Musculoskeletal neck disorders in thyroid cancer patients after thyroidectomy

Thyroid cancer (TC) is the most common type of cancer in the endocrine system, and thyroidectomy is the preferred treatment. Complications associated are still common and 80% of patients complain of posterior neck pain. The aim of this study was to analyse the long‐term musculoskeletal disorders in TC patients who had undergone thyroidectomy. An observational case–control study was carried out. Twenty‐eight patients who had undergone thyroidectomy and 28 healthy control patients were included. Outcomes were collected 6 months after surgery and included: musculoskeletal neck disorders (neck range of movement, trigger points) and functional variables (pain intensity and disability). Significant differences were found between groups in flexion (p = 0.002) and extension (p = 0.005), with lower values in the thyroidectomy group. The number of trigger points was higher in the thyroidectomy group in both scalenes (p < 0.001), both sternocleidomastoids (p < 0.001), both upper trapezius (p = 0.005 and p = 0.008), right levator scapulae (p = 0.002) and both suboccipitalis (p = 0.002). Pain intensity (p < 0.001) and the Neck Outcome Scale subscales (p < 0.05) also presented significant differences. Thyroidectomy patients, 6 months after surgery, show a significant decrease in neck range of movement and an increase in the number of trigger points. They also show greater pain intensity and more disability.     

Persistently low lymphocyte counts after FCR therapy for chronic lymphocytic leukemia are associated with longer overall survival

Decreased absolute lymphocyte counts (ALCs) following frontline therapy for chronic lymphocytic leukemia may be associated with disease control, even in patients without evidence of minimal residual disease. We studied the prognostic significance of ALCs during the first year following treatment with fludarabine, cyclophosphamide, and rituximab (FCR). We evaluated 99 patients who achieved a partial response without lymphocytosis (<4.0 × 10³cells/μL) or better after FCR. Absolute lymphocyte counts were recorded at 3‐, 6‐, 9‐, and 12‐month posttreatment and correlated with overall survival (OS) and event‐free survival (EFS). For each time point, analyses were limited to patients without lymphocytosis, so as to avoid possible biases from undocumented disease progressions. Lymphopenia (ALC < 1.0 × 10³cells/μL) at 3 m after FCR (69% of patients n = 68), was associated with a longer OS (5y OS 91% vs 64%, P = .001), as were ALC ≤ 2 × 10³ cells/μL at 6 m (5y OS 85% vs 48%, P = .004) and ALC ≤ 1.8 × 10³ cells/μL at 9 m (5y OS 93% vs 54%, P = .009). A normal‐range ALC (≤4 × 10³ cells/μL) at 12 m was also associated with a 91% 5y OS. Higher ALCs (but without lymphocytosis) were associated with shorter EFS (median EFS 27 months for ALC > 1.8 vs not reached for ALC ≤ 0.7 at 9 months, P < .0001). In conclusion, lower ALC levels in the first few months following frontline FCR therapy were associated with longer OS and EFS. Possible explanations may be that lower ALCs reflect deeper clonal suppression or protracted T_reg depletion. Absolute lymphocyte count levels may be a cheap and widely available prognostic marker, though the added value for clinical practice is the minimal residual disease era needs to be explored.     

The Characteristics of Pain Tolerance in Patients Who Underwent Unilateral Breast Cancer Surgery: The Effect of Handedness and Surgical Site to Assess the Potential Musculoskeletal Symptoms and Function

