Inferior Overall Survival Research Articles

Impact of Lymphopenia on Definitive Treatment of Locally Advanced Cervical Cancer

Pre-treatment lymphopenia prior to initiating treatment has been correlated with reduced survival in a number of different cancers. The purpose of this study is to evaluate the association between lymphopenia and survival in women with locally advanced cervical cancer (LACC) treated with primary chemoradiation (CRT). We retrospectively reviewed patients with LACC treated at a single institution from 2005 - 2021 with available lymphocyte information. Patient and treatment characteristics were recorded including age, tumor size and stage, EBRT dose/fractionation, and brachytherapy dosimetry data. Absolute lymphocyte counts (ALC) were collected prior to initiating CRT and at 3-month intervals following CRT and graded based on severity of lymphopenia using CTCAE v 5.0. Overall survival (OS), progression free survival (PFS), and local control (LC) were calculated from the start of treatment to date of last follow-up. Kaplan-Meier survival analysis was performed to evaluate whether lymphocyte changes were associated with OS, PFS, or LC. A total of 124 patients met study inclusion criteria with stage IB - IV disease (41 stage I, 41 stage II, 36 stage III, 6 stage IV) and a median follow up of 3.6 years (range 0.2-16.5 years). The median age was 49 years (range 26-77). The median EBRT dose was 45 Gy (range: 26-57.5 Gy) and 44.2% of patients received para-aortic (PA) nodal EBRT (28.8% elective and 15.4% with positive PA nodes). 5-year OS, PFS, and LC were 60.3% (95% CI 51.5-70.7), 47.5% (95% CI 39-58), and 75.5% (95% CI 67.3-82.9), respectively. Pre-treatment lymphopenia (ALC <1000 cells/mm3) was present in 11 (9%) patients. When the total cohort was divided into patients with and without pre-treatment lymphopenia, OS was statistically improved in the patients without baseline lymphopenia, with a 5-year OS of 63.2% (95% CI 53.9-73.9) versus 35.3% (95% CI 14.5-86.3) in the lymphopenia group (p = 0.034). LC also trended to being improved in the patients without lymphopenia, though this did not reach statistical significance in our small sample size of lymphopenic patients, with 5-year LC of 76.8% (95% CI 68.4-84.3) versus 67.5% (05% CI 36.6-93.8), p = 0.45. In this single institution experience of LACC treated with definitive CRT, we found that baseline lymphopenia is associated with inferior OS. Patients with higher pre-CRT ALC may represent a population with more robust immune systems, producing more favorable tumor responses to treatment. Additional studies are warranted to investigate the evolving role of combined EBRT and systemic therapy in LACC.

Pretreatment Clinical Parameters Associated with Intracranial Progression Burden Following an Initial Stereotactic Radiosurgery Course in a Multi-Institutional Brain Metastases Cohort

While brain metastasis (BM) velocity is a valuable prognostic metric at time of intracranial progression (ICP), pre-SRS risk factors for post-SRS high-burden intracranial progression (ICP) remain poorly characterized. We hypothesized that pre-SRS clinical parameters are associated with subsequent high-burden (ICP), defined as either ≥5 (ICP5) or new/progressive ≥11 BMs (ICP11). All patients completing an initial SRS course for BMs at two institutions from 1/2015-12/2020 were retrospectively identified. Patients with prior whole brain radiation therapy (WBRT) and/or BM resection were eligible. Demographic and clinical parameters were collected. ICP was defined as any radiographic concern for distant and/or in-field progression per multidisciplinary consensus. Overall survival (OS) and freedom from ICP were estimated via the Kaplan Meier method. Cox models assessed association between parameters and freedom from ICP5 and ICP11. We identified 1383 patients completed SRS, with a median follow up of 8.7 months. Patients were 54.8% female, 45.6% with KPS ≥90, and a median of 63.4 years old. Primary tumor types included non-small cell lung (48.7%), breast (14.7%), and melanoma (8.5%). 46.9% had oligometastatic disease (≤5 metastatic foci: including BMs) at SRS, and 53.4% underwent SRS for >1 BM. 10.3% of patients had undergone prior WBRT and 26.1% surgical resection. 555 patients (40.1%) experienced ICP following SRS, of whom 72.6% had 1-4, 11.5% had 5-10, and 15.9% had ≥11 new/progressive BMs. Among patients with ICP, 6-month freedom from ICP was 35.5% (95% CI: 31.1-40.5%) for those with 1-4 BMs at time of ICP, 29.7% (95% CI: 20.4-43.3%) for 5-10 BMs, and 20.5% (95% CI: 13.5-30.1%) for ≥11 BMs (p = 0.016). Respective 12-month OS rates were 56.8% (95% CI: 52.1-61.9%), 46.0% (95% CI: 35.1-60.1%), and 38.7% (95% CI: 29.4-50.9%; p<0.001). Neurologic symptoms at time of ICP were observed in 21.1% of patients with 1-4 BMs, 28.1% with 5-10 BMs, and 50.0% with new/progressive ≥11 BMs (p<0.001). On multivariable analysis, superior freedom from high-burden ICP was associated with the following pre-SRS parameters: oligometastatic burden (ICP5: HR 0.68, 95% CI: 0.47-0.99; ICP11: 0.59; 95% CI: 0.36-0.97), no prior immunotherapy (ICP11: HR 0.57, 95% CI: 0.34-0.57), and a single BM at time of initial SRS (1 vs 2 BM, ICP 5: HR 0.51, 95% CI: 0.31-0.82; ICP11: HR 0.45, 95% CI: 0.24-0.84), while primary tumor type was not associated with ICP5 or ICP11. Pre-SRS parameters including polymetastatic burden, prior receipt of immunotherapy, and >1 BM were associated with post-SRS high-burden ICP. High burden ICP developed earlier following SRS completion and was associated with higher rates of neurologic decline and inferior OS.

