ABSTRACT

BACKGROUND: Few data are available on the impact of venous thrombotic events (VTE) in patients with metastatic non-small cell lung cancer (mNSCLC) treated with immunotherapy.

METHODS: This is a secondary analysis of the ESKEYP study, a national, retrospective, multicenter study that consecutively included all PD-L1 ≥ 50% mNSCLC patients who initiated first-line treatment with pembrolizumab monotherapy. From May 2017 to November 2019, 845 patients were included (from availability of pembrolizumab in this indication in France to the authorization of the combination with chemotherapy). Impact of VTE and patient characteristics were analyzed.

RESULTS: Of the 748 patients (88.5%) with available data, the incidence of VTE was 14.8% (111/748). At pembrolizumab initiation, Khorana score was ≥ 2 for 55.0% (61/111) of them. Recurrence of VTE was reported for 4 of the 111 patients and 5 had bleeding complications. Patients with VTE were significantly younger, had more frequently long-term corticosteroids treatment and more often liver metastases. Progression-free survival (PFS) was significantly shorter in patients with VTE compared to patients without VTE: 6.1 (95% CI 4.1-9.0) months vs. 8.3 (6.9-10.3) months (p = 0.03). VTE did not significantly impact overall survival (OS): 15.2 (10.0-24.7) months with VTE and 22.6 (18.4-29.8) months without VTE (p = 0.07). In multivariate analysis for PFS and OS, HRs for VTE were 1.3 (0.99-1.71), p = 0.06 and 1.32 (0.99-1.76), p = 0.05.

CONCLUSION: The incidence of VTE appears to be as high with in first-line immunotherapy as with chemotherapy in patients with mNSCLC, with in patient with VTE, a no significant trend for lower PFS and OS in multivariate analysis. more marked impact on PFS than on OS.

PMID:37626173 | DOI:10.1007/s00432-023-05321-w

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PubMed articles on: Cancer & VTE/PE

LM02 trial Perioperative treatment with panitumumab and FOLFIRI in patients with wild-type RAS, potentially resectable colorectal cancer liver metastases-a phase II study

Front Oncol. 2023 Aug 9;13:1231600. doi: 10.3389/fonc.2023.1231600. eCollection 2023.

ABSTRACT

BACKGROUND: Twenty percent of colorectal cancer liver metastases (CLMs) are initially resectable with a 5-year survival rate of 25%-40%. Perioperative folinic acid, 5-fluorouracil, oxaliplatin (FOLFOX) increases progression-free survival (PFS). In advanced disease, the addition of targeting therapies results in an overall survival (OS) advantage. The aim of this study was to evaluate panitumumab and FOLFIRI as perioperative therapy in resectable CLM.

METHODS: Patients with previously untreated, wild-type Rat sarcoma virus (RAS), and resectable CLM were included. Preoperative four and postoperative eight cycles of panitumumab and folinic acid, 5-fluorouracil, irinotecan (FOLFIRI) were administered. Primary objectives were efficacy and safety. Secondary endpoints included PFS and OS.

RESULTS: We enrolled 36 patients in seven centers in Austria (intention-to-treat analyses, 35 patients). There were 28 men and seven women, and the median age was 66 years. About 91.4% completed preoperative therapy and 82.9% underwent liver resection. The R0 resection rate was 82.7%. Twenty patients started and 12 patients completed postoperative chemotherapy. The objective radiological response rate after preoperative therapy was 65.7%. About 20% and 5.7% of patients had stable disease and progressive disease, respectively. The most common grade 3 adverse events were diarrhea, rash, and leukopenia during preoperative therapy. One patient died because of sepsis, and one had a pulmonary embolism grade 4. After surgery, two patients died because of hepatic failure. Most common grade 3 adverse events during postoperative therapy were skin toxicities/rash and leukopenia/neutropenia, and the two grade 4 adverse events were stroke and intestinal obstruction. Median PFS was 13.2 months. The OS rate at 12 and 24 months were 85.6% and 73.3%, respectively.