BackgroundBreast cancer survivors (BCS) usually experience musculoskeletal pain and strength imbalance between surgical and nonsurgical sites.Material and methodsThis study aimed to assess the effect of handedness and surgical site on pain tolerance and upper extremity strength in BCS. A total of 96 female BCS (Mean age and BMI: 51.06 ± 9.36 years and 27.77 ± 3.75 kg/m²) were included in this study. BCS were categorized as “DoS” or “NoS” whether they had surgery on their dominant or nondominant site, respectively. Socio-demographic data, upper extremity strength, pain tolerance, and pain-related function measurements were performed by simple form, manual muscle tester, pain algometer, and Disabilities of Arm, Shoulder, and Hand's (DASH) pain subscale, respectively.ResultsPain tolerances were significantly lower in upper trapezius muscle region in the surgical site (t = -4,263, P < .001 and t = -2138, P = 0.037) while in the deltoid tuberosity, pain tolerance was significantly higher in surgical site (t = 2633, P = 0.011). Mean differences in strength in shoulder flexion and abduction were significantly lower in the DoS group compared to the NoS group (z = -3.166, P = .002 and z = -2.131, P = .033, respectively), whereas the pain subscale was significantly higher in the DoS (P = .013).ConclusionPain tolerance decreased in the upper trapezius muscle region on the surgical site irrespective of the handedness. However, in deltoid tuberosity, the effect of handedness was remarkable. Exercise programs should focus to establish a strength balance in nondominant surgery BCS since strength imbalance might be more prominent to affect them to take part in activities in daily living.     

EGFR is a potential therapeutic target for highly glycosylated and aggressive pancreatic neuroendocrine neoplasms

pNENs are relative indolent tumors with heterogeneous clinical presentation at diagnosis. It is important to establish aggressive subgroups of pNENs and identify potential therapeutic targets. Patients with pNEN (322 cases) were included to examine the association between glycosylation biomarkers and clinical/pathological traits. The molecular and metabolic features stratified by glycosylation status were assessed by RNA-seq/whole exome sequencing and immunohistochemistry. A considerable proportion of patients had elevated glycosylation biomarkers (carbohydrate antigen [CA] 19-9, 11.9%; CA125, 7.5%; carcinoembryonic antigen [CEA], 12.8%). CA19-9 (hazard ratio [HR] = 2.26, P = .019), CA125 (HR = 3.79, P = .004) and CEA (HR = 3.16, P = .002) were each independent prognostic variables for overall survival. High glycosylation group, defined as pNENs with elevated level of circulating CA19-9, CA125 or CEA, accounted for 23.4% of all pNENs. High glycosylation (HR = 3.14, P = .001) was an independent prognostic variable for overall survival and correlated with G3 grade (P < .001), poor differentiation (P = .001), perineural invasion (P = .004) and distant metastasis (P < .001). Epidermal growth factor receptor (EGFR) was enriched in high glycosylation pNENs using RNA-seq. EGFR was expressed in 21.2% of pNENs using immunohistochemistry and associated with poor overall survival (P = .020). A clinical trial focusing on EGFR expressed pNENs was initiated (NCT05316480). Thus, pNEN with aberrant glycosylation correlates with a dismal outcome and suggests potential therapeutic target of EGFR.     

The risk factors and prevalence of upper extremity impairments and an analysis of effects of lymphoedema and other impairments on the quality of life of breast cancer patients

This study aimed to determine the prevalence and identify the risk factors associated with upper extremity impairments (UEIs) in breast cancer patients and to investigate the degree to which these impairments and other characteristics influence quality of life (QoL). A total of 201 women over the age of 18 who underwent breast cancer treatment at least 6 months were included in this cross‐sectional study. All of the patients were evaluated for the presence of lymphoedema and any UEIs. UEIs divided into five subgroups: pain, restriction of shoulder range of motion (ROM), numbness and heaviness, loss of strength, and sensory deficit. QoL of the patients was evaluated by SF‐36. The prevalence of the upper extremity impairments was as follows: pain 31.8%, restriction of shoulder ROM 23.9%, numbness and heaviness 35.3%, loss of strength 8.5%, and sensory deficit 18.4%. Furthermore, lymphoedema was seen in 41.3% of patients. The multivariate model showed that lymphoedema is the only statistically significant risk factor that affects the development of UEIs (P = 0.001). However, it also revealed that lymphoedema (P = 0.001) and increased age negatively affect QoL, whereas prolongation of the follow‐up period has a favourable impact (P = 0.016). Therefore, lymphoedema diminishes QoL via an increased number of UEIs.     

