Risk of Bowel Obstruction in Patients with Mesenteric or Peritoneal Disease Receiving Peptide Receptor Radionuclide Therapy

RESULTS

In total, 159 patients were treated between April 2018 (after Food and Drug Administration approval and commercial availability of ¹⁷⁷Lu-DOTATATE) and October 2019. Eighty-one patients (51%) were at risk for bowel obstruction due to baseline mesenteric or peritoneal disease. Among the patients with mesenteric or peritoneal tumors, a majority (59 patients) had primary midgut (jejunal and ileocecal) tumors, 16 patients had primary pancreatic tumors, and 6 patients had tumors of other primary sites. Twenty-two patients were deemed to be at high risk because of extensive peritoneal disease or desmoplastic changes associated with mesenteric tumors. Among midgut NET patients with mesenteric or peritoneal disease, 80% had previously undergone resection of their primary tumor. Although 19 patients with midgut NETs had experienced prior small-bowel obstruction, 16 of those cases were related to primary tumor with or without associated mesenteric disease, and only 3 cases were related to peritoneal carcinomatosis.

After beginning PRRT, 5 patients, all falling into the high-risk category, experienced a bowel obstruction within 3 mo of a treatment with ¹⁷⁷Lu-DOTATATE. These 5 cases represented 3% of all patients treated with ¹⁷⁷Lu-DOTATATE, 6% of patients with mesenteric or peritoneal disease, and 22% of high-risk patients. All had primary small-intestine (midgut) NETs with mesenteric and peritoneal disease, the extent of which was best appreciated on ⁶⁸Ga-DOTATATE imaging. All had undergone resection of primary small-intestine tumors, and none had experienced overt bowel obstruction within the prior decade. The patient characteristics and clinical course are summarized in Table 1 and described below.

The first patient to experience bowel obstruction had progressive hepatic, mesenteric, and peritoneal disease at the time of initiation of treatment with ¹⁷⁷Lu-DOTATATE. The peritoneal tumor burden was exceptionally high (Fig. 1), and he had developed a progressive stabbing abdominal pain shortly before treatment. One week after initiating ¹⁷⁷Lu-DOTATATE, he presented with bowel obstruction, and a CT scan showed peritoneal thickening consistent with peritonitis, as well as dilatation of the proximal colon. He was started on oral dexamethasone, 4 mg twice daily, and was able to resume eating but was subsequently readmitted with recurrent bowel obstruction with a transition point at the level of the sigmoid colon. Exploratory laparotomy was performed and revealed a “frozen abdomen” caused by extensive adhesions between abdominal viscera and the anterolateral abdominal wall, leading to intestinal immobility. He was restarted on high-dose steroids and again regained a temporary ability to eat. Treatment with ¹⁷⁷Lu-DOTATATE was not resumed and his peritoneal disease progressed. He eventually developed encapsulating peritonitis and a cocoon abdomen 5 mo after treatment and died 6 mo after treatment.

• Download figure
• Open in new tab
• Download powerpoint

FIGURE 1.

(A) Maximum-intensity projection demonstrates peritoneal carcinomatosis (arrow) and liver and mediastinal metastases in patient with progressive metastatic small-bowel NET. (B–D) Axial ⁶⁸Ga-DOTATATE PET (B), attenuation-correction CT (C), and ⁶⁸Ga-DOTATATE PET/CT (D) demonstrate uptake in extensive peritoneal metastatic implants (arrows).

The second patient presented with progressive hepatic, skeletal, mesenteric, and peritoneal disease (Fig. 2). Within several minutes of her first treatment with ¹⁷⁷Lu-DOTATATE, she experienced acute nausea that resolved after administration of intravenous dexamethasone, 8 mg. She was discharged on a steroid taper but developed small-bowel obstruction 2 d after completion of steroids. The obstruction appeared to be related to tethering of bowel to a mesenteric mass (Fig. 3). She was restarted on steroids, and bowel function recovered 4 d later. She was able to tolerate her second and third ¹⁷⁷Lu-DOTATATE treatments with prophylactic steroids (oral dexamethasone, 4 mg daily for 7 d followed by a 2-wk taper). However, she developed another bowel obstruction 3 wk after her fourth treatment and underwent exploratory laparotomy, which revealed a frozen abdomen. She was restarted on high-dose steroids and was able to resume eating 3 d after surgery. She was discharged on a prednisone taper and remained free of obstruction for 2 mo. However, at the time of data collection, she had developed recurrent small-bowel obstruction and began total parenteral nutrition.

• Download figure
• Open in new tab
• Download powerpoint

FIGURE 2.

Axial ⁶⁸Ga-DOTATATE PET (A), attenuation-correction CT (B), and ⁶⁸Ga-DOTATATE PET/CT (C) demonstrate somatostatin-receptor–expressive mesenteric (arrows) and peritoneal (arrowheads) metastases. There is mild tethering of loops of bowel to mesenteric mass in right lower quadrant (arrows).

• Download figure
• Open in new tab
• Download powerpoint

FIGURE 3.

Coronal contrast-enhanced CT of abdomen and pelvis demonstrates small-bowel obstruction with dilated loops of bowel tethered to mesenteric lesion (arrow).

The third patient had progressive peritoneal disease at the time of ¹⁷⁷Lu-DOTATATE initiation, as well as liver and lymph node metastases (Fig. 4). He developed crampy abdominal pain after the second treatment and was prescribed a steroid taper. He received prophylactic steroids with his third treatment but developed bowel obstruction 5 wk after therapy. A CT scan showed multilevel obstruction secondary to peritoneal carcinomatosis. His bowel function recovered 3 d after resuming steroids, and his fourth cycle of treatment was canceled. Five months later, in the setting of increasing postprandial pain and weight loss, he underwent exploratory laparotomy with extensive peritoneal surgical debulking. Over 50 tumors were resected, including numerous colon and small-bowel implants. The surgeon noted a massive desmoplastic reaction due to peritoneal carcinomatosis. He recovered well from surgery and was able to resume a normal diet.

• Download figure
• Open in new tab
• Download powerpoint

FIGURE 4.

Axial ⁶⁸Ga-DOTATATE PET (A), attenuation-correction CT (B), and ⁶⁸Ga-DOTATATE PET/CT (C) demonstrate somatostatin-receptor–expressive peritoneal carcinomatosis (arrows), including peritoneal lesions along anastomotic suture line (arrowheads).

The fourth patient had progressive hepatic and peritoneal disease along with mesenteric and retroperitoneal disease at the time of treatment onset and complained of intermittent pelvic pain. She received 2 cycles of ¹⁷⁷Lu-DOTATATE (with prophylactic steroids after each treatment) but discontinued it after developing increased postprandial abdominal pain and vomiting. A CT scan 2 mo after the second treatment demonstrated stable disease with no evidence of bowel obstruction, but with increased tethering of pelvic bowel to tumor. She developed overt bowel obstruction a month later, with dilated small bowel and proximal colon, likely due to pelvic implants, and died 6 mo after her last PRRT treatment.

The fifth patient had progressive hepatic and mesenteric disease at the onset of PRRT treatment. He developed transient abdominal pain and nausea and vomiting 1 wk after his first cycle of PRRT, as well as developing similar symptoms along with radiographic evidence of small-bowel obstruction 1 wk after his second cycle. He was treated with a steroid taper, and his symptoms resolved. Further treatments were held pending a surgical consult.