenia (P = 0.038) compared to those with both high TPD and PTVtv or both low TPD and PTVtv.Severe lymphopenia is common during CRT for ASCC and certain patients are at higher risk for developing this treatment-related toxicity. Pre-treatment lymphocyte count, larger tumor volume, and dose to the iliac crests are each independent predictors of grade 4 lymphopenia. Additionally, closer observation should be employed when treating patients with higher prescription doses and smaller PTV total volumes. With ongoing efforts to incorporate immunotherapy in the treatment of ASCC, using predictors to detect patients at risk for severe lymphopenia will be increasingly important.

Positron Emission Tomography-Guided Bone Marrow-Sparing Radiation Therapy for Locoregionally Advanced Cervix Cancer: Final Results From the INTERTECC Phase II/III Trial

PurposeTo test effects of positron emission tomography (PET)–based bone marrow–sparing (BMS) image-guided intensity modulated radiation therapy (IG-IMRT) on efficacy and toxicity for patients with locoregionally advanced cervical cancer. Methods and MaterialsIn an international phase II/III trial, patients with stage IB-IVA cervical carcinoma were treated with either PET-based BMS-IG-IMRT (PET-BMS-IMRT group) or standard image-guided IMRT (IMRT group), with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy. The phase II component nonrandomly assigned patients to PET-BMS-IMRT or standard IMRT. The phase III trial randomized patients to PET-BMS-IMRT versus IMRT, with a primary endpoint of progression-free survival (PFS) but was closed early for futility. Phase III patients were analyzed separately and in combination with phase II patients, comparing acute hematologic toxicity, cisplatin delivery, PFS, overall survival (OS), and patterns of failure. In a post-hoc exploratory analysis, we investigated the association between pretreatment absolute lymphocyte count (ALC) and OS. ResultsIn total, 101 patients were enrolled on the phase II/III trial, including 29 enrolled in phase III (PET-BMS-IMRT group: 16; IMRT group: 13) before early closure. Median follow-up was 33 months for phase III patients and 39 months for all patients. PFS and OS at 5 years for all patients were 73.6% (95% confidence interval [CI], 64.9%-84.3%) and 84% (95% CI, 76%-92.9%]), respectively. There were no differences in number of cisplatin cycles, OS, PFS, or patterns of failure between groups for the combined cohort. The incidence of acute grade ≥ 3 neutropenia was significantly lower in the PET-BMS-IMRT group compared with IMRT for randomized patients (19% vs 54%, χ2P = .048) and in the combined cohort (13% vs 35%, χ2P = .01). Patients with pretreatment ALC ≤ 1.5 k/µL had nonsignificantly worse OS on multivariable analysis (HR 2.85; 95% CI, 0.94-8.62; adjusted P = .216), compared with patients with ALC > 1.5 k/µL. There was no difference in posttreatment ALC by treatment group. ConclusionsPET-BMS-IMRT significantly reduced acute grade ≥3 neutropenia, but not treatment-related lymphopenia, compared with standard IMRT. We found no evidence that PET-BMS-IMRT affected chemotherapy delivery or long-term outcomes, and weak evidence of an association between pretreatment ALC and OS.

Bone marrow dosimetric analysis of lymphopenia in patients with esophageal squamous cell carcinoma treated with chemoradiotherapy.

