Progression-free Survival Rates Research Articles

Neoadjuvant therapy with intensity-modulated radiotherapy combined with S-1 for borderline-resectable pancreatic cancer.

We evaluated the efficacy of neoadjuvant chemotherapy with intensity-modulated radiotherapy (NAC-IMRT) in patients with borderline-resectable pancreatic cancer (BRPC). BRPC patients were treated with IMRT (45Gy/15fr) combined with two courses of S-1 (40mg/m2 bid) before surgery. Outcomes after NAC-IMRT, surgery, and survival were then evaluated. This single-center retrospective study assessed 26 consecutive patients. Twenty-six patients (BR-PV: 7, BR-A: 19) with a median age of 73 years were enrolled from 2016 to 2021. Ten (38%) patients were 75-years-old and above. Twenty-three patients completed NAC-IMRT treatment. The median reductions in tumor size and cancer antigen 19-9 level were 13.6% and 69%, respectively. All 26 patients underwent resection within a median time of 71 days after NAC-IMRT initiation. R0 resection was achieved in 24 patients (92%). The median overall survival (OS) was 28.0 months, and the 1- and 3-year OS rates were 100% and 34%, respectively. The median progression-free survival (PFS) was 12.5 months, and the 1- and 3-year PFS rates were 50% and 32%, respectively. No significant differences were observed in OS between the patients under and over the age of 75 (29vs. 20 months, p=0.86). The 12 patients who completed NAC-IMRT, resection, and subsequent adjuvant chemotherapy (AC) exhibited a 3-year survival rate of 73%, which was significantly better than that of the patients who did not receive or complete AC (median OS, not reached vs. 19 months, p<0.001). NAC-IMRT showed outstanding clinical efficacy with acceptable tolerability in patients with BRPC, including geriatric patients.

TARGET: a phase I/II open-label multicentre study to assess safety and efficacy of fexagratinib in patients with relapsed/refractory FGFR fusion positive glioma

Abstract Background Oncogenic FGFR-TACC fusions are present in 3-5% of high-grade gliomas (HGGs). Fexagratinib (AZD4547) is an oral FGFR1-3 inhibitor with preclinical activity in FGFR-TACC+ gliomas. We tested its safety and efficacy in patients with recurrent FGFR-TACC+ HGGs. Patients and Methods TARGET (NCT02824133) is a phase I/II open-label multicenter study that included adult patients with FGFR-TACC+ HGGs relapsing after ≥1 line of standard chemoradiation. Patients received fexagratinib 80 mg bd on a continuous schedule until disease progression or inacceptable toxicity. The primary endpoint was the 6-month progression-free survival rate (PFS6). Results Twelve patients with recurrent IDH wildtype FGFR-TACC+ HGGs (all FGFR3-TACC3+) were included in the efficacy cohort (male/female ratio=1.4, median age=61.5 years). Most patients (67%) were included at the first relapse. The PFS6 was 25% (95% confidence interval 5-57%), with a median PFS of 1.4 months. All patients without progression at six months (n=3) were treated at first recurrence (versus 56% of those in progression) and remained progression-free for 14-23 months. The best response was RANO partial response in one patient (8%), stable disease in five (42%), and progressive disease in six (50%). Median survival was 17.5 months from inclusion. Grade 3 toxicities included lymphopenia, hyperglycaemia, stomatitis, nail changes, and alanine aminotransferase increase (n=1 each). No grade 4-5 toxicities were seen. A 32-gene signature was associated with benefit from FGFR inhibition in FGFR3-TACC3+ HGGs. Conclusion Fexagratinib exhibited acceptable toxicity but limited efficacy in recurrent FGFR3-TACC3+ HGGs. Patients treated at first recurrence appeared more likely to benefit, yet additional evidence is required.

High-dose chemotherapy and peripheral blood stem cell transplantation as salvage therapy in primary mediastinal nonseminomatous germ cell tumors: The Indiana University experience.

