Overall Survival Rate Research Articles

The clinical significance of elastic lamina invasion in patients with pStage II colorectal cancer: a notable prognostic indicator

BackgroundSome colorectal cancers (CRCs) are clinically diagnosed as cT4a with serosal invasion (SI). However, the cT4a is most often underdiagnosed pathologically as pT3 without SI by hematoxylin–eosin (H&E) staining alone. Using Elastica van Gieson (EVG) staining, some pT3 tumors invade the elastic lamina (EL), which extends just below the serosal layer. Recently, EL invasion (ELI) has been described as a poor prognostic factor for disease-free survival (DFS) and overall survival (OS) in patients with pStage II CRC. However, its clinicopathological significance remains unclear due to the limited number of studies and poor understanding of ELI.ObjectiveThis study investigated the association between the ELI and patient prognosis.MethodsAfter 1982, pathological diagnosis was routinely performed using H&E and EVG staining methods, and long-term follow up was performed until 2016. All clinicopathological features including ELI were prospectively registered into our computer and 569 patients with pStage II CRC were collected from the database. Based on the ELI status, pT3 was divided into three pathological categories: pT3ELI − was defined as pT3a, pT3ELI + as pT3b and unidentified EL (pT3EL −) as pT3u.ResultsUsing H&E staining alone, gross cT4a was most often pathologically underdiagnosed as pT3 (93.8%) and very rarely as pT4a, resulting in a large diagnostic discrepancy. Using EVG staining, 60.7% of the cT4a tumors were diagnosed as pT3b. The 10-year DFS and OS rates were similar for pT3a and pT3u patients. However, the 10-year DFS and OS rates of pT3b patients were significantly lower than those of pT3a patients (75.6% vs. 95.6%, p < 0.0001 and 58.4% vs. 70.6%, p = 0.0024, respectively) but did not differ from those of pT4a patients (70.6%, p = 0.5799 and 52.0%, p = 0.1116, respectively). Multivariate analysis revealed that the ELI was the strongest independent risk factor for recurrence and CRC-specific death (p < 0.0001).ConclusionsA better understanding of the ELI allows us to reconsider the diagnostic discrepancy of serosal invasion, i.e., pT3b should be considered pT4a. The ELI-based subclassification of pT3 is expected to be incorporated into the TNM staging system in the future. The ELI is a notable prognostic indicator in patients with pStage II CRC.

Population-based long-term prognosis analysis of subcutaneous gastrointestinal stromal tumors.

Subcutaneous gastrointestinal stromal tumors (scGISTs) are extremely rare tumors, and the analysis of their long-term prognosis remains unreported. Therefore, our objective is to analyze the long-term prognosis of patients with scGISTs using the Surveillance, Epidemiology, and End Results database. Patients diagnosed with GISTs between 2000 and 2019 were included in the study. To handle missing data, multiple imputation techniques were employed. Kaplan-Meier analysis and Cox proportional hazards models were used to evaluate overall survival (OS) and cancer-specific survival (CSS), and subgroup analyses were conducted for various variables. A total of 12,882 patients were enrolled, with 12,636 diagnosed with GISTs and 246 with scGISTs. In comparison to GISTs patients, scGISTs patients exhibited inferior OS [hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.45-1.98, P < 0.001] and CSS (HR 2.16, 95% CI 1.78-2.61, P < 0.001). Across various subgroups, including age, sex, surgical intervention, marital status, and chemotherapy, scGISTs patients consistently demonstrated significantly poorer OS and CSS outcomes compared to GISTs patients (P < 0.05). The 1-, 3-, and 5-year OS rates for scGISTs patients were 78.4%, 60.3%, and 49.3%, respectively, with corresponding CSS rates of 83.3%, 67.8%, and 57.4%. Notably, scGISTs patients who received surgical treatment had significantly higher 5-year OS rates (62.1% vs 30.9%, P < 0.001) and CSS rates (67.8% vs 40.0%, P < 0.001) compared to those who did not undergo surgery. Multivariate Cox regression analysis identified age, surgical status, and mitotic rate as risk factors influencing OS in scGISTs patients, while surgical status and mitotic rate were identified as risk factors affecting CSS. Compared to GISTs patients, scGIST patients exhibit a less favorable prognosis; nonetheless, surgical intervention has been demonstrated to enhance their prognosis.

Long-term outcomes of endoscopic resection of superficial esophageal squamous cell carcinoma in late-elderly patients.

