Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2021 Nov 10;39(32):3623-3632.
doi: 10.1200/JCO.21.00006. Epub 2021 Aug 25.

Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II

Maaike H M Oonk  1 , Brian Slomovitz  2 , Peter J W Baldwin  3 , Helena C van Doorn  4 , Jacobus van der Velden  5 , Joanne A de Hullu  6 , Katja N Gaarenstroom  7 , Brigitte F M Slangen  8 , Ignace Vergote  9 , Mats Brännström  10 , Eleonora B L van Dorst  11 , Willemien J van Driel  12 , Ralph H Hermans  13 , David Nunns  14 , Martin Widschwendter  15 , David Nugent  16 , Cathrine M Holland  17 , Aarti Sharma  18 , Paul A DiSilvestro  19 , Robert Mannel  20 , Dorry Boll  13 , David Cibula  21 , Al Covens  22 , Diane Provencher  23 , Ingo B Runnebaum  24 , David Luesley  25 , Patricia Ellis  26 , Timothy J Duncan  27 , Ming Y Tjiong  5 , Derek J Cruickshank  28 , Preben Kjølhede  29 , Charles F Levenback  30 , Jiri Bouda  31 , Katharina E Kieser  32 , Connie Palle  33 , Nicola M Spirtos  34 , David M O'Malley  35 , Mario M Leitao  36 , Melissa A Geller  37 , Kalyan Dhar  38 , Viren Asher  39 , Karl Tamussino  40 , Daniel H Tobias  41 , Christer Borgfeldt  42 , Jayanthi S Lea  43 , Jo Bailey  44 , Margareta Lood  45 , Brynhildur Eyjolfsdottir  46 , Stephen Attard-Montalto  47 , Krishnansu S Tewari  48 , Ranjit Manchanda  49 , Pernille T Jensen  50 , Par Persson  51 , Linda Van Le  52 , Hein Putter  7 , Geertruida H de Bock  1 , Bradley J Monk  53 , Carien L Creutzberg  7 , Ate G J van der Zee  1
Affiliations
Clinical Trial

Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II

Maaike H M Oonk et al. J Clin Oncol. .

Abstract

Purpose: The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN).

Methods: GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences.

Results: From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL.

Conclusion: Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.

