Q20. What are the impacts of new developing treatment regimens on nutritional status and outcomes?

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Q20. What are the impacts of new developing treatment regimens on nutritional status and outcomes?

Summary

It is important to consider the impact new developing treatments such as intensity modulated radiotherapy (IMRT), tomotherapy, targeted therapies such as Cetuximab, or other radiosensitiser agents, may have on nutrition outcomes. The benefits of IMRT as a new technique include the ability to limit radiation toxicity to the salivary glands and critical pharyngeal structures required for swallowing, reducing the chronic toxicities of dysphagia and xerostomia [1][2][3]. Consequently, it is anticipated that a patient’s nutritional intake would improve, however the studies are yet to measure this as a specific outcome to demonstrate this theoretical benefit.

There have been some studies on induction or neoadjuvant chemotherapy, targeted therapies and IMRT. There is one level III-2 neutral quality study [4], two level III-3 neutral quality studies [5][6][7], five level IV neutral quality studies [8][9][10][11][12] and two level IV negative quality studies [13][14].

Neoadjuvant chemotherapy

The highest level study is actually an intervention study of Megesterol Acetate in patients receiving two different types of neoadjuvant chemotherapy where use of Megesterol Acetate resulted in improved weight gain compared to the control group [4].

The remaining studies pertaining to this topic were level IV. The first of these demonstrated a positive effect of induction chemotherapy before surgery resulting in improved swallowing and diet texture, and improved quality of life (emotional, physical, and functional scales) [8]. Another study looked at nine weeks of induction chemotherapy prior to concurrent chemoradiotherapy, but outcome measures were taken two weeks pre concurrent chemoradiotherapy and one month post, so outcomes reported were more likely related to the impact of concurrent chemoradiotherapy [9]. Buiret et al. looked at outcomes of induction chemotherapy followed by radiotherapy with concomitant Cetuximab [12]. This demonstrated mean weight loss of 4.8% during entire treatment period, with 22% of patients losing >10% of body weight, and 37% requiring enteral or parenteral nutrition support. One negative quality study looked at chemotherapy treatment alone in a mixed cancer diagnosis population and reported common symptoms of mild to moderate mucositis (highest at day 8), as well as dry mouth, oral pain and difficulty chewing and swallowing [13]. The other negative quality paper reported on a decline in nutritional status post neoadjuvant chemotherapy, but limited data was reported [14].

IMRT

The studies relating to IMRT were all of level III-3 or level IV. One study looked at nutrition and swallowing outcomes post IMRT, and found 22% of patients required a gastrostomy at 1 year post treatment. This was significantly associated with aspiration and stricture rates [6]. Another study comparing standard low neck fields with IMRT, found no difference in the need for a gastrostomy tube [15]. Gunn investigated the effect of IMRT (without chemotherapy), concluding that mean weight loss during treatment was high at 10.6%. Sixty percent of patients required gastrostomy placement, with 44% requiring tube feeding for 3 months and 16% requiring tube feeding for 10 months post treatment [10]. Similarly, Studer et al. found that gastrostomy insertion was required in 29% of patients receiving IMRT (with the majority having concurrent chemotherapy), and 22% were gastrostomy dependent at 1 year post treatment [11].

Targeted Therapies

There is one level III-2 [16] and one level III-3 study [7] that compare toxicity of chemoradiotherapy versus radiotherapy and the monoclonal antibody Cetuximab. The first study [16] found that both groups exhibited similarly high levels of acute toxicity, with long-term toxicity low. The chemoradiotherapy group further demonstrated a significantly greater median weight loss than those receiving Cetuximab (4kg versus 2kg). The second [7] noted that the group receiving Cetuximab had significantly higher toxicities of grade 3 mucositis, skin dermatitis, >10% weight loss and higher need for enteral feeding. One level IV study looked at outcomes of induction chemotherapy followed by radiotherapy with concomitant Cetuximab [12]. This demonstrated mean weight loss of 4.8% during entire treatment period, with 22% of patients losing >10% of body weight, and 37% requiring enteral or parenteral nutrition support.

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Recommendation Grade
Targeted therapy treatments (e.g. Cetuximab) have high rates of weight loss, mucositis and need for tube feeding. Patient should be managed in the same way as for conventional chemoradiotherapy.
C
The impact of neoadjuvant chemotherapy on nutritional status and nutrition impact symptoms is varied with limited studies available. Patients should be monitored for symptoms to prevent decline in nutritional status.
D
IMRT has not been found to reduce toxicity significantly, with still a high rate of weight loss, mucositis and need for tube feeding. Patients should be managed in the same way as for conventional radiotherapy.
C