CONCLUSIONS: Panitumumab and FOLFIRI as perioperative therapy for resectable CLM result in a radiological objective response rate in 65.7% of patients with a manageable grade 3 diarrhea rate of 14.3%. Median PFS was 13.2 months, and the 24-month OS rate was 73.3%. These data are insufficient to widen the indication of panitumumab from the unresectable setting to the setting of resectable CLM.

PMID:37621684 | PMC:PMC10446765 | DOI:10.3389/fonc.2023.1231600

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PubMed articles on: Cancer & VTE/PE

Prediction of Venous Thromboembolism in Patients With Cancer Using Machine Learning Approaches: A Systematic Review and Meta-Analysis

05:46

PubMed articles on: Cancer & VTE/PE

No evidence for a genetic causal effect of breast cancer on venous thromboembolism: a mendelian randomization study

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PubMed articles on: Cancer & VTE/PE

Reply to "Is venous thromboembolism a time-dependent event in breast cancer patients taking tamoxifen?"

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PubMed articles on: Cancer & VTE/PE

Evaluation of anti-Xa levels in patients with venous thromboembolism within the first 48 h of anticoagulation with unfractionated heparin

05:46

PubMed articles on: Cancer & VTE/PE

Non-bacterial Thrombotic Endocarditis Related to Squamous Cell Carcinoma of the Cervix

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PubMed articles on: Cardio-Oncology

Cell membrane-camouflaged bufalin targets NOD2 and overcomes multidrug resistance in pancreatic cancer

Drug Resist Updat. 2023 Aug 21;71:101005. doi: 10.1016/j.drup.2023.101005. Online ahead of print.

ABSTRACT

AIMS: Multidrug resistance in pancreatic cancer poses a significant challenge in clinical treatment. Bufalin (BA), a compound found in secretions from the glands of toads, may help overcome this problem. However, severe cardiotoxicity thus far has hindered its clinical application. Hence, the present study aimed to develop a cell membrane-camouflaged and BA-loaded polylactic-co-glycolic acid nanoparticle (CBAP) and assess its potential to counter chemoresistance in pancreatic cancer.

METHODS: The toxicity of CBAP was evaluated by electrocardiogram, body weight, distress score, and nesting behavior of mice. In addition, the anticarcinoma activity and underlying mechanism were investigated both in vitro and in vivo.

RESULTS: CBAP significantly mitigated BA-mediated acute cardiotoxicity and enhanced the sensitivity of pancreatic cancer to several clinical drugs, such as gemcitabine, 5-fluorouracil, and FOLFIRINOX. Mechanistically, CBAP directly bound to nucleotide-binding and oligomerization domain containing protein 2 (NOD2) and inhibited the expression of nuclear factor kappa-light-chain-enhancer of activated B cells. This inhibits the expression of ATP-binding cassette transporters, which are responsible for chemoresistance in cancer cells.

CONCLUSIONS: Our findings indicate that CBAP directly inhibits NOD2. Combining CBAP with standard-of-care chemotherapeutics represents a safe and efficient strategy for the treatment of pancreatic cancer.

PMID:37647746 | DOI:10.1016/j.drup.2023.101005

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PubMed articles on: Cardio-Oncology

Anti-breast cancer-induced cardiomyopathy: Mechanisms and future directions

Biomed Pharmacother. 2023 Aug 28;166:115373. doi: 10.1016/j.biopha.2023.115373. Online ahead of print.

ABSTRACT

With the progression of tumor treatment, the 5-year survival rate of breast cancer is close to 90%. Cardiovascular toxicity caused by chemotherapy has become a vital factor affecting the survival of patients with breast cancer. Anthracyclines, such as doxorubicin, are still some of the most effective chemotherapeutic agents, but their resulting cardiotoxicity is generally considered to be progressive and irreversible. In addition to anthracyclines, platinum- and alkyl-based antitumor drugs also demonstrate certain cardiotoxic effects. Targeted drugs have always been considered a relatively safe option. However, in recent years, some random clinical trials have observed the occurrence of subclinical cardiotoxicity in targeted antitumor drug users, which may be related to the effects of targeted drugs on the angiotensin converting enzyme, angiotensin receptor and β receptor. The use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and beta-blockers may prevent clinical cardiotoxicity. This article reviews the toxicity and mechanisms of current clinical anti-breast cancer drugs and proposes strategies for preventing cardiovascular toxicity to provide recommendations for the clinical prevention and treatment of chemotherapy-related cardiomyopathy.