Patients with relapsed primary mediastinal nonseminomatous germ cell tumor have low cure rates with salvage chemotherapy or surgery. The authors report survival outcomes of patients who received high-dose chemotherapy (HDCT) and peripheral blood stem cell transplantation (PBSCT) at Indiana University. The prospectively maintained Indiana University germ cell tumor database identified 32 patients with primary mediastinal nonseminomatous germ cell tumor who progressed after first-line cisplatin-based combination chemotherapy and received HDCT and PBSCT between 2006 and 2021. Therapy included two consecutive courses of HDCT consisting of 700 mg/m2 carboplatin and 750 mg/m2 etoposide, each for 3 consecutive days, and each followed by PBSCT. A second course was not given if the patient experienced progressive disease or prohibitive toxicity. Progression-free survival and overall survival were analyzed using the Kaplan-Meier method. Medians with 95% confidence intervals were also calculated along with 2-year probabilities. The median age at HDCT was 30 years (range, 18-61 years). With a median follow-up of 4.7 years (range, 1-14 years), the 2-year progression-free survival rate was 31% (95% confidence interval, 16%-47%), and the 2-year overall survival rate was 35% (95% confidence interval, 19%-52%). At last follow-up, nine patients (28%) remained without evidence of disease, including two platinum-refractory patients and two patients who were receiving HDCT as third-line therapy. There were three treatment-related deaths. Salvage HDCT and PBSCT is an active combination in patients who have relapsed primary mediastinal nonseminomatous germ cell tumor with curative potential and prolonged survival, including in platinum-refractory and third-line settings. The authors recommend this approach for initial salvage chemotherapy in this patient population.

Robotic Stereotactic Body Radiation Therapy for Oligometastatic Liver Metastases: A Systematic Review of the Literature and Evidence Quality Assessment

Introduction: The role of stereotactic body radiation therapy (SBRT) as a locally effective therapeutic approach for liver oligometastases from tumors of various origin is well established. We investigated the role of robotic SBRT (rSBRT) treatment on oligometastatic patients with liver lesions. Material and Methods: This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The PubMed and Scopus databases were accessed by two independent investigators concerning robotic rSBRT for liver metastases, up to 3 October 2023. Results: In total, 15 studies, including 646 patients with 847 lesions that underwent rSBRT, were included in our systematic review. Complete response (CR) after rSBRT was achieved in 40.5% (95% CI, 36.66–44.46%), partial response (PR) in 19.01% (95% CI, 16.07–22.33%), whereas stable disease (SD) was recorded in 14.38% (95% CI, 11.8–17.41%) and progressive disease (PD) in 13.22% (95% CI, 10.74–16.17%) of patients. Progression-free survival (PFS) rates at 12 and 24 months were estimated at 61.49% (95% CI, 57.01–65.78%) and 32.55% (95% CI, 28.47–36.92%), respectively, while the overall survival (OS) rates at 12 and 24 months were estimated at 58.59% (95% CI, 53.67–63.33%) and 44.19% (95% CI, 39.38–49.12%), respectively. Grade 1 toxicity was reported in 13.81% (95% CI, 11.01–17.18%), Grade 2 toxicity in 5.57% (95% CI, 3.82–8.01%), and Grade 3 toxicity in 2.27% (955 CI, 1.22–4.07%) of included patients. Conclusions: rSBRT represents a promising method achieving local control with minimal toxicity in a significant proportion of patients. Further studies are needed to evaluate the role of rSBRT in the management of metastatic liver lesions.

A longer time to relapse is associated with a larger increase in differences between paired primary and recurrent IDH wild-type glioblastomas at both the transcriptomic and genomic levels

