Overview
Neuroendocrine tumours (NETs) are malignancies that arise from specialized
hormone-producing neuroendocrine cells dispersed throughout the body.
They bridge two biological worlds — the nervous system and the endocrine
glands — and can occur almost anywhere: lungs, pancreas, gastrointestinal tract,
and adrenal glands being most common.
NETs range from slow-growing indolent tumours to high-grade neuroendocrine
carcinomas (NECs) that behave like small-cell lung cancer.
Adrenal tumours include:
● Pheochromocytoma & Paraganglioma (catecholamine-secreting tumours)
● Adrenocortical carcinoma (ACC) — an aggressive cancer of the adrenal
cortex.
At Coimbatore Cancer Clinic, these rare diseases are managed through an
integrated Endocrine–Oncology board involving oncologists, endocrinologists,
nuclear-medicine specialists, and surgeons — ensuring precision diagnosis, safe
hormone control, and access to advanced molecular and nuclear therapies.
Epidemiology & Classification
● Annual incidence ≈ 5 – 7 per 100,000, but rising with better imaging.
● 60 % originate in GI tract (foregut, midgut, hindgut), 25 % in lungs, 5–10 % in
pancreas.
● WHO 2022 classification divides by site, differentiation, and grade (based
on mitotic count + Ki-67 index):
Molecular Landscape
● MEN1 mutations in pancreatic / duodenal NETs
● DAXX/ATRX loss → chromatin instability (pNET G2/G3)
● TP53 / RB1 alterations → NEC phenotype
● SDHB/SDHD in hereditary paraganglioma
● TERT, CTNNB1 in adrenocortical carcinoma
Symptoms
Diagnostic Algorithm
1. Hormonal work-up
o Chromogranin-A, 24-h urinary 5-HIAA, fasting insulin/C-peptide,
plasma metanephrines.
2. Anatomical Imaging – Contrast CT / MRI Abdomen-Pelvis.
3. Functional Imaging – ^68Ga-DOTATATE PET-CT for SSTR-positive NETs;
^18F-FDG PET for high-grade NEC.
4. Histopathology + IHC – Synaptophysin, Chromogranin, Ki-67, SSTR2A,
CD56.
5. Molecular Profiling – MEN1, DAXX, ATRX, TP53, SDHB, TMB, PD-L1.
Treatment Approach
A. Well-Differentiated NET (G1–G2)
Goal → disease control + symptom relief + hormone regulation
1. Surgery – complete resection whenever feasible (laparoscopic / robotic).
o Pancreatic NET → enucleation / Whipple / distal pancreatectomy.
o Ileal NET → segmental resection + mesenteric node clearance.
2. Somatostatin Analogues (SSAs) – Octreotide LAR 30 mg q28d or Lanreotide 120 mg q28d.
o Control symptoms + slow growth.
o PROMID & CLARINET trials: median PFS > 24 months.
3. Targeted Therapy
o Everolimus (mTOR inhibitor) – RADIANT-4: median PFS 11 mo vs 4.6 mo placebo.
o Sunitinib (VEGFR TKI) – approved for pancreatic NETs.
o Lenvatinib / Cabozantinib – promising in resistant NETs.
4. Peptide Receptor Radionuclide Therapy (PRRT)
o ^177Lu-DOTATATE delivers targeted radiation via SSTR binding.
o NETTER-1 trial: 65 % risk reduction in progression.
o Sequence: SSA → Everolimus/Sunitinib → PRRT → Chemo.
5. Chemotherapy
o Streptozocin + 5-FU or Capecitabine/Temozolomide (CAPTEM) for progressive pancreatic NETs.
6. Liver-Directed Therapy
o Radioembolization (Y-90), chemoembolization, or ablation for hepatic-dominant metastases.
B. High-Grade NET G3 & NEC
● Systemic Chemotherapy – Cisplatin + Etoposide (like SCLC) or Carboplatin
+ Irinotecan.
● Immunotherapy – PD-1/PD-L1 inhibitors (Nivolumab, Pembrolizumab,
Atezolizumab) yield durable responses in ~20 %.
● Maintenance IO for responders or PD-L1 high.
● Clinical Trials: combination IO + TKI (Lenvatinib + Pembrolizumab).
C. Adrenal Tumours
Emerging & Frontier Therapies (2024–25)
● α-PRRT (Actinium-225 DOTATATE) – 3× greater linear energy transfer.
● Radioligand combination (177Lu + 223Ra) for bone metastases.
● Immuno-PRRT hybrids – SSA conjugated to IO.
● BRAF/MEK-targeted therapy for BRAF V600E mutant LCH-like NETs.
● Circulating tumour DNA monitoring for early recurrence detection.
Follow-Up & Prognosis
● Imaging every 6 months × 2 years → yearly.
● Hormonal markers (CgA, 5-HIAA) q6 months.
● 5-year OS: G1 > 80 %, G2 ≈ 65 %, G3 ≈ 30 %, NEC ≈ 15 %.
Our Expertise @ Coimbatore Cancer Clinic
● ^68Ga-DOTATATE & ^177Lu-DOTATATE access through partner centres.
● Surgical and endocrine oncology collaboration for complex cases.
● PRRT, Everolimus, Sunitinib, and IO available locally.
● Long-term follow-up & symptom control programs.
FAQs
Can neuroendocrine tumours be cured?
Yes—if detected early and completely removed. Many others can be kept under
long-term control with PRRT and targeted drugs.
Is PRRT available in India?
Yes—through certified nuclear-medicine centres; our clinic co-ordinates referral and
monitoring.
Do hormonal symptoms disappear after therapy?
Usually within weeks of SSA or PRRT initiation; some require additional
anti-serotonin medications.