PMID:37647693 | DOI:10.1016/j.biopha.2023.115373

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PubMed articles on: Cardio-Oncology

Heterotopia of salivary gland tissue in the pancreas

Diagn Pathol. 2023 Aug 30;18(1):98. doi: 10.1186/s13000-023-01385-x.

ABSTRACT

Heterotopia of the salivary gland occurs mainly in the head and neck region of the human body, rarely in regions such as the rectum, but has never been demonstrated in the pancreas. Within a screening effort of pancreatic samples for detecting ΔNp63 expression, we discovered two pancreatic samples from a 35-year-old male showing salivary gland heterotopia. Immunohistochemical stainings were done for markers of healthy and neoplastic salivary glands and showed expression of calponin, CD142 and KRT14 but not of S100p, GFAP or CD117. A PAS-staining and Alcian Blue staining showed the presence of acid mucins. These staining patterns were consistent with non-neoplastic submandibular gland tissue comprised of abundant seromucous glands, basal cells and myoepithelial cells, all features typically absent in the pancreas. Also, no pancreatic islets of Langerhans were detected. We show for the first time that salivary gland heterotopia can occur at the location of the pancreas.

PMID:37649044 | DOI:10.1186/s13000-023-01385-x

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PubMed articles on: Cardio-Oncology

Radiation therapy in the thoracic region: Radio-induced cardiovascular disease, cardiac delineation and sparing, cardiac dose constraints, and cardiac implantable electronic devices

Cancer Radiother. 2023 Aug 28:S1278-3218(23)00138-5. doi: 10.1016/j.canrad.2023.06.027. Online ahead of print.

ABSTRACT

Radiation therapy in the thoracic region may deliver incidental ionizing radiation to the surrounding healthy structures, including the heart. Radio-induced heart toxicity has long been a concern in breast cancer and Hodgkin's lymphoma and was deemed a long-term event. However, recent data highlight the need to limit the dose to the heart in less favorable thoracic cancers too, such as lung and esophageal cancers in which incidental irradiation led to increased mortality. This article will summarize available cardiac dose constraints in various clinical settings and the types of radio-induced cardiovascular diseases encountered as well as delineation of cardiac subheadings and management of cardiac devices. Although still not completely deciphered, heart dose constraints remain intensively investigated and the mean dose to the heart is no longer the only dosimetric parameter to consider since the left anterior descending artery as well as the left ventricle should also be part of dosimetry constraints.

PMID:37648559 | DOI:10.1016/j.canrad.2023.06.027

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PubMed articles on: Cardio-Oncology

Role of echocardiography in patients treated with immune checkpoints inhibitors

J Echocardiogr. 2023 Aug 30. doi: 10.1007/s12574-023-00621-z. Online ahead of print.

ABSTRACT

Immune-related adverse events occurring in the heart (cardiac immune-related adverse events; irAEs) by immune checkpoint inhibitors (ICIs) include myocarditis, arrhythmia, conduction disturbance, pericardial diseases, and takotsubo cardiomyopathy. Cardiac irAEs are rare but life-threatening. In cardio-oncology, the study of cardiac disorders caused by cancer treatment has recently attracted attention, and such studies may elucidate the pathophysiology of cardiac irAEs and contribute to management strategies. This review discusses the pathogenic mechanisms underlying cardiac irAEs and the role of echocardiography in patients treated with ICIs.

PMID:37644319 | DOI:10.1007/s12574-023-00621-z

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Trastuzumab and ECG Changes Dilemma

Int J Hematol Oncol Stem Cell Res. 2023 Apr 1;17(2):63-64. doi: 10.18502/ijhoscr.v17i2.12641.

