No widely used prognostic tool exists to demonstrate the benefit of oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX4) in patients with advanced hepatocellular carcinoma (HCC). We aimed to ...establish a prognostic score and demonstrate the real-world efficacy of FOLFOX4 chemotherapy in Thai patients.
Between August 2017 and December 2021, we identified 58 FOLFOX4-treated patients with HCC. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were assessed. The prognostic score was constructed by stepwise Cox proportional hazards regression analysis to select variables for the best model with the lowest Akaike information criterion from all potential variables.
Forty-four patients (76%) received FOLFOX4 as first-line therapy. The ORR in the entire cohort was 8.6%, and the disease control rate was 29.3%. The PFS and OS were 3.7 and 4.8 months, respectively. Four clinically relevant variables were included in the new prognostic score to predict 6-month OS: L, the presence of lung metastasis; A, alcoholic cirrhosis; B, elevated total bilirubin level; and S, sorafenib-naïve status. Using the LABS score, patients were classified into low-, intermediate-, and high-risk groups, demonstrating OS values of 9.3, 4.2, and 2.1 months, respectively (p < 0.0001). The C-index and area under the receiver-operating characteristic curve of the score were 0.71 and 0.73, respectively.
The proposed LABS score could discriminate patients who would derive benefit from FOLFOX4 chemotherapy. FOLFOX4 chemotherapy is an option for patients who cannot receive immunotherapy and targeted therapy, particularly those with a low-risk score. However, further validation of this model via larger cohorts is warranted.
Objective
Combination fluoropyrimidine-based chemotherapy is the standard first-line treatment for metastatic colorectal cancer (CRC). We performed a propensity score (PS)-based analysis to report ...our real-world experience with long-term follow-up of this regimen for metastatic CRC.
Methods
In this retrospective study, 170 patients with newly diagnosed metastatic CRC treated with first-line combination chemotherapy between January 2003 and March 2021 were identified. Cox proportional hazards regression analysis and PS-based approaches with the logistic regression model were adopted, and the results were compared.
Results
The hazard ratio for overall survival (OS) in the oxaliplatin- and irinotecan-based groups was 0.79 (95% confidence interval = 0.56–1.11), and the median OS times in these groups were 16.8 and 13.0 months, respectively. The median time to progression (TTP) for these regimens were 9.0 and 8.9 months, respectively. The objective response rates for the oxaliplatin- and irinotecan-based groups were 42.7% and 34.6%, respectively. OS and TTP did not differ between these regimens in all PS matching models.
Conclusions
First-line treatment using fluoropyrimidine-based chemotherapy regimens in combination with oxaliplatin or irinotecan in patients with metastatic CRC provided comparable efficacy and tolerable toxicity profiles in a real-world setting with long-term follow-up.
Changes in gene expression profiling of peripheral blood mononuclear cells (PBMC) appear to represent the host's response to the cancer cells via paracrine signaling. We speculated that protein ...expression on circulating T-lymphocytes represent T-lymphocyte trafficking before infiltration into the tumor microenvironment. The possibility of using protein expression on circulating T-lymphocytes as a biomarker to discriminate early-stage non-small cell lung cancer (NSCLC) was explored. Four independent PBMC gene expression microarray datasets (GSE12771, GSE13255, GSE20189 and GSE3934) were analyzed. We selected C5AR1, CLEC4A and NLRP3 based on their significant protein expression in tumor-infiltrating lymphocytes, but not in normal lymphoid tissue. A validation study using automated flow cytometry was conducted in 141 study participants including 76 treatment-naive early-stage non-small cell lung cancer patients (NSCLC), 12 individuals with non-malignant pulmonary diseases, and 53 healthy individuals. Median ratios of C5AR1, CLEC4A and NLRP3 specific antibody staining to CD3 positive cells in early-stage NSCLC patients compared to healthy controls were 0.014 0-0.37 vs. 0.01 0-0.07, p = 0.13, 0.03 0-0.87 vs. 0.02 0-0.13, p = 0.10 and 0.19 0-0.60 vs. 0.09 0.02-0.31, p < 0.0001, respectively. Median fluorescence intensity (MFI) of CD3
C5AR1
, CD3
CLEC4A
and CD3
NLRP3
expression in early-stage NSCLC patients compared to healthy volunteers was 185 64.2-4801 vs. 107.5 27-229, p < 0.0001, 91.2 42.4-2355 vs. 71.25 46.2-103, p = 0.0005, and 1585 478-5224 vs. 758.5 318-1976, p < 0.0001, respectively. NLRP3:CD3 ratio, CD3
C5AR1
, CD3
CLEC4A
and CD3
NLRP3
MFI were significantly higher in early-stage NSCLC than healthy volunteers with an area under the ROC curve of 0.69-0.76. The CD3
NLRP3
MFI provided the most distinguishable expression at 71.5% sensitivity and 70% specificity. Furthermore, CD3
NLRP3
MFI potentially discriminated between early-stage NSCLC from malignant-mimic inflammation and infection pulmonary disease. Further validation in various pulmonary inflammatory disease might be warranted. Our proof-of-principle findings strengthen the hypothesis that malignancies generate distinctive protein expression fingerprints on circulating T-lymphocytes.