The Prognostic and Predictive Value of Pre-Treatment Total Lymphocyte Count in HPV+ Oropharyngeal Carcinoma Receiving Definitive (Chemo-) Radiation

Evidence of prognostic importance of pre-radiotherapy (RT) total lymphocyte counts (TLC) and interaction with addition of cisplatin (CRT) in HPV-positive oropharyngeal carcinoma (HPV+OPC) is conflicting. Recent data suggest patients with high TLC may not benefit from the addition of chemotherapy (Price et al, JCO 2022). We assess the prognostic and predictive value of TLC in a large single center HPV+OCP cohort. All HPV+OPC patients treated at a single academic center with definitive RT/CRT between 2005-2018 were included. Pre-treatment TLC up to 6 weeks prior to RT start were considered. Multivariable analysis (MVA) was applied to assess the prognostic importance of TLC (continuous variable), adjusted for age, gender, performance status, TNM-8 stage, and smoking status in the CRT and RT subgroups. The actuarial rates of locoregional control (LRC), distant control (DC), and overall survival (OS) were calculated using Kaplan-Meier and competing risk methods, stratified by low vs high TLC (determined using Contal and O'Quigley method for optimal cutoff). Among 1153 eligible patients, 707 (61%) were treated with CRT. Median age was 59.7 (range 22.7-92.2) years. 526 patients were (46%) TNM-8 stage I, 366 (32%) stage II and 261 (23%) stage III. Median TLC was 1.6 x 109/L (range 0.1-8.5). Median follow-up was 5.5 years. On MVA, TLC was prognostic for patients receiving CRT (OS [adjusted hazard ration (aHR) 0.55 (0.38-0.79), p = 0.002], DC [aHR 0.57 (0.37-0.88), p = 0.011], LRC [aHR 0.57 (0.36-0.89), p = 0.014]) but not RT (OS [aHR 1.04 (0.82-1.31), p = 0.74], LRC [aHR 1.26 (0.86-1.85), p = 0.23], DC [aHR 0.87 (0.64-1.19), p = 0.4)]. The optimal TLC cut-off for OS with CRT was 1.9 x 109/L. Low vs high TLC patients receiving CRT had significantly inferior 5-year DC (87% vs 93%, p = 0.017) and OS (84% vs 90%, p = 0.026). The benefit of higher TLC was most evident in stage II disease (table 1). CRT vs RT improved OS for stage II/III disease at high and low TLC. Pre-treatment TLC is prognostic in a large cohort of HPV+OPC patients receiving CRT but not RT alone. Further investigation of the interaction of cisplatin and immune response during RT is warranted. The omission of chemotherapy based on TLC is not supported.

The immunome of mobilized peripheral blood stem cells is predictive of long-term outcomes and therapy-related myeloid neoplasms in patients with multiple myeloma undergoing autologous stem cell transplant

