Korean J Pain.  2021 Oct;34(4):427-436. 10.3344/kjp.2021.34.4.427.

Usefulness of cyclic thermal therapy and red blood cell scintigraphy in patients with chemotherapy-induced peripheral neuropathy

• Kim M
• Kim EM
• Oh PS
• Lim ST
• Sohn MH
• Song EK
• Park KU
• Kim JY
• Won KS
• Jeong HJ

• KMID: 2520750
• DOI: http://doi.org/10.3344/kjp.2021.34.4.427

Abstract

Background
Pharmacological and non-pharmacological therapies have been used to treat patients with chemotherapy-induced peripheral neuropathy (CIPN). However, the effect of therapies in cancer patients has yet to be investigated comprehensively. We hypothesized that cyclic thermal therapy would improve blood flow and microcirculation and improve the symptoms driven by CIPN.
Methods
The criteria of assessment were blood volume in region of interest (ROI) in the images, and European Organization for Research and Treatment of Cancer–Quality of Life Questionnaire–Chemotherapy-Induced Peripheral Neuropathy 20 questionnaire scores. The blood volume was quantified by using red blood cell (RBC) scintigraphy. All patients were treated 10 times during 10 days. The thermal stimulations, between 15° and 41°, were repeatedly delivered to the patient’s hands.
Results
The total score of the questionnaires, the score of questions related to the upper limbs, the score of questions closely related to the upper limbs, and the score excluding the upper limbs questions was decreased. The blood volume was decreased, and the variance of blood volume was decreased. During cooling stimulation, the blood volume was decreased, and its variance was decreased. During warming stimulation, the blood volume was decreased, and its variance was decreased.
Conclusions
We suggest that cyclic thermal therapy is useful to alleviate CIPN symptoms by blood circulation improvement. RBC scintigraphy can provide the quantitative information on blood volume under certain conditions such as stress, as well as rest, in peripheral tissue.

Keyword

Antineoplastic Agents; Blood Volume; Drug-Related Side Effects and Adverse Reactions; Drug Therapy; Microcirculation; Neuralgia; Peripheral Nervous System Diseases; Polyneuropathies; Radionuclide Imaging; Scintigraphy; Small Fiber Neuropathy

Figure

• 

  Fig. 1 Scheme of the treatment protocol. One cycle was lasted a total of 6 minutes and 30 seconds, including 3 minutes and 30 seconds of cooling phase and 3 minutes of warming phase. Total of 10 cycles was performed. Patients rested for 5 minutes after five cycles of treat. The treatment was performed for a total of 1 hour and 10 minutes at 1 day.

• 

  Fig. 2 Representative images of the method of treating the patient and red blood cell scintigraphy analysis. (A) Picture of the device. The patient puts his or her hands on the device. The hand position was printed on the device. (B) The standard source which is made by 99mTc was located in the upper right side. The patients placed both hands on the cyclic therapy device. The ROIs were drawn on each distal phalanx. ROI: region of interest, Min: minimum, Max: maximum.

Reference

1. Windebank AJ, Grisold W. 2008; Chemotherapy-induced neuropathy. J Peripher Nerv Syst. 13:27–46. DOI: 10.1111/j.1529-8027.2008.00156.x. PMID: 18346229.

2. Armstrong T, Almadrones L, Gilbert MR. 2005; Chemotherapy-induced peripheral neuropathy. Oncol Nurs Forum. 32:305–11. DOI: 10.1188/05.ONF.305-311. PMID: 15759068. PMCID: PMC5913659.

3. Kumar SP, Sisodia V. 2013; Chemotherapy-induced or chemotherapy-associated? Does physical therapy play a role in prevention and/or management of peripheral neurotoxicity and neuropathy? Indian J Palliat Care. 19:77–8. DOI: 10.4103/0973-1075.110245. PMID: 23766603. PMCID: PMC3680847.

4. Wolf S, Barton D, Kottschade L, Grothey A, Loprinzi C. 2008; Chemotherapy-induced peripheral neuropathy: prevention and treatment strategies. Eur J Cancer. 44:1507–15. DOI: 10.1016/j.ejca.2008.04.018. PMID: 18571399.

5. Woo IS. 2015; Recent updates on chemotherapy-induced peripheral neuropathy. Korean J Med. 88:35–7. DOI: 10.3904/kjm.2015.88.1.35.

6. Barton DL, Wos EJ, Qin R, Mattar BI, Green NB, Lanier KS, et al. 2011; A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA. Support Care Cancer. 19:833–41. DOI: 10.1007/s00520-010-0911-0. PMID: 20496177. PMCID: PMC3338170.

7. Wickham R. 2007; Chemotherapy-induced peripheral neuropathy: a review and implications for oncology nursing practice. Clin J Oncol Nurs. 11:361–76. DOI: 10.1188/07.CJON.361-376. PMID: 17623621.

8. Sutterfield SL, Caldwell JT, Post HK, Lovoy GM, Banister HR, Ade CJ. 2018; Lower cutaneous microvascular reactivity in adult cancer patients receiving chemotherapy. J Appl Physiol (1985). 125:1141–9. DOI: 10.1152/japplphysiol.00394.2018. PMID: 30091663.

9. Akasaki Y, Miyata M, Eto H, Shirasawa T, Hamada N, Ikeda Y, et al. 2006; Repeated thermal therapy up-regulates endothelial nitric oxide synthase and augments angiogenesis in a mouse model of hindlimb ischemia. Circ J. 70:463–70. DOI: 10.1253/circj.70.463. PMID: 16565566.

10. Tepperman PS, Devlin M. 1986; The therapeutic use of local heat and cold. Can Fam Physician. 32:1110–4. PMID: 21267207. PMCID: PMC2327914.

