Gynecologic Malignancies - Board Review Summary

PART I - ENDOMETRIAL CANCER

Management Paradigm + Dose Anchors

Scenario	Default approach	Dose anchor
Low-risk stage I endometrioid	Surgery alone / observation after TAH-BSO +/- SLN staging.	No RT.
High-intermediate risk stage I	Vaginal cuff brachytherapy is the clean board answer; EBRT only for higher pelvic-risk features.	7 Gy x 3 at 5 mm or institutional equivalent.
Stage II / cervical stromal invasion	Pelvic EBRT +/- VBT; add systemic therapy by histology and molecular risk.	45-50.4 Gy pelvis; VBT boost if cuff risk.
Stage III / high-risk histology / p53abn	Combined systemic therapy and RT sequencing: chemoRT, chemo-first, or sandwich depending on residual disease and recurrence pattern risk.	45-50.4 Gy pelvis +/- PA; gross nodes often 55-60 Gy; VBT selective.
Medically inoperable uterine-confined disease	Definitive image-guided uterine brachytherapy alone for minimal invasion; EBRT + brachy for deep invasion, cervical extension, or nodal-risk features.	Brachy alone uterine CTV about 48-62.5 Gy EQD2; EBRT + HDR CTV about 65-75 Gy EQD2, GTV goal 80-90 Gy EQD2.
RT-naive vaginal / pelvic recurrence	Salvage pelvic RT +/- brachytherapy; weekly cisplatin is not routine after GOG-238.	Pelvis 45-50 Gy + brachy/boost to about 70-80+ Gy EQD2.

Epidemiology and Classification

Most common gynecologic malignancy in developed countries. About 70% are diagnosed early stage. Risk factors include obesity, nulliparity, unopposed estrogen, tamoxifen, diabetes, HTN, and Lynch syndrome / dMMR.

Type I: endometrioid grade 1-2, estrogen-responsive, favorable prognosis, often MSI/MMRd.
Type II: serous, clear cell, carcinosarcoma, and grade 3 endometrioid. More aggressive and frequently p53 abnormal.

TCGA / ProMisE Molecular Classification

Group	Frequency / clue	Behavior
POLE-mutated / ultramutated	Small subset, including some high-grade tumors	Best prognosis; active de-escalation question.
MMR-deficient / MSI-high	Common in endometrioid tumors and Lynch-associated disease	Intermediate prognosis; immunotherapy-responsive.
Copy-number low / NSMP	Common in low-grade endometrioid tumors	Intermediate prognosis; ER status and clinicopathologic risk matter.
Copy-number high / p53abn	Serous-like biology; frequent TP53 mutation	Worst prognosis; upstages early uterine-confined disease in FIGO 2023.

Classic Surgical / Nodal Risk Pearls

Finding	Board-relevant takeaway
GOG-33	Depth of myometrial invasion and grade drive pelvic/para-aortic LN risk. Deep invasion + grade 3 has the highest nodal risk.
Pelvic LN+	Positive pelvic nodes imply meaningful para-aortic risk; in GOG-33, about 37% of pelvic-node-positive patients also had PA nodes.
Low-risk nodal omission concept	Endometrioid G1-2, <=50% MI, small tumor, and no extrauterine disease were historically low-risk for lymphadenectomy omission; SLN mapping has largely replaced older full-LND logic.

FIGO 2023 Staging - Major Revision

Why this matters: FIGO 2023 fundamentally restructured endometrial staging to incorporate molecular biology and LVSI quantification. For boards, know the 2009-to-2023 reclassifications cold.

LVSI Grading - Three Tier

LVSI category	Definition	Stage impact
Absent / focal	No LVSI or single-vessel focal involvement	No stage change.
Substantial LVSI	Diffuse/multifocal LVSI in >5 vascular spaces or >50% of vessels in an area	Stage IIB independent upstager for non-aggressive histology.
Any LVSI + aggressive histology with MI	Combined aggressive biology and invasion	Stage IIC combined upstager.

Key 2009 to 2023 Reclassifications

Scenario	FIGO 2009	FIGO 2023
Aggressive histology, no MI	IA	IC new substage.
Aggressive histology with any MI	IA or IB by depth	IIC major reclassification.
Substantial LVSI	HIR feature only	IIB independent upstage.
Synchronous uterine + ovarian low-grade endometrioid	IIIA	IA3 if strict criteria are met.
Adnexal vs serosal involvement	Both IIIA	IIIA1 adnexal vs IIIA2 serosal.
Nodal disease	IIIC1 / IIIC2	Micro (i) vs macro (ii) separated.
Peritoneal vs distant metastases	Both IVB	IVB peritoneal vs IVC distant.
POLEmut, stage I/II	Not considered	IAm downstaged.
p53abn, stage I/II	Not considered	IICm p53abn upstaged.

IA3 downstaging requires superficial MI <50%, no substantial LVSI, no additional metastases, and unilateral ovarian tumor without capsule invasion or rupture.

FIGO 2023 Stage II and III Details

Substage	Definition	Risk frame
IIA	Non-aggressive histology invading cervical stroma, no extension beyond uterus	Intermediate-high.
IIB	Substantial LVSI, non-aggressive histology	High pelvic-risk feature.
IIC	Aggressive histology with any myometrial invasion	High risk.
IICm p53abn	Any stage I/II with p53 abnormal molecular subtype	Very high risk.
IIIA1 / IIIA2	Adnexal only / uterine serosal involvement	Serosal is worse.
IIIB	Vaginal or parametrial involvement	Pelvic RT usually central.
IIIC1i	Pelvic LN micrometastasis, 0.2-2 mm	Usually SLN ultrastaging finding.
IIIC1ii	Pelvic LN macrometastasis, >2 mm	Higher nodal burden.
IIIC2i / IIIC2ii	Para-aortic micro / macro, with or without pelvic nodes	Extended-field planning question.

Staging technical requirements: TAH-BSO minimum, preferably minimally invasive; grade, histotype, and LVSI documented; molecular classification encouraged; infracolic omentectomy required for serous, undifferentiated, and carcinosarcoma; SLN ultrastaging with H&E + IHC is required to distinguish IIIC1i from IIIC1ii.

