Cancer Medicine最新文献

Background

Patients with hematologic malignancies are at high risk of dying from infectious diseases. However, little attention has been paid to infectious diseases mortality (IDM) in these patients. The aim of our study is to determine the incidence and trends of IDM in patients with hematologic malignancies, identify risk factors associated with IDM, and compare the risk of IDM in patients with the general United States population.

Methods

The data of patients with hematologic malignancies between 2000 and 2020 was retrieved from the Surveillance, Epidemiology, and End Results program. Standardized mortality ratios (SMRs) and IDM rates were calculated. A competing risk model was performed to identify potential risk factors of IDM.

Results

Among 700,678 patients, 15,028 IDM were identified with an IDM rate of 401.31/100,000 person-years. Compared with the general population, the SMR of IDM was 3.34, and the elevated risk of IDM ran through the follow-up period. For all cancer subtypes, the IDM rates were highest in the first 2 months after diagnosis and gradually declined thereafter. For all patients, the early period of diagnosis, older age, male, non-Hispanic black, single or divorced/separated/widowed status, no chemotherapy, and no radiation were risk factors for IDM. For patients with Hodgkin lymphoma or non-Hodgkin lymphoma, advanced stage was also a risk factor for IDM.

Conclusion

Given the high risk of IDM in patients with hematologic malignancies, it is extremely important to identify patients at high risk of IDM and provide timely intervention to prevent early death from infections and improve prognosis.

Purpose

Our study explores the prevalence, severity, and psychological correlates of insomnia in cancer survivors, aiming to predict sleep quality based on pre-sleep arousal, pain, and worry, while examining the mediating role of dysfunctional beliefs and attitudes about sleep (DBAS).

Methods

A descriptive-correlational design was employed, with 200 cancer survivors from Tehran, Iran, selected through convenience sampling in 2022. Participants completed the Pittsburgh Sleep Quality Index (PSQI), Chronic Pain Grade (CPG), Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS), Pennsylvania Worry Questionnaire (PSWQ), and Pre-Sleep Arousal Scale (PSAS). The data were analyzed using correlation and multiple regression through SPSS-23 software.

Results

On average, 37.07 months post-treatment, 95% of survivors reported delayed sleep onset, 88.5% frequent awakenings, 72% reduced sleep duration, and 67% morning dysfunction. Significant positive associations were found between pre-sleep arousal, chronic pain (r = 0.552), worry (r = 0.161), DBAS (r = 0.363), and poor sleep quality (r = 0.607). Regression analysis indicated that physical arousal (B = 0.29, p = 0.01) and DBAS (B = 0.14, p < 0.05) were significant predictors of sleep quality, with DBAS mediating the relationship between physical arousal and sleep quality.

Conclusions

Persistent sleep problems after cancer treatment highlight the need for targeted interventions in survivorship care. Sleep-focused strategies may improve sleep quality and reduce the burden of insomnia-related issues.

Implications for Cancer Survivors

Addressing pre-sleep arousal, pain, worry, and DBAS through targeted interventions is crucial for improving sleep quality and overall quality of life in cancer survivors.

Objectives

Recent advances in the prevention of diffuse large B-cell lymphoma (DLBCL) have considerably focused on optimal strategies for preventing its recurrence in the central nervous system (CNS) in patients. This retrospective study aimed to assess the protective efficacy of intravenous high-dose methotrexate (HD-MTX) regimens in newly diagnosed patients with DLBCL presenting a high risk for CNS recurrence.

Methods

A total of 136 newly diagnosed high-risk DLBCL patients (HD-MTX group: n = 46; non-HD-MTX group: n = 90) were enrolled in this retrospective study. The primary endpoints included CNS recurrence rate, progression-free survival (PFS), overall survival (OS), and toxicity.