NO ABSTRACT

PMID:37637771 | PMC:PMC10452953 | DOI:10.18502/ijhoscr.v17i2.12641

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PubMed articles on: Cardio-Oncology

Challenges in Cardiovascular Imaging in Women with Breast Cancer

Curr Cardiol Rep. 2023 Aug 29. doi: 10.1007/s11886-023-01941-3. Online ahead of print.

ABSTRACT

Cardiovascular imaging in breast cancer patients is paramount for the surveillance of cancer therapy-related cardiac dysfunction (CTRCD); however, it comes with specific limitations. PURPOSE OF REVIEW: This review aims to describe the unique challenges faced in cardiovascular imaging of breast cancer patients, discuss evidence to support the utility of various imaging modalities, and provide solutions for improvement in imaging this unique population. RECENT FINDINGS: Updated clinical society guidelines have introduced more unifying surveillance of CTRCD, although there remains a lack of a universally accepted definition. Traditional and novel multi-modality imaging can be used to detect CTRCD and myocarditis in breast cancer patients. Cardiovascular imaging in breast cancer patients is difficult due to reconstructive surgery. Although echocardiography with myocardial strain is the cornerstone, multi-modality imaging can be used to evaluate for CTRCD and myocarditis. Novel imaging techniques to improve the diagnosis of cardiotoxicities in breast cancer patients are needed.

PMID:37642930 | DOI:10.1007/s11886-023-01941-3

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PubMed articles on: Cardio-Oncology

Nanobiotechnology-based strategies in alleviation of chemotherapy-mediated cardiotoxicity

Environ Res. 2023 Aug 24:116989. doi: 10.1016/j.envres.2023.116989. Online ahead of print.

ABSTRACT

The cardiovascular diseases have been among the most common malignancies and the first leading cause of death, even higher than cancer. The cardiovascular diseases can be developed as a result of cardiac dysfunction and damages to heart tissue. Exposure to toxic agents and chemicals that induce cardiac dysfunction has been of interest in recent years. The chemotherapy drugs are commonly used for cancer therapy and in these patients, cardiovascular diseases have been widely observed that is due to negative impact of chemotherapy drugs on the heart. These drugs increase oxidative damage and inflammation, and mediate apoptosis and cardiac dysfunction. Hence, nanotechnological approaches have been emerged as new strategies in attenuation of chemotherapy-mediated cardiotoxicity. The first advantage of nanoparticles can be explored in targeted and selective delivery of drugs to reduce their accumulation in heart tissue. Nanostructures can deliver bioactive and therapeutic compounds in reducing cardiotoxicity and alleviation toxic impacts of chemotherapy drugs. The functionalization of nanostructures increases their selectivity against tumor cells and reduces accumulation of drugs in heart tissue. The bioplatforms such as chitosan and alginate nanostructures can also deliver chemotherapy drugs and reduce their cardiotoxicity. The function of nanostructures is versatile in reduction of cardiotoxicity by chemotherapy drugs and new kind of platforms is hydrogels that can mediate sustained release of drug to reduce its toxic impacts on heart tissue. The various kinds of nanoplatforms have been developed for alleviation of cardiotoxicity and their future clinical application depends on their biocompatibility. High concentration level of chitosan nanoparticles can stimulate cardiotoxicity. Therefore, if nanotechnology is going to be deployed for drug delivery and reducing cardiotoxicity, the first pre-requirement is to lack toxicity on normal cells and have high biocompatibility.

PMID:37633635 | DOI:10.1016/j.envres.2023.116989

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PubMed articles on: Cancer & VTE/PE

Association of type of oral anticoagulation with risk of bleeding in 45,114 patients with venous thromboembolism during initial and extended treatment-A nationwide register-based study

J Intern Med. 2023 Aug 28. doi: 10.1111/joim.13712. Online ahead of print.

ABSTRACT

BACKGROUND: Safety data for different anticoagulant medications in venous thromboembolism (VTE) are scarce, in particular for extended treatment.

OBJECTIVES: To compare major bleeding rates depending on the choice of anticoagulation during initial (first 6 months) and extended treatment (6 months up to 5 years).

METHODS: A nationwide register-based study including cancer-free patients with a first-time VTE between 2014 and 2020. Cox proportional hazards models were used to compare bleeding rates.