As the population ages, the number of elderly patients with superficial esophageal squamous cell carcinoma (ESCC) is increasing. We aimed to clarify the indications for endoscopic resection (ER) in late-elderly patients with ESCC in terms of life expectancy. Patients aged ≥75years who underwent ER for ESCC at our institution from January 2005 to December 2018 were enrolled. Clinical data, including the Eastern Cooperative Oncology Group performance status, American Society of Anesthesiologists physical status (ASA-PS), Charlson comorbidity index, and prognostic nutritional index (PNI), were collected at the time of ER. The main outcome measure was overall survival (OS). Two hundred eight consecutive patients were enrolled. The patients' median age was 78years (range, 75-89years). The 5-year follow-up rate was 88.5% (median follow-up period, 6.6years). The 5-year OS rate was 79.2% (95% confidence interval [CI], 72.2-84.8), and 5-year net survival standardized for age, sex, and calendar year was 1.04 (95% CI, 0.98-1.09). In the multivariate analysis, an ASA-PS of 3 (hazard ratio, 2.45; 95% CI, 1.16-5.17) and PNI of <44.0 (hazard ratio, 2.73; 95% CI, 1.38-5.40) were independent prognostic factors. When neither of these factors was met, the 5-year OS rate was 87.8% (95% CI, 80.0-92.9), and 5-year net survival was 1.08 (95% CI, 1.02-1.14). ER for ESCC in late-elderly patients may improve life expectancy. ER is recommended in patients with a good ASA-PS and PNI.

Overall survival and disease-free survival prediction in Chinese women with breast cancer aged 70 years or older by using nomograms.

By analyzing the existing data of this study, a prediction tool for the overall breast cancer survival and disease-free survival (DFS) of elderly women was established. Clinicopathologic data were collected from elderly women with BC who were admitted to the Tianjin Medical University Cancer Institute and Hospital from August 2014 to December 2017. Independent prognostic factors for BC in elderly patients were confirmed using the Cox proportional hazards model. Nomograms were developed with these factors for predicting the 3- and 5-year overall survival (OS) as well as DFS. The nomograms' discrimination ability and calibration were assessed through the area under the curve (AUC), concordance index (C-index), decision curve analysis (DCA), and calibration plots. We enroled 889 elderly patients with BC, and the results showed that the 3-year OS rate was 93.4% (95%CI = 91.8%-95.1%), the 3-year DFS rate was 87.8% (95%CI = 85.7%-90.0%), the 5-year OS rate was 85.6% (95%CI = 83.3%-87.9%), and the 5-year DFS rate was 80.1%(95%CI = 77.5%-82.8%). The corrected C-indices of the OS and DFS nomograms were 0.799 and 0.667, respectively (95%CI = 0.767-0.830 and 0.632-0.702, respectively). Relatively high AUC values were shown by the nomograms for estimating OS and DFS. The DCA revealed that the constructed nomograms had net benefits for clinical application. The calibration curves demonstrated an excellent correspondence between the data predicted by the nomograms and the actual survival data. Survival curves indicated that risk stratification could differentiate OS and DFS. This study developed novel and practical nomograms for individual prediction of DFS and OS in elderly BC patients. These nomograms can predict 3- and 5-year OS as well as DFS in the elderly BC patient population, thereby enabling personalized risk assessment and risk-based therapy.

The New Era of Total Neoadjuvant FLOT Therapy for Locally Advanced, Resectable Gastric Cancer: A Propensity-Matched Comparison With Standard Perioperative Therapy.

The FLOT 4-AIO trial established the docetaxel-based regimen's superiority over epirubicin-based triplet therapy in terms of survival rates and acceptable toxicity for locally advanced resectable gastric (LARGC). Yet, fewer than half of the patients achieved completion of eight prescribed FLOT cycles. We proposed that administering all FLOT cycles in the form of total neoadjuvant therapy may improve completion rates and downstaging. This study contrasted total neoadjuvant therapy (FLOT x8) with standard neoadjuvant therapy (FLOT 4+4) for patients LARGC adenocarcinoma who underwent curative resection with routine D2 lymphadenectomy, focusing on histopathological outcomes, toxicity, and survival outcomes. We reviewed patients with histologically confirmed advanced clinical stage cT2 or higher, nodal positive stage (cN+), or both, with resectable gastric tumors and no distant metastases (January 2017 to July 2023). We divided patients into two groups, FLOT 4+4 and FLOT x8; FLOT 4+4 patients underwent four preoperative and four postoperative bi-weekly cycles of docetaxel, oxaliplatin, leucovorin, and fluorouracil, while FLOT x8 patients received all eight cycles preoperatively after a gradual practice change starting from January 2020. Propensity score matching adjusted for age, clinical stage, tumor location, and histology. Of the 77 patients in the FLOT x8 group, 37 were propensity-matched to an equal number in the FLOT 4+4 group. Demographics, duration of surgery, and hospital stay showed no significant differences between the groups. The FLOT x8 group exhibited a significantly higher all-cycle completion rate at 89.1% compared to FLOT 4+4's 67.6% (p < 0.01). Both groups demonstrated comparable hematological and non-hematological toxicity rates, Clavien-Dindo ≥ 3 complications, and CAP tumor regression grades. The mean number of harvested lymph nodes was 42.5 and 41.2 in the FLOT 4+4 and FLOT x8 groups, respectively. Similar rates of disease-free survival and overall survival were noted in both groups, despite a trend toward a higher pathological complete response rate, albeit not statistically significant (8.1% vs. 18.9%, p = 0.29), in the FLOT x8 group at a median follow-up of 36 months. Total neoadjuvant therapy with the FLOT x8 protocol corresponds to higher treatment completion rates, a safety profile similar to standard perioperative therapy, and a twofold increase in complete pathological response. Further research on long-term oncological outcomes is needed to confirm the effectiveness of total neoadjuvant therapy.

