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

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Abstract

Background

To compare the dosimetric advantage of three different intensity-modulated radiation therapy (IMRT) plans to a three dimensional (3D) conventional radiation treatment for anal cancer with regards to organs-at-risk (OAR) avoidance, including iliac bone marrow.

Methods

Five patients with T1-3 N0-1 anal cancer and five with T4 and/or N2-3 tumors were selected. Clinical tumor volume (CTV) included tumor, anal canal and inguinal, peri-rectal, and internal/external iliac nodes (plus pre-sacral nodes for T4/N2-3 tumors). Four plans were generated: (A) AP/PA with 3D conformal boost, (B) pelvic IMRT with conformal boost (C) pelvic IMRT with IMRT boost and (D) IMRT with simultaneous integrated boost (SIB). The dose for plans (A) to (C) was 45 Gy/25 followed by a 14.4 Gy/8 boost, and the total dose for plan (D) (SIB) was 59.4 Gy/33. Coverage of both PTV and the volume of OAR (small bowel, genitalia, iliac crest and femoral heads) receiving more than 10, 20, 30, and 40 Gy (V10, V20, V30, V40) were compared using non parametric statistics.

Results

Compared to plan (A), IMRT plans (B) to (D) significantly reduced the V30 and V40 of small bowel, bladder and genitalia for all patients. The V10 and V20 of iliac crests were similar for the N0-1 group but were significantly reduced with IMRT for the N2-3/T4 group (V20 for A = 50.2% compared to B = 33%, C = 32.8%, D = 34.3%). There was no statistical difference between 2-phase (arm C) and single-phase (SIB, arm D) IMRT plans.

Conclusion

IMRT is superior to 3D conformal radiation treatment for anal carcinoma with respect to OAR sparing, including bone marrow sparing.

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Most cited references 29

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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.

N Petrelli, M Flam, M. John … (1996)

Definitive chemoradiation (CR) has replaced radical surgery as the preferred treatment of epidermoid carcinoma of the anal canal. To determine the importance of mitomycin (MMC) in the standard CR regimen and to assess the role of salvage CR in patients who have residual tumor following CR, a phase III randomized trial was undertaken by the Radiation Therapy Oncology Group (RTOG)/Eastern Cooperative Oncology Group (ECOG). Between August 1988 and December 1991, 310 patients were randomized to receive either radiotherapy (RT) and fluorouracil (5-FU) or radiotherapy, 5-FU, and MMC. Of 291 assessable patients, 145 received 45 to 50.4 Gy of pelvic RT plus 5-FU at 1,000 mg/m2/d for 4 days, and 146 received RT, 5-FU, and MMC (10 mg/m2 per dose for two doses). Patients with residual tumor on posttreatment biopsy were treated with a salvage regimen that consisted of additional pelvic RT (9 Gy), 5-FU, and cisplatin (100 mg/m2). Posttreatment biopsies were positive in 15% of patients in the 5-FU arm versus 7.7% in the MMC arm (P = .135). At 4 years, colostomy rates were lower (9% v 22%; P = .002), colostomy-free survival higher (71% v 59%; P = .014), and disease-free survival higher (73% v 51%; P = .0003) in the MMC arm. A significant difference in overall survival has not been observed at 4 years. Toxicity was greater in the MMC arm (23% v 7% grade 4 and 5 toxicity; P < or = .001). Of 24 assessable patients who underwent salvage CR, 12 (50%) were rendered disease-free. Despite greater toxicity, the use of MMC in a definitive CR regimen for anal cancer is justified, particularly in patients with large primary tumors. Salvage CR should be attempted in patients with residual disease following definitive CR before resorting to radical surgery.

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Hematopoietic stem cell compartment: acute and late effects of radiation therapy and chemotherapy.