Upfront autologous stem cell transplant (ASCT) is the standard of care for newly diagnosed multiple myeloma (MM) patients. However, relapse is ubiquitous and therapy-related myeloid neoplasms (t-MN) post-ASCT are commonly associated with poor outcomes. We hypothesized that the enrichment of abnormal myeloid progenitors and immune effector cells (IEC) in the peripheral blood stem cells (PBSCs) is associated with a higher risk of relapse and/or development of t-MN. We performed a comprehensive myeloid and lymphoid immunophenotyping on PBSCs from 54 patients with MM who underwent ASCT. Median progression-free (PFS), myeloid neoplasm-free (MNFS), and overall survival (OS) from ASCT were 49.6 months (95% CI: 39.5-Not Reached), 59.7 months (95% CI: 55–74), and 75.6 months (95% CI: 62–105), respectively. Abnormal expression of CD7 and HLA-DR on the myeloid progenitor cells was associated with an inferior PFS, MNFS, and OS. Similarly, enrichment of terminally differentiated (CD27/CD28-, CD57/KLRG1+) and exhausted (TIGIT/PD-1+) T-cells, and inhibitory NK-T like (CD159a+/CD56+) T-cells was associated with inferior PFS, MNFS, and OS post-transplant. Our observation of abnormal myeloid and IEC phenotype being present even before ASCT and maintenance therapy suggests an early predisposition to t-MN and inferior outcomes for MM, and has the potential to guide sequencing of future treatment modalities.

Comparison of autologous, matched sibling, and alternative donor stem cell transplant outcomes for acute myeloid leukemia patients in first remission: A propensity score matching study.

Autologous hematopoietic stem cell transplantation (auto-HSCT), matched sibling donor HSCT (MSD-HSCT), and alternative donor HSCT (AD-HSCT) are viable post-remission treatment options for acute myeloid leukemia (AML). A total of 283 de novo favorable- and intermediate-risk AML patients, based on the ELN 2022 criteria, in first complete remission were initially included for propensity score matching. Following the matching process, 126 patients were selected for further analysis, with 42 patients in each of the auto-HSCT, MSD-HSCT, and AD-HSCT groups. Among the AD-HSCT group, 38 of 42 (90.5%) patients received haploidentical HSCT. In patients with persistent undetectable measurable residual disease (uMRD) before transplant (n=83), overall survival (OS) was similar across the groups. However, auto-HSCT showed a trend of increased disease-free survival (DFS) compared to AD-HSCT (HR 2.85, P=0.09), resulting in a 3-year DFS and OS of 79.1% and 82.8%, respectively. In the non-persistent uMRD group (n=38), auto-HSCT exhibited a tendency to increase the risk of relapse, particularly when compared to AD-HSCT (HR 0.24, P=0.07), but this did not result in inferior OS. The monthly direct medical cost per patient within the first 2years after HSCT was significantly lower in auto-HSCT compared to MSD-HSCT (P=0.015) and AD-HSCT (P<0.001). Our results provide evidence for the use of auto-HSCT as a viable therapeutic option for favorable- and intermediate-risk de novo AML patients in first complete remission with persistent uMRD. Additionally, our findings demonstrated a notable cost advantage associated with auto-HSCT compared to MSD-HSCT and AD-HSCT.

Myxofibrosarcoma in adolescents and young adults: a clinicopathologic study of 17 cases

Myxofibrosarcoma is a locally aggressive sarcoma that characteristically arises in the extremities of older patients. Cases arising at a younger age are rare, leading to diagnostic challenges. Our aim was to study the clinicopathologic features of myxofibrosarcoma in patients aged ≤40 years. Cases of myxofibrosarcomaand myxoid malignant fibrous histiocytomaarising in patients aged ≤40 yearswith clinical follow-up were collected from multiple institutions. Hematoxylin and eosin slides were evaluated for mitoses, necrosis, and epithelioid areas. Seventeen cases were identified (13 females, 4 males; 16-39 years; median 32 years), tumors ranged from 2.2 to 34cm (median 4.1cm). Anatomic sites includedproximal extremity (9), distal extremity (4), trunk (1), and head/neck (3). Ten were superficial, and 6 were deep-seated. Three cases were predominantly epithelioid. In untreated resection specimens, 6 were FNCLCC grade 1, 4 grade 2, and 2 grade 3. Follow-up (6-204 months, median 36 months) revealed that 2 patients experienced local recurrences, 1 distant metastasis, and 2 patients both. The 5-year overall survival (OS) and event-free survival (EFS) were 84% and 55.9%, respectively. Tumor depth and necrosis were correlated with inferior OS (P=.025, P=.005), while tumor depth was also associated with worse EFS (P=<.001). We conclude that myxofibrosarcomas arising in adolescents and young adults show similar behavior compared to their older adult counterparts. Tumor depth and necrosis are poor prognostic factors in myxofibrosarcoma in this age group. Awareness that myxofibrosarcoma can rarely present in this population is important for accurate diagnosis.

Endothelial activation and stress index as a prognostic factor of diffuse large B-cell lymphoma: the report from the nationwide multi-center Thai Lymphoma Study Group.

