Open Access

Palliative Radiotherapy Induced Severe Tumor Lysis Syndrome in a Patient With Multiple Myeloma With Skin Involvement: A Case Report and Review of Literature

KAWAMOTO TERUFUMI
KARINO TATSUKI
MURAMOTO YOICHI
OSHIMA MASAKI
KOSUGI YASUO
  &  
SHIKAMA NAOTO
Cancer Diagnosis & Prognosis Mar-Apr; 3(2): 257-263 DOI: 10.21873/cdp.10210
Received 14 December 2022 | Revised 07 December 2023 | Accepted 25 January 2023
Corresponding author
Terufumi Kawamoto, MD, Ph.D., Department of Radiation Oncology, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Tel: +81 338133111, Fax: +81 338241552, email: t-kawamoto@juntendo.ac.jp

Abstract

Background/Aim: Radiotherapy (RT) has been rarely reported as a cause of tumor lysis syndrome (TLS). Therefore, the patient characteristics and details of RT-induced TLS remain unclear, which may delay diagnosis. Herein, we report a case of palliative RT-induced severe TLS in a patient with multiple myeloma (MM) with skin involvement along with literature review. Case Report: A 75-year-old female with MM was referred to our department in February 2021 because of swelling and pruritus of the bulky tumor on her right breast and severe left leg pain. She had received chemotherapies and autologous peripheral blood stem cell transplantations since October 2012. We administered palliative RT (a single 8 Gy fraction) to the right breast, left tibia, and femur. On day 7 after RT, a shrinkage effect was observed on the right breast lesion, and left leg pain was relieved. Her laboratory results showed hyperuricemia, hyperphosphatemia, and hypercreatininemia. Initially, we considered acute renal failure (ARF) due to MM progression and planned for a follow-up after 1 week. On day 14 after RT completion, she experienced vomiting and anorexia. Her laboratory results became worse. She was admitted with the diagnosis of TLS and received intravenous fluid hydration and allopurinol. Unfortunately, the evolution was marked by severe clinical deterioration with anuria and coma, leading to death on day 35 after RT. Conclusion: It is important to determine whether ARF is due to MM progression or TLS. The occurrence of TLS should be considered in the case of a rapidly shrinking bulky tumor while receiving palliative RT.
Keywords: Multiple myeloma, palliative treatment, radiation therapy, skin, toxicity, tumor lysis syndrome

Tumor lysis syndrome (TLS) is an important oncological emergency that requires immediate diagnosis and interventional treatment. TLS is generally triggered by chemotherapy for rapidly growing malignancy, especially acute leukemia, and high-grade lymphoma. Currently, there are limited reports regarding radiotherapy (RT)-induced TLS (1). Therefore, the patient characteristics and details of RT-induced TLS remain unclear, which may delay diagnosis. Herein, we report a case of palliative RT-induced severe TLS in a patient with multiple myeloma (MM) with skin involvement along with literature review.

Case Report

The case was a 75-year-old female with a medical history of asthma. In October 2012, she was diagnosed with stage I MM [Revised International Staging System (2)] and received six cycles of bortezomib and dexamethasone chemotherapy, to which she had a complete response. Thereafter, she received autologous peripheral blood stem cell transplantation (auto-PBSCT) and bortezomib as maintenance chemotherapy in July 2013. In July 2015, her MM relapsed, and she received nine cycles of lenalidomide and dexamethasone chemotherapy, to which she had a complete response. Next, she received a second auto-PBSCT and bortezomib as maintenance chemotherapy in September 2016. However, her MM relapsed again. She received four cycles of pomalidomide and dexamethasone chemotherapy in December 2017; nine cycles of daratumumab, lenalidomide, and dexamethasone chemotherapy in April 2018; 13 cycles of carfilzomib, pomalidomide, and dexamethasone chemotherapy in January 2019; 13 cycles of elotuzumab, pomalidomide, and dexamethasone chemotherapy in March 2020; two cycles of weekly carfilzomib and dexamethasone chemotherapy in December 2020; and one cycle of isatuximab, pomalidomide, and dexamethasone chemotherapy in January 2021. She presented with multiple skin and bone lesions. At this point, she decided to receive the best supportive care. She was referred to our department in February 2021 because of swelling and pruritus of the bulky tumor on her right breast and severe left leg pain (Figure 1). Magnetic resonance imaging revealed osteolytic bone lesions. Her Eastern Cooperative Oncology Group performance status was 3 because of severe left leg pain. Before RT, her laboratory results were as follows: uric acid 4.6 mg/dl, potassium 3.4 mEq/l, phosphorus 4 mg/dl, calcium 8.8 mg/dl, sodium 145 mEq/l, creatinine 0.64 mg/dl, and lactate dehydrogenase (LDH) 296 IU/l. We administered palliative RT (a single 8 Gy fraction) to the bulky tumor on her right breast, left tibia, and femur (Figure 2). The size of the bulky tumor was 8×4×4 cm. The gross tumor volume, clinical target volume, and planning target volume were 61, 119, and 214 cc for the right breast and 18, 280, and 482 cc for the left leg, respectively. On day 7 after RT, a shrinkage effect was observed on the right breast lesion, and left leg pain was relieved. Her laboratory results were as follows: uric acid 7.7 mg/dl, potassium 3.7 mEq/l, phosphorus 6 mg/dl, calcium 8.3 mg/dL, sodium 145 mEq/l, creatinine 1.98 mg/dl, and LDH 255 IU/l. Initially, we considered acute renal failure (ARF) due to MM progression and planned for a follow-up after 1 week. On day 14 after RT, her right breast lesion was almost gone (Figure 3). However, she experienced vomiting and anorexia. Her laboratory results became worse (Table I). She was admitted with the diagnosis of TLS. She received intravenous fluid hydration and allopurinol according to the TLS treatment guidelines. Blood and urine cultures were drawn, and cefepime was initiated since aspiration pneumonia was suspected. Serial laboratory examinations showed increased creatinine levels and decreased uric acid levels (Table I). Unfortunately, the evolution was marked by severe clinical deterioration with anuria and coma, leading to death on day 35 after RT.

