Immune checkpoint inhibitors (ICIs) such as pembrolizumab have revolutionized the treatment of metastatic non-small cell lung cancer (mNSCLC). Beta-adrenergic activation contributes to cancer ...initiation and progression. While non-selective beta-blocker were found to improve the efficacy of ICIs therapy, the role of beta-1 (β
)-selective -blocker (β
B) in lung cancer patients is unknown.
To evaluate the effect of β
B on overall survival (OS) and progression-free survival (PFS) in patients diagnosed with mNSCLC and treated with pembrolizumab.
We performed a retrospective analysis of patients diagnosed with mNSCLC and treated with first-line pembrolizumab at our center.
Of 200 eligible patients, 53 (27%) were pretreated with β
B. Patients in the β
B cohort were older (73 ± 8 vs. 67 ± 10 years, p < 0.001) with a higher prevalence of cardiac risk factors and cardiovascular (CV) diseases including ischemic heart disease (32% vs. 16%, p = 0.010), heart failure (9% vs. 3%, p = 0.043) and atrial fibrillation (23% vs. 3%, p < 0.001). Compared to the non-β
B group, patient pretreated with β
B had a significant shorter median OS (12 vs. 24 months, p = 0.004) and PFS (6 vs. 8 months, p < 0.001). In a multivariate analysis, including all CV risk factors and diseases, the use of baseline β
B was a strong and independent predictor for accelerated disease progression (HR 1.92, 95%CI 1.32-2.79, p < 0.001) and shorter OS (HR 1.8, 95%, CI 1.18-2.75, p = 0.007).
The use of baseline β
B showed a strong and independent association for shorter OS and PFS in patients diagnosed with mNSCLC and treated with pembrolizumab.
Purpose: To prospectively compare two widely used seed implant techniques: pre-planning and intra-operative planning, based on 1 month post-implant CT-based evaluation.
Methods: We report results of ...a detailed 1 month post-operative dosimetric evaluation and comparison between 142 consecutive men with prostate adenocarcinoma treated by the pre-planning methodology and 214 men treated with the real-time, intra-operative seed implant method.
Results: Baseline parameters patient's age, Gleason score, clinical stage, and gland volume were similar in both groups (
p>0.05). Length of physicist time and operating room team time were more than double in the pre-planned group compared to the intra-operative one (205 vs 100 min). Based on day 30 post-implant CT, for patients treated with the pre-planning method, mean V90, V100 and V150 (percent prostate volume receiving 90, 100 and 150% of the prescribed dose) were 67.5, 58.35 and 21.5%, respectively, while for the intra-operative group they were 97.9, 95.2 and 45%, respectively (
p<0.01). Mean D90, expressed as percent of target matched peripheral dose (minimal dose covering 90% of the gland volume) was 53% for the pre-planned group and 114% for the intra-operative group of men (
p<0.01). Short-term morbidity was minimal in both groups and did not correlate with the technique employed.
Conclusions: This large-scale comparison of implant adequacy favours real-time intra-operative method. While all dosimetric parameters are significantly better with this method, no increased early morbidity was noted. Longer-term PSA-based clinical outcome should substantiate our contention of the superiority of the intra-operative method when compared to the pre-planning one.
A 66-year old female with HIV-negative classic Kaposi's sarcoma responded to mTOR targeting by rapamycin. The response was well documented by PET-CT. This case provides supporting evidence that the ...mTOR pathway may be important in the tumorigenesis of KS and that rapamycin may have activity in this disease.
