-
Current Treatment Options in Oncology Jan 2019Melanoma has several clinically and pathologically distinguishable subtypes, which also differ genetically. Mutation patterns vary among different melanoma subtypes, and... (Review)
Review
Melanoma has several clinically and pathologically distinguishable subtypes, which also differ genetically. Mutation patterns vary among different melanoma subtypes, and efficacy of immune-checkpoint inhibitors differs depending on the subtype of melanoma. In spite of the recent revolution of systemic therapies for advanced melanoma, access to innovative agents is still restricted in many countries. This review article aimed to describe the epidemiology and current status of systemic therapies for melanoma in Japan, where melanoma is rare, but access to innovative agents is available. Acral and mucosal melanomas, which are common in Asian populations, predominantly occur in sun-protected areas and share several biological features. Both the melanomas harbor KIT mutation in approximately 15% of the cases; BRAF or NRAS mutation is found in approximately 10-15% of acral melanoma, but these mutations are less frequent in mucosal melanoma. Combined use of BRAF and MEK inhibitors is one of the standards of care for patients with advanced BRAF-mutant melanoma. In patients with melanoma harboring KIT mutation in exon 11 or 13, KIT inhibitors can be a treatment option; however, none of them have been approved in Japan. Immune-checkpoint inhibitors are expected to be less effective against acral and mucosal melanomas because their somatic mutation burden is lower than those in non-acral cutaneous melanomas. A recently completed phase II trial of nivolumab and ipilimumab combination therapy in 30 Japanese patients with melanoma, including seven with acral and 12 with mucosal melanoma, demonstrated an objective response rate of 43%. Regarding oncolytic viruses, canerpaturev (C-REV, also known as HF10) and talimogene laherparepvec (T-VEC) are currently under review in early phase trials. In the adjuvant setting, dabrafenib plus trametinb combination, nivolumab monotherapy, and pembrolizumab monotherapy were approved in July, August, and December 2018 in Japan, respectively. However, most of the adjuvant phase III trials excluded patients with mucosal melanoma. A phase III trial of adjuvant therapy with locoregional interferon (IFN)-β versus surgery alone is ongoing in Japan (JCOG1309, J-FERON), in which IFN-β is injected directly into the site of the primary tumor postoperatively, so that it would be drained through the untreated lymphatic route to the regional node basin. After the recent approval of these new agents, the JCOG1309 trial will be revised to focus on patients with stage II disease. In conclusion, acral and mucosal melanomas have been treated based on the available medical evidence for the treatment of non-acral cutaneous melanomas. Considering the differences in genetic backgrounds and therapeutic efficacy of immunotherapy, specialized therapeutic strategies for these subtypes of melanoma should be established in the future.
Topics: Combined Modality Therapy; Humans; Immunotherapy; Japan; Melanoma; Molecular Targeted Therapy; Randomized Controlled Trials as Topic
PubMed: 30675668
DOI: 10.1007/s11864-019-0607-8 -
Journal of Clinical Oncology : Official... Apr 2016Placing clips in nodes with biopsy-confirmed metastasis before initiating neoadjuvant therapy allows for evaluation of response in breast cancer. Our goal was to...
Improved Axillary Evaluation Following Neoadjuvant Therapy for Patients With Node-Positive Breast Cancer Using Selective Evaluation of Clipped Nodes: Implementation of Targeted Axillary Dissection.
PURPOSE
Placing clips in nodes with biopsy-confirmed metastasis before initiating neoadjuvant therapy allows for evaluation of response in breast cancer. Our goal was to determine if pathologic changes in clipped nodes reflect the status of the nodal basin and if targeted axillary dissection (TAD), which includes sentinel lymph node dissection (SLND) and selective localization and removal of clipped nodes, improves the false-negative rate (FNR) compared with SLND alone.
METHODS
A prospective study of patients with biopsy-confirmed nodal metastases with a clip placed in the sampled node was performed. After neoadjuvant therapy, patients underwent axillary surgery and the pathology of the clipped node was compared with other nodes. Patients undergoing TAD had SLND and selective removal of the clipped node using iodine-125 seed localization. The FNR was determined in patients undergoing complete axillary lymphadenectomy (ALND).
