To determine the analgesic effect of the addition of gabapentin to opioids in the management of neuropathic cancer pain.
One hundred twenty-one consecutive patients with neuropathic pain due to ...cancer, partially controlled with systemic opioids, participated in a multicenter, randomized, double-blind, placebo-controlled, parallel-design, 10-day trial from August 1999 to May 2002. Gabapentin was titrated from 600 mg/d to 1,800 mg/d in addition to stable opioid dose. Extra opioid doses were available as needed. Zero to 10 numerical scale was used to rate average daily pain. The average pain score over the whole follow-up period was used as main outcome measure. Secondary outcome measures were: intensity of burning pain, shooting/lancinating pain, dysesthesias (also scored on 0 to 10 numerical scale), number of daily episodes of lancinating pain, presence of allodynia, and daily extra doses of opioid analgesics.
Overall, 79 patients received gabapentin and 58 (73%) completed the study; 41 patients received placebo and 31 (76%) completed the study. Analysis of covariance (ANCOVA) on the intent-to-treat population showed a significant difference of average pain intensity between gabapentin (pain score, 4.6) and placebo group (pain score, 5.4; P =.0250). Among secondary outcome measures, dysesthesia score showed a statistically significant difference (P =.0077; ANCOVA on modified intent-to-treat population = 115 patients with at least 3 days of pain assessments). Reasons for withdrawing patients from the trial were adverse events in six patients (7.6%) receiving gabapentin and in three patients receiving placebo (7.3%).
Gabapentin is effective in improving analgesia in patients with neuropathic cancer pain already treated with opioids.
Abstract Hepatocellular carcinoma (HCC) is the most common primary malignancy in the liver and is the third cause of cancer-related death worldwide. Surveillance with abdominal ultrasound should be ...offered to individuals at high risk for developing HCC. Accurate diagnosis, staging, and liver function are crucial when determining the optimal therapeutic approach. The BCLC staging system is widely endorsed in Western countries. Managing this pathology requires a multidisciplinary, personalized approach, generally with a multimodal strategy. Surgery remains the only curative option, albeit local and systemic therapy may also increase survival when surgery is not suitable. In advanced disease, systemic treatment should be offered to patients with ECOG/PS 0-1 and Child–Pugh class A.
To evaluate the safety profile and efficacy of whole brain radiotherapy (WBRT) concomitantly with temozolomide (TMZ) in patients with brain metastases (BM).
Patients with BM were randomly assigned to ...30 Gy of WBRT with or without concomitant TMZ (75 mg/m(2)/d) plus two cycles of TMZ (200 mg/m(2)/d for 5 days). The primary outcome was analysis of neurologic toxicity. The primary efficacy measures were 90-day progression-free survival of BM and the radiologic response at Days 30 and 90.
We enrolled 82 patients. No neurologic acute toxicity was observed. Grade 3 or worse hematologic toxicity was seen in 3 patients and Grade 3 or worse vomiting in 1 patient of the WBRT plus TMZ arm. The objective response rate at 30 and 90 days and overall survival were similar in both arms. The percentage of patients with progression-free survival of BM at 90 days was 54% for WBRT vs. 72% for WBRT and TMZ (p = 0.03). Death from BM was greater in the WBRT arm (69% vs. 41%, p = 0.03).
The concomitant use of RT with TMZ was well tolerated and resulted in significantly better progression-free survival of BM at 90 days. Although caution should be used, these results suggest TMZ could improve local control of BM.
Lipid metabolism plays an essential role in carcinogenesis due to the requirements of tumoral cells to sustain increased structural, energetic and biosynthetic precursor demands for cell ...proliferation. We investigated the association between expression of lipid metabolism-related genes and clinical outcome in intermediate-stage colon cancer patients with the aim of identifying a metabolic profile associated with greater malignancy and increased risk of relapse. Expression profile of 70 lipid metabolism-related genes was determined in 77 patients with stage II colon cancer. Cox regression analyses using c-index methodology was applied to identify a metabolic-related signature associated to prognosis. The metabolic signature was further confirmed in two independent validation sets of 120 patients and additionally, in a group of 264 patients from a public database. The combined analysis of these 4 genes, ABCA1, ACSL1, AGPAT1 and SCD, constitutes a metabolic-signature (ColoLipidGene) able to accurately stratify stage II colon cancer patients with 5-fold higher risk of relapse with strong statistical power in the four independent groups of patients. The identification of a group of 4 genes that predict survival in intermediate-stage colon cancer patients allows delineation of a high-risk group that may benefit from adjuvant therapy, and avoids the toxic and unnecessary chemotherapy in patients classified as low-risk group.
To obtain real-world data on ramucirumab use and effectiveness for the treatment of advanced gastric cancer (AGC) or gastroesophageal junction adenocarcinoma (GEJ).
Observational, retrospective study ...carried out in 20 Spanish hospitals, in patients who started ramucirumab treatment between December 2015 and December 2018. Descriptive analysis was conducted for patient characteristics, treatment patterns and effectiveness outcomes.
Three hundred seventeen patients were included (93.7% treated with ramucirumab-paclitaxel and 6.3% with ramucirumab); age 62.5 (11.3) years; 66.9% male. Median progression-free survival and overall survival were 3.9 months (95% CI: 3.4-4.3) and 7.4 (95% CI: 6.4-8.9) in combination regimen and 2.0 (1.1-2.8) and 4.3 (95% CI: 1.9-7.3) in monotherapy, respectively.
The study findings were consistent with available real-world studies and randomized clinical trials.
