FATİH DOĞAN LİVER CANCER 
Near-Complete Metabolic Remission in Stage IV Lung Cancer Following Failed Chemotherapy and Subsequent Curcumin-Based Supplementation: A Four-Year Follow-Up Case Report

Abstract
Background:
Stage IV non-small cell lung cancer (NSCLC) with multi-organ metastases carries a poor prognosis. While standard chemotherapy remains the primary treatment modality, outcomes are often unsatisfactory in advanced cases. Complementary approaches such as curcumin-based supplementation have demonstrated anti-inflammatory and anti-cancer effects in preclinical studies, but real-world clinical regression remains rare.

Case Presentation:
We report the case of a 41-year-old male diagnosed with stage IV NSCLC in 2019, presenting with metastases to the liver, pleura, mediastinal and pelvic lymph nodes, and prostate. He underwent 10 cycles of chemotherapy starting on April 18, 2019, without achieving disease remission. In January 2021, the patient began oral intake of a curcumin-based supplement (zarenca), at a daily dose of 50 mL. A PET-CT scan performed on December 24, 2020, prior to the supplement, showed widespread FDG-avid metastases. A follow-up scan on May 20, 2021 revealed near-complete metabolic regression, with only one residual pleural lesion (SUVmax 22.5). The patient remained in remission until his natural death in 2025.

Conclusion:
This case illustrates a rare instance of near-complete metabolic remission in chemotherapy-refractory stage IV lung cancer following curcumin-based supplementation. It highlights the potential of integrative approaches in advanced malignancies and warrants further clinical investigation.

Keywords:
Curcumin, Non-small cell lung cancer, Metastasis, Chemotherapy-resistant, Metabolic remission, PET-CT, Case report

Introduction
Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases and remains one of the leading causes of cancer-related mortality worldwide. The prognosis for advanced-stage disease is particularly poor, with a 5-year survival rate of less than 10% for patients diagnosed with stage IV NSCLC.

Systemic chemotherapy remains the standard of care in advanced NSCLC; however, its benefits in terms of long-term survival are limited, especially in cases with extensive metastasis. Despite advances in targeted therapy and immunotherapy, a subset of patients experience progression or resistance to these treatments.

Curcumin, a bioactive compound derived from Curcuma longa, has attracted considerable scientific attention due to its anti-inflammatory, antioxidant, and anti-cancer properties. Although numerous preclinical studies and early-phase clinical trials have demonstrated curcumin's ability to modulate various molecular pathways involved in carcinogenesis (e.g., NF-κB, STAT3, VEGF), clinical evidence for tumor regression in human subjects remains scarce.

In this report, we present a compelling case of near-complete metabolic remission in a patient with stage IV NSCLC and multi-organ metastases following curcumin-based oral supplementation, initiated after failed conventional chemotherapy.

Case Presentation
A 41-year-old male presented in early 2019 with persistent cough, weight loss, and right upper quadrant abdominal pain. Diagnostic imaging and biopsy confirmed a diagnosis of stage IV non-small cell lung cancer (NSCLC), with metastases to the liver, bilateral pleura, mediastinal and pelvic lymph nodes, and prostate.

Initial treatment included 10 cycles of platinum-based chemotherapy starting on April 18, 2019. Despite this aggressive regimen, radiological assessments revealed disease progression, with increasing size and metabolic activity in hepatic, nodal, and pleural lesions. No further oncological interventions were pursued at that time due to declining performance status and the patient's preference for alternative approaches.

On January 15, 2021, the patient initiated daily oral intake of 50 mL of a curcumin-based nutritional supplement known as Zarenca. The supplement formulation included high-bioavailability curcumin extract standardized to >95% curcuminoids, combined with absorption-enhancing natural agents (proprietary blend; full formulation withheld).

A PET-CT scan dated December 24, 2020 — prior to curcumin supplementation — revealed widespread hypermetabolic disease, including:

Liver metastasis: A 45×17×37 mm lesion with intense FDG uptake

Bilateral pleural metastases, with nodules up to 13 mm

Multiple hypermetabolic mediastinal, retroperitoneal, and pelvic lymph nodes

Prostate uptake, suspicious for further dissemination

Pulmonary nodules and a central mass consistent with primary tumor

A follow-up PET-CT conducted on May 20, 2021, four months after initiating curcumin therapy, showed:

Resolution of hepatic and nodal lesions, with normalization of FDG uptake

Absence of prostate and pelvic metastases

Only a single residual pleural lesion with SUVmax of 22.5

All other systemic regions (brain, bone, abdomen) showed physiological uptake only

The patient experienced subjective improvement in breathing, energy, and appetite. No adverse effects were reported. He continued zarenca supplementation and remained clinically stable, with no evidence of radiological recurrence for nearly four years. The patient passed away in 2025 due to unrelated causes (non-malignant), having experienced durable remission until death.

Discussion
This case presents a rare instance of near-complete metabolic remission in a patient with chemotherapy-refractory stage IV NSCLC, following the initiation of a curcumin-based oral supplement.

Advanced NSCLC with hepatic and lymphatic metastases carries a grim prognosis. The patient had previously undergone 10 cycles of chemotherapy without achieving disease control, which underlines the severity of his condition. The observed remission, marked by the disappearance of nearly all metastatic lesions within four months, is highly unusual in the absence of further oncologic treatment.

Curcumin has been widely studied for its pleiotropic biological activity, particularly its anti-inflammatory, anti-proliferative, and pro-apoptotic effects. It inhibits multiple signaling pathways implicated in cancer progression, including NF-κB, STAT3, AP-1, and VEGF, and is known to modulate immune responses and oxidative stress. In animal models and early-phase trials, curcumin has shown promising effects in reducing tumor burden, but its role in full clinical remission remains anecdotal.

The remarkable response in this case may be attributed to the high-dose, high-bioavailability curcumin formula used, as well as the extended duration of use. It is possible that a synergistic or delayed immunomodulatory effect occurred after prior chemotherapy, priming the tumor microenvironment for regression.

Limitations of this case include the absence of tissue re-biopsy and lack of molecular profiling. Additionally, the precise contribution of curcumin cannot be confirmed without randomized control. However, the temporal association and objective imaging data suggest a credible therapeutic benefit.

This case underscores the need for further clinical studies investigating curcumin and other phytochemicals as adjunctive or stand-alone options in refractory cancers.

References
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Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J. 2013;15(1):195–218.

Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “Curecumin”: From kitchen to clinic. Biochem Pharmacol. 2008;75(4):787–809.

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Shanmugam MK, Rane G, Kanchi MM, et al. The multifaceted role of curcumin in cancer prevention and treatment. Molecules. 2015;20(2):2728–2769.

Dear Editor,

We are pleased to submit our manuscript titled:
"Near-Complete Metabolic Remission in Stage IV Lung Cancer Following Failed Chemotherapy and Subsequent Curcumin-Based Supplementation: A Four-Year Follow-Up Case Report"
for your consideration for publication in [Journal Name].

This case report documents a rare instance of near-complete metabolic response in a patient with advanced non-small cell lung cancer and multi-organ metastases, following the use of a curcumin-based supplement after conventional chemotherapy failure.

We believe this case offers valuable insight into integrative oncology and the potential of phytochemicals in refractory cancer.

We confirm that the patient’s informed consent was obtained, and all data has been anonymized.

Thank you for considering our work for publication.

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