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Presenter : Louis Burt Nabors

Optimizing treatment for patients with low-grade gliomas should focus on the role of radiation and chemotherapy, as well as the prognostic impact of molecular diagnostics (1p/19q and IDH status). For anaplastic oligodendroglioma, focus should be placed on molecular markers (particularly 1p/19q status) and combination treatment with chemotherapy (temozolomide or PCV [procarbazine, lomustine, and vincristine]) and radiation. For patients with malignant glioblastomas, the role of methylguanine methyl-transferase (MGMT) methylation status has become increasingly important to treatment decisions. MGMT methylation status should be considered in elderly patients and/or those with low performance status (methylated patients benefit from temozolomide) and a hypofractionated radiation schedule should be used.

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Presenters : Chad A. LaGrange, M. Dror Michaelson and Colleen H. Tetzlaff

A number of therapeutic options are available for the treatment of advanced kidney cancer, including targeted therapy, immunotherapy, and nephrectomy. Choice of therapy for advanced kidney cancer is guided by risk stratification. Immunotherapy combinations are generally superior to vascular endothelial growth factor -based monotherapy, and overall survival rates continue to increase substantially. With new systemic therapy options, additional improvements have been noted in durable responses to treatment and in quality of life. Nephrectomy remains an important consideration in selected patients, particularly those with minimal burden of metastatic disease. Managing the adverse events of treatment of advanced kidney cancer requires close attention and multidisciplinary collaboration.

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Presenter : Robert W. Carlson

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Presenter : Eunice S. Wang

Acute myeloid leukemia (AML) remains difficult and challenging to treat. Recognition that AML is a genomically heterogeneous disease has given rise to several new targeted therapies (eg, inhibitors of FLT3 and IDH1/2). Because the genomic landscape of AML evolves as the disease progresses, genomic testing is advised at diagnosis and at recurrence or relapse. In addition to targeted inhibitors, several emerging therapies directed at immune responses and p53 are on the horizon. Despite these advances, the 5-year overall survival rate for AML is 28.3%. The hope is that novel combinations and emerging strategies will move the survival bar higher for patients with AML in the near future.

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Presenter : Robert I. Haddad

Immunotherapy has changed the game in the treatment of head and neck cancer (HNC). Practice-changing results from the phase III KEYNOTE-048 trial led to the approval of pembrolizumab immunotherapy alone or in combination with chemotherapy for the treatment of recurrent/metastatic HNC in the first-line setting. Testing for combined positive score (CPS) is now part of routine practice, because patients with CPS ≥1 can be started on single-agent immunotherapy in the first-line. Pembrolizumab replaces the “old” standard of care established by the EXTREME study, as trials looking at targets besides immunotherapy have proved “disappointing.” Additionally, nivolumab and pembrolizumab are both approved for use in the second-line.

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Presenter : William J. Gradishar

Systemic treatment for metastatic breast cancer now incorporates many targeted agents and a plethora of combinations specific to the breast cancer subtype. New to the treatment paradigm are fam-trastuzumab deruxtecan-nxki, and tucatinib for HER2-positive disease; the PI3K inhibitor alpelisib in combination with fulvestrant for estrogen receptor–positive and PIK3CA-mutated tumors; PARP inhibitors for patients with germline BRCA1/2 mutations; and the anti–PD-L1 agent atezolizumab in combination with albumin-bound paclitaxel for triple-negative disease with PD-L1 mutations in tumors. In addition, for estrogen receptor–positive disease, the role of CDK4/6 inhibitors increased substantially during the past year, as overall survival results have emerged. These targeted agents are greatly improving patient outcomes, and thus have all been incorporated into the NCCN Guidelines for Breast Cancer.

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Presenter : Sandy Srinivas

Numerous new options are available for the treatment of prostate cancer when it progresses beyond localized disease. Older drugs, first developed for treatment of metastatic castration-resistant prostate cancer (CRPC), are being used to treat nonmetastatic disease based on results of large randomized controlled trials. Sequencing of available treatment options is challenging for CRPC, but there is some guidance from trial data. Cross-resistance among newer hormonal drugs is a concern, and therefore switching to another class of drug is preferred. Emerging treatments on the horizon, such as PARP inhibitors in patients with BRCA2 mutations and lutetium-177 in those with prostate-specific membrane antigen (PSMA)–positive disease, may look promising to improve outcomes among those with advanced prostate cancer.

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Presenter : Gregory J. Riely

Non–small cell lung cancer (NSCLC) can no longer be considered as one disease, nor can it be treated as one. Understanding tumor histology in NSCLC is critical to understanding optimal biomarker evaluation and initial therapy. Proper biomarker evaluation includes both evaluation of PD-L1 status, as well as testing for actionable oncogenic drivers such as EGFR, ALK, ROS1, BRAF, Met Exon 14, RET, and NTRK. For patients with NSCLC and a driver oncogene, preferred treatment is targeted therapy. Conversely, for those without an oncogenic driver, preferred initial treatment is pembrolizumab in combination with chemotherapy for patients with low PD-L1 expression (1%–49%) or as a single-agent for high PD-L1 expression (≥50%). For small cell lung cancer (SCLC), the first major NCCN Guideline changes occurred in 2019, with the addition of either atezolizumab or durvalumab to platinum-based chemotherapy and etoposide as first-line therapy for patients with extensive-stage SCLC.

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Presenter : Christopher G. Willett

Excellent long-term outcomes and manageable toxicity are being achieved with contemporary treatment strategies for rectal cancer. Short-course radiotherapy is now an acceptable standard. Total neoadjuvant therapy (TNT), which incorporates induction or consolidation chemotherapy, has improved the delivery of treatment regiments. TNT is now a standard of care, although the sequencing of radiation and chemotherapy in TNT, appropriate amount of chemotherapy in TNT, and addition of irinotecan to the regimen are still being debated. Nonoperative management of rectal cancer appears to be a safe option for select patients, but it is not yet an NCCN recommendation. In addition, the omission of radiation is being evaluated as a treatment option in some cases.

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Presenter : Jennifer J.D. Morrissette

Next-generation sequencing (NGS), also known as massively parallel sequencing (MPS), offers broad detection of genetic alterations that, in approximately one-third of patients with cancer, are “actionable,” meaning that they can be targeted by available therapeutics or the detection of the alteration can lead to a change in therapy. NGS is useful in the diagnosis of patients, determining their prognosis, appropriate treatment selection, and clinical trial enrollment. Many testing panels are available, each with different abilities to detect various mutation types. Clinicians not only have to decide which test to use, but which specimen to test, and when and how often to test. Aside from unique mutations, immunotherapy markers have become important for the use of checkpoint inhibitors, and their detection and interpretation can also be challenging. Efforts are underway to simplify and validate these assays. Meanwhile, clinicians should become educated about the benefit of, means of, and interpretation of genomic testing patients across the disease course.