BackgroundWe analyzed the relationship among peripheral blood lymphocytes, exposed sternum and vertebra body bone marrow (BM), and overall survival (OS) to find BM dosimetric parameters of lymphopenia during chemoradiotherapy (CRT) for patients with esophageal squamous cell carcinoma (ESCC).MethodsWe examined 476 ESCC patients from January 2012 to January 2015, all of whom received concurrent or sequential CRT. Absolute lymphocyte counts (ALC) during radiotherapy (RT) of each patient were collected from the routine workup at the following RT times: pretreatment ALC (ALC0), at 1–5, 6–10, 11–15, 16–20, and 21–25, and more than 26 sessions (called ALC1–6, respectively). The sternum and vertebral body BM were delineated in accordance with uniform standards, and the irradiated volumes were calculated by dose‐volume histograms (DVH). The Kaplan–Meier method and Cox proportional hazards regression were used to analyze the survival of the patients. Comparisons of DVH were performed using the Mann–Whitney U test or two‐sample t‐test where appropriate.ResultsA relative volume of sternum BM irradiated by more than 20 Gy could clearly affect the peripheral blood lymphocytes. The V20 of sternum BM and V50 of vertebra body BM were related to the OS of the patients, and the level of ALC2 (at 6–10 times of RT) could predict the outcomes of patients. The Cox regression analyses showed that the 218 patients with ALC2 ≥ 0.8 × 109/L had a significantly higher OS (47.0 months vs. 30.9 months, p < 0.0001) than the 258 patients with ALC2 < 0.8×109/L.ConclusionIn patients with ESCC, the relative volume of sternum BM irradiated by more than 20 Gy was associated with lymphocytes. Patients with ALC2 ≥ 0.8 × 109/L had a significantly higher OS. The V20 of the sternum BM, the V50 of the vertebra body BM, and the level of ALC2 were significant prognostic factors in patients with ESCC.

Pretreatment Absolute Lymphocyte Count and Neutrophil-to-lymphocyte Ratio Are Prognostic Factors for Stage III Breast Cancer.

Stage III breast cancer comprises a broad spectrum of disease, including the extent of supraclavicular/internal mammary lymph node metastasis. In this study, we evaluated the usefulness of the absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) in predicting the prognosis of patients with stage III breast cancer. Seventy-five patients with stage III breast cancer who underwent surgery were included. We compared their clinicopathological factors according to the presence or not of supraclavicular/internal mammary lymph node metastasis, and pretreatment ALC or NLR. Patients with metastasis of the studied lymph nodes had a poorer prognosis in comparison to those without metastasis. In patients without these types of lymph node metastasis, both the ALC and NLR were predictive factors for relapse-free and overall survival. Among these patients, those with a low ALC or high NLR had recurrence-free and overall survival comparable to those of patients with supraclavicular/internal mammary lymph node metastasis. Pretreatment ALC and NLR were prognostic factors for patients with stage III breast cancer.

Pre-treatment absolute lymphocyte count predicts for improved survival in human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma

BackgroundThe prognostic value of pretreatment complete blood count (CBC) data, including absolute lymphocyte count (ALC) and the neutrophil-to-lymphocyte ratio (NLR), has been reported for many diseases with decreased ALC and increased absolute neutrophil count (ANC) and NLR values correlating with worse outcomes. There is minimal data relating these hematologic parameters to oropharyngeal squamous cell carcinoma (OPSCC) prognosis. This study evaluates the prognostic value of pretreatment CBC data in OPSCC on overall survival (OS) and progression-free survival (PFS) in relation to HPV status. MethodsA single-institutional retrospective review of patients with pretreatment hematologic data who received radiation for OPSCC was performed. Univariate and multivariate (UVA/MVA) Cox proportional hazard regression analyses were performed to identify prognostic variables. Translational studies related outcomes to the degree of tumor-infiltrating lymphocytes (TILs) in histologic specimens. ResultsFrom 2007 to 2018, 201 patients were treated for OPSCC. Median follow-up was 40 months. 3-year OS was 86.2% in the HPV-positive cohort, 46.3% for HPV-negative. Median NLR was 3.04. NLR ≥ 3 was associated with worse PFS (HR 1.67, p = 0.044. In the subset of 158 HPV + patients, MVA revealed increasing ALC to be associated with improved OS (HR 0.53; p = 0.040) and PFS (HR = 0.48; p = 0.0075). On UVA, high-TIL infiltration at diagnosis was associated with improved OS. ConclusionIn a cohort of HPV + OPSCC patients, increasing ALC is associated with improved OS and PFS. Our study is the first to identify pre-treatment ALC as an independent prognostic factor in HPV-associated OPSCC.