Cancer Treatment Today

Lay Summary: An introduction to IMRT and Tomotherapy

IMRT is a rapidly evolving technique, which affords a more precise radiation dose delivery of escalated doses, in appropriate cases, to targeted tumors, while sparing nearby healthy tissue structures.  The FDA clearance of numerous devices for the technical delivery of IMRT is based on the capability of this technology to incorporate accurate dose calculation algorithms, associated with a verifiable dose distribution, as managed by the treating physician, (i.e., radiation oncologist). Although, to date, no randomized trials have matured to document long-term outcomes data and efficacy for IMRT, the scientific evidence currently available indicates that IMRT permits better treatment planning and sparing of surrounding tissues, which is of particular usefulness with “Radiosensitive” tumors of the head/neck, prostate and CNS lesions where the target volume is in close proximity to critical healthy structures that must be protected.   These results may be extrapolated to the treatment of other cancers at other anatomic sites; however, a number of technical issues need to be resolved before IMRT can be recommended routinely for lung cancer use, particularly the issue of tumor mobility must be addressed, (e.g., a lung tumor moving with respiration). The NCI was sufficiently concerned about these issues to issue a recently updated report for use in planning and design of clinical trials. It can be found at http://atc.wustl.edu/home/NCI/NCI_IMRT_Guidelines_2006.pdf

A recent retrospective review of uses of IMRT in anal cancer concluded: “Preliminary outcomes suggest that concurrent chemotherapy and IMRT for anal canal cancers is effective and tolerated favorably compared with historical standards.” More studies are needed.

Tomotherapy delivers varying intensity radiation with a rotating device. The intensity is varied by the placement of “leaves” which either block or allow the passage of radiation. The rotating component of this technique allows for more specific targeting of the cancer. In conventional radiation therapy, the beam is usually delivered from several different directions, possibly 5-10. The greater the number of beam directions, the more the dose will be confined to the target cancer cells, sparing normal cells from exposure. Tomotherapy delivers radiation from every point on a helix, or spiral, instead of from just a few points. The same caveats apply.

Differences between the prescribed dose of radiation in intensity modulated radiation therapy (IMRT) and the dose that’s actually delivered may make comparison studies in lung cancer difficult to interpret. These findings were reported in the Journal of the National Cancer Institute. For lung, there remains the issue of respiratory movement which makes accurate targeting more difficult, but a variety of technique have been developed to deal with it. A 2010 guideline says: “Insufficient evidence was obtained in this systematic review; therefore, it is not possible to propose recommendations on the use of intensity-modulated radiation therapy (IMRT) for lung cancer informed by evidence.”

Currently, there are no randomized controlled trials of IMRT compared with other radiation techniques for treatment of prostate cancer. Non-randomized studies consistently demonstrate reduced rates of toxicity in IMRT-treated patients. The 2010 Agency for Healthcare Research and Quality (AHRQ) comparative evaluation of radiation treatments for clinically localized prostate cancer concluded that data on comparative effectiveness between different forms of radiation treatments are inconclusive with respect to overall or disease-specific survival. In addition, the AHRQ technology assessment states that more studies of better quality are needed to confirm or refute the suggested findings in the studies that compared outcomes in patients treated with different forms of radiation therapy. Nevertheless, prostate cancer has become an accepted modality to treat prostate cancer.

Blue Cross Blue Shield Association.  Special Report: Intensity Modulation Radiation Therapy for Cancer of the Breast or Lung.  TEC Assessment.  Chicago, IL.  December 2005; 20 (13)

Das, I., Cheng, C., Chopra, K., et al. Intensity modulated radiation therapy dose prescription, recording, and delivery: patterns of variability among institutions and treatment planning systems. Journal of the National Cancer Institute. 2008.

Bezjak A, Rumble RB, Rodrigues G, Hope A, Warde P, IMRT Indications Expert Panel. The role of IMRT in lung cancer. Toronto (ON): Cancer Care Ontario (CCO); 2010 Nov 22. Various p. (Evidence-based series; no. 21-3-5).  [46 references]

Available data are insufficient to determine whether IMRT is superior to 3D-CRT for improving health outcomes of patients with breast or lung cancer.

