Radiation Oncology/Anal canal

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Front Page: Radiation Oncology | RTOG Trials | Randomized Trials

Contents 1 Epidemiology 2 Anatomy 3 Pathology 4 Staging 4.1 Current staging 4.2 Older staging systems 5 Spread 6 Treatment Overview 7 Outcomes 8 Surgery alone 9 Radiation alone 10 Surgery vs. Primary RT 11 Primary RT vs. Chemo-RT 12 RT + various chemo options 12.1 RT dose escalation 12.2 Neoadjuvant chemo, followed by chemo-RT 13 Management of Lymph Nodes 14 Salvage 15 Treatment planning 15.1 Segmental boost technique 15.2 Inguinal node photon boost 15.3 "Diamond" technique 15.4 IMRT 16 Other histologies

[edit] Epidemiology

• Rare malignancy, <2% of all GI cancers, 4% of anorectal cancers
• Not considered an AIDS-defining illness (unlike cervical ca)
• No known association b/w anal and rectal ca.
• Incidence= 0.5-0.7 per 100,000 (1-2% of colonic ca's). 4000 cases in US.
• Anal cancer more common in women (2:1), and women tend to have cancers above the dentate line.
• Mean age 55-65

• Risk factors include:
  • receptive anal intercourse
  • immunodeficiency
  • hx of genital warts or other STD's (esp. HPV 16 & 18)
  • cigarette smoking.

[edit] Anatomy

• Anal margin: distal to anal verge. Tumors arising here are classified and treated as skin cancers
• Anal verge: region where anal squamous mucosa merges with true epidermis of perianal skin (indistinct on macroscopic examination)
• Anal canal:
  • Extends from anorectal ring (where rectum enters puborectalis sling) proximally to anal verge distally
  • Proximal aspect from anorectal ring to dentate line is colorectal mucosa (~1-2 cm)
  • Middle aspect around dentate line is transitional mucosa
  • Distal aspect from dentate line to anal verge is modified (nonkeratinizing, no skin appendages) squamous epithelium (~2 cm)
• Carcinomas at anorectal junction are problematic: if epicenter >2cm proximal to dentate line, classified as rectal. If <2cm, classified as anal
• Lymphatic drainage:
  • 1) superiorly via rectal drainage along superior hemorrhoidal vessels to inferior mesenteric LNs
  • 2) from proximal anal canal (superior to dentate line) along inferior and middle hemorrhoidal vessels to internal illiac LNs
  • 3) from distal anal canal along skin to superficial inguinal LNs

[edit] Pathology

• PMID 6639856 - 970 residents of LA County between 1972-1981
  • Squamous cell 63%
  • Transitional (cloacogenic) 23%
  • Adenocarcinoma 7%
  • Paget's, basal cell, melanoma 2% each

[edit] Staging

[edit] Current staging

AJCC 7th edition (2009)

Primary Tumor:

• Tis - carcinoma in situ
• T1 - 2 cm or less
• T2 - 2 - 5 cm
• T3 - >5 cm
• T4 - invades adjacent organ, e.g. vagina, urethra, bladder. (invasion of the rectal wall, perirectal skin, subcutaneous tissue, or sphincter muscle is not included as T4.)

Regional Nodes:

Regional lymph nodes include: perirectal, lateral sacral, internal iliac (hypogastric), inguinal

• N0 - no lymph nodes
• N1 - perirectal lymph nodes
• N2 - unilateral internal iliac or (unilateral) inguinal lymph nodes or both
• N3 - perirectal AND inguinal lymph nodes; and/or bilateral internal iliac; and/or (bilateral) inguinal lymph nodes

Distant Metastases:

• M0 - no
• M1 - yes

Stage grouping:

• 0 - Tis
• I - T1 N0
• II - T2-3 N0
• IIIA - T1-3 N1, T4 N0
• IIIB - T4 N1, Any N2, Any N3
• IV - M1

[edit] Older staging systems

AJCC 6th Edition (2002)
No changes compared to 7th edition

[edit] Spread

• Primary route local and LN
• At presentation:
  • Overall risk of regional LN involvement ~25%
  • Pelvic LN+ 30% in some series with APR
  • Inguinal LN+ 15-30%
    • If clinically negative inguinal LN, 10-15% occult positive
• Extrapelvic visceral mets 5-10%

[edit] Treatment Overview

• Historically, APR was the primary treatment modality
• Wayne State study in 1973 showed that neoadjuvant chemo-RT had pathologic complete response at surgery, sparking interest in chemo-radiation to preserve sphincter function
• Comparison of retrospective series showed a comparable/improved survival of primary RT (+/- CT) compared to surgery
• UKCCCR and EORTC trials established chemo-radation (RT + 5-FU + Mitomycin) superior to RT alone as primary treatment strategy
• RTOG 87-04 demonstrated the continued necessity of Mitomycin as part of the protocol
• RTOG 98-11 showed that concurrent 5-FU/Mitomycin remains superior to induction 5-FU/cisplatin followed by concurrent 5-FU/cisplatin

• ACR Appropriateness Criteria, 2007 PMID 17601586 (Poggi MM, J Am Coll Radiol. 2007 Jul;4(7):448-56.)

[edit] Outcomes

• 5-year overall survival (primary RT, 5-FU, Mitomycin)

5-year outcomes

Stage	OS	Local Control	Sphincter fn
T1	80%	90-100%
T2	70%	65-75%
T3-T4	50%	40-55%
Overall	65-75%	60%	70%

HIV+

• Multi-National; 2008 (1988-2006) PMID 18427149 -- "HIV-specific differences in outcome of squamous cell carcinoma of the anal canal: a multicentric cohort study of HIV-positive patients receiving highly active anti-retroviral therapy." (Oehler-Janne C, J Clin Oncol. 2008 May 20;26(15):2550-7. Epub 2008 Apr 21.)
  • Retrospective. 40 HIV+ and 81 HIV- patients, treated with RT or CRT with 5-FU/mitomycin or cisplain. Median CD4 358. HIV+ younger (48 vs. 62), male (93% vs. 25%), early stage, large-cell histology.
  • Outcome: CR HIV+ 92% vs. HIV- 96%; 5-year OS HIV+ 61% vs. HIV- 65% (NS); 5-year LC 38% vs. 87% (SS)
  • Toxicity: Grade 3-4 skin HIV+ 35% vs. HIV- 17% (SS), hematologic 33% vs. 12% (NS)
  • Conclusion: Long-term LC and acute toxicity are clinical challenges for HIV+ patients

[edit] Surgery alone

• Local Excision
  • Local excision alone considered an investigational approach
  • Mayo, 1984 PMID 6326995 -- "Carcinoma of the anal canal. A clinical and pathologic study of 188 cases." (Boman BM, Cancer. 1984 Jul 1;54(1):114-25.)
    • 188 patients with anal canal CA. Squamous cell: 20% regional LN+, 2% distant mets. Transitional: 30% regional LN+, 20% distant mets
    • Local excision: 13 patients with small (<=2 cm) and superficial invasive treated by local excision. One required APR for local recurrence, others cured
    • APR: 114/118 patients treated with primary APR, 40% recurrent disease, but 71% survived >5 years

• Abdominoperineal resection
  • Historically (until 1970s) standard treatment
  • 5-year OS 40-60%; local relapse common
  • Now reserved as salvage for patients who fail radiation, or who had prior pelvic RT

[edit] Radiation alone

Only 50% cure with doses of 50-70 Gy; high rate of toxicity.