Several prognostic models have been introduced to predict outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Endothelial activation and stress index (EASIX) is a surrogate of endothelial dysfunction which has been shown to predict outcomes of patients with various hematologic malignancies. However, the prognostic implication of EASIX for DLBCL is limited and warrants exploration. We conducted a retrospective study enrolling adult DLBCL patients including a discovery cohort from the single-centered university hospital database and a validation cohort from the independent nationwide multi-center registry. EASIX scores were calculated using creatinine, lactate dehydrogenase, and platelet levels. The receiver operating characteristic curve analysis was used to determine optimal cutoff. Statistical analysis explored the impact of EASIX on survival outcomes. A total of 323 patients were included in the discovery cohort. The optimal EASIX cutoff was 1.07 stratifying patients into low (53.9%) and high EASIX (46.1%) groups. Patients with high EASIX had worse 2-year progression-free survival (PFS) (53.4% vs. 81.5%, p<0.001) and overall survival (OS) (64.4% vs. 88.7%, p<0.001) than patients with low EASIX. Multivariate analysis revealed that older age, bulky disease, impaired performance status, and high EASIX were associated with an unfavorable OS. In the validation cohort of 499 patients, the optimal EASIX cutoff was 1.04. Similar to the discovery cohort, high EASIX score was associated with high-risk diseases, worse PFS, and inferior OS. In conclusion, EASIX score was significantly associated with survival outcomes and may be used as a simple prognostic tool to better risk-classify DLBCL.

Clinical outcomes following observation, post-operative radiation therapy, or post-operative chemoradiation for HPV-associated oropharyngeal squamous cell carcinomas

BackgroundIntermediate and high-risk features (IRFs/HRFs) for locoregional recurrence following initial surgery for oropharyngeal SCCs (OP-SCCs) were defined prior to the known association of HPV with OP-SCC. There are limited reports on practice patterns and outcomes associated with post-operative radiation therapy (PORT) or chemoradiation (POCRT) for HPV-associated OP-SCCs. Materials/Methods:The National Cancer Database was queried for patients with HPV-associated OP-SCCs managed initially with surgery with IRFs or HRFs. IRFs were defined as pT3/T4 disease, pN1-3 disease, and lymphovascular space invasion, and HRFs as positive margins and extranodal extension (ENE). Patients were stratified into no adjuvant therapy, PORT, or POCRT arms. Kaplan-Meier analysis was utilized for comparison of overall survival (OS) between treatment arms followed by a Cox multivariate (MVA) proportional-hazards model and propensity score analyses with inverse probability treatment weighting (IPTW). ResultsWe identified 6,301 patients; 51.2% had IRFs only and 48.8% had HRFs. Regarding treatment, 25.5%, 38.2%, and 36.3% of patients received no RT, PORT, and POCRT, respectively. Patients with IRFs who did not receive RT or CRT had inferior 8-year OS (81.1% vs. 87.8%; p < 0.001) that remained significant on IPTW MVA (hazard ratio (HR) = 1.69 (95% CI: 1.27–2.24; p < 0.001). Among patients with HRFs, 8-year OS was not significantly different between patients receiving PORT vs. POCRT (77.3% vs. 79.2%; p = 0.22) that remained insignificant on IPTW MVA (HR = 0.91(0.72–1.17); p = 0.48). ConclusionA significant proportion of HPV-associated OP-SCC patients with IRFs or HRFs did not receive PORT, which was associated with inferior OS. We did not demonstrate with statistical power that POCRT vs. PORT was associated with superior OS in patients with HRFs, though prospective studies are warranted.

Prognostic heterogeneity and clonal dynamics within distinct subgroups of myelodysplastic syndrome and acute myeloid leukemia with TP53 disruptions.

TP53 aberrations constitute the highest risk subset of myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). The International Consensus Classification questions the blast threshold between MDS and AML. In this study, we assess the distinction between MDS and AML for 76 patients with TP53 aberrations. We observed no significant differences between MDS and AML regarding TP53 genomics. Median overall survival (OS) was 223 days for the entire group, but prognostic discrimination within subgroups showed the most inferior OS (46 days) for AML with multihit allelic state plus TP53 variant allele frequency (VAF) > 50%. In multivariate analysis, unadjusted Cox models revealed the following variables as independent risk factors for mortality: AML (vs. MDS) (hazard ratio [HR]: 2.50, confidence interval [CI]: 1.4-4.4, p = 0.001), complex karyotype (HR: 3.00, CI: 1.4-6.1, p = 0.003), multihit status (HR: 2.30, CI 1.3-4.2, p = 0.005), and absence of hematopoietic cell transplant (HCT) (HR: 3.90, CI: 1.8-8.9, p = 0.0009). Clonal dynamic modeling showed a significant reduction in TP53 VAF with front-line hypomethylating agents. These findings clarify the impact of specific covariates on outcomes of TP53-aberrant myeloid neoplasms, irrespective of the diagnosis of MDS versus AML, and may influence HCT decisions.

