Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 11 de 11
Filter
1.
Am Soc Clin Oncol Educ Book ; 44(3): e433694, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38781565

ABSTRACT

The management of brain metastases, a potentially devastating complication of advanced cancers, has become increasingly complex with advancements in local and systemic therapies. Improved outcomes and extended survival for patients with metastatic solid tumors have led to a surge in the prevalence and possibly incidence of brain metastases, affecting up to 40% of individuals with solid tumors. Enhanced imaging technologies contribute to more accurate and early detection, shaping the understanding of the intricate landscape of this condition. Traditionally, surgery and radiation stood as the mainstays of treatment because of the limited efficacy of systemic therapies within the brain. However, emerging clinical data, particularly in melanoma, lung, and breast cancers, reveal promising results with novel systemic treatments such as immunotherapy and targeted therapies. Despite the historical exclusion of patients with active brain metastases from clinical trials, a shift is occurring toward a more inclusive approach. This chapter delves into the multifaceted challenges associated with managing brain metastases, with a focus on the evolving landscape of systemic approaches as well as the intricacies of shared decision making, providing a comprehensive overview of the current state and future directions in navigating the complexities of brain metastases management.


Subject(s)
Brain Neoplasms , Disease Management , Humans , Brain Neoplasms/secondary , Brain Neoplasms/therapy , Combined Modality Therapy
2.
Oncologist ; 29(4): e507-e513, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-37971411

ABSTRACT

Prospective and between trial comparisons indicate that first-line treatment with immune checkpoint inhibitors improves survival outcomes compared to first-line therapy with combined BRAF and MEK inhibitors in metastatic melanoma containing BRAFV600E/K mutations. Long-term outcomes for BRAF/MEK inhibition after progression on immunotherapy have not been reported. Moreover, clinical variables associated with outcome from treatment with combined BRAF/MEK inhibition were previously identified in the first-line setting but have not been investigated when targeted therapies are administered after progression on immune therapy. We performed a retrospective single institution analysis of 40 metastatic melanoma patients receiving combined BRAF/MEK inhibitors after progression on an anti-PD-1 or ipilimumab plus nivolumab to assess response rate by RECIST 1.1, progression-free and overall survival (PFS and OS). Pretreatment clinical variables were analyzed for association with OS. Ipilimumab/nivolumab was the first-line immunotherapy regimen in 39 patients (97.5%), and BRAFV600E/K mutations were present in 33 (83%) and 7 (17%) patients, respectively. The median OS from start of BRAF/MEK inhibitors was 20.3 months (1.73-106.4+, 95% CI of median 13.3-30.7). Clinical characteristics associated with worse survival prior to starting BRAF/MEK inhibitors included age > 60 years (median OS 14 vs. 28 months; HR 2.5; 95% CI 0.91-6.87, P = .023), ECOG-PS > 2 (median OS 7 vs. 33 months; HR 2.89; 95% CI 0.78-10.76, P = .018), and presence of bone metastases (median OS 9 vs. 52 months; HR 3.17; 95% CI 1.33-7.54, P = .002). These associations with shorter survival maintained their significance on multivariate analysis. If confirmed in larger cohorts, the identified prognostic variables can be used for stratification of patients in future randomized trials.


Subject(s)
Melanoma , Skin Neoplasms , Humans , Middle Aged , Melanoma/drug therapy , Melanoma/genetics , Melanoma/pathology , Immune Checkpoint Inhibitors/therapeutic use , Ipilimumab/therapeutic use , Proto-Oncogene Proteins B-raf/genetics , Nivolumab/therapeutic use , Retrospective Studies , Prospective Studies , Protein Kinase Inhibitors/therapeutic use , Mitogen-Activated Protein Kinase Kinases , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Skin Neoplasms/drug therapy
3.
Oncologist ; 28(10): e973-e976, 2023 10 03.
Article in English | MEDLINE | ID: mdl-37656608