RESULTS
Of 208 patients enrolled in this study, 191 underwent ALND, with residual disease identified in 120 (63%). The clipped node revealed metastases in 115 patients, resulting in an FNR of 4.2% (95% CI, 1.4 to 9.5) for the clipped node. In patients undergoing SLND and ALND (n = 118), the FNR was 10.1% (95% CI, 4.2 to 19.8), which included seven false-negative events in 69 patients with residual disease. Adding evaluation of the clipped node reduced the FNR to 1.4% (95% CI, 0.03 to 7.3; P = .03). The clipped node was not retrieved as an SLN in 23% (31 of 134) of patients, including six with negative SLNs but metastasis in the clipped node. TAD followed by ALND was performed in 85 patients, with an FNR of 2.0% (1 of 50; 95% CI, 0.05 to 10.7).
CONCLUSION
Marking nodes with biopsy-confirmed metastatic disease allows for selective removal and improves pathologic evaluation for residual nodal disease after chemotherapy.
Topics: Adult; Aged; Antineoplastic Agents; Axilla; Breast Neoplasms; Chemotherapy, Adjuvant; False Negative Reactions; Female; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Neoplasm, Residual; Prospective Studies; Sentinel Lymph Node Biopsy
PubMed: 26811528
DOI: 10.1200/JCO.2015.64.0094 -
European Journal of Cancer (Oxford,... Mar 2020Invasive cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in the white populations, accounting for 20% of all cutaneous malignancies. Factors...
Invasive cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in the white populations, accounting for 20% of all cutaneous malignancies. Factors implicated in cSCC etiopathogenesis include ultraviolet radiation exposure and chronic photoaging, age, male sex, immunosuppression, smoking and genetic factors. A collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organisation of Research and Treatment of Cancer (EORTC) was formed to update recommendations on cSCC classification, diagnosis, risk stratification, staging and prevention, based on current literature, staging systems and expert consensus. Common cSCCs are typically indolent tumors, and most have a good prognosis with 5-year cure rates of greater than 90%, and a low rate of metastases (<4%). Further risk stratification into low-risk or high-risk common primary cSCC is recommended based on proposed high-risk factors. Advanced cSCC is classified as locally advanced (lacSCC), and metastatic (mcSCC) including locoregional metastatic or distant metastatic cSCC. Current systems used for staging include the American Joint Committee on Cancer (AJCC) 8th edition, the Union for International Cancer Control (UICC) 8th edition, and Brigham and Women's Hospital (BWH) system. Physical examination for all cSCCs should include total body skin examination and clinical palpation of lymph nodes, especially of the draining basins. Radiologic imaging such as ultrasound of the regional lymph nodes, magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography-computed tomography (PET-CT) scans are recommended for staging of high-risk cSCC. Sentinel lymph node biopsy is currently not recommended. Nicotinamide, oral retinoids, and topical 5-FU have been used for the chemoprevention of subsequent cSCCs in high-risk patients but are not routinely recommended. Education about sun protection measures including reducing sun exposure, use of protective clothing, regular use of sunscreens and avoidance of artificial tanning, is recommended.
Topics: Carcinoma, Squamous Cell; Consensus; Dermatology; Humans; Lymph Nodes; Magnetic Resonance Imaging; Medical Oncology; Neoplasm Staging; Patient Education as Topic; Positron Emission Tomography Computed Tomography; Protective Clothing; Risk Assessment; Skin; Skin Neoplasms; Societies, Medical; Sunlight; Sunscreening Agents; Ultrasonography
PubMed: 32113941
DOI: 10.1016/j.ejca.2020.01.007 -
Seminars in Plastic Surgery Feb 2018Advances in our understanding of the lymphatic system and the pathogenesis of lymphedema have resulted in the development of effective surgical treatments. Vascularized... (Review)
Review
Advances in our understanding of the lymphatic system and the pathogenesis of lymphedema have resulted in the development of effective surgical treatments. Vascularized lymph node transfer (VLNT) involves the microvascular transplantation of functional lymph nodes into an extremity to restore physiological lymphatic function. It is most commonly performed by transferring combined deep inferior epigastric artery perforator and superficial inguinal lymph node flaps for postmastectomy breast reconstruction. For patients who do not require or are unable to undergo free abdominal breast reconstruction or have lymphedema affecting the lower extremity, several other VLNT options are available. These include flaps harvested from within the axillary, inguinal, or cervical lymph node basins, and lymph node flaps from within the abdominal cavity. This article reviews the lymph node flap options and techniques available for VLNT for lymphedema.