Efficacy of radiotherapy combined with hepatic arterial infusion chemotherapy, TKI and ICI for hepatocellular carcinoma with portal vein tumor thrombus: a retrospective cohort study.

This retrospective study was conducted to evaluate the effectiveness and safety of a new combination therapy of radiotherapy (RT), hepatic arterial infusion chemotherapy (HAIC), tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) for hepatocellular carcinoma (HCC) patients involving portal vein tumor thrombus (PVTT). A total of 71 HCC patients with PVTT were retrospectively analyzed: 45 patients were treated by 'HAIC + TKI + ICI' therapy and 26 patients by the new combination therapy. The primary outcomes were overall survival (OS), progression-free survival (PFS), and cumulative survival rate. The PFS in the 'New combination therapy' group was longer than that in the 'HAIC + TKI + ICI' group (HR 0.459, 95%CI 0.253-0.832; P = 0.008). Meanwhile, the OS in the 'New combination therapy' group was also longer than that in the 'HAIC + TKI + ICI' group (HR 0.420, 95%CI 0.198-0.894; P = 0.024). Compared with 'HAIC + TKI + ICI' group patients, the 'New combination therapy' group patients had higher 1-year PFS rate and 1-year OS rate (P = 0.029; P = 0.015). There was no significant difference in the incidence of adverse events between the two groups. The new combination therapy was an effective and safe non-surgical treatment for HCC patients with PVTT and could be considered a preferred therapy option.

Definition of early recurrence of hepatocellular carcinoma based on the concordance index and optimal treatment strategy

BackgroundHepatocellular carcinoma (HCC) has a high rate of recurrence and requires multiple treatment options. Early recurrence has been associated with poor prognosis; however, the timing of early recurrence varies in the literature. Therefore, in this study, we aimed to determine the timing of early recurrence with the best prognostic value and clarify the appropriate treatment strategy. MethodsThis retrospective study conducted to determine prognosis and treatments included 274 patients with HCC who underwent liver resection at the Saitama Cancer Center. The prognostic value of early recurrence at each surveillance period was calculated using Harrell's concordance index (C-index). ResultsThe C-index at 9 months postoperatively was 0.656, which was the highest cut-off value for early recurrence. Notably, 122 patients had no recurrence, 58 had early recurrence (<9 months), and 94 had late recurrence (≥9 months). The 5-year overall survival (OS) of patients with early recurrence was worse (16.5 %, p<0.001), whereas that of those with late and no recurrences were similar (79.2 % vs. 70.9 %, p=0.86). The 5-year OS rate of patients with late intrahepatic recurrence in the surgery group was 100 %. ConclusionThe optimal cutoff value for the timing of early recurrence was 9 months postoperatively. The early recurrence group had a high rate of extrahepatic recurrence and poor OS, whereas late recurrences were mostly intrahepatic, with no difference in prognosis between the late and no recurrence groups. Patients with intrahepatic recurrence after >9 months are considered for rehepatectomy because of its good outcomes. SynopsisThe C-index-based optimal cutoff for the timing of early HCC recurrence was 9 months postoperatively. The early recurrence group had a high rate of extrahepatic recurrence and poor OS, whereas late recurrences were mostly intrahepatic with a good prognosis.