Glioblastoma (GBM) is the most common malignant brain tumor in adults, which remains incurable and often recurs rapidly after initial therapy. While large efforts have been dedicated to uncover genomic/transcriptomic alternations associated with the recurrence of GBMs, the evolutionary trajectories of matched pairs of primary and recurrent (P-R) GBMs remain largely elusive. It remains challenging to identify genes associated with time to relapse (TTR) and construct a stable and effective prognostic model for predicting TTR of primary GBM patients. By integrating RNA-sequencing and genomic data from multiple datasets of patient-matched longitudinal GBMs of isocitrate dehydrogenase wild-type (IDH-wt), here we examined the associations of TTR with heterogeneities between paired P-R GBMs in gene expression profiles, tumor mutation burden (TMB), and microenvironment. Our results revealed a positive correlation between TTR and transcriptomic/genomic differences between paired P-R GBMs, higher percentages of non-mesenchymal-to-mesenchymal transition and mesenchymal subtype for patients with a short TTR than for those with a long TTR, a high correlation between paired P-R GBMs in gene expression profiles and TMB, and a negative correlation between the fitting level of such a paired P-R GBM correlation and TTR. According to these observations, we identified 55 TTR-associated genes and thereby constructed a seven-gene (ZSCAN10, SIGLEC14, GHRHR, TBX15, TAS2R1, CDKL1, and CD101) prognostic model for predicting TTR of primary IDH-wt GBM patients using univariate/multivariate Cox regression analyses. The risk scores estimated by the model were significantly negatively correlated with TTR in the training set and two independent testing sets. The model also segregated IDH-wt GBM patients into two groups with significantly divergent progression-free survival outcomes and showed promising performance for predicting 1-, 2-, and 3-year progression-free survival rates in all training and testing sets. Our findings provide new insights into the molecular understanding of GBM progression at recurrence and potential targets for therapeutic treatments.

The impact of purified protein derivative prior to intravesical bacillus Calmette-Guérin for the treatment of patients with non-muscle invasive bladder cancer.

The aim of this study is to investigate the impact of the intradermal injection of purified protein derivative (PPD) and PPD skin test reactions on the oncological outcomes of patients with non-muscle invasive bladder cancer (NMIBC) treated by trans-urethral resection of bladder tumor (TURBT) and adjuvant intravesical BCG. The study included 100 consecutive patients with NMIBC prospectively given intradermal PPD 1-2 weeks before starting BCG therapy. Another 100 patients with NMIBC not given intradermal PPD before starting BCG were chosen as a historical control. The control group was chosen to be matching with the study group regarding baseline characteristics. The study group was divided into 2 subgroups with positive and negative reaction to PPD skin test. Oncological outcomes, immunological markers (TNF-α and IL-6) changes and BCG side effects were evaluated. There were no significant differences between patients who received PPD or not regarding the 2-year recurrence free survival (RFS) rates and progression-free survival (PFS) rates and immunological markers changes. The 2-year RFS and PFS rates were significantly higher in patients with positive reactions. Post-induction values of immunological markers increased in all patients with a significant increase in patients with positive reactions. BCG side effects were significantly higher in patients with positive reactions. The intradermal injection of PPD before intravesical BCG has no impact on oncological outcomes of patients with NMIBC treated with TURBT and intravesical BCG. However, the PPD skin test reactions before BCG therapy can predict the oncological outcomes, BCG side effects and the immunological outcomes of patients.

PD-1 inhibitor combined with paclitaxel and cisplatin in the treatment of recurrent and metastatic hypopharyngeal/laryngeal squamous cell carcinoma: efficacy and survival outcomes

ObjectiveThis retrospective study analyzed the efficacy of PD-1 inhibitors combined with albumin-bound paclitaxel and cisplatin (TP regimen) in the treatment of recurrent and metastatic hypopharyngeal/laryngeal squamous cell carcinoma (RMHSCC/RMLSCC).MethodsPatients diagnosed and treated at the Sun Yat-sen University Cancer Center from August 1, 2020, to August 15, 2023, with histologically confirmed RMHSCC/RMLSCC were included. All patients received PD-1 inhibitors combined with albumin-bound paclitaxel (260mg/m2) and cisplatin (60mg/m2) for 3–4 cycles. The primary endpoints were overall survival (OS) and progression-free survival (PFS).ResultsA total of 50 patients with RMHSCC/RMLSCC who received TP+PD-1 inhibitor therapy were included, with an objective response rate (ORR) of 56.0% (28/50). The 1-year and 2-year OS rates were 80.2% (95% CI: 69.3%-92.9%) and 68.6% (95% CI: 52.6%-89.5%), respectively, while the 1-year and 2-year PFS rates were 44.7% (95% CI: 31.9%-62.5%) and 26.0% (95% CI: 12.6%-53.4%), respectively. Treatment-related adverse events mainly included rash, myelosuppression, gastrointestinal reactions, and hypothyroidism.ConclusionIn the treatment of RMHSCC/RMLSCC with TP + PD-1 inhibitors, survival rates of patients can be improved while ensuring the safety of the treatment regimen.