PubMed: 29636651
DOI: 10.1055/s-0038-1632401 -
Journal of Vascular Surgery. Venous and... Mar 2017Currently, lymphedema (LED) is typically diagnosed clinically on the basis of a patient's history and characteristic physical findings. Whereas the diagnosis of LED is... (Review)
Review
OBJECTIVE
Currently, lymphedema (LED) is typically diagnosed clinically on the basis of a patient's history and characteristic physical findings. Whereas the diagnosis of LED is sometimes confirmed by lymphoscintigraphy (LSG), the technique is limited in both its ability to identify disease and to guide therapy. Recent advancements provide opportunities for new imaging techniques not only to assist in the diagnosis of LED, based on anatomic changes, but also to assess contractile function and to guide therapeutic intervention. The purpose of this contribution was to review these imaging techniques.
METHODS
Literature for each technique is reviewed and discussed, and the evidence for each of these new diagnostic techniques was assessed on several criteria to determine if each could (1) establish whether disease is present, (2) determine the severity of the disease process, (3) define the pathophysiologic mechanism of the disease process, (4) demonstrate whether intervention is possible as well as what type, and (5) objectively grade the response to therapy.
RESULTS
LSG is currently the standard test to confirm LED. Duplex ultrasound (DUS) is a simple, readily available noninvasive test that can identify LED by specific tissue characteristics as well as the response to therapy. Magnetic resonance imaging and computed tomography scans similarly demonstrate the alterations in epidermal and subcutaneous tissue, but the latter can also detect obstructing neoplasms as a cause of secondary LED. Moreover, magnetic resonance lymphangiography details lymphatic vessels and nodes and their function. Newer fluorescence imaging techniques provide opportunities to image lymphatic anatomy and function. Visible microlymphangiography by fluorescein sodium is limited by tissue light absorption to imaging depths of 200 μm. Near-infrared fluorescence lymphatic imaging, a newer test using intradermal injection of indocyanine green, can penetrate several centimeters of tissue and can visualize the initial and conducting lymphatics, the lymph node basins, and the active function of lymphangions (the key module) in exquisite detail.
CONCLUSIONS
The availability and the noninvasive nature of DUS should make this modality the first choice for establishing the diagnosis of LED based on tissue changes. Further studies comparing DUS with LSG, however, are needed. The costs of magnetic resonance imaging and computed tomography limit their adoption as a means to regularly assess the lymphatics. Whereas lymphatic truncal anatomy and transit times can be delineated by the older technique of LSG, near-infrared fluorescence lymphatic imaging is rapid, highly sensitive, and repeatable and provides exquisite detail for lymphatic vessel anatomy and function of the lymphangions as well as the response to therapy.
Topics: Contrast Media; Fluorescence; Humans; Lymphatic System; Lymphedema; Lymphography; Magnetic Resonance Angiography; Sensitivity and Specificity; Tomography, X-Ray Computed; Ultrasonography, Doppler
PubMed: 28214496
DOI: 10.1016/j.jvsv.2016.10.083 -
Translational Gastroenterology and... 2017Currently, the most accurate method for identifying lymph node metastasis is intraoperative diagnosis by sentinel node (SN) biopsy. Based on the SNNS study-a recent... (Review)
Review
Currently, the most accurate method for identifying lymph node metastasis is intraoperative diagnosis by sentinel node (SN) biopsy. Based on the SNNS study-a recent large-scale, nationwide, multicenter prospective study-the SN concept seems to be scientifically valid in patients with early gastric cancer. SN biopsy is a multistep technique consisted of six essential elements: indication, the selection of a tracer, a proper tracer injection method, the objective detection of SNs, a reliable biopsy technique, and the precise detection of nodal metastasis. For SN biopsy of gastric cancer, these elements have been validated as follows: the indication should be limited to clinical T1 less than 4 cm in diameter; combination mapping with radioactive colloid and blue dye is used as the standard; and endoscopic submucosal injection is the standard tracer injection. Detection of SNs and a reliable biopsy technique are enabled by adaptation of lymphatic basin dissection, a proper biopsy technique for gastric cancer. Lymphatic basin dissection is a selective lymphadenectomy procedure for dissecting basins , collecting lymph nodes and lymphatic vessels stained with dye. Lymphatic basin dissection is superior to the ordinary pick-up method, not only for minimizing the rate of missed SNs, but also in terms of oncological safety as it complements an intraoperative frozen section diagnosis by serving as a backup dissection. Moreover, indocyanine green (ICG) fluorescence mapping has been developed in recent years. ICG fluorescence mapping is superior because of its high sensitivity and signal stability. Moreover, it is feasible for both open and laparoscopic gastrectomy in treating early gastric cancer. SN biopsy has brought dramatic changes to laparoscopic surgery for early gastric cancer. With laparoscopic SN biopsy using ICG fluorescence navigation, laparoscopic surgery for early gastric cancer has changed from the uniform standard gastrectomy with D1+ into a tailor-made function-preserving surgical procedure, such as local resection with lymphatic basin dissection.