Early-Stage Adjuvant Management

Trial	Core question	Bottom line
PORTEC-1	EBRT vs observation for intermediate-risk stage I disease	EBRT reduced locoregional recurrence but did not improve OS; many observation-arm recurrences were upper vaginal.
GOG-99	EBRT vs observation after surgical staging	Defined classic high-intermediate risk criteria; EBRT reduced recurrence, no OS benefit.
PORTEC-2	VBT vs EBRT in high-intermediate risk	VBT non-inferior to EBRT with better QOL and less GI toxicity. VBT is the HIR standard.
GOG-249	VBT + chemo vs EBRT for HIR/high-risk early-stage disease	VBT + chemo was not superior and had more pelvic/para-aortic failures and acute toxicity.
PORTEC-4a	Molecular-guided adjuvant treatment vs standard VBT	First prospective molecularly tailored adjuvant RT strategy; molecular-risk assignment can route patients to observation, VBT, or EBRT.

HIR Definitions

PORTEC-1 HIR	GOG-99 HIR
Age >=60; or grade 1-2 with >=50% MI; or grade 3 with <50% MI; or stage IIA	Age >=70 + 1 risk factor; age 50-69 + 2 risk factors; any age + 3 risk factors. Risk factors: grade 2-3, LVSI, outer-third MI.

Vaginal Brachytherapy Fractionation

Setting	Regimen	Rx point
Monotherapy, common US/PORTEC-style	7 Gy x 3	5 mm
Monotherapy	5.5 Gy x 4	5 mm
Monotherapy	5 Gy x 5	5 mm
Monotherapy, low-dose-per-fraction style	2.5 Gy x 6	5 mm
Monotherapy, surface prescription	6 Gy x 5	Surface
Post-EBRT	6 Gy x 3	Surface

VBT technical: treat 3-5 cm of upper vagina. Use the largest comfortable cylinder to reduce air gaps and mucosal hot spots. 3D planning helps evaluate air gaps and normal tissue dose. There is no single optimal HDR schedule; compare regimens by EQD2 and prescription depth.

Locally Advanced / High-Risk Endometrial

Trial	Design	Takeaway
PORTEC-3	EBRT +/- concurrent cisplatin and adjuvant carbo/pac	ChemoRT improves failure-free survival and long-term OS in high-risk disease; p53abn benefits most, POLE does not benefit from chemo.
GOG-258	ChemoRT + 4 cycles carbo/pac vs carbo/pac x 6	No OS/PFS benefit from CRT, but CRT improved locoregional control. Chemo alone is insufficient for pelvic/vaginal control.
KEYNOTE-B21	Curative-intent surgery, high-risk EC, chemo +/- RT with pembro vs placebo	No DFS benefit in all-comers; dMMR subgroup signal. Do not over-apply GY018/RUBY to completely resected disease.

PORTEC-3 vs GOG-258 reconciliation: for stage III/high-risk disease, systemic therapy is required for distant risk, but chemo alone does not replace RT for locoregional control. Practical sequencing can be chemoRT, chemo-first, or sandwich based on residual disease, histology, molecular risk, and field complexity.

Extended-Field Technique

Upper border: T12/L1, above renal hilum, for extended-field PA coverage.
Dose: pelvis/PA about 45 Gy; boost gross nodes to about 55-60 Gy when OARs allow.
Duodenum constraints: V55 <15 cc, V60 <2 cc.
Consider neoadjuvant chemotherapy before extended-field RT when PA nodes are bulky.

Immunotherapy Integration

Feature	RUBY	NRG-GY018
Agent	Dostarlimab with carbo/pac then maintenance	Pembrolizumab with carbo/pac then maintenance
Population	Primary advanced stage III/IV or first recurrent EC	Stage III/IVA with measurable disease; IVB/recurrent with or without measurable disease
dMMR PFS HR	0.28	0.30
Overall / pMMR PFS HR	0.64 overall	0.60 pMMR in FDA-label analysis
OS signal	RUBY has a clear OS signal overall	OS immature / trend in updated analyses

Clinical scenario gap: NRG-GY018 required measurable disease for stage III/IVA disease. Completely resected stage III endometrioid disease remains an evidence-gray zone for chemoimmunotherapy; integrate MMR, p53, residual disease, RT need, and guideline context.

Definitive and Salvage RT

Medically inoperable EC: brachy alone for minimal/no MI and no cervical involvement; EBRT + brachy for deep MI, cervical involvement, or nodal-risk features.
ABS targets: uterine CTV about 48-62.5 Gy EQD2 with brachy alone; with EBRT + HDR, uterine/cervix/upper vaginal CTV often 65-75 Gy EQD2 and GTV goal 80-90 Gy EQD2.
GOG-238 / NRG: in RT-naive vaginal/pelvic recurrence, adding weekly cisplatin to salvage RT did not improve PFS and increased toxicity.
TOTEM: intensive asymptomatic surveillance did not improve OS/RFS; use symptom review + exam, reserving imaging/labs for symptoms, exam findings, or high-risk individualized contexts.

PART II - CERVICAL CANCER

Management Paradigm + Dose Anchors

Scenario	Default approach	Dose anchor
IA1 without LVSI	Conization or simple hysterectomy depending fertility goals and margins.	No RT.
IA2 / IB1 <=2 cm, low risk	Fertility-sparing trachelectomy or open surgery with nodal assessment; simple hysterectomy acceptable only in carefully selected SHAPE-style patients.	No RT unless adverse pathology.
Early operable IB-IIA	Open radical hysterectomy + nodes or definitive RT. Post-op RT for Sedlis; post-op CRT for Peters criteria.	Post-op pelvis 45-50.4 Gy; high-risk post-op CRT with weekly cisplatin.
Locally advanced / node-positive / IB3+ / IIB-IVA	Definitive weekly cisplatin chemoRT + brachytherapy. Do not omit brachytherapy.	EBRT 45 Gy / 25 fx +/- nodal SIB 55-60 Gy; HR-CTV D90 goal about 85-95 Gy EQD2; package time <8 weeks.
FIGO 2014 III-IVA high-risk LACC	Add pembrolizumab to CRT/maintenance per KEYNOTE-A18 when appropriate; INTERLACE induction carbo/pac is another positive strategy, but not established to combine both.	RT dose same as definitive CRT; if using INTERLACE: induction carbo AUC2 + paclitaxel 80 mg/m2 weekly x 6.
Metastatic / recurrent	Systemic therapy +/- local RT for bleeding, pain, obstruction, oligoprogression, or durable control of limited sites.	8 Gy x 1, 20 Gy / 5 fx, 30 Gy / 10 fx, or SBRT by site/OARs.

Epidemiology, Workup, and FIGO 2018 Staging

Nearly all cervical cancers are HPV-driven. SCC is most common, followed by adenocarcinoma; clear cell is rare and associated with DES exposure.