The impact of daratumumab pretreatment on multiple myeloma patients undergoing autologous transplantation.

The anti-CD38 antibody daratumumab (Dara) has been reported to improve the prognosis of multiple myeloma (MM) patients, but its use before autologous stem cell transplantation (ASCT) remains controversial. To clarify the prognostic impact of Dara before ASCT on MM, we performed a retrospective observational analysis. We analyzed 2626 patients who underwent ASCT between 2017 and 2020. In the comparison between patients not administered Dara (Dara- group) and those administered Dara (Dara+ group), the 1-year progression-free survival (PFS) rates were 87.4% and 77.3% and the 1-year overall survival (OS) rates were 96.7% and 90.0%, respectively. In multivariate analysis, age <65 years (p = 0.015), low international staging system (ISS) stage (p < 0.001), absence of unfavorable cytogenic abnormalities (p < 0.001), no Dara use before ASCT (p = 0.037), and good treatment response before ASCT (p < 0.001) were independently associated with superior PFS. In matched pair analysis, the PFS/OS of the Dara- group were also significantly superior. For MM patients who achieved complete or very good partial response (CR/VGPR) by Dara addition before ASCT, both PFS and OS significantly improved. However, in patients who did not achieve CR/VGPR before ASCT, the PFS/OS of the Dara+ group were significantly inferior to those of the Dara- group.

Long term follow-up of patients with newly diagnosed glioblastoma treated by intraoperative photodynamic therapy: an update from the INDYGO trial (NCT03048240).

Glioblastoma remains incurable despite optimal multimodal management. The interim analysis of open label, single arm INDYGO pilot trial showed actuarial 12-months progression-free survival (PFS) of 60% (median 17.1months), actuarial 12-months overall survival (OS) of 80% (median 23.1months). We report updated, exploratory analyses of OS, PFS, and health-related quality of life (HRQOL) for patients receiving intraoperative photodynamic therapy (PDT) with 5-aminolevulinic acid hydrochloride (5-ALA HCl). Ten patients were included (May 2017 - April 2021) for standardized therapeutic approach including 5-ALA HCl fluorescence-guided surgery (FGS), followed by intraoperative PDT with a single 200J/cm2 dose of light. Postoperatively, patients received adjuvant therapy (Stupp protocol) then followed every 3months (clinical and cerebral MRI) and until disease progression and/or death. Procedure safety and toxicity occurring during the first four weeks after PDT were assessed. Data concerning relapse, HRQOL and survival were prospectively collected and analyzed. At the cut-off date (i.e., November 1st 2023), median follow-up was 23months (9,7-71,4). No unacceptable or unexpected toxicities and no treatment-related deaths occurred during the study. Kaplan-Meier estimated 23.4months median OS, actuarial 12-month PFS rate 60%, actuarial 12-month, 24-month, and 5-year OS rates 80%, 50% and 40%, respectively. Four patients were still alive (1 patient free of recurrence). At 5years-follow-up, intraoperative PDT with surgical maximal excision as initial therapy and standard adjuvant treatment suggests an increase of time to recurrence and overall survival in a high proportion of patients. Quality of life was maintained without any severe side effects. NCT03048240. EudraCT number: 2016-002706-39.

Efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in the treatment of locally advanced cervical cancer

