Clinical Characteristics and Outcomes With Specific BRAF and NRAS Mutations in Patients With Metastatic Melanoma
cancer; survival; Oncology; multicenter; BRAF; clinical features; dabrafenib; dose-escalation trial; improved; mek inhibitor trametinib; melanoma; NRAS; open-label; prognostic factor; selumetinib; stage IV; v600e; vemurafenib
BACKGROUNDHotspot mutations in BRAF and NRAS are the most common somatic events in patients with melanoma. These mutations occur at highly conserved residues, but include several different substitutions. To determine whether specific mutations are clinically important to differentiate, tumor characteristics and clinical outcomes were compared among patients with advanced melanoma with 1) BRAF V600E versus V600K mutations and 2) NRAS exon 1 versus exon 2 mutations. METHODSRetrospective clinical and pathologic data were collected for patients with advanced melanoma with BRAF or NRAS mutations. The demographics, tumor characteristics, and clinical outcomes of the patients were compared to identify significant mutation-specific associations. RESULTSAmong 302 patients with activating BRAF mutations, 76% had BRAF V600E and 24% had V600K substitutions. Compared with V600E, the presence of a V600K mutation was significantly associated with older age (median, 60.0 years vs 44.7 years; P<.001), male sex (80% vs 59%; P=.001), head/neck primary tumor location (30% vs 15%; P=.0026), shorter interval to stage IV disease (0.98 years vs 2.8 years; P=.015), and a shorter overall survival from the time of diagnosis of stage IV disease (median, 2.44 years vs 1.25 years; hazards ratio, 1.68 [P=.014]). Comparison of 136 patients with NRAS exon 1 (18%) and exon 2 (82%) mutations found an association with primary tumor histology (P=.0096) only. CONCLUSIONSThe presence of different substitutions at BRAF V600 correlates with patient demographics, tumor characteristics, and prognosis. These findings demonstrate the presence of mutation-specific clinical differences between different BRAF genotypes in patients with melanoma, and support the incorporation of this information in patient evaluation and clinical trial design. Cancer 2013;119:3821-3829. (c) 2013 American Cancer Society.
Bucheit A D; Syklawer E; Jakob J A; Bassett R L; Curry J L; Gershenwald J E; Kim K B; Hwu P; Lazar A J; Davies M A
Cancer
2013
2013-11
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1002/cncr.28306" target="_blank" rel="noreferrer noopener">10.1002/cncr.28306</a>
Current Advances in the Treatment of BRAF-Mutant Melanoma.
immunotherapy; resistance; BRAF; melanoma; metastatic
Melanoma is the most lethal form of skin cancer. Melanoma is usually curable with surgery if detected early, however, treatment options for patients with metastatic melanoma are limited and the five-year survival rate for metastatic melanoma had been 15-20% before the advent of immunotherapy. Treatment with immune checkpoint inhibitors has increased long-term survival outcomes in patients with advanced melanoma to as high as 50% although individual response can vary greatly. A mutation within the MAPK pathway leads to uncontrollable growth and ultimately develops into cancer. The most common driver mutation that leads to this characteristic overactivation in the MAPK pathway is the B-RAF mutation. Current combinations of BRAF and MEK inhibitors that have demonstrated improved patient outcomes include dabrafenib with trametinib, vemurafenib with cobimetinib or encorafenib with binimetinib. Treatment with BRAF and MEK inhibitors has met challenges as patient responses began to drop due to the development of resistance to these inhibitors which paved the way for development of immunotherapies and other small molecule inhibitor approaches to address this. Resistance to these inhibitors continues to push the need to expand our understanding of novel mechanisms of resistance associated with treatment therapies. This review focuses on the current landscape of how resistance occurs with the chronic use of BRAF and MEK inhibitors in BRAF-mutant melanoma and progress made in the fields of immunotherapies and other small molecules when used alone or in combination with BRAF and MEK inhibitors to delay or circumvent the onset of resistance for patients with stage III/IV BRAF mutant melanoma.
Hima Patel; Yacoub Nour; Mishra Rosalin; White Aaron; Long Yuan; Alanazi Samar; Garrett Joan T
Cancers
2020
2020-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.3390/cancers12020482" target="_blank" rel="noreferrer noopener">10.3390/cancers12020482</a>
From mechanisms to management: translating the neuropathic pain consensus recommendations into clinical practice.