Workup: H&P, pelvic exam/EUA as needed, cystoscopy/proctoscopy when bladder/rectal invasion is suspected, PET-CT or CT C/A/P, and pelvic MRI for local extent.
MRI pearl: superior for uterine body, parametrial invasion, and vaginal extension.

Stage	Definition
IA1 / IA2	Stromal invasion <=3 mm / >3-5 mm.
IB1 / IB2 / IB3	2018 change: size substages <2 cm / 2-<4 cm / >=4 cm.
IIA1 / IIA2	Upper 2/3 vagina, <4 cm / >=4 cm, no parametrial involvement.
IIB	Parametrial invasion, any size.
IIIA / IIIB	Lower 1/3 vagina / pelvic wall extension or hydronephrosis.
IIIC1 / IIIC2	2018 change: nodal disease upstages to pelvic nodes (IIIC1) or para-aortic nodes (IIIC2), with r or p suffix.
IVA	Bladder or rectal mucosa invasion; bullous edema alone does not qualify.
IVB	Distant organs, including lung, liver, bone, or distant lymph nodes.

Key 2018 changes: IB became three size-based substages, nodal disease became stage IIIC, imaging/pathology are formally permitted, and LVSI is documented but does not change stage. AJCC cervix Version 9 is current AJCC, but many trial eligibility frames still use FIGO 2014 or 2018.

Surgery and Postoperative Therapy

LACC trial: minimally invasive radical hysterectomy was inferior to open surgery, with worse survival and more locoregional recurrence. Open radical hysterectomy remains standard when radical hysterectomy is required.
SHAPE / ConCerv concept: carefully selected IA2/IB1, <=2 cm low-risk tumors can be treated with simple hysterectomy + nodal assessment, with less GU morbidity. Do not generalize to larger or high-risk tumors.

Risk group	Criteria	Board treatment
Sedlis / GOG-92 intermediate risk	Combinations of LVSI, depth of invasion, and tumor size after radical hysterectomy	Post-op pelvic RT, usually 45-50.4 Gy.
Peters / GOG-109 high risk	Positive margins, positive lymph nodes, or positive parametrium	Post-op chemoRT with cisplatin-based chemotherapy.

GOG-109 / Peters: post-radical-hysterectomy patients with positive margins, positive nodes, or positive parametrium had better PFS and OS with adjuvant chemoRT than RT alone. This is the classic high-risk post-op cervical answer.

Modern Postoperative De-Intensification / Intensification

Trial	Population	Takeaway
GOG-263 / KGOG1008	Sedlis-type intermediate-risk patients after radical hysterectomy	Adding weekly cisplatin to post-op RT did not clearly improve survival and increased toxicity. RT alone remains appropriate for classic Sedlis risk.
NRG/RTOG 0724	High-risk post-op patients receiving CRT for nodes/parametrium/margins	Outback carbo/pac after post-op CRT did not improve DFS/OS. Do not add routine outback chemo outside selected contexts/trials.
CERVANTES	Intermediate-risk early-stage disease after radical surgery	Ongoing: tests no adjuvant therapy vs adjuvant RT/CRT in carefully selected intermediate-risk patients.

Definitive Chemoradiation for Locally Advanced Disease

Concurrent chemo: weekly cisplatin 40 mg/m2 x 5-6 during EBRT.
EBRT: 45 Gy pelvis is standard; nodal SIB or sequential boost to about 55-60 Gy EQD2 for positive nodes.
Brachytherapy: HR-CTV D90 at least 85-90 Gy EQD2; EMBRACE-II target about 90 Gy EQD2. Do not omit brachytherapy.
Total package time: <8 weeks. Every day beyond about 8 weeks costs local control through accelerated repopulation.

ChemoRT and Intensification Trials

Trial	Question	Board takeaway
Vale meta-analysis	Concurrent chemoRT vs RT alone	OS benefit is greatest in earlier locally advanced disease: about 10% in I-IIA, 7% in IIB, 3% in III-IVA.
OUTBACK	Adjuvant carbo/pac after standard CRT	No OS/PFS benefit; more toxicity. No routine outback chemotherapy after definitive CRT.
CALLA	Durvalumab concurrent/adjuvant with CRT	No significant PFS improvement in biomarker-unselected LACC; contrasts with KEYNOTE-A18.
INTERLACE	Induction weekly carbo/pac x 6 then CRT vs CRT alone	Positive OS/PFS strategy; useful when RT start will be delayed, but not established to combine with pembrolizumab.

IMRT / Contouring

TIME-C and PARCER support IMRT to reduce bowel/GI toxicity. IMRT is standard for pelvic nodal/vaginal coverage.
CTV: entire uterus/cervix/parametria bilaterally; inferior to upper border of obturator foramen if no vaginal involvement, or 3 cm below gross vaginal disease if involved.
Vaginal ITV: with empty rectum, extend 2 cm anteriorly into bladder; with distended rectum, extend posteriorly to within 1.5 cm of posterior rectal wall.

EMBRACE-II Nodal Coverage by Risk Group

Risk group	Definition	Coverage
Low risk	<=4 cm, IA/IB/IIA1, N0, SCC, no uterine invasion	Small pelvis: internal/external iliac, obturator, presacral.
Intermediate risk	Not low risk, no high-risk nodal features	Large pelvis: small pelvis + common iliac; add inguinal if distal vaginal involvement and mesorectal if involved.
High risk	Common iliac or para-aortic node, or >=3 pathologic nodes	Large pelvis + para-aortic to renal veins/L2, at least 3 cm cranial to highest involved node.

PA contouring pearl: PA node distribution clusters in the lower third near the aortic bifurcation but can extend higher. Use T12 for PA imaging involvement, L2 for common iliac imaging involvement, and L3/L4 for standard pelvic fields when PA/common iliac are not involved.

Brachytherapy: Critical for Cervical Cancer

Brachytherapy matters. Omission is associated with worse survival, and poor implant geometry increases local recurrence risk. Implant quality is a testable board topic.

MR-Based Target Definition and Goals

Volume / OAR	Definition or goal
GTV	Macroscopic tumor at brachytherapy.
HR-CTV	GTV + whole cervix + presumed extracervical extension / grey zones.
IR-CTV	HR-CTV + margins for initial extent and regression pattern.
HR-CTV D90 EQD2	Goal >90 Gy; >85 Gy minimum.
GTV D98 EQD2	Goal >95 Gy; >90 Gy minimum.
Bladder D2cc EQD2	Planning goal <80 Gy, upper limit <90 Gy.
Rectum D2cc EQD2	Planning goal <65 Gy, upper limit <75 Gy.
Sigmoid D2cc EQD2	Planning goal <70 Gy, upper limit <75 Gy.