[edit] Surgery vs. Primary RT

• No randomized comparison with primary chemo-RT
• Shift away from surgery toward primary RT based on improved QOL (sphincter preservation, colostomy-free survival) with comparable/improved overall survival

• Stockholm, 1989 (1978-1984) PMID 2614221 -- "Management of anal epidermoid carcinoma--an evaluation of treatment results in two population-based series." (Goldman S, Int J Colorectal Dis. 1989 Dec;4(4):234-43.)
  • Retrospective comparison of 2 populations: 1) retrospective Stockholm group, 90 patients, treated by combination of surgery alone or by combinations of RT +/- CT +/- surgery, 2) prospective Uppsala trial of RT +/- CT
  • 5-year OS: Stockholm 43% vs. Uppsala 55%, if no initial dissemination 75% vs. 48%
  • Conclusion: initial treatment in anal CA should be RT (+/- CT)

[edit] Primary RT vs. Chemo-RT

• Both UKCCCR and EORTC trials showed improved local control and improved colostomy-free survival for chemo-radiation over RT alone. Neither trial showed a difference in survival
• Acute toxicity is worse in chemo-radiation, late toxicity is similar, but tolerable

• EORTC, 1997 (1987-1994) PMID 9164216 -- "Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups." (Bartelink H, J Clin Oncol. 1997 May;15(5):2040-9.)
  • Randomized. 110 patients. T3-4N0-3 or T1-2N1-3. Treated with 1) RT 45 Gy in 1.8 Gy/fx, if CR/PR then RT boost 15-20 Gy after 6 weeks or 2) RT + CI 5-FU + Mitomycin
  • Local control: RT 50% vs. CRT 68% (SS); colostomy-free survival RT 40% vs. CRT 72% (SS)
  • 5-year OS: 56%, no difference in survival
  • Toxicity: no difference in severe side effects, but anal ulcers more frequent in CRT

• UKCCCR, 1996 PMID 8874455 -- "Epidermoid anal cancer: results from the UKCCCR randomized trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research." (No Authors, Lancet. 1996 Oct 19;348(9034):1049-54.)
  • Randomized. 585 patients. 40% with large T3 or T4, 20% N+. Treated with 1)RT 45 Gy in 20-25 fxs or 2) same RT + CI 5-FU + Mitomycin. Clinical response at 6 weeks, responders RT 15 Gy boost or 25 Gy boost via Ir-192 BT, non-responders salvage surgery. Median F/U 3.5 years
  • Local failure (main endpoint): RT alone 59% vs. chemo-RT 36% (SS) for 46% risk reduction.
  • No difference in OS; CSS reduced significantly
  • Toxicity: Acute worse with chemo-RT, but late similar

[edit] RT + various chemo options

• ACCORD 03 (1999-2005)
  • Randomized. 2x2 design. 306 patients, tumor >= 4cm and/or LN+. Arm 1) induction chemo vs. Arm 2) induction chemo and higher RT dose vs. Arm 3) "standard RT" vs. Arm 4) higher RT dose
  • 2008 PMID 18191265 -- "Radiochemotherapy of locally advanced anal canal carcinoma: Prospective assessment of early impact on the quality of life (randomized trial ACCORD 03)." (Tournier-Rangeard L, Radiother Oncol. 2008 Jan 10 [Epub ahead of print])
    • Subset analysis, 119 patients. QOL pre-treatment (69%) and 2 months after therapy (47%), both (40%)
    • Outcome: Significant improvement in emotional function, global health status, insomnia, constipation, appetite, and pain. No difference among arms
    • Conclusion: Two months after treatment, QoL improved; induction chemo and/or higher RT dose didn't negatively impact QoL