Adaptive stereotactic radiosurgery for cerebral metastases of non-small cell lung cancer: a retrospective study

INTRODUCTION: Non-small cell lung cancer (NSCLC) is a common cause of brain metastases (BM). Adaptive stereotactic radiosurgery (ASRS) may be a useful option in the treatment of patients with large unresectable brain metastases (BM), but to date there are only a limited number of studies evaluating the effectiveness of this method.OBJECTIVE: To analyze the effectiveness of ASRS in patients with large BM NSCLC not subject to surgical resection.MATERIAL AND METHODS: We retrospectively analyzed data from 37 patients suffering from NSCLC with 45 large (&gt;2 cm in diameter, volume &gt;4 cm3) unresectable BM treated with the Gamma Knife Perfexion model using two- and three-fraction ASRS. Of these, 14 foci (31.1%) were metastases of squamous cell lung cancer, 31 (68.9%) were metastases of adenocarcinoma. The median volume of lesions treated with ASRS was 9.8 (range 4.6–30.6 cm3). The dynamics of volume changes between fractions and the cumulative incidence of local relapses (CILR) were studied, and ROC analysis was performed for the tumor volume parameter. Intracranial progression-free survival (iPFS) and overall survival (OS) were assessed. Statistics: To establish statistical significance of differences for related variables, the Wilcoxon test for pairwise comparisons and the Friedman test for three or more groups were used. The Kaplan-Meier method was used to calculate local control, PFS, and OS rates. The log-rank test was used to compare survival data in two groups.RESULTS: The median follow-up period was 19.4 months. With two-fraction ASRS, the median volume of metastasis decreased by 28.6% by the second session, with three-fraction — by 40.0% by the third session. The 1-year and 2-year CILR rates were 8.6±6.1%, respectively; 26.1±12.3%. In ROC analysis, the area under the curve (AUC) for tumor volume was 0.80 (95% CI 0.6– 1.0) with an optimal cutoff of 18.5 cm3. The differences in CILR between the groups with metastasis volume &lt;18.5 cm3 and ≥18.5 cm3 were statistically significant (p&lt;0.001). Median iPFS was 8.3 (95% CI 5.9–10.7) months, 1-year iPFS was 33.5±8.1%;2-year — 7.8±5.2%. Median OS was 13.2 (95% CI 9.0–17.4) months; 1-year OS — 52.9±8.7%, 2-year — 22.4±8.8%.DISCUSSION: Using two- and three-fraction ASRS, we delivered doses to large BM sufficient for a high level of local control with an acceptable risk of neurotoxicity: 1-year local control was 91.4%; 2-year — 73.9%; the incidence of radionecrosis is 8.5%. A statistically significant effect of lesion volume ≥18.5 cm3 on the risk of local recurrence was found. The iPFS and OS indicators after ASRS can be considered satisfactory for this group of patients.CONCLUSION: ASRS is an effective and perhaps optimal strategy for the treatment of large unresectable BM in patients with NSCLC, but comparison with other modern radiotherapy modalities such as stereotactic hypofractionated radiotherapy and WBRT with simultaneous integrated boost is needed.

What Is the Prognostic Value of the Pathologic Response after Neoadjuvant Radiotherapy in Soft Tissue Sarcoma? An Institutional Study Using the EORTC-STBSG Response Score.

Background/Objectives: The relationship between pathologic findings in soft tissue sarcoma (STS) after neoadjuvant treatment and oncological outcomes remains uncertain due to varying evaluation methods and cut-off values. This study aims to assess pathologic findings after neoadjuvant radiotherapy in STS using the EORTC-STBSG response score and evaluate its prognostic value. Methods: Clinical and outcome data from 44 patients were reviewed. Resected specimens were re-evaluated to measure viable cells, necrosis, fibrosis, and hyalinization. Local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were analyzed using Kaplan-Meier survival analysis. Cox proportional hazards regression was used for univariate and multivariate analyses to correlate outcomes with pathologic response. Results: The median percentages of viable cells, necrosis, and fibrosis/hyalinization were 20%, 11%, and 40%, respectively. A pathologic complete response (pCR), defined as ≤5% viable cells, was achieved in 25% of cases. Local recurrence occurred in 33% of cases, with a significantly higher rate of 64% after R1 resection compared to 22% after R0 resection. Distant metastases were observed in 42% of patients, primarily in the lungs. The 3-year rates for LRFS, DMFS, and OS were 65%, 54%, and 67%, respectively. A correlation between outcomes and tumor size, grade and histological subtype was observed. Classifying pathologic response by the EORTC-STBSG score failed to show an association with outcomes. Patients achieving pCR showed lower risk of LR and improved OS. Conclusions: While the EORTC-STBSG score did not show a prognostic value, resection specimens with ≤5% viable cells were linked to improved LRFS and OS.

Survival and prognostic factors for relapsed childhood acute lymphoblastic leukemia after treatment with the Chinese children's cancer group ALL-2015 protocol: a single center results.