PubMed: 28616598
DOI: 10.21037/tgh.2017.05.02 -
JAMA Surgery Sep 2022Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical...
IMPORTANCE
Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery.
OBJECTIVE
To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases.
DESIGN, SETTING, AND PARTICIPANTS
The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 years with melanoma metastatic to SLN(s). Data were collected from December 2004 to April 2019, and data were analyzed from July 2020 to January 2022.
INTERVENTIONS
Nodal observation with ultrasonography rather than CLND.
MAIN OUTCOMES AND MEASURES
In-basin nodal recurrence.
RESULTS
Of 823 included patients, 479 (58.2%) were male, and the mean (SD) age was 52.8 (13.8) years. Among 855 observed basins, at 10 years, 80.2% (actuarial; 95% CI, 77-83) of basins were free of nodal recurrence. By univariable analysis, freedom from regional nodal recurrence was associated with age younger than 50 years (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70; P < .001), nonulcerated melanoma (HR, 0.36; 95% CI, 0.36-0.49; P < .001), thinner primary melanoma (less than 1.5 mm; HR, 0.46; 95% CI, 0.27-0.78; P = .004), axillary basin (HR, 0.61; 95% CI, 0.44-0.86; P = .005), fewer positive SLNs (1 vs 3 or more; HR, 0.32; 95% CI, 0.14-0.75; P = .008), and SLN tumor burden (measured by diameter less than 1 mm [HR, 0.39; 95% CI, 0.26-0.60; P = .001] or less than 5% area [HR, 0.36; 95% CI, 0.24-0.54; P < .001]). By multivariable analysis, younger age (HR, 0.57; 95% CI, 0.39-0.84; P = .004), thinner primary melanoma (HR, 0.40; 95% CI, 0.22-0.70; P = .002), axillary basin (HR, 0.55; 95% CI, 0.31-0.96; P = .03), SLN metastasis diameter less than 1 mm (HR, 0.52; 95% CI, 0.33-0.81; P = .007), and area less than 5% (HR, 0.58; 95% CI, 0.38-0.88; P = .01) were associated with basin control. When looking at the identified risk factors of age (50 years or older), ulceration, Breslow thickness greater than 3.5 mm, nonaxillary basin, and tumor burden of maximum diameter of 1 mm or greater and/or metastasis area of 5% or greater and excluding missing value cases, basin disease-free rates at 5 years were 96% (95% CI, 88-100) for patients with 0 risk factors, 89% (95% CI, 82-96) for 1 risk factor, 86% (95% CI, 80-93) for 2 risk factors, 80% (95% CI, 71-89) for 3 risk factors, 61% (95% CI, 48-74) for 4 risk factors, and 54% (95% CI, 36-72) for 5 or 6 risk factors.
CONCLUSIONS AND RELEVANCE
This randomized clinical trial was the largest prospective evaluation of long-term regional basin control in patients with melanoma who had nodal observation after removal of a positive SLN. SLN biopsy without CLND cleared disease in the affected nodal basin in most patients, even those with multiple risk factors for in-basin recurrence. In addition to its well-validated value in staging, SLN biopsy may also be regarded as therapeutic in some patients.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT00297895.
Topics: Female; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Melanoma; Prognosis; Sentinel Lymph Node Biopsy; Skin Neoplasms
PubMed: 35921122
DOI: 10.1001/jamasurg.2022.2055