Discussion

We experienced a case of palliative RT-induced severe TLS in a patient with MM with skin involvement. The clinical course of this case is notable in that it was difficult to diagnose whether the renal failure was due to MM or TLS and that TLS occurred in association with the rapid shrinkage of the bulky tumor.

We could not diagnose her as having TLS at the first follow-up period because of the following reasons: First, we considered that ARF was due to MM progression because of her long clinical course. Renal failure is a common feature of MM. Studies have shown that renal failure is associated with poor survival (3). However, hypercalcemia is the common cause of renal failure in MM (3,4). On the other hand, TLS is characterized by biochemical variables such as hyperuricemia, hyperphosphatemia, hyperpotassemia, and hypocalcemia (5). In our case, her laboratory results showed hyperuricemia, hyperphosphatemia, hypercreatininemia, and normal calcium revels. The normal calcium levels were probably because the hypercalcemia from terminal MM masked the hypocalcemia from TLS. Laboratory TLS is defined as the presence of at least two or more biochemical variables within 3 days before chemotherapy or 7 days after chemotherapy (6). Clinical TLS is defined as laboratory TLS complicated by clinical manifestations such as arrhythmia, renal failure, seizure, and sudden death (6). However, this definition is not perfect since RT may lead to TLS and TLS can occur spontaneously in a rapidly proliferating and bulky tumor. Collectively, we should have diagnosed the patient as having clinical TLS at the first follow-up period despite receiving RT. Second, RT and MM can rarely cause TLS. A review article reported that chemotherapy was the most frequent cause of TLS (57%), followed by spontaneity (26%), glucocorticoid (7%), RT (3%), and others (7%). Among hematologic malignancies as a cause of TLS, the most common is leukemia (48%), followed by non-Hodgkin lymphoma (39%), MM (11%), and Hodgkin lymphoma (2%) (1).

Table II shows the available reports on RT-induced TLS (7-21). Two studies reported three cases of RT-induced TLS in MM (19,20). In another study, all 16 cases developed TLS after the initiation of RT (1). Fifteen cases received palliative RT (≤30 Gy) except one. There were many reports of relatively large irradiation fields, such as the hemi-body and spleen, and bulky tumor. Previous reviews reported that the larger the cancer mass or the higher the number of cells that will lyse with chemotherapy, the higher the risk of clinical TLS (6). TLS needs to be suspected in the case of a rapidly shrinking bulky tumor. According to the treatment guidelines for MM, a single 8 Gy fraction is preferred for bone lesions in patients with poor condition (22). Although the appropriate dose for a skin lesion remains unknown because of its rare occurrence (23), a single 8 Gy fraction was acceptable with regard to our patient’s condition. Previous studies reported that elevated pretreatment levels of LDH, creatinine, and uric acid were risk factors for TLS in patients with acute myeloid leukemia and solid tumor (24-26). The available laboratory results also showed elevated pretreatment levels of LDH. Prophylactic treatments including allopurinol, hydration prior to treatment, and urine alkalization are important for patients at risk of TLS (27). In the future, new strategies such as concurrent RT with immune checkpoint inhibitor therapy need to be developed to treat patients with TLS.