Introduction: Venetoclax (ven) and azacitidine (aza) has become the standard of care for the treatment of patients (pts) with acute myeloid leukemia (AML) who are ineligible for intensive ...chemotherapy on the basis of the phase III VIALE-A trial, which showed prolonged overall survival with ven-aza vs. placebo-aza. Pts with active additional malignancies (AM) at the time of AML diagnosis are often unfit for intensive chemotherapy but are excluded from clinical trials, including VIALE-A. We aim to compare the characteristics and outcomes of AML patients with AM vs without AM (non-AM), all treated in a real world setting. Methods: A retrospective analysis including all AML pts diagnosed between Jan 2019 and Apr 2023 and treated with ven-aza in Tel Aviv Sourasky Medical Center. We defined active malignancy as any malignancy additional to AML that was diagnosed within 2 years prior to or concomitantly with the diagnosis of AML, or receiving active treatment at the time of the diagnosis of AML. We excluded prior MDS, MPN and basal cell or localized squamous cell carcinomas of the skin. We defined patients eligible for registration trial (RTE) as pts meeting the inclusion criteria for the VIALE-A trial. We compared categorical and continuous variables as appropriate, and examined survival outcomes by a Kaplan Meier and Log-Rank test. Event free survival (EFS) was defined as time until treatment failure (2 courses of ven-aza without achievement of response), relapse, or death. Results: We analyzed 113 pts diagnosed with AML and treated with ven-aza. 17 patients had an additional AM; 11 solid and 6 hematological, at the time of AML diagnosis. Six pts had more than one additional malignancy. Six patients had newly diagnosed AM, 6 had AM in remission and were treated with maintenance therapy at the time of AML diagnosis, and 5 had an active relapsed / progressive AM. Five patients received treatment for AM concomitantly or alternating with ven-aza, including surgery, letrozole, olaparib, arabiterone acetate, pazopanib, and trabectedin. We compared the baseline characteristics and outcomes of AML pts with AM to AML pts treated with ven-aza who did not have AM (96 pts, non-AM) and pts who met inclusion criteria for the registration VIALE-A trial (57 pts, RTE). Pts with AM were younger than non-AM pts or RTE pts (11.8% over the age of 75 vs. 67% and 68%; respectively, p<0.001), and had a slightly higher baseline creatinine level than RTE pts (median=1.1 range 0.6-1.4 mg/dL vs. median=0.9 range 0.5-1.3 mg/dL; p=0.01). ECOG functional status, ELN risk category, and baseline cell counts were similar between all groups. Treatment with ven-aza was initiated within a median of 6 days from diagnosis in AM pts (range 1-20). 58.2% of AM pts achieved CR/CRi vs. 57% of non-AM pts and 68% of RTE pts (p=0.9 and p=0.46, respectively). The 30 day mortality rate for AM pts was 17.6% vs 7.3% for non-AM pts (p=0.17) and 3.5% for RTE pts (p=0.07). Causes of early mortality among AM patients were non-responsive/progressive AML (2 pts) and sepsis (1 pt). Overall, 13 of 17 AM pts died, 7 from progressive AML, 3 from progressive additional malignancy and 3 from treatment complications. Six of the AM pts underwent allogeneic stem cell transplant (35%) vs. 14 non-AM pts (14.5%, p=0.07) and 11 RTE pts (19.2%, p=0.19). Median length of follow-up was 23.8 months (95% CI, 12.9-34.7). Overall survival (OS) EFS, and relapse free survival (RFS) were similar between AM and non-AM pts. (Figure 1A). ECOG score other than 0 (p=0.009, HR=2.2 95% CI 1.2-4.1) and secondary AML type (p=0.049, HR=1.8, 95% CI 1.001-3.124) but not AM (p=0.354, HR=1.42, 95% CI 0.67-3.03) were associated with reduced overall survival in a multivariate analysis which included age, sex and ELN risk category. A trend for worse survival outcomes in AM vs. RTE pts was noted (HR=1.82, CI 0.95-3.46 p = 0.068) (Figure 1B). EFS and RFS were similar between AM and RTE pts. Conclusions: Among pts diagnosed with AML and an additional active malignancy, treatment with ven-aza in the real world setting resulted in similar response and survival rates as in patients without active malignancies, but with a trend for worse overall survival and higher early mortality than pts who meet the eligibility criteria of the VIALE-A trial. 21.8% of AM pts were alive at 24 months. These results imply that treatment for AML for pts with active malignancy with ven-aza is feasible, and should not be withheld from these pts.
The occurrence of cutaneous metastatic disease from colorectal cancer is uncommon and typically signifies widespread disease with poor prognosis. Colorectal metastases usually occur within the first ...3 years of follow up, and the median survival of patients after the appearance of cutaneous metastatic lesions is 18 to 20 months. We describe an unusual case of a 60-year-old woman with a metachronous skin lesion as the sole site of metastatic disease, and a relatively long interval between the appearance of skin metastases and death. The woman was found to have an adenocarcinoma of the rectum, a Dukes' C lesion, extending over the entire rectal wall into the perirectal fat; five of eight regional lymph nodes showed metastases. Adjuvant radiotherapy followed by chemotherapy was administered for about 1 year. A subcutaneous lump on the left abdominal wall found 16 months postoperatively was metastatic of rectal origin. A metastatic adenocarcinoma of rectal origin was found in a single left lower axillary node 26 months later. Despite metastatic work-up for the next 2 years, an enlarged and palpated metastatic left inguinal lymph node appeared and was subjected to radiation. Computerized tomography (CT) examination 5 years after the first presentation of the rectal tumor and almost 4 years after the diagnosis of abdominal skin metastases disclosed recurrent pelvic disease with severe left hydronephrosis. Treatment by systemic chemotherapy was partially successful, but she died 8 months after this chemotherapy was initiated.
Background
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer; however, at the potential cost of serious adverse events including cardiac injury.
Objective
To assess the ...baseline and longitudinal changes in high sensitivity-Troponin (hs-Tn) in patients treated with pembrolizumab as a potential predictor for the development of major adverse cardiac events (MACE) and survival.