Identifying molecular markers for tumor recurrence is critical in successfully selecting patients with colon cancer who are more likely to benefit from adjuvant chemotherapy. We investigated the ...effect of single-nucleotide polymorphisms (SNP) within genes involved in oxaliplatin and fluoropyrimidines metabolism, DNA repair mechanisms, drug transport, or angiogenesis pathways on outcome for patients with stage II and III colon cancer treated with adjuvant chemotherapy. Genomic DNA was extracted from formalin-fixed paraffin-embedded samples of 202 patients with stage II and III colon cancer receiving oxaliplatin-based adjuvant chemotherapy from January 2004 to December 2009. Genotyping was performed for 67 SNPs in 32 genes using the MassARRAY (SEQUENOM) technology. Our results were validated in an independent cohort of 177 patients treated with the same chemotherapy regimens. The combination of the selectin E (SELE) rs3917412 G>A G/G and the methylentetrahydrofolate reductase (MTHFR) rs1801133 T/T genotypes was associated with a significantly increased risk for recurrence in both the training RR = 4.103; 95% confidence interval (CI), 1.803-9.334; P = 0.001 and the validation cohorts (RR = 3.567; 95% CI, 1.253-10.151; P = 0.017) in the multiple regression analysis considering the stage, lymphovascular invasion, and bowel perforation as covariates. The combined analysis of these polymorphisms was also significantly associated with overall survival in both cohorts (RR = 3.388; 95% CI, 0.988-11.623; P = 0.052, and RR = 3.929; 95% CI, 1.144-13.485; P = 0.020, respectively). Our findings suggest that the SELE rs3917412 and MTHFR rs1801133 SNPs could serve as pharmacogenetic predictors of tumor recurrence in patients with early-stage colon cancer treated with oxaliplatin-based adjuvant chemotherapy, thus allowing personalized selection of treatment to optimize clinical outcomes.
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Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by its immunologically cold tumor microenvironment (TME) with scarce T cell infiltration and few molecular signatures of ...immune activation. To date, the immunotherapies including the immune checkpoint blockade of PD-1, and CTLA-4 either single or in combination have shown modest results in PDAC tumors. Recently, the Lymphocyte Activation Gene (LAG3) has emerged as a promising checkpoint target as indicated by preclinical and clinical data. The aim of this study is to explore the immune profile of a series of PDAC and to evaluate its prognostic impact. Methods: A 5-mm thick section of Formalin-Fixed Paraffin-Embedded (FFPE) tissue from a retrospective cohort of 28 PDAC cases were analyzed using the Precision Immunooncology panel (PIP, HTG Molecular Diagnostics) on a NextSeq 550 sequencer (Illumina). The RNA expression of 1392 immune-related genes were analyzed. Principal Components (PC) and Manhattan distance were studied for data visualization and clustering. Maxstat algorithm (maxstat v0.7-25) was used to establish optimal cut-offs for variable categorization. Log-rank and Cox regression were used for both univariate and multivariate for survival. All tests were two-tailed. The statistical analysis was performed using R studio (R version 4.0.3). Lastly, immunohistochemistry (IHC) for CD4, CD8, CD20, PD1, PD-L1, and LAG-3 proteins was performed on tissue microarrays (TMAs) to assess their correlation with RNA expression. Results: Unsupervised analysis of the gene expression identified two clusters of patients with differentially prognostic information. These two groups were defined with a logistic regression model of 14 genes ( BTLA, CXCR5, DLX6, KLHDC9, KRT13, LAG3, LGSN, MICB, SIGLEC5, SPINK5, SPN, TBX21, UPK2, ZIC5) showing for cluster1 and cluster 2 a median survival of 13 (0-97.583) and 57 (0.67-256.08) months, respectively (p-value = 0.0088). This predictive model was independently validated in the PDAC dataset of the Cancer Genome Atlas (TCGA) (p<0.0001). Interestingly, cluster 1, was characterized by the significant overexpression of LAG3 which has recently been proposed as the next immune checkpoint (IC) receptor target. Moreover, Cluster 1, exhibited the overexpression of other ICs such as PD1, PD-L1, IDO1, LIF and CTLA4, defining cluster 1 as an immunologically hot tumor. IHC for LAG3 and other ICs showed a moderate correlation with HTG results. Conclusions: In this study, a prognostic transcriptomic-based signature of 14 genes has been defined and validated for PDAC. This signature clearly identifies two prognostic groups that could constitute the basis for tailored immunotherapy with specific IC inhibitors. LAG-3 is a promising target for immunotherapy in PDAC patients.
Endoscopic resection is the common treatment in pT1 colorectal adenocarcinoma whenever possible. The presence of adverse histological factors requires subsequent lymph node evaluation.
We selected 29 ...colorectal pT1 adenocarcinoma including endoscopic polypectomies and the corresponding surgical specimens. All histologic parameters associated with N+ were evaluated by 2 pathologists, including: tumor differentiation grade, depth of invasion in the submucosa, angiolymphatic invasion (ALI), perineural invasion, chronic inflammation, tumor budding, poorly differentiated cluster, pre-existing adenoma, tumor border, and endoscopic resection margin. Univariate and multivariate logistic regression analysis were performed to assess the individual capacity of each variable to predict N+.
In the univariate analysis, rectal tumor localization, ALI and poorly differentiated cluster was significantly associated with N+. Among the significant parameters, ALI had the highest area under the ROC curve (0.875). Multivariate analysis showed no independent variables associated with N+.
We confirm that ALI and the presence of poorly differentiated cluster are frequently associated with N+ in early colorectal cancer. Consequently, these parameters should be routinely evaluated by pathologists.
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