This retrospective study was conducted to assess the survival rates and prognostic factors in children with relapsed acute lymphoblastic leukemia (ALL) who were treated according to the Chinese Children's Cancer Group ALL-2015 protocol at the Children's Hospital of Chongqing Medical University. The study cohort involving 852 evaluable children with ALL reported a total of 146 relapses during a median follow-up period of 53 months. The primary outcomes measured were the second complete remission (CR2) rates, and 5-year event-free survival (EFS) and overall survival (OS) for patients who received re-treatment post-relapse. Patient data were stratified by ALL subtype (B-ALL vs. T-ALL), age at relapse, site of relapse, and timing of relapse. Univariate and multivariate analyses were performed to identify factors significantly associated with EFS and OS. As of March 31, 2023, 146 relapses were observed, including 128 B-ALL and 18 T-ALL cases. The 8-year CIR was (19.8 ± 1.6)%, with no significant difference between B-ALL and T-ALL (P=0.271). Among the 105 patients who underwent re-treatment, 70 achieved CR2, resulting in a CR2 rate of 67.6%. The 5-year EFS and OS rates for re-treated patients were (45.0 ± 5.4)% and (56.9 ± 5.2)%, respectively. Significant differences in 5-year OS and EFS were found between B-ALL and T-ALL relapses (P < 0.001). The 5-year EFS and OS varied significantly with relapse timing and site of relapse. Factors significantly affecting EFS after relapse included the site of relapse, immunophenotyping, CR2 achievement, and hematopoietic stem cell transplantation (HSCT). Immunophenotyping, CR2 achievement, and HSCT were also identified as significant factors affecting OS after relapse. Despite treatment with the CCCG-ALL-2015 protocol, a significant relapse rate was observed, with 72% of children opting for re-treatment post-relapse. The study highlights the importance of considering specific prognostic factors to inform tailored treatment strategies for relapsed childhood ALL. The findings emphasize the need for further research into improving therapeutic approaches for this patient population. This retrospective study was conducted to assess the survival rates and prognostic factors in children with relapsed acute lymphoblastic leukemia (ALL) who were treated according to the Chinese Children's Cancer Group ALL-2015 protocol at the Children's Hospital of Chongqing Medical University.

Preoperative scoring system for the prediction of risk of lymph node metastasis in cervical cancer

The study aimed to develop and validate a preoperative scoring system to predict the risk of lymph node metastasis (LNM) in cervical cancer (CC). A total of 426 stage IB1–IIA1 CC patients were randomly divided into two sets. A logistic regression model was used to determine independent factors that contribute to LNM. A preoperative scoring system was developed based on beta (β) coefficients. An area under the receiver operating curve (AUC) was used to test for model discrimination. Five-year overall survival (OS) rate was 91.7%. Multivariable logistic regression analysis showed that FIGO stage, tumor size, depth of invasion on MRI, and squamous cell carcinoma antigen levels were independent risk factors in the development set (all P < 0.05). The AUCs of the scoring system for the development and validation sets were 0.833 (95% CI = 0.757–0.909) and 0.767 (95% CI = 0.634–0.891), respectively. Patients who scored 0–2, 3–5, and 6–8 were classified into low-risk, medium-risk, and high-risk groups. Predicted rates were in accord with observed rates in both sets. The 5-year OS rates of the new groups were also significantly different for the entire group, development set, and validation set (all P < 0.05). LNM affects the prognosis of CC patients. The scoring system can be used to assist in evaluating the risk of LNM in CC patients preoperatively. It is easy to obtain and can provide reference for clinical treatment decision-making.

Stereotactic body radiotherapy versus lenvatinib for hepatocellular carcinoma with portal vein tumor thrombosis: a propensity matching score analysis

Background and objectivesThe purpose of this study was to investigate the survival benefit of Stereotactic Body Radiotherapy (SBRT) versus lenvatinib as first-line therapy in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT).Materials and methods147 HCC patients with PVTT were included in this retrospective study, 70 were treated with SBRT and 77 of were treated with lenvatinib. Propensity score matching (PSM) analysis was employed to balance the differences in baseline characteristics between the two groups. Overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) were compared between the two groups. In addition, the safety of patients in both groups was also evaluated.ResultsAfter PSM, 38 patients were matched in each of the two groups. The median OS was 14.5 (95% CI: 10.1–18.9) and 11.1 (95% CI: 9.3–12.9) months in the SBRT and lenvatinib groups, respectively (P = 0.014). The median PFS was 6.8 (95% CI: 5.1–8.5) and 5.0 (95% CI: 3.0–7.0) months, respectively (P = 0.010). The 1-, 2-years OS rates in the two groups were 65.8% vs. 39.5% and 31.6% vs. 10.5%, respectively. The 6-, 12-months PFS rates in the two groups were 57.9% vs. 44.7% and 28.9% vs. 10.5%, respectively. In addition, the SBRT group had a better ORR than the lenvatinib group (52.6% vs. 23.7%, P = 0.009). Patients with good response to SBRT had better survival. Cox proportional hazard model showed that SBRT was an important prognostic factor for OS and PFS. The incidence of hypertension (34.2% vs. 0%) was higher in the LEN group, however, both treatment modalities were well tolerated in the two groups of patients.ConclusionIn HCC patients with PVTT, SBRT had a better survival benefit than Lenvatinib treatment as first-line therapy.