PubMed Disclaimer

Conflict of interest statement

Brian SlomovitzConsulting or Advisory Role: Clovis Oncology, AstraZeneca, Genentech, Incyte, Agenus, GlaxoSmithKline, GOG Foundation, Myriad Genetics, Merck, Eisai Ignace VergoteConsulting or Advisory Role: Amgen, AstraZeneca, Clovis Oncology, Carrick Therapeutics, Deciphera, Elevar Therapeutics, Genmab, GlaxoSmithKline, Immunogen, Jazz Pharmaceuticals, Mersana, MSD, Novocure, OCTIMET Oncology NV, Oncoinvent, Sotio, Verastem, Zentalis, Roche, MillenniumResearch Funding: Roche, Genmab, Amgen, OncoinventTravel, Accommodations, Expenses: Roche, AstraZeneca, Tesaro, Amgen, MSD/Merck Mats BrännströmStock and Other Ownership Interests: EUGIN Sweden Martin WidschwendterStock and Other Ownership Interests: Sola Diagnostics, BreOva HealthPatents, Royalties, Other Intellectual Property: Patents relevant for risk prediction or diagnosis of women's cancers Paul A. DiSilvestroConsulting or Advisory Role: AstraZeneca, AgenusResearch Funding: Janssen Oncology, Tesaro, AstraZeneca, Genentech, AbbVie Robert MannelConsulting or Advisory Role: Tesaro Dorry BollResearch Funding: AstraZeneca David CibulaConsulting or Advisory Role: AstraZeneca, Sotio, Roche, GlaxoSmithKline Diane ProvencherConsulting or Advisory Role: AstraZeneca, GlaxoSmithKlineResearch Funding: AstraZeneca, AbbVie Ingo B. RunnebaumConsulting or Advisory Role: AbbVie (I), Amgen, AstraZeneca, Clovis Oncology, GlaxoSmithKline, Oncgnostics, Tesaro Preben KjølhedeResearch Funding: Leo Pharma AB Katharina E. KieserHonoraria: AstraZenecaConsulting or Advisory Role: MerckResearch Funding: AstraZeneca Nicola M. SpirtosResearch Funding: AbbVie, AstraZeneca, Genentech/Roche, Clovis Oncology, Seattle GeneticsPatents, Royalties, Other Intellectual Property: Application No. PCT/US 2019/19465 Cannabis Based Therapeutic and Method of Use Application No, US Patent 0024098766 Compounds Cannabidiol and Flavanones 63/047550 (July 1, 2020) 63/055458 (July 23, 2020) David M. O'MalleyConsulting or Advisory Role: Janssen Oncology, AstraZeneca, Clovis Oncology, Tesaro, Novocure, AbbVie, Genentech/Roche, OncoQuest, Immunogen, GOG Foundation, Translational Genomics Research Institute, Agenus, Marker Therapeutics, Eisai, Genelux, Iovance Biotherapeutics, Ambry Genetics, Tarveda Therapeutics, Leap Therapeutics, Myriad Genetics, GlaxoSmithKline, Regeneron, Sorrento Therapeutics, Rubius Therapeutics, Elevar Therapeutics, Novartis, Seagen, BBI Healthcare, Arquer Diagnostics, Toray Medical, Takeda, InxMed, Celsion, Roche Diagnostics MSAResearch Funding: Amgen, AstraZeneca, Genentech/Roche, Regeneron, Immunogen, Janssen Research & Development, Clovis Oncology, EMD Serono, Ergomed, Ajinomoto, Cerulean Pharma, PharmaMar, Array BioPharma, Bristol Myers Squibb, Agenus, Tesaro, TRACON Pharma, Genmab, Seattle Genetics, Iovance Biotherapeutics, Leap Therapeutics, Merck, AbbVie/Stemcentrx, AbbVie, Mersana, Eisai, BBI Healthcare, Sumitomo Dainippon Pharma Oncology Mario M. LeitaoHonoraria: Intuitive SurgicalConsulting or Advisory Role: Intuitive Surgical, Ethicon/Johnson & Johnson, Medtronic, TakedaResearch Funding: KCITravel, Accommodations, Expenses: Intuitive Surgical Melissa A. GellerResearch Funding: Tesaro, Genentech, FATE Therapeutics, Morphotek, Bayer Karl TamussinoOther Relationship: Medtronic Daniel H. TobiasConsulting or Advisory Role: Ethicon Jayanthi S. LeaConsulting or Advisory Role: Roche Brynhildur EyjolfsdottirOther Relationship: Intuitive Surgical Krishnansu S. TewariHonoraria: Tesaro, Clovis OncologyConsulting or Advisory Role: Roche/Genentech, Tesaro, Clovis Oncology, AstraZenecaSpeakers' Bureau: Roche/Genentech, AstraZeneca, Merck, Tesaro, Clovis OncologyResearch Funding: AbbVie, Genentech/Roche, Morphotek, Merck, RegeneronTravel, Accommodations, Expenses: Roche/Genentech Ranjit ManchandaHonoraria: AstraZeneca Linda Van LeConsulting or Advisory Role: EyePoint Pharmaceuticals, Novartis, Advarum, Neurotech, Iveric, Gemini Therapeutics, NaegisResearch Funding: GOG Partners Trial Bradley J. MonkLeadership: US OncologyHonoraria: AbbVie, Advaxis, Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Asymmetric Therapeutics, Boston Biomedical, ChemoID, Clovis Oncology, Deciphera Pharmaceuticals, Eisai, Geistlich Pharma, Genmab/Seattle Genetics, ImmunoGen, Immunomedics, Incyte, Iovance Biotherapeutics, Laekna Health Care, Merck, Mersana, Myriad Pharmaceuticals, Nucana, Oncomed, Oncoquest, Oncosec, Perthera, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Senti Biosciences, Takeda, Tarveda Therapeutics, Tesaro/GSK, Vavotar Life Sciences, Vascular Biogenics, Vigeo Therapeutics, GOG Foundation, Starton Therapeutics, Elevar Therapeutics, Novocure, Gradalis, Karyopharm TherapeuticsConsulting or Advisory Role: AbbVie, Advaxis, Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Asymmetric Therapeutics, Boston Biomedical, ChemoCare, ChemoID, Clovis Oncology, Deciphera Pharmaceuticals, Eisai, Geistlich Pharma, Genmab/Seattle Genetics, GOG Foundation, ImmunoGen, Immunomedics, Incyte, Iovance Biotherapeutics, Laekna Health Care, Merck, Mersana, Myriad Pharmaceuticals, Nucana, Oncomed, Oncoquest, Oncosec, Perthera, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Senti Biosciences, Takeda, Tarveda Therapeutics, Tesaro/GSK, Vavotar Life Sciences, Vascular Biogenics, Vigeo Therapeutics, Gradalis, Karyopharm Therapeutics, Sorrento Therapeutics, NovocureSpeakers' Bureau: Roche/Genentech, AstraZeneca, Clovis Oncology, Eisai, Tesaro/GSK, MerckResearch Funding: Novartis, Amgen, Genentech, Lilly, Janssen, Array BioPharma, Tesaro, Morphotek, Pfizer, Advaxis, AstraZeneca, Immunogen, Regeneron, Nucana Carien L. CreutzbergConsulting or Advisory Role: MerckResearch Funding: Elekta, Varian Medical SystemsNo other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Flowchart of GROINSS-V II. FNA, fine needle aspiration cytology; IC, informed consent; IFL, inguinofemoral lymphadenectomy; RT, radiation therapy; SN, sentinel node.
FIG 2.
FIG 2.
Isolated ipsilateral groin recurrences in patients with SN micrometastases ≤ 2 mm. Radiotherapy versus no further treatment (HR, 0.11; 95% CI, 0.02 to 0.76). Patients who underwent IFL instead of radiotherapy were excluded. HR, hazard ratio; IFL, inguinofemoral lymphadenectomy; SN, sentinel node.
FIG 3.
FIG 3.
Isolated ipsilateral groin recurrences in patients with SN macrometastases > 2 mm. Per protocol analysis, radiotherapy versus IFL (HR, 3.2; 95% CI, 1.2 to 8.3). Six patients who received no treatment were excluded from this analysis. HR, hazard ratio; IFL, inguinofemoral lymphadenectomy; RT, radiation therapy; SN, sentinel node.
FIG 4.
FIG 4.
Long-term morbidity. *P < .0001; **P = .001. IFL, inguinofemoral lymphadenectomy; RT, radiation therapy; SN, sentinel node.
FIG 5.
FIG 5.
Survival analysis of all GROINSS-V II patients. (A) Disease-specific death for all patients. (B) Overall survival for all patients. (C) Disease-specific death of patients with SN macrometastases. IFL, inguinofemoral lymphadenectomy; RT, radiation therapy; SN, sentinel node.
See this image and copyright information in PMC