TP53 alterations in relapsed childhood acute lymphoblastic leukemia

TP53 alterations are frequent relapse‐acquired mutations in childhood acute lymphoblastic leukemia (ALL). The present study evaluated the clinical significance of relapsed childhood ALL in Taiwan. Diagnostic and/or relapsed bone marrow or peripheral blood was obtained from 111 children with relapsed ALL who were initially treated by using Taiwan Pediatric Oncology Group (TPOG) ALL protocols from January 1997 to May 2018. Mutations were detected by PCR and sequencing, as well as by multiplex ligation‐dependent probe amplification to detect copy number alterations. Copy number and/or sequence alterations of TP53 were detected in 29% (28 of 98) and in 46% (6 of 13) of patients with relapsed B‐cell and T‐cell ALL, respectively. This incidence was much higher than that in several similar studies conducted in Caucasian populations. Seventy percent of all TP53 alterations were gained at relapse in 67 matched samples by back‐tracking matched diagnostic samples. TP53 alterations were associated with lower 5‐year event‐free survival (EFS) and overall survival (OS) rates (P = .013 and P = .0002, respectively). Multivariate analysis confirmed the prognostic significance of TP53 alterations. Forty‐five patients received hematopoietic stem‐cell transplantations post‐relapse. Patients with TP53 alterations (14/45) had inferior 5‐year EFS and OS than patients without TP53 alterations after transplantation (P = .002 and P = .001, respectively). The significance of these TP53 alterations for patients who received transplantations was confirmed by multivariate analysis. In conclusion, TP53 alterations were enriched and useful as prognostic markers in relapsed childhood ALL.     

Clinical significance of signal regulatory protein alpha (SIRPα) expression in esophageal squamous cell carcinoma

Signal regulatory protein alpha (SIRPα) is a type I transmembrane protein that inhibits macrophage phagocytosis of tumor cells upon interaction with CD47, and the CD47-SIRPα pathway acts as an immune checkpoint factor in cancers. This study aims to clarify the clinical significance of SIRPα expression in esophageal squamous cell carcinoma (ESCC). First, we assessed SIRPα expression using RNA sequencing data of 95 ESCC tissues from The Cancer Genome Atlas (TCGA) and immunohistochemical analytic data from our cohort of 131 patients with ESCC. Next, we investigated the correlation of SIRPα expression with clinicopathological factors, patient survival, infiltration of tumor immune cells, and expression of programmed cell death-ligand 1 (PD-L1). Overall survival was significantly poorer with high SIRPα expression than with low expression in both TCGA and our patient cohort (P < .001 and P = .027, respectively). High SIRPα expression was associated with greater depth of tumor invasion (P = .0017). Expression of SIRPα was also significantly correlated with the tumor infiltration of M1 macrophages, M2 macrophages, CD8⁺ T cells, and PD-L1 expression (P < .001, P < .001, P = .03, and P < .001, respectively). Moreover, patients with SIRPα/PD-L1 coexpression tended to have a worse prognosis than patients with expression of either protein alone or neither. Taken together, SIRPα indicates poor prognosis in ESCC, possibly through inhibiting macrophage phagocytosis of tumor cells and inducing suppression of antitumor immunity. Signal regulatory protein alpha should be considered as a potential therapeutic target in ESCC, especially if combined with PD-1-PD-L1 blockade.     

Independent prognostic value of pre-treatment 18-FDG-PET in high-grade gliomas

The prognostic value of PET with (18F)-fluoro-2-deoxy-d-glucose (FDG) has been shown in high-grade gliomas (HGG), but not compared with consensual prognostic factors. We sought to evaluate the independent predictive value of pre-treatment FDG-PET on overall (OS) and event-free survival (EFS). We retrospectively analyzed 41 patients with histologically-confirmed HGG (31 glioblastomas and 10 anaplastic gliomas). The pre-treatment uptake of FDG was assessed qualitatively by five-step visual metabolic grading, and quantitatively by the ratio between the tumor and contralateral maximal standardized uptake value (T/CL). EFS and OS following PET were compared with FDG uptake by univariate analysis, and by two multivariate analyses: one including main consensual prognostic factors (age, KPS, extent of surgery and histological grade), and the other including the classification system of the Radiation Therapy Oncology Group (Recursive Partitioning Analysis, RPA). Median OS and EFS were 13.8 and 7.4 months, respectively, for glioblastomas, and over 25.8 and 12 months, respectively, for anaplastic gliomas (P = 0.040 and P = 0.027). The T/CL ratio predicted OS in the entire group [P = 0.003; Hazard Ratio (HR) = 2.3] and in the glioblastoma subgroup (P = 0.018; HR = 2), independently of age, Karnofsky performance status, histological grade, and surgery, and independently of RPA classification. T/CL ratio tended to predict EFS in the whole group (P = 0.052). The prognostic value of visual metabolic grade on OS was less significant than T/CL ratio, both in the entire group and in the glioblastoma subgroup (P = 0.077 and P = 0.059). Quantitative evaluation of the ratio between the maximal tumor and contralateral uptake in pre-treatment FDG-PET provides significant additional prognostic information in newly-diagnosed HGG, independently of consensual prognostic factors.     

Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II,double-blind,placebo-controlled,randomized trial

A double-blind placebo-controlled randomized phase II trial was performed to determine whether High Dose Vitamin D2 supplementation (HDD) in women receiving adjuvant anastrozole improves aromatase inhibitor-induced musculoskeletal symptoms (AIMSS) and bone loss. Patients with early breast cancer and AIMSS were stratified according to their baseline 25-hydroxy vitamin D (25OHD) level. Stratum A (20–29 ng/ml) received either HDD 50,000 IU capsules weekly for 8 weeks then monthly for 4 months or placebo. Stratum B (10–19 ng/ml) received either HDD for 16 weeks and then monthly for 2 months, or placebo. AIMSS was assessed by the Brief Pain Inventory-Short Form (BPI-SF), the Fibromyalgia Impact Questionnaire (FIQ), and the Health Assessment Questionnaire-Disability Index (HAQ-DI) at baseline, 2, 4, and 6 months. Bone Mineral Density (BMD) was measured at baseline and at 6 months. The primary endpoint of the study was the change-from-baseline musculoskeletal pain. The secondary endpoint was the percent change in BMD at 6 months. Sixty women were enrolled. Baseline characteristics were comparable between the groups. At 2 months, FIQ pain (P = 0.0045), BPI worst-pain (P = 0.04), BPI average-pain (P = 0.0067), BPI pain-severity (P = 0.04), and BPI interference (P = 0.034) scores were better in the HDD than placebo group. The positive effect of HDD on AIMSS was stronger across all time points in Stratum B than Stratum A (FIQ pain, P = 0.04; BPI average, P = 0.03; BPI severity, P = 0.03; BPI interference, P = 0.04). BMD at the femoral neck decreased in the placebo and did not change in the HDD group (P = 0.06). Weekly HDD improves AIMSS and may have a positive effect on bone health. Vitamin D supplementation strategies for breast cancer patients on AI should be further investigated.     

Autologous Hematopoietic Cell Transplantation Versus Chemotherapy Alone for Immunoglobulin Light Chain Amyloidosis: A Retrospective Study

IntroductionImmunoglobulin light chain (AL) amyloidosis is caused by the deposition of monoclonal immunoglobulin light chains, for which autologous hematopoietic cell transplantation (AHCT) is one of the most effective therapies. In small studies comparing AHCT with chemotherapy alone, AHCT was associated with better survival.Patients and MethodsIn this study, we compared the outcomes of AHCT with those of chemotherapy alone in 232 patients. We retrospectively reviewed the outcomes in 74 patients who underwent AHCT with those of 158 patients treated only with chemotherapy.ResultsThe median event-free survival (EFS) (73 vs. 9 months; P < .001) and overall survival (OS) (not achieved vs. 39 months; P < .001) were superior in the AHCT group versus those in the chemotherapy group. On multivariate analysis, AHCT was significantly associated with better EFS (hazard ratio, 0.410; 95% confidence interval, 0.241-0.697; P = .0010) and OS (hazard ratio, 0.313; 95% confidence interval, 0.155-0.636; P = .0013) than chemotherapy alone. Even when patients with severe findings (mean left ventricular thickness > 12 mm, brain natriuretic peptide level > 400 pg/mL, and creatinine level > 2.0 mg/dL) and elderly patients (age > 65 years) were excluded, both EFS and OS were significantly better in the AHCT group than in the chemotherapy group upon univariate and multivariate analyses.ConclusionAHCT yielded better EFS and OS than chemotherapy alone in patients with AL amyloidosis. AHCT should be considered for eligible patients.     