Radiotherapy with 15 × 2.633 Gy vs. 20 × 2.0 Gy in Patients with Malignant Spinal Cord Compression and Favorable Survival Prognoses: A Secondary Analysis of the RAMSES-01 Trial.

Many patients with malignant spinal cord compression (MSCC) who are not candidates for neurosurgery receive radiotherapy alone. This study compared 15 × 2.633 Gy over three weeks to 20 × 2.0 Gy over four weeks in patients with favorable survival prognoses. The outcomes of 34 patients treated with 15 × 2.633 Gy (equivalent dose 41.6 Gy10) in the RAMSES-01 trial were compared to 239 patients from an existing database receiving 20 × 2.0 Gy using propensity-score-adjusted Cox and logistic regression models. All patients had favorable survival prognoses. Endpoints included local progression-free survival (LPFS), improvement of motor function, post-treatment ambulatory status, and overall survival (OS). After propensity score adjustment, the 12-month rates of LPFS and OS were 98.1% (RAMSES-01 cohort) vs. 91.6% (p = 0.265) and 79.1% vs. 82.2% (p = 0.704), respectively. Regarding improvement of motor function, 15 × 2.633 Gy appeared superior (p = 0.073). No significant difference was observed regarding ambulatory status (p = 0.822). The three-week regimen for MSCC has similar outcomes and reduces treatment time when compared to a four-week regimen.

First-line pembrolizumab with or without chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma: 5-year follow-up of the Japanese population of KEYNOTE‑048.

Previously reported results from phase III KEYNOTE-048 demonstrated similar or improved overall survival (OS) with pembrolizumab or pembrolizumab-chemotherapy versus cetuximab-chemotherapy (EXTREME) in Japanese patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We report results in Japanese patients from KEYNOTE-048 after 5years of follow-up. Patients with R/M HNSCC of the oropharynx, oral cavity, hypopharynx, or larynx were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or EXTREME. Primary endpoints were OS and progression-free survival. Efficacy was evaluated in the programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, PD-L1 CPS ≥ 1, and total Japanese populations. In Japan, 67 patients were enrolled (pembrolizumab, n = 23; pembrolizumab-chemotherapy, n = 25; EXTREME, n = 19). Median follow-up was 71.0months (range, 61.2-81.5); data cutoff, February 21, 2022. 5-year OS rates with pembrolizumab versus EXTREME were 35.7% versus 12.5% (hazard ratio [HR] 0.38; 95% CI 0.13-1.05), 23.8% versus 12.5% (HR 0.70; 95% CI 0.34-1.45), and 30.4% versus 10.5% (HR 0.54; 95% CI 0.27-1.07) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. 5-year OS rates with pembrolizumab-chemotherapy versus EXTREME were 20.0% versus 14.3% (HR 0.79; 95% CI 0.27-2.33), 10.5% versus 14.3% (HR 1.18; 95% CI 0.56-2.48), and 8.0% versus 12.5% (HR 1.11; 95% CI 0.57-2.16) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. After 5years of follow-up, pembrolizumab and pembrolizumab-chemotherapy showed long-term clinical benefits; results further support these treatments as first-line options for Japanese patients with R/M HNSCC. NCT02358031.

Association of baseline neutrophil-to-lymphocyte ratio and prognosis in melanoma patients treated with PD-1/PD-L1 blockade: a systematic review and meta-analysis.