ABS HDR starting regimens after 45 Gy EBRT: 7 Gy x 4, 6 Gy x 5, 5 Gy x 6, or 5.5 Gy x 5. For image-guided planning, these are starting points; optimize to HR-CTV D90 about 85-95 Gy EQD2 while respecting OAR constraints.

EMBRACE-I: MR-guided adaptive brachytherapy produced about 92% 5-year local control with acceptable severe morbidity, establishing the modern IGBT benchmark.

Immunotherapy and Induction Chemo

KEYNOTE-A18 / FDA approval: pembrolizumab + CRT followed by maintenance improved PFS, with OS benefit in updated analyses. The FDA approval is for FIGO 2014 stage III-IVA cervical cancer; exploratory review showed benefit concentrated in stage III-IVA rather than IB2-IIB node-positive disease.

INTERLACE: induction carbo AUC2 + paclitaxel 80 mg/m2 weekly x 6 before standard CRT improved OS and PFS. Key exclusion: PA+ disease. A practical use case is when RT setup will be delayed.

Integration: both A18 and INTERLACE are positive, but combining induction carbo/pac with pembro-CRT is not established. Choose a coherent strategy rather than stacking all new intensification by reflex.

PART III - VULVAR CANCER

Management Paradigm + Dose Anchors

Scenario	Default approach	Dose anchor
T1a, DOI <=1 mm	Wide local excision; no groin staging if truly microinvasive.	No RT.
T1b/T2 clinically N0, resectable	Radical local excision + SLN mapping if eligible; inguinofemoral LND if SLN-ineligible or clinically suspicious nodes.	Adjuvant vulva RT 45-50.4 Gy for selected negative-margin risk; 54-60 Gy for close/positive margins if no re-excision.
SLN micrometastasis <=2 mm	Groin RT alone acceptable after GROINSS-V2.	Groin/elective nodal RT typically 45-50 Gy.
SLN macrometastasis >2 mm or ECE	Inguinofemoral LND +/- adjuvant nodal RT; RT strongly favored for >=2 nodes or ECE.	LN+ no ECE 50-55 Gy; ECE 54-64 Gy.
Locally advanced / unresectable	Definitive or preoperative chemoRT, usually weekly cisplatin; reassess for surgery only if needed.	Elective vulva/nodes 45-50 Gy; gross primary/nodes 60-70 Gy.
Metastatic / symptomatic recurrence	Systemic therapy and local RT for palliation or selected durable local control.	20 Gy / 5 fx, 30 Gy / 10 fx, or individualized re-irradiation/SBRT.

Pathology and Staging

Category	HPV-associated	HPV-independent / TP53 wt	HPV-independent / TP53 mut
Precursor	HSIL	Verrucous precursor / vaVIN	dVIN
Prognosis / RT behavior	Best; p16+ likely more RT-responsive	Intermediate	Worst

T/N	FIGO	Definition
T1a	IA	<=2 cm and stromal invasion <=1 mm.
T1b	IB	>2 cm or any size with invasion >1 mm.
T2	II	Extension to distal 1/3 urethra, distal 1/3 vagina, or anus.
T3	IIIA / IVA	Upper urethra/vagina, bladder or rectal mucosa, or fixed to bone.
N1a / N1b	IIIA / IIIB	1-2 nodes each <=5 mm, or one node >5 mm.
N2a / N2b	IIIA / IIIB	3+ nodes each <=5 mm, or 2+ nodes >5 mm.
N2c	IIIC	Lymph-node metastasis with extracapsular spread.
N3	IVA	Fixed or ulcerated lymph node.
M1	IVB	Distant metastasis, including pelvic nodes.

Regional nodes are inguinofemoral. Pelvic node involvement is M1/stage IVB in vulvar cancer, unlike cervical cancer.

Margins, Nodes, and Adjuvant Vulva RT

Heaps-style recurrence risks: margins <8 mm, tumor thickness >=10 mm, DOI >9 mm, infiltrative growth, and LVSI.
Modern margin nuance: highest local recurrence risk is with very close margins, especially <3 mm, positive margins, or precursor lesion at the margin. If re-excision is not feasible, adjuvant vulvar RT is favored.

Scenario	Dose
Post-op negative margins	45-50.4 Gy
Post-op close/positive margins	54-60 Gy
Uninvolved inguinofemoral nodes	45-50 Gy
Inguinofemoral LN+, no ECE	50-55 Gy
Inguinofemoral LN+ with ECE	54-64 Gy

Node-Positive Vulvar Landmarks

GROINSS-V1: in unifocal tumors <4 cm, clinically N0, DOI >1 mm, SLN-negative patients can observe the groin; 2-year groin recurrence was about 3%.

GOG-37: node-positive vulvar cancer randomized pelvic LND vs bilateral groin/pelvic EBRT. RT reduced cancer-related death; benefit was most pronounced with 2+ nodes or extracapsular spread.

GROINSS-V2 / GOG-270: SLN micromets <=2 mm can receive groin RT alone; SLN macromets >2 mm had excess groin recurrence with RT alone and need inguinofemoral LND +/- RT.

NCCN-Style SLN Algorithm

SLN negative - observe.
SLN micrometastasis - adjuvant groin RT.
SLN macrometastasis - inguinofemoral LND.
>=2 positive nodes or ECE - adjuvant RT.
Mapping Rules: For tumors <4 cm with DOI >1 mm. If tumor is within 2 cm of the midline (e.g., involving the urethra or clitoris), perform bilateral SLN mapping. If >2 cm from midline, unilateral is acceptable.

Locally Advanced / Unresectable Vulvar

Trial	Regimen	Results
GOG-101	Neoadjuvant cis/5-FU + RT 47.6 Gy	48% cCR, 31% pCR; very few persistently unresectable.
GOG-205	EBRT 45 Gy + boost to 57.6 Gy + weekly cisplatin	64% cCR and 50% pCR; classic current standard backbone.
GOG-279	Gemcitabine/cisplatin + IMRT	Higher pCR but high grade 3+ toxicity; not a simple replacement for weekly cisplatin.