Use of concomitant proton pump inhibitors, statins or metformin in patients treated with pembrolizumab for metastatic urothelial carcinoma: data from the ARON-2 retrospective study.

Concomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the impact of concomitant use of proton pump inhibitors (PPI), statins, or metformin on outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pembrolizumab. We collected data from the hospital medical records of patients with mUC treated with pembrolizumab as second-line therapy at 87 institutions from 22 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate. We carried out a survival analysis by a Cox regression model. A total of 802 patients were eligible for this retrospective study; the median follow-up time was 15.3months. PPI users compared to non-users showed inferior PFS (4.5 vs. 7.2months, p = 0.002) and OS (8.7 vs. 14.1months, p < 0.001). Concomitant PPI use remained a significant predictor of PFS and OS after multivariate Cox analysis. The use of statins or metformin was not associated with response or survival. Our study results suggest a significant prognostic impact of concomitant PPI use in mUC patients receiving pembrolizumab in the real-world context. The mechanism of this interaction warrants further elucidation.

Different patterns of failure in two treatment regimens for primary central nervous system lymphoma, a retrospective analysis of 124 cases in Taiwan

To explore prognostic factors and outcomes of primary central nervous system lymphoma (PCNSL) of diffuse large B-cell lymphoma (DLBCL) in Taiwan, 124 PCNSL-DLBCL patients (from 1995 to 2021) were retrospectively analyzed. Mainly, two treatment modalities including sandwich chemoradiotherapy and modified MATRix regimen were employed in these patients. Overall survival (OS) was determined by log-rank test and time-dependent Cox analysis. Median OS of all patients was 27.1 months. 47 (37.9%) patients who underwent sandwich chemoradiotherapy had a complete remission (CR) rate of 87.2%, median OS of 53.9 months, and progression free survival (PFS) of 42.9 months. 11 (8.9%) patients who underwent modified MATRix regimen had CR rate of 72.7%, median OS of 18.9, and PFS of 11.2 months. There are no significant OS differences between treatment groups or addition of Rituximab. Patients treated with the modified MATRix regimen experienced a higher early mortality rate followed by a survival plateau. IELSG low-risk group had significantly improved OS and PFS than IELSG intermediate- or high-risk group. In multivariant analysis, age > 60 years old and bilateral cerebral lesions are associated with significantly inferior OS. Sandwich chemoradiotherapy demonstrated better early survival and reduced treatment-related toxicity for PCNSL patients compared to the modified MATRix regimen. However, the long-term follow-up revealed a higher rate of treatment failure events in the sandwich chemoradiotherapy group. IELSG and MSKCC scores served as reliable risk assessment models. Incorporating bilateral cerebral lesions as a risk factor further improved risk evaluation.

Prognostic Role of Dynamic Changes in Serological Markers in Metastatic Hormone Naïve Prostate Cancer.

We investigated whether inter-patient variation in the dynamic trajectory of hemoglobin (Hb), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and prostate-specific antigen (PSA) can prognosticate overall survival (OS) in de novo mHSPC. This is a secondary analysis of the LATITUDE trial in which high-risk de novo mHSPC patients were randomly assigned to receive either androgen deprivation therapy (ADT) plus abiraterone or ADT plus placebo. We used a five-fold cross-validated joint model approach to determine the association of temporal changes in the serological markers with OS. Decision curve analysis was applied to determine the net benefit. When dynamic changes in Hb, LMR, NLR, PLR, and PSA were included in a multivariate joint model, an increase in the log of the current value of PSA (HR: 1.24 [1.20-1.28]) was associated with inferior OS. A multivariate joint model that captured dynamic trajectory of Hb, NLR, PLR, LMR, and PSA up to 24 months, showed a net benefit over the "treat all" strategy at a threshold of probability of approximately ≥30% while no net benefit was seen when dynamic change in PSA was omitted. Our joint model could be used for designing future adaptive trials investigating sequential treatment personalization.

Incidence, risk factors, and outcomes of venous thromboembolism in patients undergoing surgery for retroperitoneal tumors: A propensity-matched retrospective cohort study.

