Incidence and treatment of hypercalcemia in cancer patients receiving radiotherapy: a retrospective review of practice at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) from 2012 to 2015

Abstract

Background: Cancer induced hypercalcemia (CIH) is the most frequent metabolic oncologic emergency and occurs in up to 44.1% of all cancer patients at some time in their disease course. It occurs in patients with both solid and hematologic malignancies. CIH occurs mostly in patients with advanced cancer and is an indicator of poor prognosis. Timely diagnosis and intervention is lifesaving and also may enhance patient compliance with primary and supportive treatment and quality of life. This study aimed to describe the incidence, clinical patterns and treatment outcomes of hypercalcemia in cancer patients receiving Radiation therapy in Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg. Materials and Methods: This was a retrospective descriptive study, 125 patients who were admitted at the Radiation oncology ward CMJAH for hypercalcemia management from January 2012 to December 2015, were analyzed. Demographic data, relevant clinical information such as Stage of the disease, type of cancer, level of hypercalcemia, toxicity and Response to the treatment were recorded. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS_version 23). The incidence of hypercalcemia, clinical patterns, treatment outcomes and toxicities were evaluated. The study was approved by the Human Research Ethics Committee medical (HRECM) of the University of Witwatersrand with Clearance certificate number M140546. Results: Of the 125 patients analysed, males to females ratio was 1:1. The most frequent site of primary cancer diagnosis in patients with hypercalcemia was gynaecological malignancies 31 (24.8%), followed by head and neck cancers 23 (18.4%), prostate 19 (15.2%), breast cancer 17 (13.6%), gastrointestinal malignancies 12 (9.6%), multiple myeloma 5 (4%), lung cancer 3 (2.4%) and other malignancies 15 (12%). Most patients had metastatic disease and uncontrolled primary disease 78 (62.4%) compared to primary controlled disease 47 (37.6%). Bone metastasis were present in 51 (41%) of patients. Clinical presentation of patients with hypercalcemia was mainly Neuromuscular 41 (32.8%), nausea/vomiting 37 (29.6%), Polyuria 20 (16%), mental 16 (12.8) and Polydipsia 9 (7.2%).

Most of patients had severe hypercalcemia with pre-treatment corrected serum calcium level of > 2.9 mmol/L 77 (61.6%), 28 (22.4%) had Corrected serum Calcium between 2.71-2.89 mmol/L and 20 (16%) had corrected serum calcium between 2.56-2.70 mmol/L. One hundred and four patients (83.2%) received hydration + bisphosphonates and 21 (16.8%) of patients received hydration alone and non-received haemodialysis. One week post treatment majority of patients had ≤2.55 mmol/L Serum level of Calcium 81 (64.8%), 11 patients (8.8%) had serum level of calcium 2.56-2.71 mmol/L, 23 patients (18.4%) had serum calcium between 2.71-2.89 mmol/L and only 10 patients (8.0%) had serum level of calcium ≥2.9 mmol/L. The corrected serum calcium was 2.4770 ± 0.34512 mmol/L one week after treatment. One month post treatment majority of patients 99 (79.2%) remains to have normal serum level of calcium ≤2.55 mmol/L and only about 11 (8.8%) patients had ≥2.9 mmol/L. Forty four patients (35.2%) had relapse in 33 days (median) time and were subsequently treated with hydration and bisphosphonates. As the patients were enrolled from radiation oncology ward, most were treated with either radiation alone 72 (57.6%) or Concurrent chemo radiation 15 (12.0%) as treatment modalities for their primary cancer. Patients who received chemotherapy first and then radiotherapy for the treatment for their primary cancer were 37 (29.6%). Fourteen (58%) patients with pre-treatment calcium level of 2.56-2.70 mmol/L received hydration alone and 76 (98%) of patients with serum pre-treatment calcium of ≥2.9 mmol/L were treated with hydration + bisphosphonates (P=0.001). Side effects to bisphosphonates were mainly gastrointestinal: Nausea/vomiting 42 (33.6%) patients, Constipation 14 (11.2%), abdominal pain 13 (10.4), Diarrhoea 11 (8.8) and anorexia 1 (0.8) patients. Other toxicities reported were fever 12 (9.6%) patients and hypocalcaemia 14 (11.2%). Eighteen patients (14.4%) did not report any side effect to treatment. Conclusion: Hypercalcemia of malignancy is a common finding in patients with advanced stage cancers. Hypercalcemia of malignancy usually presents with markedly elevated calcium levels and patients are therefore usually symptomatic. For acute management of hypercalcemia, rehydration is the mainstay of treatment because all patients tend to have

dehydration. Bisphosphonates are potent calcium lowering agents, but they require careful administration and are contraindicated in patients with declined renal function. Common bisphosphonates toxicities are mainly gastrointestinal: Nausea/vomiting, constipation, abdominal pain, diarrhoea and anorexia. Other toxicities reported were fever and hypocalcaemia.