Table 3.

Correlation between PDTO treatment effect and patient clinical outcomes across various cancer types.

Cancer type	Classification	Sample size	Comments	Reference
Bladder	Non-muscle invasive Muscle invasive	2	PDTOs can predict drug responses and identify effective therapies for patients.	[177]
Brain tumor metastasis	Oligodendroglioma (OA), Grade III OA, Grade II. Colon cancer metastasis to the brain.	3	Treatments identified through PDTO testing can improve patient outcomes. For example, one patient treated based on PDTO results experienced complete tumor regression and remained free of recurrence for over 15 months.	[183]
Breast	Her2+ (2) TNBC (2) Luminal B (1)	5	In HER-2+ patients, the response of the tissue-derived organoids to the drugs was consistent with the patient's clinical response. The organoids derived from triple-negative and luminal B-types responded like parental tumors.	[178]
	Luminal B TNBC Her2+	6	PDTO pharmaco-phenotyping results guided treatments. The clinical outcomes were partial response, stable disease, or disease-free.	[126]
Colorectal	Metastatic	22	Patients with high levels of circHAS2 expression demonstrated a notable sensitivity to anlotinib treatment. In a phase 2 clinical trial, 14 patients expressing high levels of circHAS2 yielded meaningful clinical remission, with a DCR of 100.0% and an ORR of 85.7%	[181]
	Metastatic	9	Sensitivity was limited to 66.7%, with five false negative cases in total. The most significant potential for standard-of-care PDTO testing lies in selecting first- and second-line treatments, especially when multiple viable therapy options exist.	[185]
	Metastatic	34	At the two-month mark, 17 out of 34 patients achieved progression-free survival, surpassing the pre-defined minimal relevant difference compared to historical controls from randomized trials.	[184]
		11	The research reported an approximately 80% concordance rate between the responses of PDTOs and the clinical responses observed in donor patients.	[190]
	Metastatic	3	The study demonstrates a clear correlation between PDTO drug treatment responses and patients' original tumor responses, supporting using PDTOs as a preclinical platform for precision medicine in colorectal cancer.	[191]
	Metastatic	6	No lasting clinical responses from treatment decisions guided by organoids. No correlation between PDTOs and patient outcomes.	[188]
	Metastatic	71	The patient-derived tumor organoid model demonstrated a sensitivity of 63.33%, a specificity of 94.12%, and an accuracy of 79.69% in predicting responses to chemotherapy regimens.	[180]
	Metastatic	9	A correlation between patient outcomes and PDTO results was observed with Gemcitabine and Regorafenib. FOLFOX did not correlate strongly with patient outcomes based on PDTO results.	[187]
	Metastatic	10	PDTOs to predict the outcomes of irinotecan-based chemotherapy is clinically feasible.	[186]
	Metastatic	1	This study is among the first to prospectively investigate the use of PDTOs to predict treatment responses for individual cancer patients.	[192]
Esophagogastric adenocarcinoma		13	The study defined a PDTO-derived threshold value that accurately classified patients into pathological responders and non-responders with high sensitivity (90%), specificity (100%), and accuracy (92%) based on the FLOT response. The receiver operating characteristic (ROC) analysis for FLOT testing yielded an area under the curve (AUC) of 0.994.	[179]
Gastric		3	An example of direct correlation is when one patient who received a 5-FU-based drug post-operatively exhibited progressive disease, and the PDTO culture also did not respond to the same treatment. In another example, two patients. who were treated with cisplatin and 5-FU-based drugs after surgery showed substantial tumor shrinkage.	[193]
Gastrointestinal	Metastatic	14	The PDTOs showed 100% sensitivity, 93% specificity, 88% positive predictive value, and 100% negative predictive value in forecasting response to targeted agents or chemotherapy in patients.	[172]
Glioblastoma		7	Three out of seven patients exhibited a reduction in Ki67+ cells following treatment with temozolomide and radiation, indicating a positive response to the therapy. However, the study did not consistently correlate PDTO responses with MGMT methylation status, a recognized predictive marker for temozolomide response. This implies that, although some individual cases showed encouraging correlations, a broader, definitive connection between PDTO treatment responses and the original tumor characteristics was not established.	[171]
