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Radiotherapy instead of inguinofemoral lymphadenectomy in vulvar cancer patients with a metastatic sentinel node: results of GROINSS-V II
  1. MHM Oonk1,
  2. B Slomovitz2,
  3. P Baldwin3,
  4. H van Doorn4,
  5. J van der Velden5,
  6. J de Hullu6,
  7. B Slangen7,
  8. K Gaarenstroom8,
  9. I Vergote9,
  10. M Brannstrom10,
  11. E van Dorst11,
  12. W van Driel12,
  13. R Hermans13,
  14. D Nunns14,
  15. M Widschwendter15,
  16. D Nugent16,
  17. C Holland17,
  18. P DiSilvestro18,
  19. A Sharma19,
  20. R Mannel20,
  21. D Boll13,
  22. A Covens21,
  23. D Cibula22,
  24. D Provencher23,
  25. D Luesley24,
  26. P Ellis25,
  27. T Duncan5,
  28. M Tjiong26,
  29. D Cruickshank27,
  30. P Kjolhede28,
  31. C Levenback29,
  32. J Bouda30,
  33. K Kieser31,
  34. I Runnebaum32,
  35. C Palle33,
  36. N Spirtos34,
  37. D O’Malley35,
  38. M Leitao36,
  39. M Geller37,
  40. K Tamussino38,
  41. K Dhar39,
  42. D Tobias40,
  43. C Borgfeldt41,
  44. T Myers42,
  45. J Lea43,
  46. J Bailey44,
  47. P Persson45,
  48. B Monk46,
  49. C Creutzberg8 and
  50. A van der Zee47
  1. 1University Medical Center Groningen, Groningen, The Netherlands
  2. 2University of Miami, Miami, FL, USA
  3. 3Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital, Cambridge, UK
  4. 4Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam
  5. 5Amsterdam University Medical Centers, University of Amsterdam, Amsterdam
  6. 6Radboud University Medical Center, Nijmegen
  7. 7Maastricht University Medical Center, Maastricht
  8. 8Leiden University Medical Center, Leiden, The Netherlands
  9. 9University Hospital Leuven, Leuven, Belgium
  10. 10Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
  11. 11UMC Utrecht Cancer Center, Utrecht
  12. 12CGOA, Location The Netherlands Cancer Institute, Amsterdam
  13. 13Catharina Hospital, Eindhoven, The Netherlands
  14. 14Nottingham University Hospitals NHS Trust, Nottingham
  15. 15University Collega London, Institute for Women’s Health, London, UK
  16. 16Leeds Teaching Hospitals NHS Trust, Leeds
  17. 17Saint Mary’s Hospital, Manchester University NHS Trust, Manchester, UK
  18. 18Rhode Island Hospital, Providence, RI, USA
  19. 19University Hospital Llandough, Llandough, UK
  20. 20Stephenson Cancer Center, University of Oklahoma, Oklahoma, OK, USA
  21. 21University of Toronto, Odette Cancer Center, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
  22. 22First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic
  23. 23University of Montreal, Cancer Institute Montreal CHUM, Montreal, QC, Canada
  24. 24Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham
  25. 25Royal Surrey County Hospital NHS Trust, Guildford, UK
  26. 26Amsterdam UMC, Location VUmc, Amsterdam, The Netherlands
  27. 27James Cook University Hospital, Middlesbrough, UK
  28. 28Linkoping University, Linköping, Sweden
  29. 29MD Anderson Cancer Center, Houston, TX, USA
  30. 30Medical Faculty Hospital Pilsen, Charles University, Pilsen, Czech Republic
  31. 31Dalhousie University, Halifax, NS, Canada
  32. 32Jena University Hospital, Friedrich Schiller University, Jena, Germany
  33. 33Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark
  34. 34Women’s Cancer Center of Nevada, Las Vegas, NV
  35. 35Ohio State University Comprehensive Cancer Center, Columbus, OH
  36. 36Memorial Sloan Kettering Cancer Center, New York City, NY
  37. 37University of Minnesota, Minneapolis, MN, USA
  38. 38Medical University Graz, Graz, Austria
  39. 39Singleton Hospital, Swansea, UK
  40. 40Morristown Medical Center, Morristown, NJ, USA
  41. 41Skane University Hospital, Lund University, Lund, Sweden
  42. 42Baystate Medical Center, Springfield, MA
  43. 43University of Texas Southwestern Medical Center, Dallas, TX, USA
  44. 44St Michaels Hospital, Bristol, UK
  45. 45Uppsala University, Uppsala, Sweden
  46. 46St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA
  47. 47University Medical Center Groningen, University of Groningen, Groningen, The Netherlands


Introduction/Background Introduction: GROINSS-V II investigated whether radiotherapy is a safe alternative for inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN).

Methodology Methods: In GROINSS-V II, a prospective multicentre phase II trial, patients were included with early-stage squamous cell carcinoma (SCC) of the vulva (diameter <4cm) without suspicious lymph nodes at imaging, who had primary surgery with SN-procedure. In case of a metastatic SN (metastasis of any size), radiotherapy was given to the groin(s) (50Gy). In case of a negative SN, patients were followed-up for ≥2 years. Stopping rules were defined for both groups to monitor groin recurrence rate.

Results From December 2005 until October 2016, 1552 eligible patients were registered. SN-metastasis occurred in 324/1552 (21%) patients. After 54 months of inclusion the stopping-rule for SN-positive patients was activated; interim analysis showed an increased risk for groin recurrence in case of SN-metastasis >2 mm and/or extranodal extension (ENE). After amendment of the protocol only patients with SN-micrometastasis ≤2 mm received radiotherapy, while those with SN metastasis >2 mm underwent IFL (with radiotherapy if >1 metastasis or ENE). Final analysis after ≥2 years of follow-up revealed six isolated groin recurrences in 157 patients with a SN-micrometastasis (3.8%). Four could not be considered radiotherapy failures: two developed recurrence in the contralateral (SN-negative) groin, two refused radiotherapy. Twenty-eight patients did not get radiotherapy (2 recurrences;7.1%). Among 129 patients who received radiotherapy to the groin(s) only two isolated groin recurrences were diagnosed (1.6%: 95%CI:0–3.8%). The combination of radiotherapy with SN was associated with minimal toxicity: 5/118(4.2%) grade 3 toxicity, no grade 4 or 5 toxicity. In 38/1222 SN-negative patients (3.1%: 95%CI:2.1–4.1%) isolated groin recurrences were diagnosed with clear protocol violations in 6 patients: incomplete treatment of the groin (n=3); primary tumor >4cm (n=1); not all SNs visualized on the lymphoscintigram removed (n=2). After exclusion of these protocol violations an isolated groin recurrence rate of 2.6% (95%CI:1.7–3.5%) was observed.

Conclusion Radiotherapy to the groins is a safe alternative for IFL in patients with SN metastasis ≤2 mm, with minimal toxicity. We further established the safety of omitting IFL in patients with SCC of the vulva <4cm and a negative SN. For patients with SN metastasis >2 mm, radiotherapy with a total dose of 50Gy was no safe alternative for IFL; dose escalation and/or chemoradiation should be investigated in these patients.

Disclosure Funded by Dutch Cancer Society.

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