Contouring: primary CTV is GTV + 2 cm respecting skin and bone unless involved. Include entire vulva, sparing mons for posterior lesions when appropriate. Add entire vagina if vaginal involvement, at least 2 cm superior anorectum if anus involved, and urethral extension depending on urethral involvement. Nodal CTV includes bilateral inguinofemoral, external iliac, obturator, and internal iliac; add presacral for upper vaginal/cervical involvement and mesorectal/perirectal/presacral for anal canal involvement.

Simulation Pearls

Supine, frog-legged in vac bag.
Wire scars, primary GTV, and vulvar skin borders; mark anus, urethra, and clitoris.
MRI simulation preferred, or CT simulation with MRI fusion.
Use bolus with TLD/OSLD verification for skin dose.
Keep package time <=15 weeks.

PART IV - VAGINAL CANCER

Management Paradigm + Dose Anchors

Scenario	Default approach	Dose anchor
Stage IA, <=2 cm superficial lesion	Vaginal brachytherapy preferred; surgery only when margin-negative resection is low morbidity.	Intracavitary VBT individualized, usually to surface or 5 mm by thickness.
Stage IB >2 cm or thicker lesion	Pelvic EBRT + intracavitary/interstitial brachytherapy boost.	EBRT 45-50 Gy + brachy to total about 70-80 Gy EQD2.
Stage II-IVA	Platinum-based chemoRT + brachytherapy boost.	EBRT 45-50 Gy to vagina/nodes +/- PA; total target dose often 70-85 Gy EQD2.
Lower-third vaginal involvement	Include bilateral inguinofemoral nodes in the elective field.	Groins typically 45-50 Gy; boost involved nodes.
Recurrent / metastatic	Salvage local therapy if encompassable and RT history permits; otherwise palliative/systemic approach.	20 Gy / 5 fx, 30 Gy / 10 fx, interstitial salvage, or SBRT by site/OARs.

Key Principles and Staging

Nearly all vaginal SCC is HPV-driven, like cervix; this contrasts with vulvar cancer, where only a subset is HPV-associated.
Early-stage disease strongly favors RT over surgery in many cases because surgical complication rates can be high.
Lower-third vaginal disease changes nodal coverage by adding groins.

Stage	Definition
I	Confined to vaginal wall.
II	Invades subvaginal tissue, not pelvic wall.
III	Extends to pelvic wall, hydronephrosis/nonfunctioning kidney, or regional nodal disease.
IVA	Invades bladder or rectal mucosa or extends beyond true pelvis.
IVB	Distant metastases.

Brachytherapy Boost

Target concept: GTV-Tres is residual tumor at brachytherapy; CTV-THR is residual tumor plus abnormal/thickened/irregular vaginal wall within initial tumor extent; CTV-TIR adds margins for initial disease extent.

Situation	Dose	Approximate intent
Upper/mid vagina, no nearby OARs	8 Gy x 3 interstitial	About 80 Gy EQD2 total.
Lower vagina or abutting bowel/urethra/rectum	6 Gy x 3 interstitial	About 70 Gy EQD2 total.

ABS vaginal interstitial principle: lesions thicker than about 0.5 cm at brachytherapy generally need interstitial technique. After EBRT, total dose commonly aims for 70-75 Gy EQD2 for distal/OAR-adjacent disease and 80-85 Gy for bulky residual or poor EBRT response.

EBRT and Survivorship

EBRT typically 45-50 Gy / 25 fx to vagina + pelvic/groin nodes +/- PA nodes with concurrent weekly platinum.
Lower-third vaginal disease: include inguinal nodes.
Encourage vaginal dilators after definitive cervical/vaginal RT and after vaginal/vulvar RT when stenosis risk is meaningful, regardless of sexual activity.
Use moisturizers/lubricants proactively; consider topical estrogen or systemic hormone therapy when clinically appropriate and not contraindicated.

PART V - OVARIAN / FALLOPIAN TUBE / PRIMARY PERITONEAL CANCER

Management Paradigm + Dose Anchors

Scenario	Default approach	RT / dose anchor
Apparent early-stage epithelial	Surgical staging/cytoreduction +/- adjuvant platinum chemotherapy by stage, grade, and histology.	No routine adjuvant RT.
Advanced stage III-IV epithelial	Primary debulking if optimally cytoreducible, or neoadjuvant carbo/pac then interval debulking then additional platinum-taxane chemotherapy.	No routine consolidative RT.
CR/PR after first-line platinum	Maintenance is biomarker/systemic: BRCA, HRD, and bevacizumab exposure drive PARP +/- bevacizumab vs observation/bev continuation.	No RT role for maintenance.
Isolated symptomatic recurrence	Local RT for pain, bleeding, obstruction, nodal/soft-tissue mass, bone, brain, or morbidity-prevention sites.	8 Gy x 1, 20 Gy / 5 fx, 30 Gy / 10 fx; tailor to bowel/OARs.
Oligometastatic / oligoprogressive recurrence	Selected SBRT or conformal RT can provide durable local control when systemic disease is otherwise controlled.	Often 24-40 Gy in 3-5 fx depending on site, size, prior RT, and bowel proximity.
Rare ovarian germ cell tumors	Surgery + platinum chemotherapy usually curative; dysgerminoma is radiosensitive historically, but RT is now rarely used.	Reserve RT for unusual salvage/palliation after multidisciplinary review.

Key Principles and Staging

Epithelial ovarian, fallopian tube, and primary peritoneal cancers are managed together. High-grade serous carcinoma is the dominant board-relevant histology and often arises from the fallopian tube fimbria.
FIGO pattern: stage I confined to ovary/tube; stage II pelvic extension; stage III peritoneal disease outside pelvis and/or retroperitoneal nodes; stage IV distant metastasis, with IVA malignant pleural effusion and IVB parenchymal or extra-abdominal disease including inguinal nodes.
Workup: CT chest/abdomen/pelvis, CA-125 and relevant markers, surgical-pathologic staging/cytoreduction, plus germline and somatic BRCA/HRD testing.

Systemic Treatment / Maintenance Pearl

Backbone: carboplatin/paclitaxel after primary or interval debulking; bevacizumab is added/continued in selected advanced/high-risk presentations.
Maintenance logic: BRCA-mutated disease strongly supports PARP maintenance; HRD-positive disease supports PARP-based maintenance, including olaparib + bevacizumab when bev was part of induction. HRD-negative/unknown disease is individualized.
Board trap: older questions may describe niraparib as all-comer maintenance. Current US first-line niraparib maintenance labeling is for HRD-positive advanced ovarian cancer after CR/PR to platinum chemotherapy.