Comment in

References

    1. Van der Zee AG, Oonk MH, De Hullu JA, et al. : Sentinel node dissection is safe in the treatment of early-stage vulvar cancer. J Clin Oncol 26:884-889, 2008 - PubMed
    1. Levenback CG, Ali S, Coleman RL, et al. : Lymphatic mapping and sentinel lymph node biopsy in women with squamous cell carcinoma of the vulva: A Gynecologic Oncology Group study. J Clin Oncol 30:3786-3791, 2012 - PMC - PubMed
    1. Pouwer AW, Hinten F, van der Velden J, et al. : Volume-controlled versus short drainage after inguinofemoral lymphadenectomy in vulvar cancer patients: A Dutch nationwide prospective study. Gynecol Oncol 146:580-587, 2017 - PubMed
    1. Oonk MH, van Hemel BM, Hollema H, et al. : Size of sentinel-node metastasis and chances of non-sentinel-node involvement and survival in early-stage vulvar cancer: Results from GROINSS-V, a multicentre observational study. Lancet Oncol 11:646-652, 2010 - PubMed
    1. Taylor A, Rockall AG, Powell ME: An atlas of the pelvic lymph node regions to aid radiotherapy target volume definition. Clin Oncol (R Coll Radiol) 19:542-550, 2007 - PubMed