In conclusion, it is important to determine whether ARF is due to MM progression or TLS. The occurrence of TLS should be considered in the case of a rapidly shrinking bulky tumor while receiving palliative RT. Prophylactic treatments including allopurinol, hydration prior to treatment, and urine alkalization are important for patients at risk of TLS.

Conflicts of Interest

The Authors declare no conflicts of interest in relation to this study.

Authors’ Contributions

Terufumi Kawamoto prepared the manuscript and conducted the literature search, reviewed and edited the manuscript. TK, YM, MO, YK, and NS reviewed the manuscript. All Authors have read and approved the final manuscript.

Acknowledgements

The Authors would like to thank Dr. Makoto Sasaki, a specialist in hematology, for his useful discussions.

References

1 Firwana BM Hasan R Hasan N Alahdab F Alnahhas I Hasan S & Varon J Tumor lysis syndrome: a systematic review of case series and case reports. Postgrad Med. 124(2) 92 - 101 2012. PMID: 22437219. DOI: 10.3810/pgm.2012.03.2540
2 Palumbo A Avet-Loiseau H Oliva S Lokhorst HM Goldschmidt H Rosinol L Richardson P Caltagirone S Lahuerta JJ Facon T Bringhen S Gay F Attal M Passera R Spencer A Offidani M Kumar S Musto P Lonial S Petrucci MT Orlowski RZ Zamagni E Morgan G Dimopoulos MA Durie BG Anderson KC Sonneveld P San Miguel J Cavo M Rajkumar SV & Moreau P Revised international staging system for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol. 33(26) 2863 - 2869 2015. PMID: 26240224. DOI: 10.1200/JCO.2015.61.2267
3 Alexanian R Barlogie B & Dixon D Renal failure in multiple myeloma. Pathogenesis and prognostic implications. Arch Intern Med. 150(8) 1693 - 1695 1990. PMID: 2383164.
Pubmed |
4 Bladé J & Rosiñol L Renal, hematologic and infectious complications in multiple myeloma. Best Pract Res Clin Haematol. 18(4) 635 - 652 2005. PMID: 16026742. DOI: 10.1016/j.beha.2005.01.013
5 Cairo MS & Bishop M Tumour lysis syndrome: new therapeutic strategies and classification. Br J Haematol. 127(1) 3 - 11 2004. PMID: 15384972. DOI: 10.1111/j.1365-2141.2004.05094.x
6 Howard SC Jones DP & Pui CH The tumor lysis syndrome. N Engl J Med. 364(19) 1844 - 1854 2011. PMID: 21561350. DOI: 10.1056/NEJMra0904569
7 Tomlinson GC & Solberg LA Jr Acute tumor lysis syndrome with metastatic medulloblastoma. A case report. Cancer. 53(8) 1783 - 1785 1984. PMID: 6199103. DOI: 10.1002/1097-0142(19840415)53:8<1783::aid-cncr2820530829>3.0.co;2-f
8 Malik IA Vellozo P Khurshid M & Khan A Radiation induced tumour lysis syndrome in a patient with leukaemia. J Pak Med Assoc. 42(8) 191 - 193 1992. PMID: 1433798.
Pubmed |
9 Schifter T Cohen A & Lewinski UH Severe tumor lysis syndrome following splenic irradiation. Am J Hematol. 60(1) 75 - 76 1999. PMID: 9883811. DOI: 10.1002/(sici)1096-8652(199901)60:1<75::aid-ajh14>3.0.co;2-2
10 Rostom AY El-Hussainy G Kandil A & Allam A Tumor lysis syndrome following hemi-body irradiation for metastatic breast cancer. Ann Oncol. 11(10) 1349 - 1351 2000. PMID: 11106126. DOI: 10.1023/a:1008347226743
11 Yamazaki H Hanada M Horiki M Kuyama J Sato T Nishikubo M Ishida T & Inoue T Acute tumor lysis syndrome caused by palliative radiotherapy in patients with diffuse large B-cell lymphoma. Radiat Med. 22(1) 52 - 55 2004. PMID: 15053177.
Pubmed |
12 Chen SW Hwang WS Tsao CJ Liu HS & Huang GC Hydroxyurea and splenic irradiation-induced tumour lysis syndrome: a case report and review of the literature. J Clin Pharm Ther. 30(6) 623 - 625 2005. PMID: 16336296. DOI: 10.1111/j.1365-2710.2005.00684.x