RESULTS: We included 6558 patients on warfarin, 18,196 on rivaroxaban, and 19,498 on apixaban. At 6 months, 4750 (72.4%) remained on warfarin, 11,366 (62.5%) on rivaroxaban, and 11,940 (61.2%) on apixaban. During initial treatment, major bleeding rates were 3.86 (95% CI 3.14-4.58), 2.93 (2.55-3.31), and 1.95 (1.65-2.25) per 100 patient-years for warfarin, rivaroxaban, and apixaban, respectively, yielding adjusted hazard ratios (aHRs) of 0.89 (95% CI 0.71-1.12) for rivaroxaban versus warfarin, 0.55 (0.43-0.71) for apixaban versus warfarin, and 0.62 (0.50-0.76) for apixaban versus rivaroxaban. During extended treatment, major bleeding rates were 1.55 (1.19-1.91), 1.05 (0.85-1.26), and 0.96 (0.78-1.15) per 100 patient-years for warfarin, rivaroxaban, and apixaban, respectively, with aHRs of 0.72 (0.53-0.99) for rivaroxaban versus warfarin, 0.60 (0.44-0.82) for apixaban versus warfarin, and 0.85 (0.64-1.12) for apixaban versus rivaroxaban. Previous bleeding and increasing age were risk factors for bleeding both during initial and extended treatment.

CONCLUSION: Apixaban had a lower bleeding risk than warfarin or rivaroxaban during initial treatment. During extended treatment, bleeding risk was similar for apixaban and rivaroxaban, and higher with warfarin.

PMID:37641391 | DOI:10.1111/joim.13712

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PubMed articles on: Cancer & VTE/PE

Edoxaban for 12 Months Versus 3 Months in Cancer Patients With Isolated Distal Deep Vein Thrombosis (ONCO DVT study): An Open-label, Multicenter, Randomized Clinical Trial

Circulation. 2023 Aug 28. doi: 10.1161/CIRCULATIONAHA.123.066360. Online ahead of print.

ABSTRACT

Background:The optimal duration of anticoagulation therapy for isolated distal deep vein thrombosis (DVT) in patients with cancer is clinically relevant, but the evidence is lacking. The prolonged anticoagulation therapy could have a potential benefit for prevention of thrombotic events, however, it could also increase the risk of bleeding. Methods:In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 60 institutions in Japan, we randomly assigned cancer patients with isolated distal DVT, in a 1-to-1 ratio, to receive either a 12-month or 3-month edoxaban treatment. The primary endpoint was a composite of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death at 12 months. The major secondary endpoint was major bleeding at 12 months, according to the criteria of the International Society on Thrombosis and Hemostasis. The primary hypothesis was that a 12-month edoxaban treatment was superior to a 3-month edoxaban treatment with respect to the primary endpoint. Results:From April 2019 through June 2022, 604 patients were randomized, and after excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group. The mean age was 70.8 years, 28% of the patients were men, and 20% of the patients had symptoms of DVT at baseline. The primary endpoint of a symptomatic recurrent VTE event or VTE-related death occurred in 3 of the 296 patients (1.0%) in the 12-month edoxaban group and in 22 of the 305 (7.2%) in the 3-month edoxaban group (odds ratio, 0.13; 95% CI, 0.03 to 0.44). The major secondary endpoint of major bleeding occurred in 28 of the 296 patients (9.5%) in the 12-month edoxaban group and in 22 of the 305 (7.2%) in the 3-month edoxaban group (odds ratio, 1.34; 95% CI, 0.75 to 2.41). The prespecified subgroups did not affect the estimates on the primary endpoint. Conclusions:In cancer patients with isolated distal DVT, 12 months was superior to 3 months for an edoxaban treatment with respect to the composite outcome of a symptomatic recurrent VTE or VTE-related death.