Adult; Female; Aged; Inflammation; Pain Measurement; Comorbidity; Education; Neoplasm Metastasis; Drugs; Perception; Clinical Trials; Middle Age; Sarcoidosis; Analgesics; Drug Therapy; Combination; Antidepressive Agents; Treatment Outcomes; Cancer Patients; Chronic Pain; Treatment Duration; Breast Neoplasms; Visual Analog Scaling; Lung Neoplasms; Melanoma; Rectal Neoplasms; Continuing (Credit); Transdermal Patches; Lidocaine – Administration and Dosage; Analgesics – Administration and Dosage; Analgesics – Adverse Effects; Cytokines – Physiology; Gabapentin – Administration and Dosage; Neural Transmission – Physiology; Neuralgia – Classification; Neuralgia – Drug Therapy; Neuralgia – Physiopathology; Opioid – Administration and Dosage; Peripheral Nervous System – Physiopathology; Tramadol – Administration and Dosage; Tricyclic – Administration and Dosage
Chronic neuropathic pain poses a treatment challenge, and is associated with significant psychologic distress, physical disability, and impaired functioning, which impact the activities of daily living. Efforts to provide relief are often inadequate and/or require polypharmacy. This has spurred interest among researchers and clinicians alike to develop early, intensive treatments that target the molecular and cellular mechanisms involved in pain transduction, transmission, and modulation, or ideally, that prevent neuropathic pain from occurring in the first place. Currently, researchers are attempting to capitalize on our understanding of neuropathic pain pathophysiology to develop drugs that interrupt distinct activities involved in its perpetuation. In this regard, several potential agents (eg, NMDA and AMPA/kainate antagonists) are in phase 2 and 3 clinical trials. In the interim, evolving data and evidence-based neuropathic treatment recommendations provide guidance for selecting first- and second-line medications that alone or in combination offer acceptable neuropathic pain control and allow clinicians to bridge the gap between current knowledge and its application in the clinical setting. Hopefully, as basic and clinical science progresses, further treatment advances and management tools will be found to improve the care of patients who live with neuropathic pain.
Chevlen E; Davies PS; Rhiner M
Journal of the American Academy of Nurse Practitioners
2005
2005-06-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Inguinal lymph node dissection in the era of minimally invasive surgical technology
Background: Inguinal lymph node dissection (ILND) is an essential step in both treatment and staging of several malignancies including penile and vulvar cancers. Various open, video endoscopic, and robotic-assisted techniques have been utilized so far. In this review, we aim to describe available minimally invasive surgical approaches for ILND, and review their outcomes and complications.
Methods: The PubMed, Wiley Online Library, and Science Direct databases were reviewed in February 2020 to find relevant studies published in English within 2000-2020.
Findings: There are different minimally invasive platforms available to accomplish dissection of inguinal nodes without jeopardizing oncological results while minimizing postoperative complications. Video Endoscopic Inguinal Lymphadenectomy and Robotic Video Endoscopic Inguinal Lymphadenectomy are safe and achieve the same nodal yield, a surrogate metric for oncological adequacy. When compared to open technique, Video Endoscopic Inguinal Lymphadenectomy and Robotic Video Endoscopic Inguinal Lymphadenectomy may offer faster postoperative recovery and fewer postoperative complications including wound dehiscence, necrosis, and infection. The relatively high rate and severity of postoperative complications hinders utilization of recommended ILND for oncologic indications. Minimally invasive approaches, using laparoscopic or robotic-assisted platforms, show some promise in reducing the morbidity of this procedure while achieving adequate short and intermediate term oncological outcomes.
Reza Nabavizadeh
Benjamin Petrinec
Behnam Nabavizadeh
Amitabh Singh
Sudhir Rawal
Viraj Master
Urol Oncol
. 2023 Jan;41(1):1-14. doi: 10.1016/j.urolonc.2020.07.026. Epub 2020 Aug 25
2022
English
Inguinal lymph node dissection in the era of minimally invasive surgical technology.
Melanoma; Penile cancer; Endoscopic; Inguinal lymph nodes; Inguinal lymphadenectomy; Minimally invasive; Robotic; Video-assisted; Vulvar cancer
Background: Inguinal lymph node dissection (ILND) is an essential step in both treatment and staging of several malignancies including penile and vulvar cancers. Various open, video endoscopic, and robotic-assisted techniques have been utilized so far. In this review, we aim to describe available minimally invasive surgical approaches for ILND, and review their outcomes and complications.; Methods: The PubMed, Wiley Online Library, and Science Direct databases were reviewed in February 2020 to find relevant studies published in English within 2000-2020.; Findings: There are different minimally invasive platforms available to accomplish dissection of inguinal nodes without jeopardizing oncological results while minimizing postoperative complications. Video Endoscopic Inguinal Lymphadenectomy and Robotic Video Endoscopic Inguinal Lymphadenectomy are safe and achieve the same nodal yield, a surrogate metric for oncological adequacy. When compared to open technique, Video Endoscopic Inguinal Lymphadenectomy and Robotic Video Endoscopic Inguinal Lymphadenectomy may offer faster postoperative recovery and fewer postoperative complications including wound dehiscence, necrosis, and infection. The relatively high rate and severity of postoperative complications hinders utilization of recommended ILND for oncologic indications. Minimally invasive approaches, using laparoscopic or robotic-assisted platforms, show some promise in reducing the morbidity of this procedure while achieving adequate short and intermediate term oncological outcomes. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Nabavizadeh R;Petrinec B;Nabavizadeh B;Singh A;Rawal S;Master VA
Urologic Oncology
2020
2020-08-25
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1016/j.urolonc.2020.07.026" target="_blank" rel="noreferrer noopener">10.1016/j.urolonc.2020.07.026</a>