Radiation Role

No routine adjuvant RT for epithelial ovarian cancer. Whole-abdominal RT is historical and rarely used because systemic therapy/maintenance drive outcomes and bowel toxicity is limiting.
Use RT selectively for palliation, morbidity prevention, or local control of limited recurrence: painful bone/soft tissue disease, bleeding, obstruction, nodal masses, brain metastases, or oligoprogressive sites.
SBRT can have high local control in selected small-volume ovarian recurrences, but evidence is mostly retrospective/phase II-level; present it as selected local therapy, not a routine survival-improving standard.
Clear Cell Histology: MDACC retrospective series demonstrated that for locoregionally recurrent disease treated with definitive involved-field RT, the clear cell subtype had significantly superior 5-year PFS and OS compared to other ovarian histologies.
Prior surgery, carcinomatosis, bowel adhesions, and bevacizumab exposure raise bowel/perforation/fistula concerns. Coordinate timing with medical oncology and keep bowel constraints conservative.

PART VI - BRACHYTHERAPY AT A GLANCE

Core framework — read this first

α/β = 10 for tumor (HR-CTV, GTV, IR-CTV); α/β = 3 for late-responding OARs (bladder, rectum, sigmoid, bowel, vagina).
All target and OAR goals are cumulative EBRT + brachy in EQD2, not brachy alone. The "85 Gy HR-CTV D90" target is the sum, not a single fraction.
Cervix prescription point: HR-CTV D90, not point A. ICRU 89 replaced ICRU 38; point A is still reported for legacy comparison.
VBT: always specify prescription depth (5 mm vs surface) — same nominal dose differs in mucosal EQD2 by 30-50%.
Total package time (start EBRT → last brachy fraction): aim <7-8 weeks. Beyond 8 weeks ≈1% local control lost per day via accelerated repopulation.

A. Cervix — EMBRACE-II target goals (EQD2, α/β = 10)

From the EMBRACE-II protocol (Pötter 2018); outcome benchmarks validated in EMBRACE-I.

Volume	Metric	Planning aim	Limit (acceptable)
GTV-Tres (residual gross tumor)	D98	≥95 Gy	≥90 Gy
HR-CTV	D90	≥90 Gy	≥85 Gy
HR-CTV	D98	≥75 Gy	—
IR-CTV	D90	≥60 Gy	—
Point A (legacy)	—	Reported; typically 75-85 Gy	—

Dose-response anchor: HR-CTV D90 ≥85 Gy → ≈96% 3-year local control in tumors ≤30 cc and ≈91% in tumors >30 cc. Bulkier disease pushes the aim toward 90-95 Gy.

B. Cervix — EMBRACE-II OAR constraints (D2cc, EQD2, α/β = 3)

OAR	Metric	Planning aim	Limit
Bladder	D2cc	<80 Gy	<90 Gy
Rectum	D2cc	<65 Gy	<75 Gy
ICRU recto-vaginal point	Point dose	<65 Gy	<75 Gy
Sigmoid	D2cc	<70 Gy	<75 Gy
Bowel	D2cc	<70 Gy	<75 Gy
Vagina (PIBS ± 2 cm)	Point dose	<65 Gy	—

PIBS = posterior-inferior border of pubic symphysis, a vaginal-length reference point. PIBS±2cm acts as a surrogate for mid/lower vaginal dose; aim <65 Gy EQD2 to limit vaginal stenosis and dyspareunia.

C. Cervix — HDR fractionation starting points (after 45 Gy EBRT)

Brachy regimen	HR-CTV brachy contribution (EQD2, α/β = 10)*	Notes
7 Gy × 4	≈48 Gy	EMBRACE-II standard; total HR-CTV ≈92 Gy EQD2.
8 Gy × 3	≈43 Gy	Shortens package time; popular when efficiency matters.
6 Gy × 5	≈40 Gy	Lower dose/fraction; OAR-friendly.
5.5 Gy × 5	≈35 Gy	For smaller residual disease.
5 Gy × 6	≈38 Gy	Lowest dose/fraction option.

*Assumes prescription to HR-CTV D90. Add to EBRT EQD2 (≈44 Gy from 45 Gy/25 fx with α/β = 10) for total target dose.

Optimize, don't prescribe blindly: these are starting points. The deliverable is HR-CTV D90 of 85-95 Gy EQD2 while keeping every OAR D2cc within limits. Switch from intracavitary alone (T+O, T+ring) to IC/IS hybrid (interstitial needles) when HR-CTV ≥30-40 cc, parametrial extension persists at brachy, or IC alone cannot achieve target coverage without OAR violation.

D. Endometrial vaginal cuff brachytherapy (VBT) — monotherapy

Anchor regimen: PORTEC-2 used 7 Gy × 3 at 5 mm depth, weekly, upper half of vagina. ABS guidelines accept multiple equivalent regimens.

Regimen	Prescription depth	EQD2 at Rx point (α/β = 3)*	Comment
7 Gy × 3	5 mm	≈42 Gy at 5 mm	PORTEC-2 standard; most common in US.
5.5 Gy × 4	5 mm	≈34 Gy at 5 mm	NCCN-listed alternative.
5 Gy × 5	5 mm	≈33 Gy at 5 mm	Lower dose/fx alternative.
2.5 Gy × 6	5 mm	≈13 Gy at 5 mm	Low-dose-per-fraction style; toxicity-sparing.
6 Gy × 5	Surface	≈36 Gy at surface	Surface Rx; dose falls steeply to 5 mm.
30 Gy / 6 fx (5 Gy × 6)	5 mm	≈39 Gy at 5 mm	Mayo-style schedule.

*EQD2 calculated at the prescription depth. Mucosal (surface) dose is always higher than the 5 mm prescription dose.

Technical: treat the upper 3-5 cm of vagina (PORTEC-2 = upper half). Use the largest comfortable cylinder (typically 2.5-3.5 cm diameter) to minimize air gaps and mucosal hot spots. 3D planning recommended to assess air gaps and OAR dose. About 95% of vaginal lymphatics lie within 3 mm of the mucosal surface, which is the rationale for the standard 5 mm prescription depth.

Prescription depth trap: a "6 Gy × 5" regimen delivers very different mucosal dose at surface vs 5 mm. Always specify depth in board answers, plan documentation, and dictations.

E. Endometrial VBT — boost after pelvic EBRT

Regimen	Prescription depth	Comment
6 Gy × 3	Surface	Most common cuff boost after 45 Gy EBRT.
5 Gy × 3	Surface	Toxicity-sparing alternative.
4 Gy × 3	5 mm	Common 5 mm-depth boost.
5 Gy × 2	5 mm	Shorter course alternative.
4-6 Gy × 2-3	Surface or 5 mm	ABS-accepted range; individualize by histology, residual risk, and OAR proximity.