Head and neck		21	In the adjuvant treatment setting, PDTO viability at 2 Gy showed the strongest correlation with clinical response (n = 15), although this correlation was not statistically significant. For patients who received primary RT, no statistically significant correlation was observed between organoid response and clinical relapse (n = 6).	[194]
Lung	Adenocarcinoma Squamous cell adenocarcinoma Small cell lung cancer Other types	21	The study successfully correlated the drug responses of lung PDTOs derived from 21 patients with their respective clinical outcomes and genetic profiles, highlighting the potential of this approach in personalized medicine for lung cancer treatment.	[122]
	Adenocarcinoma Squamous cell adenocarcinoma	34	The PDTOs maintained the sensitivity of the corresponding parental tumors to targeted therapies, demonstrating their usefulness in validating or identifying biomarker-drug combinations.	[174]
Mesothelioma		2	Patient 1 showed a strong response to cisplatin/ pemetrexed, which aligned with the patient's clinical response to this treatment. Patient 2 did respond to carboplatin and pemetrexed; the response was not strong.	[195]
Ovary	High grade serous	1	Drug responses in matched organoid lines derived from a single patient's primary chemosensitive and recurrent chemoresistant ascites.	[88]
		5	Same PDTOs as [88]. PDTO drug response often reflects patients’ clinical response. However, PDTOs derived from different tumor locations within the same patient demonstrated differential drug responses. Additionally, organoids established from the same patient at different time points showed variability in their responses to drugs, indicating that tumor heterogeneity can significantly affect treatment outcomes.	[189]
Pancreas		9	Six patients with progression-free survival (PFS) longer than the median were treated with at least one drug that their PDTO was sensitive to. This resulted in a mean PFS of 332 days, significantly higher than the expected 180 days.	[92]
Prostate	Neuroendocrine (metastatic)	4	Two of the four PDTOs exhibited treatment responses consistent with the patient's clinical outcomes. One showed significant sensitivity to the aurora kinase inhibitor alisertib, which aligned with the patient's response in a Phase 2 trial of the same drug. The other one did not respond to alisertib, mirroring the lack of response observed in the patient during the clinical trial. However, this organoid did respond to the MEK inhibitor cobimetinib, indicating that while not all PDTOs matched perfectly, there were notable correlations in treatment responses.	[182]
Rectal		80	Irradiation: 16 patients with organoids sensitive to irradiation responded well to neoadjuvant chemoradiation, while 64 patients with resistant organoids had varied responses. 5-FU: Exposure to 10 mM 5-FU showed significant variability in PDTO responses. Among 53 patients with 5-FU-resistant PDTOs, 38 had poor responses, and 15 had good responses. Irinotecan: 32 PDTOs were sensitive, with most patients responding well, except for 7 cases. Overall, 34 patients had good clinical responses, and their PDTOs were sensitive to at least one treatment (irradiation, 5-FU, or irinotecan). Conversely, 34 patients responded poorly, with their organoids resistant to all treatments. The analysis showed a strong correlation (AUC of 0.882) between PDTO data and clinical outcomes.	[173]
		7	Seven had sufficient clinical follow-up to provide complete progression-free survival (PFS) data. PDTOs exhibited a range of radiation sensitivities, corresponding to the clinical responses observed in the patients.	[99]

Abbreviations: PDTO: patient-derived tumor organoid; OA: oligodendroglioma; Her2: human epidermal growth factor receptor 2; TNBC: triple-negative breast cancer; DCR: disease control rate; ORR: objective response rate; FOLFOX: folinic acid, fluorouracil (5-FU), oxaliplatin; ROC: receiver operating characteristic, AUC: area under the curve; FLOT: Fluorouracil, leucovorin, oxaliplatin, Taxotere; MGMT: O-6-methylguanine-DNA methyltransferase; RT: radiation therapy; MEK: mitogen-activated protein kinase kinase; PFS: patient-free survival.