imrt for the treatment of anal cancer
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IMRT for the Treatment of Anal Cancer. Kristen O’Donnell, MS3 December 12, 2007. Anal Cancer: Just the Facts. Estimated new cases in the US in 2007 4,650 Estimated Deaths 690 Pathology ~80% Squamous cell carcinoma, Other 20% adenocarcinoma or melanoma. - PowerPoint PPT PresentationTRANSCRIPT
IMRT for the Treatment of Anal Cancer
Kristen O’Donnell, MS3
December 12, 2007
Anal Cancer: Just the Facts
Estimated new cases in the US in 2007 4,650
Estimated Deaths 690
Pathology ~80% Squamous cell carcinoma,
Other 20% adenocarcinoma or melanoma.
HPV associated, same pathogenic serotypes as cervical cancer, 16 & 18
(Jemal et al., 2007; Hansen and Roach, 2007)
Anal Cancer: Just the FactsAnatomy:
3-4 cm anal canal
Anal verge to dentate line
Lymph node drainage:
Perirectal
Internal iliac
Inguinal nodes
(Up-to-date; cancerbackup.org)
Staging
TT0
Tis
T1 <2 cm
T2 >2 cm but <5 cm
T3 >5 cm
T4 invades adjacent organs
NN0
N1 perirectal
N2 unilateral internal iliac or inguinal
N3 perirectal and inguinal and/or bilateral inguinal and/or internal iliac
MM0
M1 distant metastases(Hansen and Roach, 2007)
Current Standard is Definitive Chemoradiotherapy for Anal Cancer
Radiotherapy alone vs. Chemoradiotherapy.
45 Gy alone or w/ concomitant 5-FU and mitomycin
UKCCCR, 1996: 585 epidermoid anal cancer patients with any stage disease randomized
EORTC, 1997: 110 patients with stage IIIA-B anal cancer randomized
(UKCCCR, 1996; Bartelink et al., 1997)
Current Standard is Definitive Chemoradiotherapy for Anal Cancer
EORTC No significant difference in acute toxicity
Diarrhea and skin reaction most common
Better complete remission rates 54%80%18% improvement in locoregional control32% improvement in Colostomy-free survival at 5 years
UKCCCRSignificantly decreases local recurrence
59% 36% local failure rate, Relative risk of 0.54
Decreases cancer related risk of death after 3 years
39% 28% anal cancer mortality, Relative risk 0.71
No significant overall survival benefit after 3 years
Radiotherapy 58% and Chemoradiotherapy 65%
(EORCT, Bartelink et al., 1997)
Current Standard is Definitive Chemoradiotherapy for Anal
Cisplatin and 5-FU chemotherapy with radiation therapy is an alternative regimen
Provides similar locoregional control, colostomy free survival and overall survival to 5-fu and mitomycin with radiotherapyCauses less toxicity (Hung et al., 2003)
RTOG 98-11: Standard concomitant 5-FU/mitomycin chemRT vs. Induction with 5-FU/Cisplatin then 5-FU/Cisplatin + RT
Reduced hematologic toxicityDecreased colostomy free survivalComplicated by induction treatment design (Gunderson et al., 2006)
Anal Cancer Trial II being conducted in the UK
(Das et al., 2007)
Rates of Locoregional Recurrence with Definitive Chemoradiotherapy
UKCCCR: 36% at 3 years
EORTC: ~32% at 5 years
M.D. Anderson: 14% at 3 years Study of 167 patients treated with definitive chemoRT for anal cancer.
(Das et al., 2007)
Patterns of Locoregional Recurrence
Das et al. at M.D. Anderson found:75% Recurred at anus or rectum21% Presacral and/or iliac regions
5/5 had RT field start at the bottom of the SI joints– 3/5 recurred above RT field, 1/5 marginal, 1/5 recurred
both above and within field
4% (1 patient) Inguinal recurrenceCompared to cited 8-15% risk of inguinal recurrence in studies of patients not receiving inguinal RT.
Locoregional control benefit from RT RT is very effective at inguinal nodes and iliac nodes with adequate treatment coverage.Need better local control at primary tumor site.
How will IMRT change these statistics?(Das et al., 2007)
IMRT
Utilizes detailed beam shapingCreates unique conformal distributions and sharp dose gradients
Increase the ability to:Target specific volumes
Limit normal tissue exposure
Use in the treatment of head and neck, prostate and gynecologic cancers.
IMRT in anal cancer
New application gaining support
Early studies show reduced toxicity rates with comparable local control and survival statistics.