ABSTRACT

BACKGROUND: HER2 immunohistochemistry (IHC) reproducibility is suboptimal for HER-low cases (IHC 1+ or 2+). METHODS: The Yale cohort included 214 stages I-II estrogen receptor positive breast cancers with IHC scores 0, 1+, and 2+ and routine Oncotype DX Recurrence Score (RS) results. The Exact Sciences (ES) cohort included 9 57 624 patients who had an Oncotype DX RS assay that assigns HER2-negative, equivocal, or positive status based on HER2 mRNA levels. RESULTS: HER2 mRNA levels varied across IHC categories but with increasing medians of 9.10 (n = 89), 9.20 (n = 71), and 9.45 (n = 54) in IHC 0, 1+, and 2+, respectively. 22.4% of HER2-low (1+/2+) cancer had RS > 25. Over 98% of HER-low cancers were HER2-negative by Oncotype DX assignment. CONCLUSIONS: Cancers with higher mRNA levels exist within IHC 0 and low categories, most of the HER2-low patients by IHC have low RS indicating no benefit from current adjuvant chemotherapies.


Subject(s)
Breast Neoplasms , Receptor, ErbB-2 , Humans , Female , Receptor, ErbB-2/genetics , Reverse Transcriptase Polymerase Chain Reaction , Reproducibility of Results , Receptors, Estrogen/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/analysis , Prognosis
4.
Future Oncol ; 19(28): 1945-1951, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37767612

ABSTRACT

Neoadjuvant chemotherapy is widely used in the therapy of stage II-III breast cancers and pathologic complete response (pCR; ypT0/is, ypN0) predicts excellent long-term survival. However, the correlation between improvement in pCR rate and survival is highly variable across trials. A major limitation of pCR is that it does not capture downstaging in patients with residual disease. We previously introduced the residual cancer burden score that measures pathologic response on a continuous scale. Comparison of residual cancer burden score distributions between trial arms reflects treatment efficacy more accurately than differences in pCR rate. We developed the treatment efficacy score as a new statistical metric that appears to be a better surrogate for trial arm-level survival improvement than pCR rate difference.

5.
Breast Cancer Res Treat ; 201(2): 289-298, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37378695

ABSTRACT

PURPOSE: Programmed death-ligand 1 (PD-L1) expression is required for benefit from immune checkpoint inhibitors in metastatic triple negative breast cancer (TNBC). In contrast, in the neoadjuvant setting patients benefited regardless of PD-L1 expression. We hypothesized that, in stages II-III breast cancers, low levels of PD-L1 expression may be sufficient to confer sensitivity to therapy and focal expression could be missed by a biopsy. METHODS: In this study, we examined intratumor spatial heterogeneity of PD-L1 protein expression in multiple biopsies from different regions of breast cancers in 57 primary breast tumors (n = 33 TNBC, n = 19 estrogen receptor-positive [ER-positive], n = 5 human epidermal receptor 2-positive [HER2 +]). E1L3N antibody was used to assess PD-L1 status and staining was scored using the combined positivity score (CPS) with PD-L1 positive defined as CPS ≥ 10. RESULTS: Overall, 19% (11/57) of tumors were PD-L1 positive based on positivity in at least 1 biopsy. Among TNBC, PD-L1 positivity was 27% (9/33). The discordance rate, defined as the same tumor yielding PD-L1 positive and negative samples in different regions, was 16% (n = 9) in the whole study population and 23% (n = 7) in TNBC. Cohen's kappa coefficient of agreement was 0.214 for the whole study and 0.239 for TNBC, both of which falling into a non-statistically significant fair agreement range. Among all PD-L1 positive cases, 82% (n = 9/11) had positivity in only one of the tissue assessments. CONCLUSION: These results indicate that the overall 84% concordance is driven by concordant negative results. In PD-L1 positive cancers, within-tumor heterogeneity in PD-L1 expression exists.


Subject(s)
B7-H1 Antigen , Triple Negative Breast Neoplasms , Humans , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , Triple Negative Breast Neoplasms/metabolism , Biomarkers, Tumor/metabolism , Biopsy
6.
Br J Cancer ; 128(3): 459-460, 2023 02.
Article in English | MEDLINE | ID: mdl-36216884

ABSTRACT

Recent technological advances uncovered intricate biological processes underlying intratumor heterogeneity with clinical implications. These insights led to novel biomarkers for immunotherapies, justified serial tumour biopsies for therapeutic target profiling, inspired new treatment strategies, and ultimately might yield novel therapeutics that target clonal interdependence.