F. Definitive endometrial brachy — medically inoperable

Scenario	Approach	EQD2 target (α/β = 10)
Minimal/no MI, no cervix involvement, low-risk histology	Brachy alone (Heyman/Rotte capsules or T±O/ring)	Uterine CTV 48-62.5 Gy
Deep MI, cervical extension, or nodal-risk features	EBRT 45 Gy + HDR boost	CTV 65-75 Gy; GTV 80-90 Gy

Applicator choice: Heyman/Rotte capsules pack the fundus for bulky uterus; conventional tandem ± ovoids/ring suffice for smaller cavities. MRI-based planning is the modern standard for image-guided uterine brachy.

G. Vaginal cancer brachytherapy

Situation	Approach	Total EQD2 target
Stage IA, ≤2 cm, superficial (≤5 mm thick)	Intracavitary cylinder alone	Individualized; prescribe to surface or 5 mm by lesion thickness.
Stage IB+ or residual >5 mm thick at brachy	Interstitial after EBRT 45-50 Gy	Total target 70-85 Gy EQD2.
Lower vagina or adjacent to urethra/rectum/bowel	6 Gy × 3 interstitial	≈70 Gy total.
Upper/mid vagina, OARs distant, bulky residual	8 Gy × 3 interstitial	≈80 Gy total.

ABS principle: if residual tumor is >0.5 cm thick at brachy, use interstitial technique (not cylinder alone). Apply the same volumetric framework as cervix: GTV-Tres (residual), CTV-THR (residual + abnormal vaginal wall in initial extent), CTV-TIR (with initial-extent margins).

H. High-yield technical pearls and traps

ICRU 89 replaced ICRU 38 for cervix brachy reporting: volumetric (D90, D2cc) replaced legacy point A and ICRU bladder/rectum point doses. Point A is still reported for historical comparison.
IC/IS hybrid use: EMBRACE-II expects >20% of cohorts to receive intracavitary/interstitial hybrid implants. Threshold to add needles: HR-CTV ≥30-40 cc, parametrial extension, asymmetric residual, or IC alone undershoots target/violates OARs.
Implant geometry matters: air gaps, tandem deviation, and poor packing all increase local failure risk and OAR dose simultaneously. Implant quality is a testable board topic.
Cervix brachy cannot be omitted in definitive treatment. External boost (SBRT, IMRT cone-down) does not substitute — omission is associated with worse survival.
Cumulative dose framework: the 85 Gy HR-CTV D90 target is EBRT + brachy summed in EQD2. EBRT 45 Gy/25 fx ≈ 44 Gy EQD2 to target (α/β=10).
Package time: aim <7-8 weeks total (start EBRT → last brachy fraction). ≈1% local control loss per day beyond 8 weeks.
Vaginal lymphatics: ≈95% lie within 3 mm of the mucosal surface — rationale for the 5 mm Rx depth in cuff brachy.
Cylinder sizing: use the largest comfortable diameter; smaller cylinders create mucosal hot spots and more air gaps at the dome.
EBRT contribution to OAR D2cc: the standard EMBRACE assumption is that EBRT delivers prescription dose uniformly to the OAR D2cc; some institutions now use patient-specific DVH addition for more accurate cumulative dose.

I. Acronym cheat sheet

Term	Meaning
HR-CTV	High-risk CTV: residual GTV + whole cervix + grey zones at brachy.
IR-CTV	Intermediate-risk CTV: HR-CTV + margins for initial extent and regression pattern.
GTV-Tres	Residual gross tumor at time of brachy ("Tres" = residual at time of brachytherapy).
D90 / D98	Dose covering 90% / 98% of the target volume.
D2cc	Dose to the most-irradiated 2 cc of an OAR; volume-based replacement for ICRU rectum/bladder point doses.
PIBS	Posterior-inferior border of pubic symphysis (EMBRACE-II vaginal-length reference point).
IGABT / IGBT	Image-guided (adaptive) brachytherapy; MRI is the gold-standard modality.
IC / IS / IC-IS	Intracavitary / interstitial / hybrid combined applicator.
T+O / T+R	Tandem and ovoids / tandem and ring (classic intracavitary applicators).
EQD2	Equivalent dose in 2 Gy fractions; standardized framework for comparing fractionation schedules.
ICRU 89	Current cervix brachy reporting standard; introduced volumetric reporting (D90, D2cc), replacing ICRU 38 point-based reporting.

CROSS-CUTTING HIGH-YIELD POINTS

Endometrial FIGO 2023 is heavily tested: especially POLEmut / IAm, p53abn / IICm, aggressive histology no-MI becoming IC, and substantial LVSI as independent IIB upstager.
Substantial LVSI: >5 vascular spaces or >50% of vessels in an area.
Nodal classifications: endometrial separates IIIC1i vs IIIC1ii; cervical FIGO 2018 uses r vs p suffixes; vulvar uses node size, number, and ECE.
Pelvic insufficiency fractures (PIF): The 5-year actuarial incidence of PIF following pelvic EBRT for gynecologic malignancies is approximately 15%.
PORTEC-2: VBT is the HIR standard. PORTEC-3: chemoRT matters in high-risk disease. GOG-258: chemo alone does not replace RT for locoregional control.
GOG-238: do not routinely add weekly cisplatin to salvage RT for RT-naive vaginal/pelvic endometrial recurrence.
Sedlis = post-op RT for cervical high-intermediate risk; Peters = post-op chemoRT for positive margins, positive nodes, or positive parametrium.
Cervix brachytherapy cannot be omitted: aim HR-CTV D90 about 85-95 Gy EQD2; total package time should be <8 weeks.
KEYNOTE-A18: pembro + chemoRT for FIGO 2014 III-IVA cervical cancer. INTERLACE: induction carbo/pac then CRT is an alternative positive strategy. Combining both is not established.
OUTBACK and CALLA are negative: no routine outback chemo after CRT, and durvalumab + CRT was not positive in unselected LACC.
GOG-37: RT beat pelvic LND strategy for node-positive vulvar cancer.
GROINSS-V2: SLN micromets get RT alone; SLN macromets need IFL +/- RT.
Vulvar pelvic nodes are M1 / IVB, unlike cervical cancer where pelvic nodes are regional.
Lower-third vaginal cancer requires inguinal nodal coverage.
Ovarian/fallopian/primary peritoneal cancer is primarily surgical/systemic: no routine adjuvant RT for epithelial disease. RT is selective for palliation, local control, oligoprogression, or rare salvage scenarios.
Ovarian maintenance: think BRCA / HRD / bevacizumab exposure before naming a PARP strategy.
Duodenum constraints for extended-field RT: V55 <15 cc, V60 <2 cc.