Immunotherapy treatments that target programmed cell death receptor-1 (PD-1) or its ligand (PD-L1) have revolutionized the treatment of metastatic melanoma and currently represent the standard first-line treatment for this type of cancer. However, it is still not entirely clear which biomarkers are cost-effective, simple, and highly reliable. This systematic review and meta-analysis aims to analyze the predictive value of the baseline neutrophil-lymphocyte ratio (NLR) regarding disease progression and overall survival of patients with metastatic melanoma undergoing treatment with PD-1/PD-L1 blockade. PubMed, Scopus, and Web of Science were searched for studies comparing high versus low NLR. We performed the meta-analysis using RStudio v4.4.2 software. A total of 20 studies and 2691 patients were included, all with diagnoses of melanoma. The majority of the individuals were male 2278 (84, 65%). The median overall survival (OS) and progression-free survival (PFS) ranged from 5.0 to 44.4 and from 1.8 to 15.0 months, respectively. Compared with the high NLR ratio, the low exposure group achieved better rates of OS [hazard ratio (HR), 2.07; 95% CI, 1.73-2.48; P < 0.00001; I² = 47%]. Regarding PFS, there was a statistically significant difference between groups with tendencies toward the low NLR exposure group (HR, 1.59; 95% CI, 1.39-1.81; P < 0.00001; I²=31%]. This systematic review and meta-analysis revealed significant lower OS in melanoma patients treated with PD-1/PD-L1 blockade who had elevated baseline NLR values. Furthermore, an increased PFS was observed in patients with a lower baseline NLR value. This study highlights NLR as an important prognostic biomarker for patients with metastatic melanoma who are candidates for treatment with PD-1 and PD-L1.

Combination of anlotinib and sintilimab for the treatment of recurrent or metastatic head and neck squamous cell carcinoma: a single-arm prospective study

To investigate whether blocking both programmed cell death protein and vascular endothelial growth factor receptor could offer superior anticancer activity in these patients without compromising safety. In this study, patients were administered oral anlotinib (12 mg/day) on days 1–14 and intravenous sintilimab (200 mg) on day 1 of a 3-weekly cycle. The primary endpoints included the objective response rate and disease control rate. The secondary endpoints included overall survival (OS) and safety. Ten eligible patients were enrolled between June 2019 and May 2022, and eight patients underwent radiographic assessments. The results showed an objective response rate of 50% (partial and complete response in four and zero patients, respectively) and a disease control rate of 100%; four patients demonstrated stable disease for at least 8 weeks. The median OS was 4.37 (in our study, the score was 7), and the OS rate at 12 months was 37.5%. The Kaplan–Meier survival curve showed that the group with high blood glucose levels had a significantly shorter duration of survival than those with normal blood glucose levels. Adverse events of grade 3 and higher occurred in 50% of patients, and the most common severe adverse events included tumor pain (50%), hypertension (37.5%), tumor hemorrhage (25%), and decreased appetite (25%). The combination of anlotinib and sintilimab showed promising efficacy in controlling tumor size. However, the disappointing OS rate suggests that anti-vascular endothelial growth factor receptor agents should be used cautiously after radical radiation therapy. The combination used in this study demonstrated a toxicity profile comparable to that of other agents used in this setting. These findings warrant further investigation into the potential clinical utility of this combination.

Distinct clinical profiles and patient outcomes in aCML and CNL.

The classification of atypical chronic myeloid leukemia (aCML) and chronic neutrophilic leukemia (CNL) as a single disease entity remains a topic of debate. To elucidate the characteristics of both entities, this retrospective cohort study was conducted, encompassing 36 cases of aCML and 18 cases of CNL. We discovered that aCML and CNL presented distinct blood counts, genetics, molecular profiles and outcomes. Specifically, hemoglobin levels (P < 0.001) and platelet counts (P < 0.001) were significantly lower in aCML cases than in CNL cases, with no significant difference in mean white blood cells (P = 0.637). The proportion of abnormal karyotypes was higher in aCML cases compared with CNL cases (P = 0.010). Notably, we found that aCML and CNL showed distinct gene expression profiles by transcriptome sequencing technology. The median follow-up duration for the entire cohort was 8months (rang 0.4 to 36.6months), and the median overall survival (OS) was significantly shorter in aCML cases (7.3months, 95%CI 5.4 to 20.5months) than in CNL cases (median OS not reached). The one-year OS rate for aCML patients was 31.0% (9/29), compared to 92.9% (13/14) for CNL patients. In conclusion, our study supports the notion that aCML and CNL are indeed distinct disease entities characterized by unique hematological features and clinical outcomes.

Pembrolizumab for the First-Line Treatment of Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma: Results from the Single-Arm, Open-Label, Phase III KEYNOTE-913 Study.