Mutation status and burden can improve prognostic prediction of patients with lower‐risk myelodysplastic syndromes

Patients with lower‐risk myelodysplastic syndromes (LR‐MDS) as defined by the International Prognostic Scoring System (IPSS) have more favorable prognosis in general, but significant inter‐individual heterogeneity exists. In this study, we examined the molecular profile of 15 MDS‐relevant genes in 159 patients with LR‐MDS using next‐generation sequencing. In univariate COX regression, shorter overall survival (OS) was associated with mutation status of ASXL1 (P = .001), RUNX1 (P = .031), EZH2 (P = .049), TP53 (P = .016), SRSF2 (P = .046), JAK2 (P = .040), and IDH2 (P = .035). We also found significantly shorter OS in patients with an adjusted TET2 variant allele frequency (VAF) ≥18% versus those with either an adjusted TET2 VAF <18% or without TET2 mutations (median: 20.4 vs 47.8 months; P = .020; HR = 2.183, 95%CI: 1.129‐4.224). After adjustment for IPSS, shorter OS was associated with mutation status of ASXL1 (P < .001; HR = 4.306, 95% CI: 2.144‐8.650), TP53 (P = .004; HR = 4.863, 95% CI: 1.662‐14.230) and JAK2 (P = .002; HR = 5.466, 95%CI: 1.848‐16.169), as well as adjusted TET2 VAF ≥18% (P = .008; HR = 2.492, 95% CI: 1.273‐4.876). Also, OS was increasingly shorter as the number of mutational factors increased (P < .001). A novel prognostic scoring system incorporating the presence/absence of the four independent mutational factors into the IPSS further stratified LR‐MDS patients into three prognostically different groups (P < .001). The newly developed scoring system redefined 10.1% (16/159) of patients as a higher‐risk group, who could not be predicted by the currently prognostic models. In conclusion, integration of the IPSS with mutation status/burden of certain MDS‐relevant genes may improve the prognostication of patients with LR‐MDS and could help identify those with worse‐than‐expected prognosis for more aggressive treatment.     

E-selectin gene S128R polymorphism is associated with poor prognosis in patients with stage II or III colorectal cancer

Some host-related factors may predict the risk of metastasis after surgery of colorectal cancer (CRC). The endothelial adhesion molecule E-selectin is implicated in the metastatic spread of CRC. We postulated that some polymorphisms within the E-selectin gene, especially the S128R polymorphism, may increase the risk of metastases by facilitating adhesion of tumour cells to the endothelium. We collected blood samples for DNA extraction from 264 patients treated for stage II or III CRC and from 310 healthy controls in order to assess three polymorphisms within the E-selectin gene (S128R, G98T and L554F) and one within the P-selectin gene (V640L). Genotypes were analysed by the allelic discrimination TaqMan real-time PCR assay. The S128R polymorphism was detected in 59 patients (22.3%) and was strictly correlated with the G98T polymorphism. In multivariate analysis, the S128R polymorphism was associated with shorter event-free survival (EFS) and overall survival (OS) in the whole population (EFS: P = .003, HR 1.82, 95% CI 1.23–2.70; OS: P < 10^–4, HR 4.31, 95% CI 2.46–10.99), in patients with stage II CRC(EFS: P = .04, HR 1.92, 95% CI 1.02–3.60; OS: P = .02, HR 4.44, 95% CI 1.16–17.03), and in patients with stage III CRC (EFS: P = .04, HR 1.68, 95% CI 1.01–2.80; OS: P = .001, HR 4.04, 95% CI 1.73–9.46). L554F and V640L polymorphisms had no prognostic value. The S128R polymorphism is a constitutional factor associated with a higher risk of relapse and death in patients treated for CRC. This polymorphism detection may permit better selection of patients suitable for adjuvant therapy, especially among those with stage II disease.     