Methods
We performed a retrospective analysis of cancer patients treated with pembrolizumab at our center. All participants had baseline measurements of hs-TnI prior to initiation of pembrolizumab (T1), with half of the patients performing follow-up measurements at their second encounter for therapy introduction (T2). We first evaluated the prevalence of abnormally elevated serum hs-TnI (> 50 nanogram per liter) at T1 and T2. We then evaluated the predictive value of abnormal levels at T1 or T2 in relation to the development of MACE (composite outcomes of myocarditis, acute coronary syndrome, heart failure, venous thromboembolism, cardiovascular hospitalization and cardiovascular mortality) and all-cause mortality.
Results
Among 135 patients, the mean age was 72 years, predominantly male (61%). Abnormally elevated hs-TnI at T1 was observed in 7 (5%) patients and emerged as a significant independent predictor for MACE (HR 8.1, 95% CI 1.67–37.4,
p
= 0.009) and all-cause mortality (HR 5.37, 95% CI 2.1–13.57,
p
< 0.001). Abnormally elevated hs-TnI at T2 was observed in 8 (11%) patients and emerged as a significant independent predictor for MACE (HR 10.49, 95% CI 1.68–65.5,
p
= 0.009), but not for mortality (
p
= 0.200).
Conclusions
Abnormally elevated baseline and follow-up hs-TnI served as significant independent predictors for MACE, with an increased risk of development being 8–tenfold. Furthermore, elevated baseline hs-TnI showed a predictive value for all-cause mortality.
Graphical abstract
Central illustration: Novel immune checkpoint inhibitor (ICIs) therapy has been found to revolutionize cancer therapy through increased activation of host immune systems to target and reduce tumor burden, but may come at the cost of serious adverse cardiac events. Identification of early biomarkers for the prediction and detection of these events is necessary.
Introduction
Existing prognostic tools for retroperitoneal sarcomas (RPS) utilize parameters that can be accurately determined only postoperatively. This study evaluated the application of the ...neutrophil‐to‐lymphocyte ratio (NLR) and C‐reactive protein (CRP) levels for predicting prognosis in primary RPS.
Materials and Methods
We retrospectively analyzed our database of patients with primary RPS operated between 2008 and 2018. The NLR was calculated from preoperative blood tests and its association with outcomes was determined.
Results
The NLR values of 78 suitable patients were analyzed. Patients were classified in the NLR‐high group if the NLR was ≥2.1. High‐grade tumors were more common in the NLR‐high group (71.6% vs 48%, P = .02). NLR‐high patients had impaired overall survival (OS) and progression‐free survival (PFS) compared to NLR‐low patients (median OS not reached vs 74 months 95% confidence interval CI: 21.6‐126.4, P = .03; median PFS not reached vs 48 months 95% CI: 6.5‐98.6, P = .06, respectively). Multivariate analysis showed statistical significance only for PFS but not for OS (hazard ratio HR = 4.1, P = .03; HR = 2.3, P = .3). Patients with low CRP levels had improved OS and PFS.
Conclusions
The NLR may serve as a preoperative, easily derived marker for prognosis in RPS. Serum biomarkers may prove useful in these large and spatially heterogeneous tumors.
Abstract only
e23544
Background: Abdominal desmoid tumors are locally aggressive, non-metastatic tumors that develop mainly in Familial adenomatous polyposis (FAP) patients, within the mesentery or ...abdominal wall. Understanding and implications of treatment regimens are evolving. We aimed to assess course, treatment and outcomes of FAP and non-FAP abdominal desmoids and their related genetic alterations. Methods: Retrospective cohort study. Demographics, tumor characteristics, oncological and surgical history, complications, genetic-testing and mortality data were retrieved from two tertiary referral centers. Results: Sixty-two patients were identified (46 FAP, 16 non-FAP) with a median follow up of 72.4 months. Thirty-eight patients (61.3%) underwent surgical procedures: twelve urgent and 26 elective. Out of 33 tumor resections, 39.4% recurred. Hormonal therapy, COX-inhibitors, chemotherapy, imatinib and sorafenib were used in 35(56.4%), 30(48.4%), 18(29.1%), 7(11.3%) and 8(12.9%) of patients, respectively, with 2 years progression-free survival of 67.8%, 57.7%, 38.4%, 28.5%, respectively. Only 1/9 patients treated with sorafenib had disease progression after a median follow up of 6.8 months. Forty-one patients (66.1%) suffered complications: bowel obstruction (30.6%), hyperalimentation (14.5%), ureteral obstruction (12.9%), perforation (11.3%), abscess formation (3.2%) and spinal cord compression (3.2%). Two patients died. Non-FAP patients presented with three renal-cell carcinomas and one germ-cell tumor and carried pathogenic mutations in CHEK2, BLM, ERCC5, MSH6 and PALB2. Conclusions: Abdominal desmoids are mostly FAP-related and are associated with severe outcomes. We report a group of non-FAP abdominal desmoids that includes patients with additional cancer-related gene alterations. This interesting group should undergo genetic consultation and be further explored.
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