The phase III KEYNOTE-913 study was conducted to evaluate the efficacy and safety of pembrolizumab as first-line therapy in patients with advanced Merkel cell carcinoma (MCC). The aim was to report results from the primary analysis of KEYNOTE-913. Patients with recurrent locally advanced or metastatic MCC received pembrolizumab 200mg intravenously every 3weeks for up to 35 treatments (~2 years). The primary end point was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary end points were duration of response (DOR) and progression-free survival (PFS) per RECIST v1.1 by BICR, overall survival (OS), and safety and tolerability. Fifty-five patients were treated with pembrolizumab. The median time from first dose to data cutoff (February 15, 2024) was 50.3 months (range 38.7-59.4). The ORR was 49% (95% confidence interval [CI] 35-63), with 12 complete responses and 15 partial responses. The median DOR was 39.8 months (range 4.8-52.5+), and the 24-month DOR rate was 69%. The median PFS was 9.3 months (95% CI 3-26), and the 24-month PFS rate was 39%. The median OS was 24.3 months (95% CI 12.4 to not reached), and the 24-month OS rate was 51%. Any-grade treatment-related adverse events (AEs) occurred in 38 patients (69%); 13 patients (24%) experienced grade 3-5 AEs. The most common treatment-related AEs were fatigue (n = 12 [22%]), pruritus (n = 12 [22%]), and lipase increase (n = 10 [18%]). One patient died of treatment-related Guillain-Barré syndrome. Pembrolizumab provided durable antitumor activity and promising survival and had a manageable safety profile in patients with recurrent locally advanced or metastatic MCC, supporting its use in this population. Clinicaltrials.gov, NCT03783078.

Lymphomas of the submandibular gland: a nationwide cohort study.

This study explores the epidemiology, incidence, and survival outcomes associated with lymphomas of the submandibular gland (SMG) and examines the influence of autoimmune diseases on these parameters. This retrospective nationwide cohort study analysed data from patients diagnosed with SMG lymphomas in Denmark between 2000 and 2020. Information was extracted from medical records, the National Pathology Register, and the Danish Lymphoma Database. Survival analyses were conducted using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models, focusing on lymphoma subtypes and autoimmune diseases. The cohort consisted of 101 patients with a lymphoma diagnosis and involvement of the SMG. Large B-cell lymphoma (LBCL) was diagnosed in 33 cases (32.7%), follicular lymphoma (FL) in 29 cases (28.7%), extranodal marginal zone lymphoma (EMZL) in 27 cases (26.7%), and 12 cases (11.9%) with other subtypes. EMZL had a significantly longer overall survival (OS) compared to other subtypes, with a median OS of 12.4 years (95% CI 11.2-12.4) vs. 8.4 years (95% CI 6.0-12.2). EMZL and FL showed favourable 5-year OS rates of 95% and 89%, respectively. LBCL had a 5-year OS rate of 65%. Age over 60 significantly negatively impacted OS. Traditional poor prognostic indicators did not significantly affect OS. A notable association between EMZL and autoimmune diseases was observed, particularly with Sjögren's syndrome, indicated by an increased relative risk of 2.67 (CI 95% 0.45-16.01). Lymphomas of the SMG are rare and have ambiguous clinical presentations. This study provides novel epidemiological, clinical, and prognostic information.

The seven-day cumulative post-esophagectomy inflammatory response predicts cancer recurrence

BackgroundThe relationship between postoperative cumulative systemic inflammation and cancer survival needs to be investigated. We developed an approach to the prognostication of postoperative esophageal cancer by establishing low and high cut-off values for the C-reactive protein (CRP) area under the curve (AUC) at 7 and 14 days after esophagectomy.MethodsOne hundred and twenty-five consecutive patients with biopsy-proven invasive esophageal squamous cell carcinoma (SCC) who underwent esophagectomies were evaluated. Postoperative CRP levels were analyzed for the first 14 days after surgery. The AUC on days 7 and 14 were calculated and compared with clinicopathological features and survival. The cut-off values for CRP at 7 days (CRP 7 d) and 14 days (CRP 14 d) were 599 mg/L and 1153 mg/L, respectively.ResultsThe patients in the low CRP 7 d group had significantly better recurrence-free survival (RFS) and overall survival (OS), not that in the low CRP 14d group. The OS rates in the high CRP groups at PODs 1, 3, 10, and 14 were significantly lower than those in the low CRP groups. Postoperative complications were more common in the high CRP groups on PODs 3, 10, and 14. Univariate analyses revealed that pTNM stage, depth of tumor invasion, tumor location, lymph node involvement, and CRP 7 d were significant prognostic factors for both OS and RFS. The Cox proportional hazards model identified pTNM, tumor location, and CRP 7d as independent prognostic factors for the RFS and OS.ConclusionsEarly prediction of patients with postoperative complications, and adequate management will suppress the elevation of CRP 7 d and further suppress the CRP value in the late postoperative period, which may improve the prognosis of esophageal cancer patients after esophagectomy.