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References

  1. Kam MK, Leung SF, Zee B, Chau RM, Suen JJ, Mo F, et al. Prospective randomized study of intensity-modulated radiotherapy on salivary gland function in early-stage nasopharyngeal carcinoma patients. J Clin Oncol 2007 Nov 1;25(31):4873-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17971582.
  2. Pow EH, Kwong DL, McMillan AS, Wong MC, Sham JS, Leung LH, et al. Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial. Int J Radiat Oncol Biol Phys 2006 Nov 15;66(4):981-91 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17145528.
  3. Nutting CM, Morden JP, Harrington KJ, Urbano TG, Bhide SA, Clark C, et al. Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol 2011 Feb;12(2):127-36 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21236730.
  4. 4.0 4.1 Mantovani G, Macciò A, Bianchi A, Curreli L, Ghiani M, Santona MC, et al. Megestrol acetate in neoplastic anorexia/cachexia: clinical evaluation and comparison with cytokine levels in patients with head and neck carcinoma treated with neoadjuvant chemotherapy. Int J Clin Lab Res 1995;25(3):135-41 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8562975.
  5. Turaka A, Li T, Nicolaou N, Lango MN, Burtness B, Horwitz EM, et al. Use of a conventional low neck field (LNF) and intensity-modulated radiotherapy (IMRT): no clinical detriment of IMRT to an anterior LNF during the treatment of head-and neck-cancer. Int J Radiat Oncol Biol Phys 2011 Jan 1;79(1):65-70 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20385457.
  6. 6.0 6.1 Caudell JJ, Schaner PE, Desmond RA, Meredith RF, Spencer SA, Bonner JA. Dosimetric factors associated with long-term dysphagia after definitive radiotherapy for squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 2010 Feb 1;76(2):403-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19467801.
  7. 7.0 7.1 7.2 Walsh L, Gillham C, Dunne M, Fraser I, Hollywood D, Armstrong J, et al. Toxicity of cetuximab versus cisplatin concurrent with radiotherapy in locally advanced head and neck squamous cell cancer (LAHNSCC). Radiother Oncol 2011 Jan;98(1):38-41 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21159400.
  8. 8.0 8.1 Barringer DA, Hutcheson KA, Sturgis EM, Kies MS, Lewin JS. Effect of induction chemotherapy on speech and swallowing function in patients with oral tongue cancer. Head Neck 2009 May;31(5):611-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19107949.
  9. 9.0 9.1 Silver HJ, Dietrich MS, Murphy BA. Changes in body mass, energy balance, physical function, and inflammatory state in patients with locally advanced head and neck cancer treated with concurrent chemoradiation after low-dose induction chemotherapy. Head Neck 2007 Oct;29(10):893-900 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17405169.
  10. 10.0 10.1 Gunn GB, Endres EJ, Parker B, Sormani MP, Sanguineti G. A phase I/II study of altered fractionated IMRT alone for intermediate T-stage oropharyngeal carcinoma. Strahlenther Onkol 2010 Sep;186(9):489-95 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20803186.
  11. 11.0 11.1 Studer G, Peponi E, Kloeck S, Dossenbach T, Huber G, Glanzmann C. Surviving hypopharynx-larynx carcinoma in the era of IMRT. Int J Radiat Oncol Biol Phys 2010 Aug 1;77(5):1391-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20056352.
  12. 12.0 12.1 12.2 Buiret G, Combe C, Favrel V, Pommier P, Martin L, Ecochard R, et al. A retrospective, multicenter study of the tolerance of induction chemotherapy with docetaxel, Cisplatin, and 5-Fluorouracil followed by radiotherapy with concomitant cetuximab in 46 cases of squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 2010 Jun 1;77(2):430-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19775831.
  13. 13.0 13.1 Chan CW, Chang AM, Molassiotis A, Lee IY, Lee GC. Oral complications in Chinese cancer patients undergoing chemotherapy. Support Care Cancer 2003 Jan;11(1):48-55 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12527954.
  14. 14.0 14.1 Picker H, Bichler E. Nutritional and immunological investigations in head and neck cancer patients before and after therapy. Arch Otorhinolaryngol 1985;242(2):149-53 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/2415099.
  15. Turaka A, Li T, Nicolaou N, Lango MN, Burtness B, Horwitz EM, et al. Use of a conventional low neck field (LNF) and intensity-modulated radiotherapy (IMRT): no clinical detriment of IMRT to an anterior LNF during the treatment of head-and neck-cancer. Int J Radiat Oncol Biol Phys 2011 Jan 1;79(1):65-70 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20385457.
  16. 16.0 16.1 Jensen AD, Krauss J, Weichert W, Bergmann ZP, Freier K, Debus J, et al. Disease control and functional outcome in three modern combined organ preserving regimens for locally advanced squamous cell carcinoma of the head and neck (SCCHN). Radiat Oncol 2011 Sep 23;6:122 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21942981.

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