Results

The 2-year CNS recurrence rates (median follow-up period: 25.5 months; 95% confidence interval: 21.0–30.0) were 4.3% and 11.1% in the HD-MTX and non-HD-MTX groups (p = 0.337), respectively. Additionally, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 70.7% versus 60.8% and 72.9% versus 60.8% (p = 0.013 and p = 0.024), respectively. The subgroup analysis for PFS and OS revealed that patients classified as the National Comprehensive Cancer Network (NCCN)—International Prognostic Index (IPI) low- or intermediate-risk, at a younger age, and without B symptoms demonstrated potential benefits from the HD-MTX treatment. In total, 46 patients completed 92 cycles of HD-MTX treatment, of which, 49 cycles were administered on day 6 of the R-CHOP regimen, with an average delay of no more than 4 days. In contrast, the remaining 43 cycles were initiated on days 10–14 following the completion of the R-CHOP regimen, with an average delay of 15 days. Interestingly, the incidence of hematological or non-hematological toxicity did not differ significantly among the groups.

Conclusion

Owing to the lack of robust evidence, the role of HD-MTX in preventing CNS recurrence could not be conclusively determined. Nevertheless, some patients could tolerate the treatment, such as younger individuals and those at NCCN-IPI low or intermediate risk, suggesting the efficacy of intravenous HD-MTX administration on day 6 as an optimal strategy for preventing CNS recurrence of DLBCL.

Objective

Dual checkpoint inhibitor therapy with nivolumab and ipilimumab has been FDA approved for a number of cancer sites. However, its role in the treatment of ACC and non-ACC salivary gland carcinomas (non-ACC SGC) is not well established.

Methods and Analysis

We performed Simon's two-stage prospective single-institution Phase II clinical trial of nivolumab with ipilimumab. Two cohorts were analyzed: patients with metastatic/recurrent ACC and patients with non-ACC SGC. The primary endpoint was median progression-free survival (PFS); secondary endpoints were overall response rate (ORR), overall survival (OS), and toxicity.

Results

Patient enrollment was prematurely terminated due to funding constraints. In total, 19 patients with ACC and 5 patients with non-ACC SGC were enrolled. The patients with ACC had a median OS of 30.0 months (95% CI 15.3-NR months), a median PFS of 8.3 months (95% CI 5.5–30.0 months), and a disease control rate (DCR) of 53% (10/19). The ORR in the ACC group was 5% (CR 0%, n = 0; confirmed PR 5%, n = 1), with one patient having continued stable disease at the time of trial conclusion. The patients with non-ACC SGC had a median OS of 10.4 months (95% CI 6.21-NR months), a median PFS of 6.21 months (95% CI 2.83-NR months), and a DCR of 40% (2/5). The ORR in this cohort was 0%.

Conclusion

In patients with recurrent or metastatic ACC and non-ACC SGC, the combination of nivolumab with ipilimumab resulted in moderate disease control. Further studies are warranted to validate our findings.

Trial number: NCT03146650.

Background

Although most patients with cutaneous melanoma (CM) will have a negative sentinel lymph node biopsy (SLNB), up to 20%–30% of these patients will recur. The 31-gene expression profile (31-GEP) test has been prospectively validated to identify patients at low (Class 1A), intermediate (Class 1B/2A), and high (Class 2B) risk of SLN positivity and recurrence.

Methods

DECIDE is a prospective, multicenter study to assess the effect of 31-GEP testing on SLNB performance rates in patients with T1–T2 tumors considering SLNB and to study long-term outcomes. Here, we assessed outcomes in patients with a Class 1A 31-GEP result (n = 130).

Results

Of Class 1A patients, 63 had an SLNB, with a 3.2% SLN positivity rate (2/63). No Class 1A patients, regardless of SLN status, experienced a recurrence (2-year median follow-up).

Conclusions

These results are consistent with previous studies that showed the 31-GEP can identify patients at low risk of SLN positivity and recurrence.

Background

In the phase 3 ponatinib-3001 trial (PhALLCON, NCT03589326), ponatinib demonstrated superior efficacy over imatinib with comparable safety in patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). This post hoc analysis evaluated the net benefits of ponatinib using a quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) approach.