BackgroundEvaluate the efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in treating locally advanced cervical cancer (LACC).MethodsRetrospective data was collected from LACC patients who were treated at our institution. These patients were categorized into three groups: the single-agent cisplatin (DDP) chemoradiotherapy group, the paclitaxel plus cisplatin (TP) chemoradiotherapy group, and the nanoparticle albumin-bound (nab-) paclitaxel combined with cisplatin (nPP) chemoradiotherapy group. The primary endpoints were overall survival (OS) and progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR) and incidence of adverse events (AEs).ResultsA total of 124 patients were enrolled (32 in the DDP group, 41 in the TP group, and 51 in the nPP group). There were differences in OS (P = 0.041, HR 0.527, 95% CI 0.314–0.884) and PFS (P = 0.003, HR 0.517, 95% CI 0.343–0.779) between the three groups. Notably, the 2-year OS rate was significantly higher in the nPP group compared to the DDP group (92.2% vs. 85.4%, P = 0.012). The 2-year PFS rates showed a marked increase in the TP group (78.0% vs. 59.4%, P = 0.048) and the nPP group (88.2% vs. 59.4%, P = 0.001) relative to the DPP group, with multiple comparisons indicating that the 2-year PFS rate was significantly superior in the nPP group versus the DDP group (88.2% vs. 59.4%, P = 0.001). Moreover, the ORR was also significantly higher in the nPP group than in the DDP group (P = 0.013); and no statistically significant differences were found in the incidence of AEs among the groups (P > 0.05).ConclusionsIn LACC treatment, the two cisplatin-based doublet chemotherapy regimens are associated with better outcomes, with the nab-paclitaxel plus cisplatin regimen showing better efficacy than the paclitaxel plus cisplatin regimen. Furthermore, the AEs associated with these regimens were deemed tolerable. These findings could provide a reference for the clinical treatment of LACC. However, further prospective studies are needed to verify it.

Efficacy and safety of anlotinib in patients with desmoid fibromatosis: a retrospective analysis

Efficacy and safety of anlotinib in patients with desmoid fibromatosis: a retrospective analysis

Prognostic value of skeletal muscle measured by CT at the T4 level in advanced EGFR-positive non-small cell lung cancer patients treated with ecotinib

Objective: To investigate the prognostic value of skeletal muscle measured by CT at the level of the fourth thoracic vertebra (T4) in advanced epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) patients treated with ecotinib. Methods: The study retrospectively reviewed clinical and pathological characteristics of 176 patients with advanced EGFR-positive NSCLC who received ecotinib and underwent chest CT scans at Wuhan Union Hospital between January 2017 and October 2020. Among them, 70 were male and 106 were female, with ages ranging from 27 to 80 (58.6±10.6) years. As of August 21, 2021, the median follow-up duration was 19.2 months (95%CI: 15.3 to 23.7 months). The optimal cut-off value of skeletal muscle density (T4-SMD) on CT images at the T4 level were determined using X-tile software. Kaplan-Meier analysis and log-rank test were used to plot progression-free survival curves. Cox proportional hazards regression models were employed to analyze factors influencing 1-year progression-free survival (PFS), and a nomogram prognostic model was constructed accordingly. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were utilized to evaluate the predictive value of the nomogram. Results: The T4-SMD [M (Q1,Q3)] of 176 patients was 42.56 (37.05, 45.93) HU. Patients were divided into low T4-SMD group (n=122) and high T4-SMD group (n=54) based on the cut-off value (The values for males and females were 49.44 and 41.41 HU, respectively) of T4-SMD. The median PFS time and 1-year PFS rate in the low T4-SMD group were significantly lower than those in the high T4-SMD group [10.4 (95%CI: 9.3-11.8) vs 13.7 (95%CI: 11.1-18.5) months, 36.1% vs 59.3%, respectively, P=0.034]. Eastern Cooperative Oncology Group performance status (HR=3.308, 95%CI: 1.183-9.247, P=0.023), lactate dehydrogenase level (HR=1.852, 95%CI: 1.037-3.307, P=0.037), systemic immune-inflammation index (HR=1.772, 95%CI: 1.019-3.080, P=0.043), and T4-SMD (HR=0.563, 95%CI: 0.325-0.974, P=0.040) were prognostic factors for 1-year PFS in advanced EGFR-positive NSCLC patients treated with ecotinib. A nomogram for predicting 1-year PFS of advanced EGFR-positive NSCLC patients treated with ecotinib was constructed based on the four indicators selected by multivariate Cox regression analysis. The area under the ROC curve of the nomogram was 0.775 (95%CI: 0.676-0.874). The calibration curve showed good consistency between the predicted and actual 1-year PFS. DCA demonstrated good clinical prediction effectiveness of the nomogram. Conclusion: Low T4-SMD is a prognostic risk factor for patients with advanced EGFR-positive NSCLC receiving icotinib therapy.

