Important Studies Flashcards
Risk factors
UCLA “Heaps study”: Heaps et al, Gynecol Oncol, 1990. 135 s/p surgical resection. Pathologic features associated with local recurrence
“Local recurrence risk factors in order of significance: Stage, Margin, Depth, Growth pattern, Vascular invasion, Keratin amount, Mitotic activity
NOT: Tumor size, Nucleoli, grade
Margin <8mm had LR of 48%
Margin <5mm had LR of 57%”
These risk factors are used as indications for treatment with radiation therapy. Ideally this approach would be validated externally or in a randomized trial, but since vulvar cancers are relatively uncommon, this has not been performed.
RT vs. pelvic lymphadenectomy
GOG 37: “Homesley et al, Obstet Gynecol, 1986
Kunos et al, Obstet Gynecol, 2009”. 114 Positive groin nodes after vulvectomy and lymphadenectomy.
“RT 45-50 Gy to bilateral pelvic and inguinal nodes (excludes primary) vs. pelvic node resection”
“2-yr OS 68% RT vs. 54% surgery
On subanalysis, effect only in ECE and ≥2 nodes
6-yr groin recurrence 5% vs. 24%
6-yr OS 51% vs. 41% (benefit only in palpable N+, ECE, ulcerated, or ≥2 nodes)
Lymphedema 16 vs. 22% (NS)”
Adjuvant RT improved OS in palpable N+, ECE, ulcerated, and ≥2 nodes, compared to pelvic LND after radical vulvectomy and inguinal LND.
This could be viewed as showing the benefit of RT vs obs. Why randomize vs. pelvic nodal dissection? Pelvic nodes in vulva are considered metastatic.
RT vs. groin dissection
GOG 88: Stehman et al, IJROBP, 1992. 58 clinically N0 “Radical vulvectomy →
→50 Gy inguinal RT to 3 cm depth vs. →groin dissection + pelvic dissection if positive”
“Closed early due to excessive recurrences in RT arm. 19% relapse in RT vs. 0 in surgery.
20% in surgery arm were N+ and treated with RT
OS 63% vs. 88%”
Groin dissection has superior OS and LC compared to inguinal RT.
Criticism: Dose Rx was to 3 cm, leading to underdosage. LF of 18% is comparable to historical GOG failure rate of 24%.
False negative and positive in SLN bx
GOG 173: Levenback et al, JCO, 2012. 452 ≥1 mm invasion, size ≥2 cm to <6 cm, clinically node negative
“Phase II SLN → inguinal dissection to all (regardless of SLN status)”
“8.3% with false negative nodes
FN predictive value 3.7%
For tumors <4 cm, FNPV 2.0%”
SLNB has favorable FNR and is a reasonable approach.
LND after +SLN bx
GROINSS-V: “Van der Zee et al, JCO, 2008
Te Grootenhuis et al, Gynecol Oncol, 2016”
623 T1-2, <4cm, DOI ≥1 mm, clinically negative inguinal LNs: SLN → if positive, inguinal LND
"•SLN negative 5/10-yr LR 25%/36% 5-yr groin recurrence 2.5% •SLN positive 5/10-yr LR 33%/46% 5-yr groin recurrence 8%
3-yr OS 97%
If LR, 10-yr DSS decreased 90% -> 69%
wound breakdown 12% vs. 34%
Lymphedema 2% vs. 25%”
Inguinal LND guided by SNLB leads to low groin failure.
Worsening of DSS after LR supports the practice of treating the vulva with RT.
RT after +SLN bx
GROINSS-VII GOG 270: Oonk et al, SGO, 2020. 1552 depth >1mm in all, T1-T2N0, <4cm, not encroaching urethra, vagina, or anus.
“Phase II
SLNB→
Adjuvant RT for SLN+. Observe SLN-.
≤2mm nodal met, no ECE: 50 Gy RT to ipsilateral groin & ipsilateral low pelvis
> 2mm nodal met or ECE: after the initial no LND cohort was terminated, arm was modified to complete LND, then 56 Gy RT to ipsilateral groin and pelvis”
“≤2 mm cohort: per protocol groin failure 1.6%
> 2 mm cohort: Terminated early due to excess failures
grade 3 toxicity in 4%”
“In micrometastasis of ≤2 mm on SLNB, radiation therapy can replace LND.
In micrometastasis of >2 mm on SLNB, LND is required prior to radiation.”
Neoadjuvant chemoRT in unresectable
GOG 101: “Moore et al, IJROBP, 1998
Montana et al, IJROBP, 2000”.
96 unresectable T3 or T4, unresectable N2 or N3
“Phase II: split course 47.6 Gy RT + cis/5FU
Nodes included for N2-N3 disease”
55% OS. Nodal pCR 40% and primary pCR 30%
Neoadjuvant chemoRT is effective with high pCR and favorable OS.
Neoadjuvant chemoRT in unresectable, dose escalation
GOG 205: Moore et al, Gynecol Oncol, 2012. 58 T3, T4, N+.
“Phase II:
→RT 57.6 Gy/ 32 fx + weekly cis
→ resection
cCR defined by biopsy, pCR defined by surgical resection”
“cCR 64%
pCR in 50% [compare to 40% in GOG 101] (59% had surgery)”
Dose escalation in neoadjuvant chemoRT further improves pCR compared to historical trial.
Neoadjuvant chemoRT in unresectable, dose escalation, IMRT
GOG 279 (ongoing)
52 locally advanced vulva T2-T3, N0-3, not amenable to resection
“Phase II:
IMRT 64 Gy (45-50 Gy to groin and pelvis) + cis/ gem → resection
Goal: pCR 65% or greater
10 Gy boost for 3+ LN, ECE, or +margin”
Midline block
University of Minnesota: Dusenbery et al, IJROBP, 1994.
27 Stage III/IV with +LN treated with RT and midline block. Retrospective. Median dose 45 Gy. 26/27 had midline block.
“48% recurrence within midline block.
63% recurrences total”
Midline block in pelvic RT leads high recurrence rates within the block. This study may be used to support inclusion of the primary when treating nodes, but do observe its small sample size and retrospective nature.