Das, I., Cheng, C., Chopra, K., et al. Intensity modulated radiation therapy dose prescription, recording, and delivery: patterns of variability among institutions and treatment planning systems. Journal of the National Cancer Institute. 2008. Blue Cross

K . Ohnishi , H . Liu , Z . Liao , S . Yom , H . Jin , X . Wei , P . Allen , S . Tucker , R . Mohan , R . Komaki Clinical Outcomes and Treatment Planning Strategies for Advanced-Stage Non-Small Cell Lung Cancer (NSCLC) Treated With Intensity Modulated Radiation Therapy (IMRT) and Concurrent Chemotherapy (CCT)
International Journal of Radiation OncologyBiologyPhysics , Volume 69 , Issue 3 , Pages S522 – S522, 2007

http://atc.wustl.edu/home/NCI/NCI_IMRT_Guidelines_2006.pdf

J. K. Salama, L. K. Mell, D. A. Schomas, R. C. Miller, K. Devisetty, A. B. Jani, A. J. Mundt, J. C. Roeske, S. L. Liauw, and S. J. Chmura
Concurrent Chemotherapy and Intensity-Modulated Radiation Therapy for Anal Canal Cancer Patients: A Multicenter Experience
J. Clin. Oncol., October 10, 2007; 25(29): 4581 – 4586.

Parliament MB, et al: Preservation of oral health-related quality of life and salivary flow rates after inverse-planned intensity- modulated radiotherapy (IMRT) for head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):663-73.

Lee N, et al Intensity-modulated radiation therapy in head and neck cancers: An update. Head Neck. 2007 Apr;29(4):387-400.

Graff P, et al: Impact of intensity-modulated radiotherapy on health-related quality of life for head and neck cancer patients: Matched-pair comparison with conventional radiotherapy. Int J Radiat Oncol Biol Phys. 2007 Feb 6;

National Cancer Institute (NCI). National Cancer Institute Guidelines for the use of Intensity Modulated Radiation Therapy in Clinical Trials. Bethesda, MD: NCI; January 14, 2005

Garden AS, et al: Disease-control rates following intensity-modulated radiation therapy for small primary oropharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2007 Feb 1;67(2):438-44. Epub 2006 Dec 4.

Braam PM, et al: Intensity-modulated radiotherapy significantly reduces xerostomia compared with conventional radiotherapy. Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4):975-80. Epub 2006 Sep 11.

Agency for Healthcare Research and Quality (AHRQ) Technology Assessments. Comparative evaluation of radiation treatments for clinically locazlized prostate cancer: an update.  Available from: http://www.cms.gov/coveragegeninfo/downloads/id69ta.pdf

Wilt TJ, Shamliyan T, Taylor B et al. Comparative effectiveness of therapies for clinically localized prostate cancer. Comparative Effectiveness Review No. 13. Agency for Healthcare Research and Quality. February 2008.

Pearson SD, Ladapo, Prosser L. Intensity modulated radiation therapy (IMRT) for localized prostate cancer. Institute for Clinical and Economic Review. 2007.

Staffurth, J. A review of the clinical evidence for intensity-modulated radiotherapy. Clin Oncol (R Coll Radiol). 2010 Oct;22(8):643-57.

Zelefsky, MJ, Levin, EJ, Hunt, M, et al. Incidence of late rectal and urinary toxicities after three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2008 Mar 15;70(4):1124-9.

Esophageal Cancer

To date there are insufficient clinical outcome study data comparing intensity modulated radiation therapy (IMRT) with three-dimensional conformal radiation therapy (3DCRT) in the treatment of gastrointestinal (GI) cancers. However, evidence from 19 non-comparative dosimetric and outcome studies has suggested that IMRT is an option for esophageal, gastric, bile duct, pancreatic, rectal, and anal cancers. These studies have demonstrated that IMRT can reduce radiation dose to organs at risk (OAR), while managing to deliver the prescribed radiation dose to target volumes. For this reason, IMRT may be considered a viable treatment option, as it is ethical to recommend a treatment with little known harm over one with greater expected harm prior to scientific proof of the difference in harm being established.

Wong RKW, Rumble RB, Warde P, IMRT Indications Expert Panel. The role of IMRT in gastrointestinal cancers. Toronto (ON): Cancer Care Ontario (CCO); 2010 Oct 29. Various p. (Evidence-based series; no. 21-3-10).  [28 references]