Methods

Overall survival (OS) time for patients from PhALLCON was partitioned into three health states: TOX (time with grade 3+ treatment-emergent adverse events [TEAEs] before disease progression), TWiST (time without toxicity before progression), and REL (time from progression until death or end of follow-up). Q-TWiST was calculated as the sum of health utility-weighted restricted mean durations of the three states. A relative Q-TWiST gain of ≥ 10% was considered clinically important. Sensitivity analyses were conducted by varying TOX and REL utilities, follow-up time, and the TOX definition (using grade 2+ TEAEs or patient-perceived treatment tolerability assessed by the FACT-GP5).

Results

Among all randomized patients (ponatinib n = 164, imatinib n = 81), restricted mean OS was similar between arms (1082.2 vs. 1024.8 days; p = 0.373). In the base-case analysis, mean TWiST was 214.5 days longer with ponatinib versus imatinib (95% CI 70.3–358.7; p = 0.004), REL was shorter by 175.9 days (325.4–26.5; p = 0.021), and TOX was not significantly different between arms (p = 0.228). The relative Q-TWiST gain (10.98%) was clinically important. Sensitivity analyses consistently supported the robustness of the base-case findings.

Conclusion

Ponatinib may prolong quality-adjusted survival compared with imatinib, supporting the benefit–risk profile of ponatinib as a front-line treatment for Ph+ ALL.

Trial Registration

NCT03589326

Background

Fear of cancer recurrence (FCR) is a pervasive concern among lymphoma survivors and their family caregivers, influencing psychological and physical health. Given the substantial burden of FCR, identifying its predictors is crucial for targeted interventions that could enhance palliative care. We aimed to evaluate the prevalence of FCR in lymphoma survivors and their caregivers, as well as associated factors

Methods

A total of 118 patients with lymphoma, along with their family caregivers, were recruited from Hacettepe University Cancer Institute between March 2024 and May 2024. Psychological assessments were conducted using the Depression Anxiety Stress Scales (DASS-21), the Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF) and the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)

Results

High levels of FCR were experienced by 50.8% (n = 60) of lymphoma survivors and 57.6% (n = 68) of their caregivers. There was a positive correlation between the FCR of the survivors and caregivers (r = 0.349, p < 0.001). Poor overall quality of life (QoL) (aOR: 4.279, 95% CI: 1.738–10.531, p = 0.002), recent diagnosis (< 3 year) (aOR: 5.135, 95% CI: 1.852–14.238, p = 0.002), survivors' anxiety (aOR: 2.540, 95% CI: 1.014–6.363, p = 0.002) and caregivers' FCR (aOR: 2.970, 95% CI: 1.119–7.879, p = 0.029) were associated with high levels of FCR in lymphoma survivors.

Conclusion

We observed high FCR levels in over half the survivors with lymphoma and a higher FCR risk in patients with anxiety, poor QoL and caregiver FCR. These findings highlight the critical need for developing comprehensive care plans and interventions targeting FCR in patients with lymphoma.

Background

This study was conducted to identify the risk of residual or recurrent high-grade squamous intraepithelial lesions or worse (HSIL+) in patients with successful conization and to develop a customized management strategy.

Methods

This retrospective study included 939 patients who underwent cold knife conization (CKC) for cervical intraepithelial neoplasia 3 at a hospital in China between January 1, 2013 and December 31, 2020. Demographic characteristics and test results were obtained before and 6, 12, and 24 months after CKC and annually thereafter. Human papillomavirus (HPV) persistence was defined as HPV positive at both 6 and 12 months after CKC, and the primary endpoint was residual or recurrent HSIL+ after CKC.

Results

The mean follow-up period was 68.8 months. In total, 61 (6.5%) patients had HPV persistence, and 19 (2.0%) had residual or recurrent HSIL+. The risk of residual or recurrent HSIL+ was increased in patients with HPV infection at 6 months (hazard ratio [HR], 84.6; 95% confidence interval [CI], 11.2–641) and 12 months (HR, 214; 95% CI, 28.1–1625) after CKC, and HPV persistence after CKC (HR, 244; 95% CI, 32.2–1854). Comparing two different colposcopic referral criteria for HPV persistence and HPV positive 6 months post-CKC, substantially fewer colposcopies were performed per case of residual or recurrent HSIL+ detected in patients with HPV persistence after CKC (3.39 vs. 8.28).