Subject(s)
Neoplasms , Humans , Neoplasms/therapy , Neoplasms/drug therapy , Genetic Heterogeneity
7.
Adv Cancer Res ; 155: 215-244, 2022.
Article in English | MEDLINE | ID: mdl-35779875

ABSTRACT

Cancer therapeutics are dynamically evolving, and include traditional chemotherapy and hormone therapy, as well as more recently developed treatment modalities, such as tyrosine kinase inhibitors, monoclonal antibodies and the revolutionary approach based on immune checkpoint inhibition. These regimens are unfortunately not free of adverse events, and patients with cancer are a susceptible population experiencing a myriad of disease and treatment toxicities combined. In this review, we present the latest overview of the management of the most common systemic cancer treatment symptoms and the science of symptom management supporting these strategies. We discuss cancer-related cognitive impairment, ocular toxicity, ototoxicity, oral mucosal toxicities, gastrointestinal toxicities, renal toxicity, aromatase inhibitor-induced musculoskeletal symptoms, chemotherapy-induced peripheral neuropathy, and immunotherapy-induced autoimmunity derived from systemic therapies for cancer. In summary, we review the future directions and ideal goals of symptom science research in order to benefit patients utilizing a comprehensive individualized approach.


Subject(s)
Antineoplastic Agents, Immunological , Drug-Related Side Effects and Adverse Reactions , Immunotherapy , Neoplasms , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/therapeutic use , Drug-Related Side Effects and Adverse Reactions/prevention & control , Humans , Immunotherapy/adverse effects , Neoplasms/therapy
8.
Clin Cancer Res ; 28(17): 3720-3728, 2022 09 01.
Article in English | MEDLINE | ID: mdl-35903931

ABSTRACT

PURPOSE: The incidence of triple-negative breast cancer (TNBC) is higher among Black or African American (AA) women, yet they are underrepresented in clinical trials. To evaluate safety and efficacy of durvalumab concurrent with neoadjuvant chemotherapy for stage I-III TNBC by race, we enrolled additional AA patients to a Phase I/II clinical trial. PATIENTS AND METHODS: Our study population included 67 patients. The primary efficacy endpoint was pathologic complete response (pCR; ypT0/is, N0) rate. χ2 tests were used to evaluate associations between race and baseline characteristics. Cox proportional hazards models were used to assess association between race and overall survival (OS) and event-free survival (EFS). Multivariate logistic regression analyses were used to evaluate associations between race and pCR, immune-related adverse events (irAE) and recurrence. RESULTS: Twenty-one patients (31%) self-identified as AA. No significant associations between race and baseline tumor stage (P = 0.40), PD-L1 status (0.92), and stromal tumor-infiltrating lymphocyte (sTIL) count (P = 0.57) were observed. pCR rates were similar between AA (43%) and non-AA patients (48%; P = 0.71). Three-year EFS rates were 78.3% and 71.4% in non-AA and AA patients, respectively [HR, 1.451; 95% confidence interval (CI), 0.524-4.017; P = 0.474]; 3-year OS was 87% and 81%, respectively (HR, 1.72; 95% CI, 0.481-6.136; P = 0.405). The incidence of irAEs was similar between AA and non-AA patients and no significant associations were found between irAEs and pathologic response. CONCLUSIONS: pCR rates, 3-year OS and EFS after neoadjuvant immunotherapy and chemotherapy were similar in AA and non-AA patients. Toxicities, including the frequency of irAEs, were also similar.


Subject(s)
Breast Neoplasms , Triple Negative Breast Neoplasms , Antibodies, Monoclonal , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biomarkers , Breast Neoplasms/drug therapy , Female , Humans , Neoadjuvant Therapy , Triple Negative Breast Neoplasms/pathology
9.
Curr Oncol ; 29(1): 383-391, 2022 01 16.
Article in English | MEDLINE | ID: mdl-35049708

ABSTRACT

Metastatic breast cancer (MBC) patient outcomes may vary according to distinct health care payers and different countries. We compared 291 Alberta (AB), Canada and 9429 US patients < 65 with de novo MBC diagnosed from 2010 through 2014. Data were extracted from the provincial Breast Data Mart and from the National Cancer Institute's SEER program. US patients were divided by insurance status (US privately insured, US Medicaid or US uninsured). Kaplan-Meier and log-rank analyses were used to assess differences in OS and hazard ratios (HR) were estimated using Cox models. Multivariate models were adjusted for age, surgical status, and biomarker profile. No difference in OS was noted between AB and US patients (HR = 0.92 (0.77-1.10), p = 0.365). Median OS was not reached for the US privately insured and AB groups, and was 11 months and 8 months for the US Medicaid and US uninsured groups, respectively. The 3-year OS rates were comparable between US privately insured and AB groups (53.28% (51.95-54.59) and 55.54% (49.49-61.16), respectively). Both groups had improved survival (p < 0.001) relative to the US Medicaid and US uninsured groups [39.32% (37.25-41.37) and 40.53% (36.20-44.81)]. Our study suggests that a universal health care system is not inferior to a private insurance-based model for de novo MBC.