The ability of the survival nomogram developed in the EACH study and albumin-bilirubin (ALBI) grade to predict the survival of advanced hepatocellular carcinoma (HCC) patients receiving oxaliplatin ...plus 5-fluorouracil/leucovorin (FOLFOX4) remains unvalidated. Here, we comprehensively evaluated these prognostic tools.
The survival nomogram and ALBI grade of each patient were assessed, and the area under the receiver operating curve (AUROC) and Harrell's C-index for the risk classification model were calculated.
Overall, 76 HCC patients who received FOLFOX4 between August 2017 and June 2023 were included. The survival nomogram classified patients into low-, intermediate-, and high-risk groups, with a median overall survival (OS) of 9.82, 10.64, and 3.70 months, respectively (
= 0.23). The AUROC was 0.621 and Harrell's C-index was 0.589. However, the ALBI grade categorized all patients into grade 1, 2, and 3, with a median OS of 9.82, 6.83, and 1.58 months, respectively (
= 0.00024). The AUROC was 0.663 and Harrell's C-index was 0.663.
The ALBI grade can be a potential prognostic tool. However, the survival nomogram does not provide clear discrimination. Therefore, FOLFOX4 should be an option for patients with ALBI grade 1 who cannot receive immunotherapy or targeted therapy. Additional prospective studies with a larger cohort are warranted to validate the survival nomogram and ALBI grade as prognostic tools.
: Although cisplatin plus 5-fluorouracil (5-FU) is the standard first-line treatment for advanced-stage esophageal squamous cell carcinoma (ESCC), carboplatin was substituted for cisplatin in ...cisplatin-ineligible patients. The efficacy of carboplatin plus 5-FU for advanced-stage ESCC remains unreported.
: This retrospective study analyzed first-line treatment-carboplatin plus 5-FU, cisplatin plus 5-FU, or best supportive care (BSC)-in advanced-stage ESCC patients at a tertiary hospital in Thailand (2012-2022). Survival was assessed using the Kaplan-Meier method, compared via the log-rank test, and adjusted through propensity score matching. Significance was set at
< 0.05.
: Of 256 patients, 39.9% received carboplatin plus 5-FU, 27.7% cisplatin plus 5-FU, and 32.4% BSC. Carboplatin was significantly associated with older age, poorer performance status, more comorbidities, chronic kidney disease, and lower creatinine clearance. Median overall survival (OS) for carboplatin plus 5-FU, cisplatin plus 5-FU, and BSC was 8.05 (HR 0.31 0.23, 0.43 vs. BSC,
< 0.001; HR 1.06 0.78, 1.44 vs. cisplatin plus 5-FU,
= 0.7), 8.43, and 3.64 months, respectively. No significant OS difference was observed between carboplatin and cisplatin treatments after propensity score matching. Median progression-free survival (PFS) and objective response rates (ORR) showed no significant difference between carboplatin and cisplatin treatments.
: Despite less favorable baseline characteristics of patients receiving carboplatin plus 5-FU, this combination exhibited comparable OS, PFS, and ORR to cisplatin plus 5-FU in real-world scenarios. Furthermore, it significantly improved OS over BSC. Consequently, carboplatin plus 5-FU should be considered as an alternative regimen, particularly for advanced-stage ESCC patients who are ineligible for cisplatin.
Testicular neuroendocrine tumor associated with teratoma is a rare disease. Very few cases have been reported in the literature, particularly cases involving visceral metastasis. Teratoma with ...somatic malignant transformation (SMT) is associated with a worse prognosis compared to teratoma without SMT. Previous data have suggested that chemotherapy regimens should be directed toward the transformed histology; however, those suggestions were based on patients with rhabdomyosarcoma, adenocarcinoma, and primitive neuroectodermal subtypes. To the best of our knowledge, only 2 cases with visceral metastasis have been reported, and a better outcome with the bleomycin/etoposide/cisplatin regimen, which responds strongly to germ cell tumors, has been reported in these cases. In contrast, 2 others with lymph node metastasis did not respond to these regimens. Here, we report a case of a patient with testicular neuroendocrine carcinoma associated with teratoma who achieved a good response to chemotherapy.
The mainstay systemic treatment for non-oncogenic addictive advanced stage non-small cell lung cancer is chemotherapy. Anti-angiogenic agents are additive compounds that enhance disease control and ...lead to improvement of overall survival benefit. Recently PD-(L)1 blockage, a checkpoint inhibitor, has been adopted as another line of treatment. A sequential strategy to enhance the efficacy of combination docetaxel and nintedanib after immunotherapy, correlated with genomic mutation, has been explored.