11. Johnson JM, Minson CT, Kellogg DL Jr. 2014; Cutaneous vasodilator and vasoconstrictor mechanisms in temperature regulation. Compr Physiol. 4:33–89. DOI: 10.1002/cphy.c130015. PMID: 24692134.

12. Maeda H, Kurose T, Nosaka S, Kawamata S. 2014; Microvascular circulation at cool, normal and warm temperatures in rat leg muscles examined by histochemistry using Lycopersicon esculentum lectin. Acta Histochem. 116:1096–103. DOI: 10.1016/j.acthis.2014.05.006. PMID: 24998628.

13. Salmi AM, Hong C, Futrell JW. 1999; Preoperative cooling and warming of the donor site increase survival of skin flaps by the mechanism of ischaemic preconditioning: an experimental study in rats. Scand J Plast Reconstr Surg Hand Surg. 33:163–7. DOI: 10.1080/02844319950159406. PMID: 10450572.

14. Roque FR, Hernanz R, Salaices M, Briones AM. 2013; Exercise training and cardiometabolic diseases: focus on the vascular system. Curr Hypertens Rep. 15:204–14. DOI: 10.1007/s11906-013-0336-5. PMID: 23519745.

15. Bang SH, Oh YS, Park HJ, Lee TK, Yang JS, Lee SM, et al. 1992; Evaluation of finger blood flow with Tc-99m MDP (methylene diphosphonate). Korean J Intern Med. 7:94–101. DOI: 10.3904/kjim.1992.7.2.94. PMID: 1306078. PMCID: PMC4532110.

16. Kunnen JJ, Dahler HP, Doorenspleet JG, van Oene JC. 1988; Effects of intra-arterial ketanserin in Raynaud's phenomenon assessed by 99MTc-pertechnetate scintigraphy. Eur J Clin Pharmacol. 34:267–71. DOI: 10.1007/BF00540954. PMID: 2840293.

17. Sarikaya A, Ege T, Firat MF, Duran E. 2004; Assessment of digital ischaemia and evaluation of response to therapy by 99mTc sestamibi limb scintigraphy after local cooling of the hands in patients with vasospastic Raynaud's syndrome. Nucl Med Commun. 25:207–11. DOI: 10.1097/00006231-200402000-00019. PMID: 15154713.

18. Kaminaga T, Takada K, Kutomi K, Imai E, Furui S. 2002; Improvement in cold-induced Raynaud's syndrome with administration of ticlopidine hydrochloride detected by Tc-99m DTPA human serum albumin scintigraphy. Clin Nucl Med. 27:131–2. DOI: 10.1097/00003072-200202000-00013. PMID: 11786746.

19. Garai I, Csiki Z, Galuska L. 2005; Is MIBI the best choice for the evaluation of hand perfusion during cold test provocation? Nucl Med Commun. 26:269–70. DOI: 10.1097/00006231-200503000-00012. PMID: 15722908.

20. Habash RW, Bansal R, Krewski D, Alhafid HT. 2006; Thermal therapy, part 1: an introduction to thermal therapy. Crit Rev Biomed Eng. 34:459–89. DOI: 10.1615/CritRevBiomedEng.v34.i6.20. PMID: 17725479.

21. Postma TJ, Aaronson NK, Heimans JJ, Muller MJ, Hildebrand JG, Delattre JY, et al. 2005; The development of an EORTC quality of life questionnaire to assess chemotherapy-induced peripheral neuropathy: the QLQ-CIPN20. Eur J Cancer. 41:1135–9. DOI: 10.1016/j.ejca.2005.02.012. PMID: 15911236.

22. Wolf SL, Barton DL, Qin R, Wos EJ, Sloan JA, Liu H, et al. 2012; The relationship between numbness, tingling, and shooting/burning pain in patients with chemotherapy-induced peripheral neuropathy (CIPN) as measured by the EORTC QLQ-CIPN20 instrument, N06CA. Support Care Cancer. 20:625–32. DOI: 10.1007/s00520-011-1141-9. PMID: 21479990. PMCID: PMC3329939.

23. Hing WA, White SG, Bouaaphone A, Lee P. 2008; Contrast therapy--a systematic review. Phys Ther Sport. 9:148–61. DOI: 10.1016/j.ptsp.2008.06.001. PMID: 19083715.

24. Mols F, van de Poll-Franse LV, Vreugdenhil G, Beijers AJ, Kieffer JM, Aaronson NK, et al. 2016; Reference data of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-CIPN20 Questionnaire in the general Dutch population. Eur J Cancer. 69:28–38. DOI: 10.1016/j.ejca.2016.09.020. PMID: 27814471.

25. Piao CH, Fan YJ, Nguyen TV, Song CH, Jeong HJ, Chai OH. 2020; Effects of thermal therapy combined with blue light-emitting diode irradiation on trimellitic anhydride-induced acute contact hypersensitivity mouse model. J Dermatolog Treat. doi: 10.1080/09546634.2020.1809622. DOI: 10.1080/09546634.2020.1809622. PMID: 32783679.

26. Diskin CJ, Stokes TJ, Dansby LM, Carter TB, Radcliff L, Thomas SG. 1999; Towards an understanding of oedema. BMJ. 318:1610–3. DOI: 10.1136/bmj.318.7198.1610. PMID: 10364127. PMCID: PMC1115975.

27. Wang SJ, Lee CH, Kang HG, Kim KW, Kim M, Jeong HJ, et al. 2021; Peripheral vasoreactivity in acute ischemic stroke with hemiplegia. Sci Rep. 11:8531. DOI: 10.1038/s41598-021-88050-9. PMID: 33879816. PMCID: PMC8058338.