CONSOLIDATED DOSE TABLE

Setting	Dose / regimen	Comment
Endometrial VBT monotherapy	7 Gy x 3 at 5 mm	Common HIR cuff-brachy anchor.
Endometrial pelvic EBRT	45-50.4 Gy	Stage II, pelvic-risk, stage III sequencing.
Endometrial gross nodes	55-60 Gy	Boost/SIB when OARs allow.
Medically inoperable EC, brachy alone	48-62.5 Gy EQD2	Minimal/no invasion and no cervix/nodal risk.
Medically inoperable EC, EBRT + HDR	65-75 Gy EQD2 CTV; 80-90 Gy EQD2 GTV	Deep invasion, cervical extension, or nodal-risk features.
Cervix definitive EBRT	45 Gy / 25 fx	With weekly cisplatin and brachytherapy.
Cervix positive nodes	55-60 Gy EQD2	Pelvic nodes may receive small brachy contribution; PA nodes do not.
Cervix HR-CTV D90	85-95 Gy EQD2	Modern image-guided brachy target.
Cervix HDR starting points after 45 Gy	7 Gy x 4, 6 Gy x 5, 5 Gy x 6, 5.5 Gy x 5	Optimize to target and OAR constraints.
Post-op cervix pelvis	45-50.4 Gy	Sedlis or Peters pathway.
Vulvar negative-margin risk	45-50.4 Gy	Selected adjuvant vulva RT.
Vulvar close/positive margins	54-60 Gy	If re-excision not feasible.
Vulvar gross primary/nodes	60-70 Gy	Definitive or unresectable disease.
Vaginal EBRT	45-50 Gy	Pelvic +/- groin/PA nodes with platinum.
Vaginal brachy total dose	70-85 Gy EQD2	Depends on residual, location, and OARs.
Ovarian palliation	8 Gy x 1, 20 Gy / 5, 30 Gy / 10	Symptom-directed.
Ovarian oligometastatic SBRT	24-40 Gy / 3-5 fx	Selected local control strategy.

KEY LANDMARK TRIALS (memorize)

Trial	Disease	One-line takeaway
GOG-33	Endometrial surgical staging	Grade/depth predict pelvic and PA nodal risk; pelvic LN+ implies high PA risk.
PORTEC-1	Endometrial stage I	EBRT reduces LRR, no OS benefit; many failures are vaginal.
GOG-99	Endometrial early-stage	Defined HIR; EBRT reduces recurrence, no OS benefit.
PORTEC-2	Endometrial HIR	VBT non-inferior to EBRT with better QOL.
GOG-249	Endometrial HIR/high-risk	VBT + chemo not superior to EBRT; more nodal failures.
PORTEC-3	Endometrial high-risk	ChemoRT improves FFS and long-term OS; p53abn benefits most; POLE does not benefit.
GOG-258	Endometrial III/IVA or serous/clear cell	Chemo alone insufficient for locoregional control; CRT does not improve OS vs chemo alone.
PORTEC-4a	Endometrial HIR	Molecular-guided adjuvant therapy is feasible and management-changing.
GOG-238 / NRG	Recurrent endometrial	RT alone for classic RT-naive vaginal/pelvic recurrence; cisplatin adds toxicity without PFS benefit.
NRG-GY018	Advanced/recurrent endometrial	Pembro + carbo/pac improves PFS in dMMR and pMMR advanced/recurrent disease.
RUBY	Advanced/recurrent endometrial	Dostarlimab + carbo/pac improves PFS and has an OS signal.
KEYNOTE-B21	Adjuvant high-risk endometrial	No DFS benefit in all-comers after curative surgery; dMMR subgroup signal.
GOG-92 / Sedlis	Cervix post-radical hysterectomy	Post-op EBRT for HIR defined by LVSI, invasion depth, and size.
GOG-109 / Peters	Cervix post-op high-risk	ChemoRT beats RT alone for margin+, LN+, or parametrium+.
LACC	Early cervical surgery	Open radical hysterectomy beats MIS radical hysterectomy.
SHAPE / ConCerv	Low-risk early cervical	Simple hysterectomy can replace radical hysterectomy in carefully selected <=2 cm low-risk disease.
Vale meta-analysis	Cervix CRT	Concurrent chemoRT improves OS, most in earlier locally advanced stages.
OUTBACK / CALLA	LACC intensification	Outback chemo and durvalumab + CRT were negative.
EMBRACE-I	Cervix IGBT	Modern MR-IGBT benchmark with excellent local control.
EMBRACE-II	Cervix IGBT protocol	Prospective dose prescription protocol with planning aims and limits for targets and OARs.
KEYNOTE-A18	LACC FIGO 2014 III-IVA	Pembro + CRT improves outcomes; FDA approval is stage III-IVA.
INTERLACE	LACC	Induction weekly carbo/pac then CRT improves OS/PFS.
GROINSS-V1	Early vulvar SLN	SLN-negative groin observation is safe in selected unifocal tumors <4 cm.
GROINSS-V2 / GOG-270	Vulvar SLN+	Micromets get RT alone; macromets require IFL +/- RT.
GOG-37	Node-positive vulvar	Groin/pelvic RT reduced cancer death vs pelvic LND strategy.
GOG-205	Unresectable vulvar	Weekly cisplatin + RT to 57.6 Gy produced strong cCR/pCR.
GOG-279	Unresectable vulvar	Gem/cis + IMRT increased pCR but with high toxicity.
SOLO-1	BRCA-mutated advanced ovarian	Olaparib maintenance after platinum response markedly improves PFS.
PRIMA	Advanced ovarian after platinum response	Niraparib maintenance improves PFS; current US first-line label is HRD-positive disease.
PAOLA-1	HRD-positive ovarian receiving bevacizumab	Olaparib + bevacizumab maintenance is a key HRD-positive strategy.
GOG-218 / ICON7	Advanced ovarian	Bevacizumab with chemotherapy/maintenance improves PFS in selected advanced/high-risk patients.
Ovarian local RT / SBRT series	Recurrent ovarian	RT can palliate or control selected limited sites; it is not routine adjuvant therapy.