A retrospective cohort study of 56 patients from 8 centers in Thailand who received combination docetaxel and nintedanib
the Thai nintedanib Named Patient Use program was conducted. Demographic characteristics, treatment details, and treatment responses were retrieved from medical records.
The majority of patients were male (62.5%) with adenocarcinoma subtype (88%). Thirty-five percent had sensitizing
mutation. Combination docetaxel and nintedanib was given as second to fourth line of treatment. Median PFS of docetaxel/nintedanib was 5.6 months 95% CI 4.8-6.9. Median OS of the entire cohort was 22.5 months 95% CI 20.2-31.1. Among them, only four patients received this combination after immunotherapy which limited the validity of efficacy analysis. Median PFS of those four patients was 7.9 months range 5.2-9.1 which was slightly higher than the remaining cohort (median PFS 4.5 months, 95% CI: 4.0-6.0,
-value 0.09). Among the adenocarcinoma subtype, a relapse-time of platinum-doublet chemotherapy of more than 6 months was solely indicated as a benefit of combination docetaxel/nintedanib treatment compared to the relapse-time of platinum-doublet chemotherapy of less than 6 months by multivariate HR of PFS 0.32 95% CI: 0.14-0.68,
-value 0.003.
Combination docetaxel and nintedanib provided more benefit in relapse-time of platinum-doublet chemotherapy of more than 6 months in advanced stage adenocarcinoma lung cancer. Neither
nor
alteration influenced the outcome of treatment.
Hepatitis B virus reactivation (HBVr) following chemotherapy (CMT) is well-known among hematologic malignancies, and screening recommendations are established. However, HBVr data in solid organ ...malignancy (SOM) patients are limited. This study aims to determine hepatitis B surface antigen (HBsAg) screening rates, HBV prevalence, and the rate of significant hepatitis caused by HBVr in SOM patients undergoing CMT.
Based on the Oncology unit's registration database from 2009-2013, we retrospectively reviewed records of all SOM patients ≥18 years undergoing CMT at Songklanagarind Hospital who were followed until death or ≥6 months after CMT sessions. Exclusion criteria included patients without baseline liver function tests (LFTs) and who underwent CMT before the study period. We obtained and analyzed baseline clinical characteristics, HBsAg screening, and LFT data during follow-up.
Of 3,231 cases in the database, 810 were eligible. The overall HBsAg screening rate in the 5-year period was 27.7%. Screening rates were low from 2009-2012 (7.8-21%) and increased in 2013 to 82.9%. The prevalence of HBV among screened patients was 7.1%. Of those, 75% underwent prophylactic antiviral therapy. During the 6-month follow-up period, there were three cases of significant hepatitis caused by HBVr (4.2% of all significant hepatitis cases); all were in the unscreened group.
The prevalence of HBV in SOM patients undergoing CMT in our study was similar to the estimated prevalence in general Thai population, but the screening rate was quite low. Cases of HBVr causing significant hepatitis occurred in the unscreened group; therefore, HBV screening and treatment in SOM patients should be considered in HBV-endemic areas.
Objective
This study investigated disease‐free survival and oncological outcomes in penile cancer patients treated surgically at a high‐volume center and identified the prognostic factors for ...disease‐free survival.
Methods
A retrospective analysis was conducted on primary penile cancer patients diagnosed and treated at Songklanagarind Hospital, Thailand, between January 2001 and December 2021. Disease‐free survival (DFS) was assessed using Kaplan–Meier survival curves, and Cox proportional hazard models were used for multivariate analysis.
Results
The study included 188 patients with primary penile cancer. The majority (98.4%) were uncircumcised. Tumor staging revealed 40.6% with T1 tumors, 72.9% with well‐differentiated tumors, and 23.5% diagnosed at stage IIIA. The recurrence rate was 19.1%, with a mean time to recurrence of 25.9 months. Disease‐free survival rates at 1, 3, and 5 years were 81.1%, 70.9%, and 70.9%, respectively. Median overall survival was 16.43 months, with survival rates at 1, 3, and 5 years at 67.7%, 42.7%, and 35.4%, respectively. Cox proportional hazard models showed significant associations between disease‐free survival and a higher T stage, a high level of CRP (>15 mg/L), delayed onset of symptoms, primary lesion location, groin node metastasis, lymphovascular invasion, and pelvic lymph node metastases. However, multivariate analysis revealed that a higher primary tumor stage (T) was the only independent prognostic factor for disease‐free survival.
Conclusion
This study presents one of the largest cohorts investigating disease‐free survival outcomes in penile cancer treatment at a single institution over a prolonged period. A higher pathologic T stage is a significant prognostic factor for disease‐free survival. Further large‐scale prospective studies are needed for validation.
PDF