Indoleamine 2, 3‐dioxygenase 1 promoter hypomethylation is associated with poor prognosis in patients with esophageal cancer

Indoleamine 2, 3‐dioxygenase 1 (IDO1) is a primary enzyme that generates immunosuppressive metabolites. It plays a major role in tumor immunology and is a potential immune‐based therapeutic target. We have reported that IDO1 protein expression was associated with an unfavorable clinical outcome in esophageal cancer. Recently, it has been reported that IDO1 expression is regulated by methylation of the IDO1 promoter. Thus, the aim of this study was to examine the relationship between IDO1 expression, IDO1 promoter methylation, and clinicopathological features in esophageal cancer. We first confirmed changes in IDO1 expression levels in vitro by treating cells with 5‐azacytidine. We then evaluated the relationship between IDO1 expression levels, IDO1 promoter methylation (bisulfite pyrosequencing), and clinicopathological features using 40 frozen samples and 242 formalin‐fixed, paraffin‐embedded samples resected from esophageal cancer patients. We treated cell lines with 5‐azacytidine, and the resulting hypomethylation induced significantly higher IDO1 expression (P < .001). In frozen samples, IDO1 expression levels correlated inversely with IDO1 promoter methylation levels (R = ?0.47, P = .0019). Furthermore, patients in the IDO1 promoter hypomethylation group (n = 67) had a poor prognosis compared with those in the IDO1 promoter hypermethylation group (n = 175) (overall survival, P = .011). Our results showed that IDO1 promoter hypomethylation regulated IDO1 expression and was associated with a poor prognosis in esophageal cancer patients.     

Treatment of Adults and Young Adults with Acute Lymphoblastic Leukemia: Real Life Data from Two Centers in Slovakia

IntroductionThe results of treatment of acute lymphoblastic leukemia (ALL) from the low population countries are missing in the literature.Patients and methodsWe retrospectively examined biological characteristics and survival of 90 patients with ALL.ResultsAt median follow-up 17 months, 52 men and 38 women were eligible for the analysis with median age 43 years (18–74). As for the risk stratification, 25.6% of patients were in standard risk, 46.7% in high risk and 27.8% in very high-risk group. Complete remission achieved 88.9% of patients. We observed 5.6% of induction deaths and 4.5% of resistant disease. 47.8% of the patients underwent allogeneic stem cell transplantation (alloSCT), 59% in the young adults (YA; < 40 years) and 40% in adult group (≥ 40 years). We noticed 32.6% relapses overall with median survival of relapsed patients 3.9 months. YA patients had longer survival than adults: 3-year overall survival (OS) 65.0% vs 30.2%; (HR = 0.36; 95% CI 0.2–0.64; P = .001) and event free survival (EFS) 51.5% vs 21.9%; (HR = 0.45; 95% CI 0.26–0.78; P = .005). There was significant difference in 3-year EFS between risk groups in YA patients 90.9%, 48.0%, 11.4%; (P = .001). OS after alloSCT individually for the YA was 62.6% and for adults 39.1%, hazard ratio (HR) = 0.49 (95% CI 0.20–1.21); (P = .095). We observed 14% early deaths, 25.6% late deaths and 3 relapses (7%) after allogeneic stem cell transplantation.ConclusionsOur data proved that even in a low population country similar result can be achieved as in larger ones while using well designed adapted protocols from leukemic study groups.     

The expression and clinical significance of the androgen receptor and E-cadherin in triple-negative breast cancer

