Successful stereotactic body radiation therapy for stage I non-small cell lung cancer with malignant hypercalcemia — Case report

Abstract

In patients with lung malignancy, the development of malignant hypercalcemia (MH) carries a dismal prognosis and represents a major therapeutic challenge given that conventional medical treatments have limited durability. Robust and lasting hypercalcemic reversal and symptomatic relief have been documented following surgical tumor resection. Stereotactic body radiation therapy (SBRT) has emerged as an effective treatment modality in medically inoperable patients with Stage I non-small cell lung cancer (NSCLC). In the current report, SBRT achieved durable tumor control and calcemic correction in a medically inoperable 79 year-old man with Stage I NSCLC patient with parathyroid hormone-related peptide (PTHrP)-induced MH.

Introduction

Malignant hypercalcemia (MH) accounts for 40% of hypercalcemia cases, and occurs in patients with osteolytic metastases and/or paraneoplastic syndromes.¹ Lung malignancy, both small cell and non-small cell types, have been identified in more than 20% of patients with parathyroid hormone-related peptide (PTHrP)-induced MH.² The overall prognosis for MH is poor, with a 1-year survival rate of 10-30% and a median survival of 1-3 months.³

MH represents a major therapeutic challenge given that conventional medical management serves only as a temporizing measure with limited therapeutic durability.^5,6 Modern stereotactic body radiation therapy (SBRT) has proven to be an excellent treatment option for medically inoperable patients with early stage non-small cell lung cancer (NSCLC).⁷ Here for the first time, we report the case of a 79 year-old man with Stage I NSCLC and MH that was successfully treated using lung SBRT. We then discuss the utility of lung SBRT in patients with MH secondary to early stage NSCLC. Patient informed consent was obtained in accordance with local and institutional laws and regulations.

Case Report

A 79 year-old Caucasian man with a 20 pack-years smoking history sought medical attention for polyuria, polydipsia, and lower extremity cramping. The patient also endorsed anorexia, nausea, a 20-pound weight loss, and mental confusion. His initial workup was remarkable for elevated serum calcium (Ca) of 12.1 mg/dL (normal reference range 8.5 to 10.2 mg/dL) and low albumin of 2.5 g/dL (normal reference range 3.4 to 4.8 g/dL). PTHrP was significantly elevated at 4.2 pmol/L (normal reference range 0.0 to 1.5). Chest computed tomography (CT) revealed a 2.1 x 2.3 cm (anterior-posterior x medial-lateral) spiculated lesion in the left upper lobe lung. Staging whole-body positron emission tomography (PET) identified a solitary hypermetabolic left upper lobe lung mass (standardized uptake values max of 14.2) without mediastinal nodal or distant metastases (Figure 1A-B). CT-guided biopsy of the lung mass demonstrated poorly-differentiated non-small cell carcinoma on pathology.

Figure 1.

Tumor Size and Metabolic Activity Before and After SBRT Completion.

A-B Initial chest computed tomography (CT) and positron emission tomography (PET) prior to stereotactic body radiation therapy (SBRT). C-D 3-month follow-up chest CT and PET after SBRT completion. Arrows indicate left upper lung tumor on CT and its corresponding fluorine-18-deoxyglucose (FDG) activity on PET.

The patient subsequently underwent 6 consecutive hospitalizations for recurrent hypercalcemic crises. Inpatient intravenous fluids and pamidronate only achieved transient serum Ca correction and symptomatic improvement. The patient deemed medically inoperable due to his severe COPD and poor performance status (ECOG score of 3). He was subsequently referred for SBRT which involved immobilization in a whole-body fixation system and delineation of radiation target volume of the mobile left upper lobe tumor as aided by four-dimensional CT simulation. The planned target volume (PTV) was 33.2 cc, generated via a 3-mm margin expansion from the internal gross tumor volume (IGTV) of 17.8 cc. The tumor was treated with 9 non-coplanar conformal beams totaling 54 Gray in 3 daily fractions over the course of 8 days.

The patient tolerated SBRT well and experienced calcemic normalization and symptomatic resolution within one month of lung SBRT completion. His Ca level at the initiation and one month after SBRT were 12.0 and 10.3 mg/dL, respectively (Figure 2). Follow up CT and PET performed in 3 months showed significant decrease in tumor size with minimal fluorine-18-deoxyglucose (FDG) activity (Figure 1C-D). At his 20-month follow-up, the patient reported no noticeable adverse effect from SBRT and repeat chest CT showed reduction of the tumor to 1.4 x 1.2 cm. His serum Ca remained within normal limits with values ranging from 8.7 to 9.1 mg/dL within the 3 to 18 months after SBRT (Figure 2).

Figure 2.

Serum Calcium Levels Before and After SBRT Completion.

Serum calcium (Ca) levels measured prior to and at 1, 3, 6, and 18-month follow-up after stereotactic body radiation therapy (SBRT) completion. Red dashed line indicates upper normal limit for serum Ca level (10.2 mg/dL) while * indicates completion of 8-day SBRT course.

Discussion

The accepted convention to achieve lasting therapeutic response in PTHrP-induced MH is definitive treatment of the underlying malignancy.^1,5,6 For early stage NSCLC, complete tumor resection via open thoracotomy or minimally-invasive video-assisted thoracoscopy is widely considered standard of care in medically operable patients.⁸ Surgical removal of PTHrP-secreting tumors has demonstrated robust and durable hypercalcemia reversal and symptomatic resolution.^9,10 However, MH patients generally have poor performance status and typically requires calcemic correction with intravenous fluids and bisphosphonates prior to surgery.^6,11

Despite his temporary calcemic correction during inpatient admissions, our patient remained medically inoperable due to his severe COPD and poor performance status. In recent years, SBRT has emerged as a promising therapeutic avenue for early stage NSCLC in surgically high-risk patients.^8,13 One large retrospective study in medically inoperable, elderly patients with early stage NSCLC found that SBRT yielded significantly enhanced overall survival compared to observation alone.⁷ For our patient, lung SBRT achieved not only stable tumor size reduction but also lasting calcemic normalization for 18 months post-SBRT, a dramatic improvement over the anticipated course for MH patients.

Conclusion

In conclusion, our report supports that lung SBRT is effective for achieving both durable tumor control and calcemic correction in medically-inoperable early-stage NSCLC with PTHrP-induced MH.