# Radiation Oncology/Vagina/Treatment

* Front Page: Radiation Oncology | RTOG Trials | Randomized Trials
Vaginal Cancer Treatment

## Overview

* Primary radiotherapy is considered treatment of choice in most localized vaginal cancer.
** Favorable tumor control
** Primary radiotherapy consists of external beam radiotherapy +/- brachytherapy boost
** EBRT is typically AP/PA 40-45 Gy, with Brachytherapy boost to 50-80 Gy depending on stage. Inferior border is typically 4cm below most caudad extent of disease (localized with platinum marker). Medial inguinofemoral LN included with distal 1/3 vagina lesions
** Brachytherapy alone may be considered for <2cm, well differentiated lesion, <0.5cm thick
** Radiation typically contraindicated in verrucous carcinoma.
* Primary chemo-RT has been reported by couple institutions, with tolerable toxicity and good control
* Surgical management would include radical hysterectomy, partial vaginectomy, and bilateral lymphadenectomy.
** Surgery worsens functional outcome as compared to radiation.
* 5-year survival:
| Stage 0 | 96% |
| Stage I | 73% |
| Stage II | 58% |
| Stage III/IV | 36% |

## Primary Radiotherapy

* Indiana University; 2009 PMID 19509572 -- "Indiana University experience in the management of vaginal cancer." (Sinha B, Int J Gynecol Cancer. 2009 May;19(4):686-93.)
** Retrospective. 45 patients, treated with RT alone (n=30), chemo-RT (n=9), and surgery + RT (n=6). Median tumor dose 73 Gy. Median F/U 5.8 years
** Outcome: 5-year PFS 77%, OS 71%. 5-year OS by stage: I 92%, II 82%, III/IVA 20%. Only stage predicted for outcome
** Conclusion: Early stage vaginal cancer can be managed with RT; stage III and IV have poor outcome
* Munster, Germany; 2009 (1968-2005) PMID 19330296 -- "Long-term results of radiotherapy in primary carcinoma of the vagina." (Hegemann S, Strahlenther Onkol. 2009 Mar;185(3):184-9. Epub 2009 Mar 28.)
** Retrospective. 41 patients , treated with RT alone. Pelvic dose 50 Gy, involved inguinal dose 60 Gy, intravaginal BT in 63% to 40 Gy LDR or 42/6 HDR. Stage I 17%, Stage II 32%, Stage III 32%, Stage IV 19%
** Outcome: OS 1-year 85%, 5-years 41%, 10-years 27%. CR in 51%, PR 41%.
** Toxicity: Acute G3+ 24%, late G3 7% (1 rectovaginal fistula, 1 epithelial necrosis, 1 radiation colitis)
** Conclusion: Definitive RT is the treatment of choice, with reasonable toxicity
* M.D. Anderson; 2005 (1970-2000) PMID 15850914 -- "Definitive radiation therapy for squamous cell carcinoma of the vagina." (Frank SJ, Int J Radiat Oncol Biol Phys. 2005 May 1;62(1):138-47)
** 193 patients treated w/ definitive RT. In general, EBRT 40-45 Gy in 20-25 fx, followed by brachytherapy to deliver a total (including EBRT) 75-80 Gy.
** Outcome: 85% DSS at 5 yrs for stage I, 78% DSS for stage II, 58% DSS for stage III-IV. Control in pelvis at 5 yrs - 86% for stage I, 84% for stage II, 71% for stage III-IV.
** Predominant mode of failure was locoregional (68% for stage I-II, 83% stage III-IV); 82% DSS if <4cm, 60% if >4cm.
** Conclusion: Excellent outcome with RT alone; however, therapy must be individualized
* Vienna (Austria)
** 2003 PMID 12829129 -- "High-dose-rate (HDR) brachytherapy with or without external beam radiotherapy in the treatment of primary vaginal carcinoma: long-term results and side effects." (Mock U, Int J Radiat Oncol Biol Phys. 2003 Jul 15;56(4):950-7.)
*** Retrospective. 86 patients. Stage 0-II treated with intravaginal HDR alone (30%), Stage II-IV HDR + EBRT (65%), palliative EBRT in 5%
*** Outcome: 5-year OS: Stage 0 83%, Stage I 41%, Stage II 43%, Stage III 37%, Stage IV 0%; DFS 100%, 77%, 50%, 23%, 0%.
*** Toxicity: bladder/rectum <2%, vagina up to 6%
*** Conclusion: HDR well tolerated, and effective
** 2001 PMID 11264612 -- "Radiotherapy alone for invasive vaginal cancer: outcome with intracavitary high dose rate brachytherapy versus conventional low dose rate brachytherapy." (Kucera H, Acta Obstet Gynecol Scand. 2001 Apr;80(4):355-60.)
*** Retrospective. 190 patients, 80 patients with HDR +/- EBRT compared with historical group of 110 LDR +/- EBRT
*** Outcome: No difference in OS, local and distant recurrences
*** Conclusion: HDR at least similar in outcome, with better delivery
* MSKCC Brachytherapy; 1992 PMID 1429100 -- "The importance of brachytherapy technique in the management of primary carcinoma of the vagina." (Stock RG, Int J Radiat Oncol Biol Phys. 1992;24(4):747-53.)
** Retrospective. 49 patients treated w/ definitive RT. Brachy techniques included intracavitary (HDR vag cylinder, LDR T&O, LDR vag cylinder) and interstitial.
** Outcome: 5-year OS Stage I 44%, Stage II 48%, Stage III 40%, Stage IV 0%. Improved OS with additional brachytherapy (50% vs. 9%, SS)
** For stage II and III, trend to improved OS w/ use of interstitial implant (80% vs 45% DFS for stage II, 75% vs 44% DFS for stage III)
* Washington University - Retrospective
** 1999 (1953-1991) PMID 10219792 -- "Factors affecting long-term outcome of irradiation in carcinoma of the vagina." (Perez CA, Int J Radiat Oncol Biol Phys. 1999 Apr 1;44(1):37-45.)
*** 212 pts (192 invasive, 20 in situ) treated w/ definitive RT.
*** 10-yr DFS 94% for Stage 0, 80% for Stage I, 55% for Stage IIA, 35% for Stage IIB, 38% for Stage III, 0% for Stage IV. Distant metastasis 13% Stage I, 30% IIA, 52% IIB, 50% III, and 47% IV.
*** Conclusion: "Radiation therapy is an effective treatment for patients with vaginal carcinoma, particularly Stage I. More effective irradiation techniques, including optimization of dose distribution combining external irradiation and interstitial brachytherapy in tumors beyond Stage I, are necessary to enhance locoregional tumor control. The high incidence of distant metastases emphasizes the need for earlier diagnosis and effective systemic cytotoxic agents to improve survival in these patients."
** 1988 PMID 3198434 -- "Definitive irradiation in carcinoma of the vagina: long-term evaluation of results." (Perez CA, Int J Radiat Oncol Biol Phys. 1988 Dec;15(6):1283-90.)
*** Retrospective. 165 patients treated w/ definitive RT. Stage I generally treated w/ brachy alone (intracavitary or interstitial) w/ 86% local control in pelvis.
*** Outcome: 10 yr OS 75% for stage I, 55% for IIA, 43% for IIB, 32% for III.
* University of Utah; 2016- Retrospective SEER
** PMID 27036631 -- "Brachytherapy improves survival in primary vaginal cancer." (Orton AW, Gynecol Oncol. 2016 Apr 141(3):501-506.)
*** 2517 pts treated w/ definitive RT alone v.s. BT (boost or solo modality). Propensity score matched analysis of benefit of BT.
*** Median OS improved with inclusion of BT (6.1 vs. 3.6 years). Utilization of BT has decreased over study period by 0.5% per year. NNT to prevent one death due to vaginal cancer was 8. All FIGO stages benefitted from BT; larger tumors and higher stages benefitted more.
*** Conclusion: "Brachytherapy improves survival for women with all stages of vaginal cancer (especially larger tumors), and should be encouraged for all suitable patients."