Venous thromboembolism (VTE) is a common postoperative complication; however, incidence and risk stratification of postoperative VTE in patients with retroperitoneal tumor remains unclear. We aim to quantify incidence, identify risk factors, and determine outcomes of VTE in patients undergoing retroperitoneal tumor surgery. We retrospectively reviewed characteristics, perioperative outcomes, and overall survival (OS) of patients (VTE and non-VTE) who underwent retroperitoneal tumor surgery between 2015 and 2020. Perioperative and oncologic outcomes were compared using propensity-matching and Cox analyses. Of 1223 patients with retroperitoneal tumor surgery, 2.1% had VTE. Age (odds ratio [OR] 1.140, 95% confidence interval [CI] 1.053-1.239, P=0.004), recurrence (OR 1.851, 95% CI 1.241-2.761, P=0.003), and vascular resection (OR 2.036, 95% CI 1.054-3.934, P=0.034) were independent risk factors, with significant between-group differences regarding age, recurrence, sarcoma, organ resection, vascular resection, and operation time. No between-group differences in 30-day all-cause mortality (8% vs. 4%, OR 0.657, 95% CI 0.375-1.151, P=0.427) and major complications (12% vs. 8%, OR 0.775, 95% CI 0.483-1.244, P=0.572) were observed. Mean hospitalization duration (20.1 vs. 22.9d, OR 1.153, 95% CI 1.022-1.386, P=0.033) and ICU stay (3.2 vs. 5.5d, OR 1.193, 95% CI 1.034-1.347, P=0.012) were shorter in non-VTE versus VTE, respectively, with inferior OS (hazard ratio [HR] 2.090, 95% CI 1.014-4.308, P=0.046) in VTE. Age, recurrence, and vascular resection are positively associated with VTE, which is associated with inferior OS.

TP53 mutations identify high-risk events for peripheral T-cell lymphoma treated with CHOP-based chemotherapy.

Nodal peripheral T-cell lymphomas (PTCL), the most common PTCLs, are generally treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based curative-intent chemotherapy. Recent molecular data have assisted in prognosticating these PTCLs, but most reports lack detailed baseline clinical characteristics and treatment courses. We retrospectively evaluated cases of PTCL treated with CHOP-based chemotherapy that had tumors sequenced by the Memorial Sloan Kettering Integrated Mutational Profiling of Actionable Cancer Targets next-generation sequencing panel to identify variables correlating with inferior survival. We identified 132 patients who met these criteria. Clinical factors correlating with an increased risk of progression (by multivariate analysis) included advanced-stage disease and bone marrow involvement. The only somatic genetic aberrancies correlating with inferior progression-free survival (PFS) were TP53 mutations and TP53/17p deletions. PFS remained inferior when stratifying by TP53 mutation status, with a median PFS of 4.5months for PTCL with a TP53 mutation (n= 21) vs 10.5months for PTCL without a TP53 mutation (n= 111). No TP53 aberrancy correlated with inferior overall survival (OS). Although rare (n= 9), CDKN2A-deleted PTCL correlated with inferior OS, witha median of 17.6months vs 56.7months for patients without CDKN2A deletions. This retrospective study suggests that patients with PTCL with TP53 mutations experience inferior PFS when treated with curative-intent chemotherapy, warranting prospective confirmation.

Baseline serum tumor markers predict the survival of patients with advanced non-small cell lung cancer receiving first-line immunotherapy: a multicenter retrospective study

BackgroundThis study aimed to investigate the association between baseline serum tumor markers (STMs) (carcinoembryonic antigen [CEA], neuron-specific enolase [NSE], cytokeratin-19 fragment [CYFRA21-1], carbohydrate antigen 19–9 [CA19-9], and carbohydrate antigen 125 [CA125]) and the efficacy of first-line immunotherapy in patients with advanced non-small cell lung cancer.MethodsThis multicenter retrospective study evaluated patients who received first-line immunotherapy between July 2017 and July 2022. The endpoints were progression-free survival (PFS) and overall survival (OS), as defined by the Response Evaluation Criteria in Solid Tumors version 1.1. We divided the patients into three groups based on STM levels: Group A ≥ threefold upper limit of normal, threefold upper limit of normal > Group B > upper limit of normal, and Group C ≤ upper limit of normal.ResultsIn total, 716 patients were included in this study. In Cox proportional hazards analyses, the STM levels in Group C were independently associated with superior PFS and OS in patients with lung adenocarcinoma (LUAD). Except for CA19-9 level, the STM levels in Group C were independently associated with superior PFS and OS in patients with lung squamous carcinoma (LUSC). Except for CEA and CA19-9 levels, the levels in Group A were independently associated with inferior PFS and OS in patients with LUAD and LUSC.ConclusionsSerum CEA, NSE, CYFRA21-1, and CA125 levels can predict PFS and OS in patients with LUAD and LUSC, and serum CA19-9 levels can predict PFS and OS in patients with LUAD. The higher the serum NSE, CYFRA21-1, and CA125 levels, the worse the PFS and OS in patients with LUAD and LUSC. In addition, the higher the serum CA19-9 level, the worse the OS in patients with LUAD.

Impact of androgen receptor alterations on cell-free DNA genomic profiling on survival outcomes in metastatic castration-resistant prostate cancer.