• RTOG 98-11 / Intergroup (1998-2005) -- Concurrent 5-FU/Mitomycin C vs. Induction/concurrent cisplatin/5-FU
  • Randomized. 644 patients. Anal canal (squamous, basaloid, or cloacogenic), T2-T4, any N (by clinical, imaging, or biopsy). AIDS patients excluded. Arm 1) Concurrent 5-FU 1000 mg/m2 + Mitomycin C 10 mg/m2 + RT vs. Arm 2) Induction cisplatin 75 mg/m2 + 5-FU C.I. 1000 mg/m2 x2 cycles followed by concurrent cisplatin/5-FU (same doses) + RT
  • RT: large pelvic field (top border at L5/S1) to 30.6 Gy, with field reduction to bottom of SI joints for additional 14.4 Gy (to 45 Gy). Boost tumor + LN for T3, T4, or N+, or residual after 45 Gy for additional 10-14 Gy (2 Gy/fx) for total of 55-59 Gy. Use 2-2.5 cm margin for boost. Inferior field includes anus and tumor with margin of 2.5 cm. AP/PA or 4 field box. AP field includes inguinals. PA field extends laterally to 2cm beyond sciatic notch. Inguinal field: electrons to divergence of PA field; 36 Gy if N0, or 45 Gy if N+; depth measured by CT but at least 3cm depth. Inguinal boost with electrons. May have 10 day break as needed. Protocol (PDF)
  • 5-years; 2008: PMID 18430910 — "Fluorouracil, Mitomycin, and Radiotherapy vs Fluorouracil, Cisplatin, and Radiotherapy for Carcinoma of the Anal Canal." (Ajani JA et al, JAMA. 2008 Apr 23;299(16):1914-1921.) Median F/U 2.5 years
    • Outcome: 5-year DFS MMC 60% vs cisplatin 54% (NS); 5-year OS 75% vs 70% (p=0.10); LRR 25% vs 33%, DM 15% vs 19%. Worse colostomy rate: MMC 10% vs cisplatin 19% (SS).
    • Toxicity: Severe long-term toxicity similar (11% vs. 10%), higher severe hematologic toxicity with MMC.
    • Conclusion: Trial findings do not support use of cisplatin instead of mitomycin
  • Comment PMID 18519948 (Glynne-Jones R, Mount Vernon): Problem may have been with neoadjuvant chemo (NACT) as part of the protocol rather than with cisplatin not being effective. No comparison of concurrent 5-FU vs concurrent 5-FU/cisplatin with RT
  • Author Reply PMID 19047300 (Ajani JA, MDACC): Discussion of cancer stem cell role, and how the concept may impact sequencing of therapy
  • Further Exchange PMID 19398570 (Ajani JA, reply Glynne-Jones R).

• RTOG 87-04 (1988-1991) -- RT + 5-FU +/- Mitomycin
  • Randomized. 291/310 patients. Treated with 1) RT 45-50.4 Gy + 5-FU + Mitomycin or 2) RT + 5-FU. Residual tumor on post-treatment bx salvaged with pelvic RT 9 Gy + 5-FU + cisplatin
  • 1996 PMID 8823332 -- "Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study." (Flam M, J Clin Oncol. 1996 Sep;14(9):2527-39.)
    • Local control: post-treatment bx RT/5-FU 15% vs. RT/5-FU/MMC 8% (NS), 4-year colostomy rate 22% vs. 9% (SS), DFS 51% vs. 73% (SS)
    • Toxicity: MMC arm 23% vs. 7% (SS)
    • Conclusion: Despite greater toxicity, use of Mitomycin is justified