Subject(s)
Breast Neoplasms , Alberta , Female , Humans , Insurance Coverage , Medicaid , Medically Uninsured , United States
10.
BMC Pulm Med ; 22(1): 11, 2022 Jan 06.
Article in English | MEDLINE | ID: mdl-34986814

ABSTRACT

BACKGROUND: Cancer-associated pulmonary embolism (PE) places a significant burden on patients and health care systems. METHODS: A retrospective cross-sectional analysis of the National Inpatient Sample (NIS) database was performed in patients with acute PE from 2002 to 2014. Among patients hospitalized with PE, we investigated the differences in clinical outcomes and healthcare utilization in patients with and without cancer. A multivariate logistic regression model was applied to calculate adjusted odds ratios (OR) to estimate the impact of cancer on clinical outcomes. Wilcoxon rank sum tests were used to determine the differences in healthcare utilization between the two cohorts. RESULTS: Among 3,313,044 patients who were discharged with a diagnosis of acute PE, 84.2% did not have cancer, while 15.8% had cancer as a comorbidity (56% metastatic cancer, 35% solid tumor without metastasis, and 9% lymphoma). Patients with cancer had a higher mean age but lower rates of common comorbidities except for coagulation deficiency than patients without a cancer diagnosis. In patients with cancer, the rate of IVC filter placement was higher (21.7% vs. 13.11%, OR 1.76 (95% CI 1.73-1.79); p < 0.0001) and thrombolytic use lower (1.34% vs. 2.15%, OR 0.68 (95% CI 0.64-0.72); p < 0.0001). Patients with cancer hospitalized for PE had a higher all-cause in-hospital mortality (11.8% vs. 6.6%, OR 1.79 (95% CI 1.75-1.83); p < 0.0001), longer length of stay (6 vs. 5 days; p < 0.0001), higher total charge per hospitalization ($30,885 vs. $27,273; p < 0.0001), and higher rates of home health services upon discharge (35.8% vs. 23.2%; p < 0.0001) compared with those without cancer. CONCLUSION: Concurrent cancer diagnosis in patients hospitalized for acute PE was associated with a 90% increase in all-cause mortality, longer length of stay, higher total charge per hospitalization, and higher rates of home health services upon discharge. The majority (56%) of patients with cancer had metastatic disease. Furthermore, there were identifiable differences in the intervention for acute PE between the two groups.


Subject(s)
Neoplasms/complications , Pulmonary Embolism/complications , Pulmonary Embolism/epidemiology , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Databases, Factual , Female , Hospital Mortality , Humans , Male , Middle Aged , Neoplasms/epidemiology , Retrospective Studies , Risk Factors , Treatment Outcome , United States/epidemiology
11.
Case Rep Oncol Med ; 2019: 7183747, 2019.
Article in English | MEDLINE | ID: mdl-31781445

ABSTRACT

INTRODUCTION: The management of patients with advanced malignancies is challenging, although recent advances with immunotherapy have shown better outcomes. Pembrolizumab has been associated with a variety of immune-related side effects, but the occurrence of aseptic meningitis is rare. CASE: A 55-year-old male with a history of metastatic lung adenocarcinoma previously treated with pembrolizumab presented with persistent severe headaches and photophobia. Subsequent workup with cerebrospinal fluid analysis showed elevated opening pressure, increased nucleated cells with 30% lymphocytes, elevated protein levels, and normal glucose levels. The patient was started on high doses of IV steroids and progressed with significant improvement of his symptoms. DISCUSSION: Given the rarity of this side effect, this case is a reminder that immune checkpoint inhibitors can cause aseptic meningitis and its early recognition is important for initiation of therapy with steroids and prompt discontinuation of the immunotherapy agent.

SELECTION OF CITATIONS
SEARCH DETAIL
...