Area of active studyRadiation Therapy Oncology Group is currently enrolling for a phase II trial (RTOG 0529).
IMRT Dosimetry studiesChen et al. Conventional AP/ PA pelvic fields vs. Conformal avoidance IMRT planning in 2 patients
Same PTV with IMRT plan assigned dose constraints for femoral heads and external genitalia. Comparable PTV coverage:
IMRT plan: 97-98% of PTV at 90% prescribed dose Conventional AP/PA: 94% of PTV at 90% prescribed dose
IMRT spared femoral heads 58-59% vs. 71-72% of prescribed dose and genitalia 55-63% vs. 78-97% with conventional planning
(Chen et al. 2005)
IMRT Dosimetry studiesLin and Ben-Josef Designed 9-field, non-coplanar IMRT plans for 5 patients with anal cancerVolumes:
GTV=anal tumor and positive nodesCTV= GVT + inguinal and iliac nodesPTV=CTV + 5 mm expansion
IMRT planning, 1° priority=PTV coverage2° priority=limiting dose to organs at riskUtilized Equivalent uniform dose for optimization
(Lin and Ben-Josef, 2007) ASCO Abstract
IMRT Dosimetry studiesResults:
Homogenous dose coverage 95% of PTV receiving 99% of prescribed dose
IMRT to treat anal cancer should decrease toxicity and has potential to improve local control.
(Lin and Ben-Josef, 2007) ASCO Abstract
Perineum Genitalia Small Bowel
Bladder Femoral Necks
Pelvis Sacrum
Dose Constraint (Gy)
36 36 50 50 45 50 50
Mean dose with IMRT (Gy)
13.5
±5.9
19.4 ±16.1
18.9
± 8.2
28.8
± 3.2
15.9
± 2.3
15.9
± 1.3
24.8
± 2.4
Clinical use of IMRT for anal cancer
Single institution study of 17 anal cancer patients treated with definitive chemoRT using IMRT planning.
Comparative dosimetric analysis of 7 patients: IMRT planning vs. 3-D AP/PA planning
Significant reduction in small bowel, bladder and perineum doses
ToxicityAll patients had mild-mod dermatitis No treatment breaks due to GI or skin toxicityAll GI and bladder toxicities were ≤ grade 2.
– EORTC trial showed frequent grade 3 GI and skin toxicity
Hematologic toxicity unchangedslightly worse than rate in RTOG trial
(Milano et al., 2005; Bartelink et al., 1997)
Clinical use of IMRT for anal cancer
Single institution study of 17 anal cancer patients treated with definitive chemoRT using IMRT planning
Similar outcomes to standard treatment14/17 complete response2 year progression free survival 65%Overall survival 91%Colostomy free survival 82%Local control 82%Distant control 74%
(Milano et al., 2005)
Multicenter experience with IMRT for anal cancer
53 patients treated at three academic medical centers with IMRT and chemotherapy for definitive treatment of anal cancer.
Toxicity58% completed treatment without interruption
Improved GI toxicity rates and severity Grade 3 in 15% with no Grade 4 RTOG 98-11: 34% of patients had Grade 3 - 4
Dermatologic, Grade 3 in 38%Similar to studies with 2-wk treatment breaksBetter than the 48% in RTOG 98-11
Hematologic toxicities were severe and common Grade 3 and 4 in 58% of patients as worstSimilar to RTOG 98-11 rates of 60%
(Salama et al., 2007)
Multicenter experience with IMRT for anal cancer
53 patients treated at three academic medical centers with IMRT and chemotherapy for definitive treatment of anal cancer.
ResponseComplete response in 92%Local recurrence rate 13% @ 18 months18-month colostomy free survival 83.7%18-month distant recurrence free survival 92.3%
(Salama et al., 2007)
Summary
Dosimetric studies and small clinical trials have shown reduced dosing and toxicity to normal structures with the use of IMRT.
No decreases in treatment effectiveness or local control rates have been detected.
Limited sample sizes and duration of follow-up minimize the ability to detect small variations in local control rates.
Future Studies using IMRT for Anal Cancer
RTOG 0529 A Phase II Evaluation of Dose-Painted IMRT in Combination with 5-Fluorouracil and Mitomycin-C for Reduction of Acute Morbidity in Carcinoma of the Anal Canal.
59 patients with histologically-proven, invasive primary squamous, basaloid, or cloacogenic carcinoma of the anal canal; Stage 2-4 and N0-N3 stage.
Currently enrolling