• Wayne State (original CRT studies)
  • 1985 PMID 3918441 — Leichman et al. "Cancer of the anal canal. Model for preoperative adjuvant combined modality therapy." Am J Med. 1985 Feb;78(2):211-5.
    • >2cm tumors (T2 or greater). 5-FU(1000 mg/m2) x 96 hours CI x 2 cycles (days 1-4, 29-32); mitomycin-C (15 mg/m2) bolus, day 1. XRT: 3000 cGy (200 cGy/fx, 3 weeks). Fields: AP/PA to pelvis and inguinals. Post-treatment biopsy at 4-6 weeks.
    • Originally required APR following this preoperative therapy. However, first 5 of 6 patients who underwent APR had pathologic complete response. For the remaining patients, APR was required only for patients with a positive post-treatment biopsy.
    • Results: 45 pts. negative biopsy: 84%. None with (-) biopsy had cancer recurrence. 89% survival (at 50 months) for those with (-) biopsy. All seven pts with (+) biopsy had recurrence and died of cancer.
    • Conclusion: APR is not necessary in patients with complete response after chemo/XRT. Chemo/XRT is definitive treatment, not neoadjuvant or adjuvant.
  • 1983 PMID 6831348 -- "Combined preoperative radiation and chemotherapy for squamous cell carcinoma of the anal canal." (Nigro ND, Cancer. 1983 May 15;51(10):1826-9.)
    • 28 patients. Treated with neoadjuvant RT 30 Gy (tumor+margin, pelvic LN, inguinal LN) + chemotherapy (5-FU/Mitomycin), followed by surgery 4-6 weeks later
    • 12 APR: 7 had no residual tumor, 1 had microscopic tumor only, 5 residual tumor (all >7 cm diameter). 14 complete clinical disappearance of tumor on post-treatment biopsy. 2 clinically free, but no biopsy or surgery done
    • Side effects: transient proctitis, leukopenia, thrombocytopenia
  • 1973 PMID 4830803 -- "Combined therapy for cancer of the anal canal: a preliminary report." (Nigro ND, Dis Colon Rectum. 1974 May-Jun;17(3):354-6.)
    • First report of 3 patients s/p neoadjuvant RT 30 Gy + concurrent 5-FU/Mitomycin, who showed pathologically complete response at time of surgery

• RTOG 83-14 (1989) (1983-87)

  5-FU/mitomycin-C/XRT

  • 79 pts. T1-4, N0. XRT: 40.8 Gy (170 cGy/fx, 24 fx). Mitomycin-C (10mg/m2) on day 2; 5-FU (1000 mg/m2; 4-day CI) on days 2, 28. Biopsy 6-8 weeks post-treatment. APR if biopsy positive.
  • 10% positive biopsies. At 3-years, OS 73%, DFS 61%.
  • Abstract — Sischy et al. "Definitive irradiation and chemotherapy for radiosensitization in management of anal carcinoma: interim report on Radiation Therapy Oncology Group study no. 8314." J Natl Cancer Inst. 1989 Jun 7;81(11):850-6.

[edit] RT dose escalation

• RTOG 92-08 PMID 9166533 -- "Dose escalation in chemoradiation for anal cancer: preliminary results of RTOG 92-08." (John M, Cancer J Sci Am. 1996 Jul-Aug;2(4):205-11.)
  • Dose-escalation, split course RT. 47 patients, cancer >= 2cm. RT 59.6 Gy split course with 2-week break. Comparison with RTOG 87-04
  • After unexpectedly high rates of colostomy (23%), treatment break was eliminated. 20 patients were treated. 9 completed protocol, 9 required treatment break anyway. Median RT dose 41 Gy (Abstract ASTRO 1997). Colostomy rate 11%
  • Conclusion: No improvement in local control in split-course RT. Suggest continuous RT, but may have to accept higher acute toxicity

[edit] Neoadjuvant chemo, followed by chemo-RT

• Stockholm, 2005 (Sweden) (1985-2000) PMID 15629599 -- "Epidermoid anal cancer: a review of a population-based series of 308 consecutive patients treated according to prospective protocols." (Nilsson PJ, Int J Radiat Oncol Biol Phys. 2005 Jan 1;61(1):92-102.)
  • Retrospective. 308 patient treated with 1) RT alone, 2) RT + bleomycin, or 3) neoadjuvant cisplatin followed by RT alone
  • 5-year OS: 68%
  • Neoadjuvant platinum + RT: better CR (92% vs. 76%), and better 5-year OS (63% vs. 44%) compared to RT +/- bleomycin in locally advanced tumors

[edit] Management of Lymph Nodes

Elective RT

• Elective irradiation of pararectal and medial internal illiac LNs accepted
• Inguinal LN RT causes little morbidity, and reduces risk of LN failure from 25% to 5% (Perez 4th ed). However, Lyon experience (PMID 11443612) suggests elective inguinal RT may not be necessary