Androgen receptor (AR) gene alterations, as detected by circulating tumor cell-free DNA (cfDNA) genomic profiling, have been shown to emerge after a variable duration of androgen signaling inhibition. AR alterations were associated with inferior outcomes on treatment with androgen receptor pathway inhibitors (ARPI) in the first line metastatic castration-resistant prostate cancer (mCRPC) setting in a phase 2 trial. Here in, we assessed the impact of these AR alterations on survival outcomes in a real-world patient population of mCRPC experiencing disease progression on an ARPI. In this IRB-approved retrospective study, consecutively seen patients with a confirmed diagnosis of mCRPC, with disease progression on a treatment with ARPIs in the first line mCRPC setting, with no prior exposure to an ARPI in the castration sensitive setting, and with available cfDNA profiling from a CLIA certified laboratory were included. Patients were categorized based on AR status: wild-type (ARwt ) or alteration-positive (AR+ ). The objective was to correlate overall survival (OS) after disease progression on the first-line ARPI with the presence or absence of AR alterations. Kaplan-Meier and Cox Regression Tests were used as implemented in R-Studio (v.4.2). A total of 137 mCRPC patients were eligible: 69 with ARwt versus 68 with AR+ . The median OS posttreatment with the first ARPI was significantly higher for ARwt than AR+ patients (30.1 vs. 15.2 mos; p < 0.001). Of 108 patients who received a subsequent line of therapy, 63 received an alternate ARPI (AR+ 39 vs. 24 ARwt ), while 20 received a taxane-based therapy (11 AR+ vs. 9 ARwt ). Among patients receiving an alternate ARPI, AR+ had numerically shorter OS (16.8 vs. 30.4 mos, p = 0.1). Among patients receiving taxane-based regimens, the OS was not significantly different between AR+ and ARwt (14.5 vs. 10.1 mos, p = 0.18). In this real-world study, mCRPC patients with AR alterations on cfDNA had inferior OS after disease progression on the first ARPI, compared to those who did not, and may impact outcomes on a subsequent ARPI but not on subsequent taxane-based therapy received. By providing survival estimates for patients with or without AR alterations, our data may aid in patient counseling, prognostication, treatment decision, and for designing future clinical trials in this setting.

Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate.

The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.

The impact of insurance status on progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC)

Abstract Background In addition to the previously studied socioeconomic factors associated with health disparities, insurance status can serve as a prognostic factor associated with overall survival in RCC patients (Zhang et al., Future Oncol 2019). Moreover, within this population, having access to health insurance has been reported to result in earlier detection of disease (Javier-DesLoges et al., JAMA Netw Open 2021). In this study, we explored the impact of primary and secondary insurance status on PFS and OS in patients receiving first line systemic therapy for mRCC. Methods Patients with mRCC from two NCI-designated comprehensive cancer centers diagnosed between 1990 and 2022 with available insurance information were retrospectively identified using institutional databases. Primary insurance information was categorized into three groups—Medicare, private insurance, and Medicaid/no insurance—while secondary insurance was defined by the presence or absence of secondary coverage. PFS and OS were estimated by Kaplan-Meier method and compared based on insurance status using log-rank tests. Univariate and multivariate Cox proportional hazard regression models were used to examine the impact of insurance status on PFS and OS. Results In total, 645 patients with mRCC had accessible information and were included in our analysis. Of these, 344 (53.3%), 250 (38.8%), and 51 (7.9%) had primary Medicare, private insurance, and Medicaid/no insurance, respectively. Overall, most patients were male (73.0%), with a median age of 60.0 (22.0-94.0) at time of diagnosis. The most commonly rendered first-line treatments were monotherapy with targeted agents (66.4%), dual immunotherapy (13.6%), and targeted/immunotherapy combinations (10.2%). Median PFS for the entire cohort was 6.6 months (95% CI, 5.9-7.7). Median PFS for patients with primary Medicare was 7.7 months (95%, CI 7.0-9.0), 5.5 months (95% CI, 4.0-7.0) for patients with private insurance, and 4.9 months (95% CI, 3.8-8.1) for Medicaid/uninsured patients. Using an overall log-rank test, a significant difference in PFS among the three groups with different primary insurance was observed (p&amp;lt;0.0001). The median PFS for patients with secondary insurance was 8.1 months (95% CI, 6.6-11.3) compared to 6.1 months (95% CI, 5.5-7.4) for patients without secondary insurance. A multivariate Cox model with adjustment for other factors (such as age, gender, and ethnicity) revealed a statistically significant difference in PFS between patients with and without secondary insurance (p=0.0281). Median OS for the entire cohort was 36.8 months (95% CI, 32.4-44.3). Median OS for patients with primary Medicare, private insurance, and Medicaid/no insurance was 49.0 months (95%, CI 41.8-55.3), 28.5 months (95% CI, 24.1-35.7), and 21.6 months (95% CI, 17.5-42.3), respectively. By an overall log-rank test, a significant difference in OS across the three groups of primary insurance was observed (p=0.0003). No statistically significant differences in OS were observed between patients with and without secondary insurance. Overall, patients with primary Medicare had superior median PFS (p=0.0327) and OS (p=0.0004) compared to those with Medicaid/no insurance; although patients with private insurance had a lower risk of progression and death compared to those with Medicaid/no insurance, the result was not statistically significant. Conclusions In this real-world study, we investigated the impact of insurance status on clinical outcomes in patients with mRCC receiving systemic therapy. mRCC patients with primary Medicaid/no insurance or private insurance had inferior median PFS and OS compared to those with primary Medicare. Moreover, patients with secondary insurance had superior PFS over those with primary insurance alone. Overall, our findings suggest that insurance status may serve as a determinant of clinical outcomes. These hypothesis-generating data warrant external validation in prospective studies.