PMID:37638968 | DOI:10.1161/CIRCULATIONAHA.123.066360

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Sternum Metastases: From Case-Identifying Strategy to Multidisciplinary Management

Diagnostics (Basel). 2023 Aug 17;13(16):2698. doi: 10.3390/diagnostics13162698. ABSTRACTWe aimed to overview the most recent data on sternal metastases from a multidisciplinary approach (diagnosis strategies, outcome, and histological reports). This narrative review based on a PubMed search (between January 2020 and 22 July 2023) using key words such as "sternal", "manubrium", and "metastasis" within the title and/or abstract only included original papers that specifically addressed secondary sternal spreading of cancer in adults, for a total of 48 original articles (14 studies and 34 single case reports). A prior unpublished case in point is also introduced (percutaneous incisional biopsy was used to address a 10 cm sternal tumour upon first admission on an apparently healthy male). The studies (n = 14) may be classified into one of three groups: studies addressing the incidence of bone metastases (including sternum) amid different primary cancers, such as prostate cancer (N = 122 with bone metastases, 83% of them with chest wall metastases), head and neck cancers (N = 3620, 0.8% with bone metastases, and 10.34% of this subgroup with sternum involvement); and glioblastoma (N = 92 with bone metastases, 37% of them with non-vertebral metastases, including the sternum); assessment cohorts, including breast cancer (N = 410; accuracy and sensitivity of PET/CT vs. bone scintigraphy is superior with concern to sternum spreading) and bone metastases of unknown origin (N = 83, including a subgroup with sternum metastases; some features of PET/CT help the differentiation with multiple myeloma); and cohorts with various therapeutic approaches, such as palliative arterial embolization (N = 10), thymic neuroendocrine neoplasia (1/5 detected with sternum metastases), survival rates for sternum metastases vs. non-sternum chest wall involvement (N = 87), oligo-metastatic (sternal) breast cancer (3 studies, N = 16 for all of them), oligo-metastatic head and neck cancer (N = 81), conformal radiotherapy (N = 24,215, including an analysis on sternum spreading), and EBRT followed by MR-HIFU (N = 6). Core data coming from the isolated case reports (N = 34) showed a female to male ratio of 1.6; the females' ages were between 34 and 80 (mean of 57.28) and the males' ages varied between 33 and 79 (average of 58.78) years. The originating tumour profile revealed that the most frequent types were mammary (N = 8, all females) and thyroid (N = 9, both women and men), followed by bladder (N = 3), lung (N = 2), and kidney (N = 2). There was also one case for each of the following: adenoid cystic carcinoma of the jaw, malignant melanoma, caecum MiNEN, a brain and an extracranial meningioma, tongue carcinoma, cholangiocarcinoma, osteosarcoma, and hepatocellular carcinoma. To our knowledge, this is the most complex and the largest analysis of prior published data within the time frame of our methods. These data open up new perspectives of this intricate, dynamic, and challenging domain of sternum metastases. Awareness is a mandatory factor since the patients may have a complex multidisciplinary medical and/or surgical background or they are admitted for the first time with this condition; thus, the convolute puzzle will start from this newly detected sternal lump. Abbreviations: N = number of patients; n = number of studies; PET/CT = positron emission tomography/computed tomography; EVRT = external beam radiotherapy; MR-HIFU = magnetic resonance-guided high-intensity focused ultrasound; MiNEN = mixed neuroendocrine-non-neuroendocrine tumour.

PMID:37627957 | PMC:PMC10453928 | DOI:10.3390/diagnostics13162698

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Venous thrombotic events and impact on outcomes in patients treated with first-line single-agent pembrolizumab in PD-L1 ≥ 50% advanced non small cell lung cancer

J Cancer Res Clin Oncol. 2023 Aug 25. doi: 10.1007/s00432-023-05321-w. Online ahead of print.

ABSTRACT

BACKGROUND: Few data are available on the impact of venous thrombotic events (VTE) in patients with metastatic non-small cell lung cancer (mNSCLC) treated with immunotherapy.

METHODS: This is a secondary analysis of the ESKEYP study, a national, retrospective, multicenter study that consecutively included all PD-L1 ≥ 50% mNSCLC patients who initiated first-line treatment with pembrolizumab monotherapy. From May 2017 to November 2019, 845 patients were included (from availability of pembrolizumab in this indication in France to the authorization of the combination with chemotherapy). Impact of VTE and patient characteristics were analyzed.