Inguinal Nodes (+)

• Surgical approaches vary from radical dissection to local excision
• Surgery usually followed by RT or CRT
• Local control good (~80%) unless LNs ulcerated or fixed (Perez 4th ed)

Pelvic Nodes (+)

• Primary treatment with CRT or neoadjuvant CRT followed by APR

[edit] Salvage

• Local failure rate after CRT ~30%
  • ~50% persistent disease
  • ~50% recurrent disease (somewhat arbitrarily defined as DFS >6 months)
• APR appears to have curative potential; further chemo-RT is good first line option based on RTOG 87-04
  • 5-year OS after APR 25-60%

• MD Anderson, 2007 (1990-2002) PMID 17103253 -- "Results of surgical salvage after failed chemoradiation therapy for epidermoid carcinoma of the anal canal." (Mullen JR, Ann Surg Oncol. 2007 Feb;14(2):478-83.)
  • Retrospective. 31 patients radical salvage (11 for persistent and 20 for recurrent disease) after failure of sphincter-conserving therapy. Median F/U 2.4 years
  • 5-year OS: 64%
  • Predictors of salvage failure: initial RT dose <55 Gy (37% vs. 75%), initial LN+
  • Conclusion: long-term survival following salvage can be achieved

• RTOG 87-04 (1988-1991) RT + 5-FU +/- Mitomycin
  • 1996 PMID 8823332 -- "Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study." (Flam M, J Clin Oncol. 1996 Sep;14(9):2527-39.)
    • Please see above for main study outcomes. All salvage in this trial was first chemo-RT (additional 9 Gy through reduced 10x10 field or 9 Gy to inguinal LNs; with 5-FU 1000 mg/m2/d and 100 mg/m2 cisplatin), and only on residual disease after salvage were they offered APR. 25 patients salvaged, 22 post-salvage bx
    • 4-year salvage outcome: 12/22 (55%) negative biopsy; 4 disease free, 4 subsequent APR and free of disease, 1 died without disease, 3 died with disease. Overall 7/22 (32%) without colostomy
    • If failed salvage, APR in 9/10 (90%); 3 disease free, 1 died without disease, 6 died with disease
    • Conclusion: APR should not be immediately undertaken; 5-FU/cisplatin/RT good first line salvage

• Veterans Affairs, 1994 (1987-1991) PMID 8024357 -- "Recurrent squamous cell carcinoma of the anal canal. Predictors of initial treatment failure and results of salvage therapy." (Longo WE, Ann Surg. 1994 Jul;220(1):40-9.)
  • Retrospective. All patients treated in VA system. 405 identified, 164 evaluable squamous cell. 84% sphincter-preserving procedures, 16% radical surgery. 83% multimodality (surgery + chemo and RT mean 42Gy). Recurrences in 43/149 (30%) potentially curable patients
  • Predictors of recurrence: stage at diagnosis and method of treatment
  • Salvage: APR 53% alive vs. chemor +/- RT 19% alive
  • Conclusion: Salvage APR has curative potential, chemo and RT salvage disappointing

[edit] Treatment planning

[edit] Segmental boost technique

• • Yale, 2004 PMID 15275740 — Moran et al. "Improved treatment of pelvis and inguinal nodes using modified segmental boost technique: dosimetric evaluation." Int J Radiat Oncol Biol Phys. 2004 Aug 1;59(5):1523-30.

[edit] Inguinal node photon boost

• • Indianapolis, 2001 PMID 11295207 — "A technique for inguinal node boost using photon fields defined by asymmetric collimator jaws." Dittmer PH et al. Radiother Oncol. 2001 Apr;59(1):61-4.
  • Treats the pelvis using PA field, pelvis + inguinals using AP field, plus a further boost to the inguinals using AP photons with asymmetric collimator jaws (using the same isocenter).