Long-term survival outcomes and immune checkpoint inhibitor retreatment in patients with advanced cervical cancer treated with camrelizumab plus apatinib in the phase II CLAP study.

Camrelizumab plus apatinib have demonstrated robust antitumor activity and safety in patients with advanced cervical cancer (CLAP study; NCT03816553). We herein present the updated long-term results of the CLAP study and explore potential biomarkers for survival. The outcomes of patients who underwent immune checkpoint inhibitor (ICI) retreatment were also reported. In this phase II trial, eligible patients received camrelizumab 200 mg intravenously every two weeks and apatinib 250 mg orally once daily in 4-week cycles for up to two years. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent. Between January 21 and August 1, 2019, a total of 45 patients were enrolled. Data were analyzed as of July 31, 2023, representing > 48 months since treatment initiation for all patients. Nine (20.0%) patients completed the 2-year study. The median duration of response (DOR) was 16.6 months, and 45.0% of patients achieved a DOR of ≥ 24 months. The 12-month progression-free survival (PFS) rate was 40.7% (95% confidence interval [CI], 25.2-55.6), with an 18-month PFS rate of 37.8% (95% CI, 22.7-52.8). The median overall survival (OS) was 20.3 months (95% CI, 9.3-36.9), and the 24-month OS rate was 47.8% (95% CI, 31.7-62.3). Age > 50 years, programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥ 1 (versus [vs.] < 1), CPS ≥ 10 (vs. < 1), high tumor mutational burden, and PIK3CA mutations were associated with improved PFS (hazard ratio [HR] < 1) and longer OS (HR < 1). Eight patients who initially responded in the CLAP trial but later experienced disease progression were retreated with ICIs. Among them, 2 (25.0%) achieved a partial response, while 5 (62.5%) had stable disease. Notably, four patients who received retreatment with ICIs survived for more than 45 months. No new safety signals were identified in the present study. Long-term survival follow-up data demonstrated that camrelizumab plus apatinib has robust, sustained, and durable efficacy in patients with advanced cervical cancer who progress after first-line platinum-based chemotherapy. No new safety signals were noted with long-term treatment.

Outcomes of patients in nasopharyngeal adenoid cystic carcinoma in the IMRT era: a single-center experience

ObjectiveNasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with special biological features. Controversies exist regarding the treatment approach and prognostic factors in the IMRT era. This study aimed to evaluate the long-term outcomes and management approaches in NACC.MethodsFifty patients with NACC at our institution between 2010 and 2020 were reviewed. Sixteen patients received primary radiotherapy (RT), and 34 patients underwent primary surgery.ResultsBetween January 2010 and October 2020, a total of 50 patients with pathologically proven NACC were included in our analysis. The median follow-up time was 58.5 months (range: 6.0–151.0 months). The 5-year overall survival rate (OS) and progression-free survival rate (PFS) were 83.9% and 67.5%, respectively. The 5-year OS rates of patients whose primary treatment was surgery and RT were 90.0% and 67.3%, respectively (log-rank P = 0.028). The 5-year PFS rates of patients whose primary treatment was surgery or RT were 80.8% and 40.7%, respectively (log-rank P = 0.024). Multivariate analyses showed that nerve invasion and the pattern of primary treatment were independent factors associated with PFS.ConclusionsDue to the relative insensitivity to radiation, primary surgery seemed to provide a better chance of disease control and improved survival in NACC. Meanwhile, postoperative radiotherapy should be performed for advanced stage or residual tumours. Cranial nerve invasion and treatment pattern might be important factors affecting the prognosis of patients with NACC.