Triple-negative breast cancer (TNBC) has a poor prognosis and lacks prognostic indicators. The androgen receptor (AR) and E-cadherin are involved in the pathogenesis of breast cancer, but their roles are not clearly defined. We designed this study to evaluate AR and E-cadherin expression and to determine their relationships with the clinicopathologic parameters of triple-negative breast cancer. The present study included 127 TNBC patients. Immunohistochemical stains for AR and E-cadherin were performed, and the relationships between AR and E-cadherin expression and clinicopathologic data and prognosis were analyzed. We found that in TNBC patients, AR was expressed in 16(12.6%) cases, and E-cadherin was expressed in 41(33.0%) cases. AR expression was associated with tumor grade (P = 0.004) and menopausal status (P = 0.017), and E-cadherin expression was associated with node status (P= 0.016). A multivariate analysis demonstrated that tumor size, tumor grade, lymph node status, and E-cadherin were of prognostic significance for disease-free interval and overall survival. Compared with AR-positive patients, AR-negative patients showed significantly poorer outcomes with respect to the disease-free interval (P = 0.047) and overall survival (P = 0.038). E-cadherin-negative patients experienced shorter disease-free interval (P = 0.016) and poorer overall survival (P = 0.012) than did E-cadherin-positive patients. An AR-positive and E-cadherin-negative expression profile was associated with recurrence or metastasis (P = 0.036). Moreover, as the expression of nuclear AR increased (25% vs. 33.3%, P = 0.361), less E-cadherin staining was observed in TNBC samples. This finding suggested that AR and E-cadherin expression could be a useful prognostic marker for classifying subgroups of TNBC.     

The relationship between pain,fatigue, sleep disorders and quality of life in adult patients with acute leukaemia: During the first year after diagnosis

The aim of this study was to investigate the relationship between pain, fatigue, sleep disorders and quality of life and assess the most powerful predictor of quality of life in patients with acute leukaemia. In this cross‐sectional multicentre study, 406 patients were recruited. Data were collected using the Iranian Short‐Form 36‐item Health Survey, the Pittsburgh Sleep Quality Index, and the Numeric Rating Scale for Pain and Fatigue Intensity. It was found that pain and fatigue had direct relationship with sleep disorders. Statistically significant relationships were reported between pain, fatigue, sleep disorders and QoL. Also, a statistically significant relationship was found between pain and QoL (p < .001). Pain, fatigue and sleep disorders in total had the predictive power for quality of life (R² = 36%). The most powerful predictor of quality of life was pain. It is suggested that healthcare professionals note the importance of patients' symptoms in clinical investigations and take appropriate measures for their management. The assessment of pain as the most powerful predictor of quality of life can be considered a basis for the improvement of quality of life, fatigue and sleep quality in patients with acute leukaemia.     

Impact of comorbidity on survival in peripheral T‐cell lymphomas: A Swedish Lymphoma Registry study

Comorbidity impacts survival in B‐cell lymphoma patients, but the influence in peripheral T‐cell lymphomas (PTCLs) has been little studied. To investigate the impact of comorbidity on outcome in PTCL, we identified adult patients with newly diagnosed PTCL from 2000 to 2009 in the Swedish Lymphoma Registry. Data on comorbidity at diagnosis were retrospectively collected according to the Charlson Comorbidity Index (CCI). Comorbid conditions were present in 263 out of 694 (38%) patients. A CCI score of ≥2 was associated with inferior overall survival (OS) (hazard ratio [HR] 1.63, P < .001) and progression‐free survival (HR 1.54, P < .001) in multivariate analysis. In patients undergoing front‐line autologous stem cell transplantation (auto SCT), CCI >0 was associated with inferior OS (HR 2.40, P = .013). Chemotherapy regimens were classified as curative or low‐intensity treatments. Among patients aged ≥75 years (n = 214), low‐intensity and curative treatment groups had similar OS (HR 0.8, P = .6), also when adjusted for CCI. In summary, our results demonstrate CCI to be independently associated with survival in PTCLs. Even limited comorbidity impacted survival after front‐line auto SCT, which needs to be considered in treatment decisions. Intensive anthracycline‐based chemotherapy in elderly PTCL patients might be of limited benefit.     