[edit] "Diamond" technique

• McGill
  • 2007 PMID 17276620 — "Conformal therapy improves the therapeutic index of patients with anal canal cancer treated with combined chemotherapy and external beam radiotherapy." (Vuong T, Int J Radiat Oncol Biol Phys. 2007 Apr 1;67(5):1394-400.)
  • 2003 PMID 12788191 — "Contribution of conformal therapy in the treatment of anal canal carcinoma with combined chemotherapy and radiotherapy: results of a phase II study." (Vuong T, Int J Radiat Oncol Biol Phys. 2003 Jul 1;56(3):823-31.)

[edit] IMRT

• Multicenter; 2007 (2000-2006) PMID 17925552 -- "Concurrent chemotherapy and intensity-modulated radiation therapy for anal canal cancer patients: a multicenter experience." (Salama JK, J Clin Oncol. 2007 Oct 10;25(29):4581-6.
  • Prospective. 53 patients (62% T-2, 67% N0, 15% HIV+) treated with concurrent chemo (5-FU/mitomycin, or FU alone) and RT. Primary sites and involved LN median 51.5 Gy, pelvis and inguinal LN median 45 Gy. Median F/U 14 months
  • Toxicity: Grade 3 GI 15%, dermatologic 38%; Grade 4 leukopenia 30%, neutropenia 34%. Treatment break in 41%, median 4 days
  • Conclusion: Effective, and compares favorably with historical standards

• France (Montpellier), 2007 PMID 18005443 — "Optimal organ-sparing intensity-modulated radiation therapy (IMRT) regimen for the treatment of locally advanced anal canal carcinoma: a comparison of conventional and IMRT plans." (Menkarios C, Radiat Oncol. 2007 Nov 15;2:41.)
  • Treatment planning study. Compared: 1) AP/PA + 3D-CRT boost, 2) Pelvic IMRT + 3D-CRT boost, 3) Pelvic IMRT + IMRT boost, 4) IMRT with simultaneous integrated boost.
  • Conclusion: Compared to conventional plan, all IMRT plans reduced the dose to bowel, bladder, genitalia, and bone marrow.

• U Chicago, 2005 PMID 16168830 "Intensity-modulated radiation therapy (IMRT) in the treatment of anal cancer: toxicity and clinical outcome." Milano MT et al. Int J Radiat Oncol Biol Phys. 2005 Oct 1;63(2):354-61.
  • IMRT remarkably well tolerated, with minimal toxicity.

[edit] Other histologies

Adenocarcinoma:

• Rare Cancer Network: (1974-2000) - PMID 12873671 — "Management of primary anal canal adenocarcinoma: a large retrospective study from the Rare Cancer Network." Belkacémi Y et al. Int J Radiat Oncol Biol Phys. 2003 Aug 1;56(5):1274-83.
  • Multicenter, retrospective. 82 pts treated by surgery+RT (45 pts), chemo/RT (31), and APR alone (6).
  • Higher survival in pts receiving chemo/RT. Recommend APR only for salvage.

• MD Anderson; 2003 (1976-1988) PMID 12573754 -- "Chemoradiation for adenocarcinoma of the anus." (Papagikos M, Int J Radiat Oncol Biol Phys. 2003 Mar 1;55(3):669-78.)
  • Retrospective. 16 patients, localized adenocarcinoma of anal canal. Treated with RT (n=9), excisional bx + RT (n=5), or adjuvant RT after APR (n=2). Concurrent 5-FU in 11/16. Compared with epidermoid group (n=92) treated with chemo-RT. Median F/U 3.7 years
  • Outcome: 5-year LR 54% (vs epidermoid 18%, SS). DM 66% (vs. 10%, SS). 5-year DFS 19% (vs. 77%, SS). 5-year OS 64% (vs 85%, SS).
  • Conclusion: Localized adenoCA of anus have high rate of pelvic failure and DM compared with epidermoid histology. Recommend APR, and consideration of adjuvant chemotherapy