## Chemo-RT

* Ryukyus, Japan; 2008 (2002-2005) PMID 18704634 -- "Concurrent chemoradiation for locally advanced squamous cell carcinoma of the vagina: case series and literature review." (Nashiro T, Int J Clin Oncol. 2008 Aug;13(4):335-9. Epub 2008 Aug 15.)
** Retrospective. 6 patients (Stage II 2, Stage III 1, Stage IVA 3). Pelvic EBRT 50 Gy, then 2 patients vaginal BT, 4 EBRT boost, total dose 60-66 Gy. Concurrent cisplatin 20 mg/m2 x5d Q3W
** Outcome: 1/2 Stage II patients died of disease at 2 years, 1/1 Stage III patients local failure at 1 year, remaining 4 patients disease-free 1.5-4.5 years later
** Toxicity: 1 vesico-vaginal fistula; no G3-5 toxicity
** Conclusion: Chemo-RT effective and should be considered in high-risk disease
* Ontario; 2007 (1999-2004) PMID 17512130 -- "Primary vaginal cancer treated with concurrent chemoradiation using cis-platinum." (Samant R, Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):746-50.)
** Retrospective. 12 patients, 50% Stage II, 33% Stage III, 17% Stage IVA. Treated with concurrent weekly cisplatin 40mg/m2 + RT (EBRT 45/25 + interstitial/intracavitary BT 30 Gy)
** Outcome: 5-year OS 66%, PFS 75%, LRC 92%
** Conclusion: Concurrent cisplatin+RT feasible, excellent control
* UC Davis; 2004 (1986-1996) PMID 14764038 -- "Chemoradiation for primary invasive squamous carcinoma of the vagina." (Dalrymple JL, Int J Gynecol Cancer. 2004 Jan-Feb;14(1):110-7.)
** Retrospective. 14 patients, 21% Stage I, 71% Stage II, 7% Stage III. Treated with primary chemo-RT. Median RT dose 63 Gy, chemo 5-FU or cisplatin/5-FU or mitomycin
** Outcome: OS 65% at median 8.3 years
** Conclusion: Concurrent chemo-RT effective
* Princess Margaret; 1995 (1974-1989) PMID 7705681 -- "Carcinoma of the vagina--experience at the Princess Margaret Hospital (1974-1989)." (Kirkbride P, Gynecol Oncol. 1995 Mar;56(3):435-43.)
** Retrospective. 153 patients, 128 RT, 26 concurrent chemo
** Outcome: 5-year DSS Stage 0 100%, Stage I/II 77%, Stage III/IV 56%
** Toxicity: severe late complication 6%
** Conclusion: RT effective, dose >=70 Gy recommended

## Sequellae of Radiation Therapy

* Early: External beam radiation to the vagina causes extreme pain and moist desquamation to the entire genital/perineal area.
* Late: Vaginal stenosis/fibrosis (vaginal dilators recommended to minimize), cystitits, proctitis, rectovaginal or vesicovaginal fistula