Conclusions

The risk of residual or recurrent HSIL+ was higher in patients with HPV persistence after CKC. In patients with negative margins, extending the follow-up interval to 12 months may reduce the number of HPV tests and colposcopy referral rates while maintaining HSIL+ detection.

Objective

Sarcomas are a heterogeneous group of malignancies, low disease-control levels and the limited durability of responses have prompted the exploration of various novel immunotherapeutic approaches. To preliminarily explore the feasibility of cancer vaccines based on cancer testis antigen in the immunotherapy of sarcomas, we investigate the expression of Cancer/Testis Antigens (CTA) MAGE-A4, PRAME, MAGE-A1, KK-LC-1, and NY-ESO-1 in bone and soft tissue sarcomas, with the aim of assessing their potential for use in sarcoma immunotherapy and determining their expression levels in different subtypes.

Methods and Results

We employed immunohistochemistry and multiplex immunostaining microarrays (MI chips) to assess the expression of MAGE-A4, PRAME, MAGE-A1, KK-LC-1, and NY-ESO-1 in 21 cases of undifferentiated pleomorphic sarcoma (UPS), 26 cases of smooth muscle sarcoma, 28 cases of liposarcoma, 40 cases of osteosarcoma (OS), and 13 cases of chondrosarcoma. MAGE-A1 showed the highest expression in osteosarcoma (32.50%), while it was lower in liposarcoma and undifferentiated pleomorphic sarcoma (10.71% and 10.00%) and undetectable in chondrosarcoma. MAGE-A4 expression was elevated in osteosarcoma and undifferentiated pleomorphic sarcoma (40.00% and 33.00%), but lower in liposarcoma and smooth muscle sarcoma (17.00% and 33.00%). NY-ESO-1 expression was relatively low across all sarcoma subtypes. PRAME expression was highest in undifferentiated pleomorphic sarcoma (47.62%) and low in chondrosarcoma (7.69%). None of the sarcomas expressed KK-LC-1. Additionally, while there was no statistically significant correlation between CTA expression and patient age or gender, some differences related to age and gender were observed.

Conclusions

CTA expression in bone and soft tissue sarcomas was correlated with both CTA type and sarcoma subtype, showing relatively high levels of expression in undifferentiated pleomorphic sarcoma (UPS) and osteosarcoma (OS). The poly-expression of MAGE-A4, PRAME, and MAGE-A1 across all subtypes suggests that these antigens may serve as potential targets for sarcoma-specific immunotherapy.

Background

Cancer is characterized by accelerated glycolysis with enhanced glucose uptake and lactate production, a phenomenon termed Warburg effect (WE). We studied the incidence and clinical impact of Warburg-driven lactic acidosis in lymphoma.

Methods

Patients admitted with newly diagnosed or relapsed/refractory lymphoma and documented lactate levels during the first week of admission were included. Patients with lactatemia were classified as secondary (with a recognizable cause for elevated lactate) or none (WE group).

Results

WE and secondary lactatemia were documented in 58 and 44 patients (15% and 12% of evaluable patients, respectively). Both WE and secondary lactatemia were associated with poor short-term survival. WE at presentation correlated with tumor burden, with most patients having aggressive disease, advanced stage, and extranodal involvement. WE was associated with high rates of early death (26% and 43% at 30- and 60-days, respectively). Higher lactate levels correlated with worse survival. Earlier initiation of chemotherapy was associated with a (nonsignificant) trend toward better outcomes, whereas steroid and/or thiamine therapy did not alter patient outcomes. Glucose administration was associated with worse survival.

Conclusion

WE-driven lactatemia is associated with high tumor burden and increased short-term mortality in lymphoma. Prompt initiation of anti-lymphoma therapy may improve outcomes.