Prognostic Potential of Pulmonary Hypertension in Patients with Hematologic Malignancy.

Cardiovascular diseases present a great burden for survivors of hematologic malignancy (HM). However, the effect of pulmonary hypertension (PH) on the clinical outcome of patients with HM remains unknown. This study aims to evaluate the prognostic potential of PH in patients with HM and explore the related clinical determinants. This retrospective study included 220 patients with HM and PH and 220 controls without PH, the case-matching cohort analysis was performed based on age, sex, the year of diagnosis and disease type. The baseline characteristics and overall survival (OS) of the patients with HM with or without PH were compared. The cumulative overall survival was analyzed using the Kaplan-Meier curves and the log-rank test. Multivariate Cox proportional hazard models were conducted to identify the predictors of OS. PH was found in 11.98% (302/2520) of the patients with HM. The PH group had lower levels of hemoglobin, platelet, albumin, fibrinogen and Bcell count; whereas the levels of lactate dehydrogenase, N terminal pro B type natriuretic peptide, D-dimer, fibrinogen degradation products and C-reactive protein were higher. Additionally, the PH group had a higher prevalence of atrial fibrillation. Survival analysis revealed that the PH group had an inferior OS compared to the non-PH group (16.9 vs. 37.6months, p = 0.002). Further subgroup analysis revealed that the severe PH group had the worst OS, followed by the moderate and the mild PH groups (8.7 vs. 14.7 vs. 23.7months, p < 0.001). Multivariate analysis showed that PH was an independent predictor for unfavorable clinical outcomes. Coexisting PH was associated with inferior clinical outcomes in patients with HM, and the severe PH group had the worst prognosis. The study may provide additional risk stratification for patients with HM.

Prognostic significance of ETP phenotype and minimal residual disease in T-ALL: a Children’s Oncology Group study

AbstractThe early thymic precursor (ETP) immunophenotype was previously reported to confer poor outcome in T-cell acute lymphoblastic leukemia (T-ALL). Between 2009 and 2014, 1256 newly diagnosed children and young adults enrolled in Children’s Oncology Group (COG) AALL0434 were assessed for ETP status and minimal residual disease (MRD) using flow cytometry at a central reference laboratory. The subject phenotypes were categorized as ETP (n = 145; 11.5%), near-ETP (n = 209; 16.7%), or non-ETP (n = 902; 71.8%). Despite higher rates of induction failure for ETP (6.2%) and near-ETP (6.2%) than non-ETP (1.2%; P < .0001), all 3 groups showed excellent 5-year event-free survival (EFS) and overall survival (OS): ETP (80.4% ± 3.9% and 86.8 ± 3.4%, respectively), near-ETP (81.1% ± 3.3% and 89.6% ± 2.6%, respectively), and non-ETP (85.3% ± 1.4% and 90.0% ± 1.2%, respectively; P = .1679 and P = .3297, respectively). There was no difference in EFS or OS for subjects with a day-29 MRD <0.01% vs 0.01% to 0.1%. However, day-29 MRD ≥0.1% was associated with inferior EFS and OS for patients with near-ETP and non-ETP, but not for those with ETP. For subjects with day-29 MRD ≥1%, end-consolidation MRD ≥0.01% was a striking predictor of inferior EFS (80.9% ± 4.1% vs 52.4% ± 8.1%, respectively; P = .0001). When considered as a single variable, subjects with all 3 T-ALL phenotypes had similar outcomes and subjects with persistent postinduction disease had inferior outcomes, regardless of their ETP phenotype. This clinical trial was registered at AALL0434 as #NCT00408005.