Peter Mauch, Louis Sandy Constine, Joel Greenberger … (1995)

The bone marrow is an important dose-limiting cell renewal tissue for chemotherapy, wide-field irradiation, and autologous bone marrow transplantation. Over the past 5-10 years a great deal has been discovered about the hematopoietic stem cell compartment. Although the toxicity associated with prolonged myelosuppression continues to limit the wider use of chemotherapy and irradiation, ways are being discovered to circumvent this toxicity such as with the increasing use of cytokines. This review describes what is known of how chemotherapy and irradiation damage stem cells and the microenvironment, how cytokines protect hematopoietic cells from radiation damage and speed marrow recovery after chemotherapy or marrow transplantation, and how various types of blood marrow cells contribute to engraftment and long-term hematopoiesis after high doses of cytotoxic agents and/or total body irradiation.

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Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research.

SJ Arnott, D Cunningham, JMA Northover (1996)

Non-surgical management of anal cancer by radiotherapy alone or combined with chemotherapy has, in uncontrolled studies, yielded similar local tumour control and survival rates to surgery. However, whether the addition of chemotherapy improves outcome without adding to morbidity is not known. Our trial was designed to compare combined modality therapy (CMT) with radiotherapy alone in patients with epidermoid anal cancer. From 856 patients considered for entry to our multicentre trial, 585 patients were randomised to receive initially either 45 Gy radiotherapy in twenty or twenty-five fractions over 4-5 weeks (290 patients) or the same regimen of radiotherapy combined with 5-fluorouracil (1000 mg/m2 for 4 days or 750 mg/m2 for 5 days) by continuous infusion during the first and the final weeks of radiotherapy and mitomycin (12 mg/m2) on day 1 of the first course (295 patients). We assessed clinical response 6 weeks after initial treatment: good responders were recommended for boost radiotherapy and poor responders for salvage surgery. The main endpoint was local-failure rate (> or = 6 weeks after initial treatment); secondary endpoints were overall and cause-specific survival. Analysis was by intention-to-treat. In the radiotherapy and CMT arms, respectively, five and three were ineligible, and six and nine died 6 weeks after initial treatment. After a median follow-up of 42 months (interquartile range 28-62), 164 of 279 (59%) radiotherapy patients had a local failure compared with 101 of 283 (36%) CMT patients. This gave a 46% reduction in the risk of local failure in the patients receiving CMT (relative risk 0.54, 95% CI 0.42-0.69, p < 0.0001). The risk of death from anal cancer was also reduced in the CMT arm (0.71, 0.53-0.95, p = 0.02). There was no overall survival advantage (0.86, 0.67-1.11, p = 0.25). Early morbidity was significantly more frequent in the CMT arm (p = 0.03), but late morbidity occurred at similar rates. Our trial shows that the standard treatment for most patients with epidermoid anal cancer should be a combination of radiotherapy and infused 5-fluorouracil and mitomycin, with surgery reserved for those who fall on this regimen.

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Author and article information

Journal

Journal ID (nlm-ta): Radiat Oncol

Title: Radiation Oncology (London, England)

Publisher: BioMed Central

ISSN (Electronic): 1748-717X

Publication date Collection: 2007

Publication date (Electronic): 15 November 2007

Volume: 2

Page: 41

Affiliations

[1 ]Département de Radio-Oncologie, Hôpital Maisonneuve-Rosemont, Montréal, Canada.

[2 ]Département d'Oncologie Radiothérapie et de Radiophysique, CRLC Val d'Aurelle-Paul Lamarque, Montpellier, France.

[3 ]Unité de Biostatistiques, CRLC Val d'Aurelle-Paul Lamarque, Montpellier, France.

Article

Publisher ID: 1748-717X-2-41

DOI: 10.1186/1748-717X-2-41

PMC ID: 2204019

PubMed ID: 18005443

SO-VID: 9a6a27f5-54cb-443f-9d35-7f43aecc3602

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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

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Abstract

Background

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Karger: Oncology

Most cited references 29

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.

Hematopoietic stem cell compartment: acute and late effects of radiation therapy and chemotherapy.

Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research.

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