RESULTS: Of the 748 patients (88.5%) with available data, the incidence of VTE was 14.8% (111/748). At pembrolizumab initiation, Khorana score was ≥ 2 for 55.0% (61/111) of them. Recurrence of VTE was reported for 4 of the 111 patients and 5 had bleeding complications. Patients with VTE were significantly younger, had more frequently long-term corticosteroids treatment and more often liver metastases. Progression-free survival (PFS) was significantly shorter in patients with VTE compared to patients without VTE: 6.1 (95% CI 4.1-9.0) months vs. 8.3 (6.9-10.3) months (p = 0.03). VTE did not significantly impact overall survival (OS): 15.2 (10.0-24.7) months with VTE and 22.6 (18.4-29.8) months without VTE (p = 0.07). In multivariate analysis for PFS and OS, HRs for VTE were 1.3 (0.99-1.71), p = 0.06 and 1.32 (0.99-1.76), p = 0.05.

CONCLUSION: The incidence of VTE appears to be as high with in first-line immunotherapy as with chemotherapy in patients with mNSCLC, with in patient with VTE, a no significant trend for lower PFS and OS in multivariate analysis. more marked impact on PFS than on OS.

PMID:37626173 | DOI:10.1007/s00432-023-05321-w

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LM02 trial Perioperative treatment with panitumumab and FOLFIRI in patients with wild-type RAS, potentially resectable colorectal cancer liver metastases-a phase II study

Front Oncol. 2023 Aug 9;13:1231600. doi: 10.3389/fonc.2023.1231600. eCollection 2023.

ABSTRACT

BACKGROUND: Twenty percent of colorectal cancer liver metastases (CLMs) are initially resectable with a 5-year survival rate of 25%-40%. Perioperative folinic acid, 5-fluorouracil, oxaliplatin (FOLFOX) increases progression-free survival (PFS). In advanced disease, the addition of targeting therapies results in an overall survival (OS) advantage. The aim of this study was to evaluate panitumumab and FOLFIRI as perioperative therapy in resectable CLM.

METHODS: Patients with previously untreated, wild-type Rat sarcoma virus (RAS), and resectable CLM were included. Preoperative four and postoperative eight cycles of panitumumab and folinic acid, 5-fluorouracil, irinotecan (FOLFIRI) were administered. Primary objectives were efficacy and safety. Secondary endpoints included PFS and OS.

RESULTS: We enrolled 36 patients in seven centers in Austria (intention-to-treat analyses, 35 patients). There were 28 men and seven women, and the median age was 66 years. About 91.4% completed preoperative therapy and 82.9% underwent liver resection. The R0 resection rate was 82.7%. Twenty patients started and 12 patients completed postoperative chemotherapy. The objective radiological response rate after preoperative therapy was 65.7%. About 20% and 5.7% of patients had stable disease and progressive disease, respectively. The most common grade 3 adverse events were diarrhea, rash, and leukopenia during preoperative therapy. One patient died because of sepsis, and one had a pulmonary embolism grade 4. After surgery, two patients died because of hepatic failure. Most common grade 3 adverse events during postoperative therapy were skin toxicities/rash and leukopenia/neutropenia, and the two grade 4 adverse events were stroke and intestinal obstruction. Median PFS was 13.2 months. The OS rate at 12 and 24 months were 85.6% and 73.3%, respectively.

CONCLUSIONS: Panitumumab and FOLFIRI as perioperative therapy for resectable CLM result in a radiological objective response rate in 65.7% of patients with a manageable grade 3 diarrhea rate of 14.3%. Median PFS was 13.2 months, and the 24-month OS rate was 73.3%. These data are insufficient to widen the indication of panitumumab from the unresectable setting to the setting of resectable CLM.

PMID:37621684 | PMC:PMC10446765 | DOI:10.3389/fonc.2023.1231600

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Prediction of Venous Thromboembolism in Patients With Cancer Using Machine Learning Approaches: A Systematic Review and Meta-Analysis

JCO Clin Cancer Inform. 2023 Aug;7:e2300060. doi: 10.1200/CCI.23.00060.