Frailty Index is Associated with Treatment Decisions for Stage I Non-Small Cell Lung Cancer at a High-Burden Safety-Net Hospital

BackgroundLobectomy remains the cornerstone of care for stage I NSCLC while sublobar resection and stereotactic body radiation therapy (SBRT) are reserved for patients with smaller tumors and/or poor operative risk. Herein, we investigate the effect of patient frailty on treatment modality for stage I NSCLC at a safety-net hospital.Patients and MethodsA retrospective chart review was performed of stage I NSCLC patients between 2006 and 2015. Demographics, patient characteristics, and treatment rates were compared to a National Cancer Database cohort of stage 1 NSCLC patients. Patient frailty was assessed using the MSK-FI.ResultsIn our cohort of 304 patients, significantly fewer patient were treated via lobectomy compared to national rates (P < .001). Advanced age (P = .02), lower FEV1 (P < .001) and DLCO (P < .001), not socioeconomic factors, were associated with higher utilization of non-lobectomy (sublobar resection or SBRT). Patients with lower MSK-FI were more likely to receive any surgical treatment (P = .01) and lobectomy (P = .03). Lower MSK-FI was an independent predictor for use of lobectomy over other modalities (OR 0.75, P = .04). MSK-FI (OR 0.64, P = .02), and FEV1 (OR 1.03, P < .001) were independently associated with use of SBRT over any surgery.ConclusionOur safety-net hospital performed fewer lobectomies and lung resections compared to national rates. Patient frailty and clinical factors were associated with use of SBRT or sublobar resection suggesting that the increased illness burden of a safety-net population may drive the lower use of lobectomy. The MSK-FI may help physicians stratify patient risk to guide stage I NSCLC management.     

Primary prophylaxis of invasive fungal infections with posaconazole or itraconazole in patients with acute myeloid leukaemia or high‐risk myelodysplastic syndromes undergoing intensive cytotoxic chemotherapy: A real‐world comparison

This is an observational‐retrospective study comparing the real‐world outcomes associated with posaconazole vs itraconazole as prophylaxis treatments. Two hundred and ninety‐three patient admissions attributable to 174 patients were included in the study. Patients were treated with itraconazole (n = 114 admissions; 39%) or posaconazole (n = 179; 61%). Antifungal prophylaxis failure (APF) due to treatment‐related adverse events (in 34 out of 293 patient admissions; 11.6%) was more frequent in the posaconazole group (6.1% vs 15.1%; P = .024). There were 9 patient admissions for episodes of APF due to probable/proven breakthrough fungal infection (primary endpoint): 6 and 3 in the itraconazole and posaconazole group respectively (5.3% vs 1.7%; P = .095). All of them were associated with invasive pulmonary aspergillosis (IPA). APF was more frequent with itraconazole (65% vs 30%; P < .001), along with failure due to possible/probable/proven IPA (25% vs 10%; P = .002) and overall failure by any of the 3 different causes of prophylaxis failure (70% vs 38%; P < .001). In agreement with clinical trial data, this real‐world evidence supports the use of posaconazole over itraconazole in AML or MDS patients undergoing intensive chemotherapy.     

Quantitative fragment analysis of FLT3-ITD efficiently identifying poor prognostic group with high mutant allele burden or long ITD length

Mutation of the fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD), which is one of the most frequent genetic alterations, strongly contributes to an increased risk of treatment failure and to poor prognosis. In this study, we established quantitative fragment analysis of FLT3-ITD simultaneously measuring mutant allele burden and length, verified the analytical performance and evaluated the clinical significance in adult acute myeloid leukemia (AML) patients. FLT3-ITD was detected in 73 of 363 adult AML patients (20.1%) and high mutant allelic burden (⩾50%, n=13) and long ITD length (⩾70 base pairs, n=15) were significantly associated with inferior overall survival (OS; P=0.002 and 0.005, respectively) and event-free survival (EFS; P=0.004 and 0.007, respectively). FLT3-ITD poor prognostic group was identified as patients with high allele burden or long ITD length (n=24), which revealed significant adverse clinical outcome for both OS (P<0.001) and EFS (P<0.001). In cytogenetically normal AML, even FLT3-ITD low allele burden and short length was associated with poorer OS (P=0.037) and EFS (P=0.044) than wild type, whose influence was overcome when hematopoietic stem cell transplantation was performed. In minimal residual disease monitoring, FLT3-ITD negativity after consolidation therapy was a valuable predictor of better OS (P<0.001) and EFS (P<0.001). FLT3-ITD poor prognostic group with high mutant allele burden or long ITD length is efficiently identified by quantitative fragment analysis.