13 Noh GY Choe DH Kim CH & Lee JC Fatal tumor lysis syndrome during radiotherapy for non-small-cell lung cancer. J Clin Oncol. 26(36) 6005 - 6006 2008. PMID: 19029410. DOI: 10.1200/JCO.2008.19.4308
14 Jain S Harrison C McMullin MF & Houston RF Tumour lysis syndrome after splenic irradiation in a patient with JAK2 V617F post-polycythaemia vera myelofibrosis. Clin Oncol (R Coll Radiol). 22(10) 893 2010. PMID: 20692135. DOI: 10.1016/j.clon.2010.07.002
15 Kaplan MA Kucukoner M Alpagat G & Isikdogan A Tumor lysis syndrome during radiotherapy for prostate cancer with bone and bone marrow metastases without visceral metastasis. Ann Saudi Med. 32(3) 306 - 308 2012. PMID: 22588444. DOI: 10.5144/0256-4947.2012.306-308
16 Dar L Gendelman O & Amital H Tumor lysis syndrome presenting in a patient with metastatic melanoma treated with radiation therapy. Isr Med Assoc J. 16(7) 456 - 457 2014. PMID: 25167696.
Pubmed |
17 Alkan A Kütük T Karcı E Yaşar A Hiçsönmez A & Utkan G Radiation-induced tumor lysis syndrome in chronic lymphocytic leukemia. Turk J Haematol. 33(3) 248 - 250 2016. PMID: 27093891. DOI: 10.4274/tjh.2015.0259
18 Stuart S & Auten J A rare seizure: Tumor lysis syndrome after radiation therapy of a solid tumor. Am J Emerg Med. 35(6) 941.e3 - 941.e4 2017. PMID: 28132791. DOI: 10.1016/j.ajem.2017.01.023
19 Yavorkovsky LL Jing W & Baker R An upsurge of the serum free light chains as a possible missing link in tumour lysis syndrome in multiple myeloma. Br J Haematol. 188(5) 732 - 735 2020. PMID: 31573682. DOI: 10.1111/bjh.16231
20 Cailleteau A Touzeau C Jamet B Guimas V Jouglar E & Supiot S Cytokine release syndrome and tumor lysis syndrome in a multiple myeloma patient treated with palliative radiotherapy: A case report and review of the literature. Clin Transl Radiat Oncol. 32 24 - 28 2021. PMID: 34816023. DOI: 10.1016/j.ctro.2021.11.004
21 Schiff JP Spraker MB Duriseti S Shaikh S Murad HF Mutch DG Robinson CG Kavanaugh J & Lin AJ Tumor lysis syndrome in a patient with metastatic endometrial cancer treated with lattice stereotactic body radiation therapy. Adv Radiat Oncol. 7(1) 100797 2021. PMID: 34761139. DOI: 10.1016/j.adro.2021.100797
22 Tsang RW Campbell BA Goda JS Kelsey CR Kirova YM Parikh RR Ng AK Ricardi U Suh CO Mauch PM Specht L & Yahalom J Radiation therapy for solitary plasmacytoma and multiple myeloma: Guidelines from the International Lymphoma Radiation Oncology Group. Int J Radiat Oncol Biol Phys. 101(4) 794 - 808 2018. PMID: 29976492. DOI: 10.1016/j.ijrobp.2018.05.009
23 Nguyen SK & Dagnault A Radiotherapy for multiple myeloma with skin involvement. Curr Oncol. 17(5) 74 - 77 2010. PMID: 20975884. DOI: 10.3747/co.v17i5.618
24 Montesinos P Lorenzo I Martín G Sanz J Pérez-Sirvent ML Martínez D Ortí G Algarra L Martínez J Moscardó F de la Rubia J Jarque I Sanz G & Sanz MA Tumor lysis syndrome in patients with acute myeloid leukemia: identification of risk factors and development of a predictive model. Haematologica. 93(1) 67 - 74 2008. PMID: 18166787. DOI: 10.3324/haematol.11575
25 Gemici C Tumour lysis syndrome in solid tumours. Clin Oncol (R Coll Radiol). 18(10) 773 - 780 2006. PMID: 17168213. DOI: 10.1016/j.clon.2006.09.005
26 Oiwa K Morita M Kishi S Okura M Tasaki T Matsuda Y Tai K Hosono N Ueda T & Yamauchi T High risk of tumor lysis syndrome in symptomatic patients with multiple myeloma with renal dysfunction treated with bortezomib. Anticancer Res. 36(12) 6655 - 6662 2016. PMID: 27919998. DOI: 10.21873/anticanres.11274
27 Pession A Melchionda F & Castellini C Pitfalls, prevention, and treatment of hyperuricemia during tumor lysis syndrome in the era of rasburicase (recombinant urate oxidase). Biologics. 2(1) 129 - 141 2008. PMID: 19707436. DOI: 10.2147/btt.s1522