Dickkopf-related protein 1 as a biomarker of local immune status and worse prognosis of Oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is an infiltrative malignancy characterized by a significantly elevated recurrence rate. Dickkopf-related protein 1 (DKK1), which plays an oncogene role in many cancers, acts as an inhibitor of the Wingless protein (Wnt) signaling pathway. Currently, there is a lack of consensus regarding the role of DKK1 in OSCC or its clinical significance. To examine the role and effect of DKK1 in OSCC. The identification of differentially expressed genes (DEGs) in OSCC was conducted by utilizing databases such as The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A comprehensive analysis of gene expression profile interactions (GEPIA) and Kaplan-Meier curve were conducted to investigate the associations among DEGs, patient survival and prognosis in individuals with OSCC. The biological function of DKK1 in OSCC was investigated by using molecular biology approaches. The expression of DKK1 was found to be upregulated in OSCC tissues at various stages. High levels of DKK1 expression exhibited a positive correlation with the overall survival (OS) and progression-free survival (PFS) rates among OSCC patients. DKK1 knockdown suppressed the proliferation and induced apoptotic response in OSCC cells. Moreover, DKK1 exerted a positive regulatory effect on HMGA2 expression, thereby modulating cell growth and apoptosis in OSCC. The expression of DKK1 was found to be positively correlated with the infiltration of immune cells in patients with OSCC. Additionally, higher levels of CD4 + T cells were associated with improved 5-year survival rates. DKK1 is a prognostic biomarker for patients with OSCC.

Tumor necrosis serves as an important pathological characteristic of stage I-II colon cancer.

The long-term prognosis of colon cancer patients remains little changed with relatively high mortality and morbidity. Since the most widely used prognostic parameter TNM staging system is less satisfactory in predicting prognosis in early-stage cancers, numerous clinicopathological factors, including tumor necrosis, have been proposed for prognosis stratification, but substantial evidences are still lacking for early-stage colon cancer. In the retrospective study, a total of eligible 173 stage I-II colon cancer patients, who received tumor radical resection and lymphadenectomy in the local hospital between January 1, 2010, and December 31, 2018, were enrolled for analyzing the prognostic role of tumor necrosis. The primary endpoints included 5-year overall survival (OS) and progression-free survival (PFS). The median follow-up of enrolled early-stage colon cancer patients was 58.3 months. The 2-year and 5-year OS rates were 88.3% and 68.2%, respectively, and the 2-year and 5-year PFS rates were 85.6% and 62.7%, respectively. Seventy-eight patients (45.1%) were diagnosed with tumor necrosis by pathological examination. Demographic analysis revealed a significant association of tumor necrosis with larger tumor size and a marginal association with vascular invasion. Kaplan-Meier survival curves demonstrated that tumor necrosis was associated with worse OS (log-rank P = 0.003) and PFS (log-rank P = 0.002). The independent unfavorable prognostic effect of tumor necrosis was further validated in univariate and multivariate Cox regression analysis (hazard ratio = 1.91 (1.52-2.40), P = 0.004). The current study confirmed the independent prognostic role of tumor necrosis from pathological review in early-stage colon cancer patients. This pathological criterion promises to help in identifying high-risk subgroup from early-stage colon cancer patients, who may benefit from strict follow-up and adjuvant therapy.

Active surveillance and emerging medical treatment options for desmoid: when and for whom?

This article discusses the evolving approaches to desmoid tumors management, shedding light on recent developments. Active surveillance has become the primary approach for managing primary peripheral desmoid tumors. This strategy was initially based on evidence from retrospective studies. Roughly 50% of cases managed with active surveillance show spontaneous stabilization or regression. Recent prospective trials conducted in Italy, The Netherlands, and France (2022-2023) confirm the efficacy of active surveillance, revealing 3-year progression-free survival rates ranging from 53.4 to 58%. For the patients under active surveillance, decisions regarding treatment are based on significant tumor growth or progressive symptoms. Moreover, three contemporary randomized trials investigated medical treatments for progressive or recurrent desmoid tumors. Sorafenib, pazopanib, and nirogacestat demonstrated clinical activity, as evidenced by favorable progression-free survival and objective response rates. Active surveillance has solidified its position as the primary management approach for desmoid tumors, validated by three robust prospective studies. Three recent randomized trials explored medical treatment for progressive or recurrent desmoid tumors, revealing promising clinical activities.

A retrospective study of clinical outcomes for patients with esophageal cancer who were treated with radiotherapy alone

Introduction: Patients with esophageal cancer who are in a poor general condition receive radiotherapy alone, but outcomes are often unsatisfactory. The aim of this study was to clarify recent outcomes of radiotherapy alone for esophageal cancer. Methods: Patients who underwent 50 Gy or more of radiotherapy without chemotherapy were retrospectively reviewed. Endpoints were overall survival (OS), disease-specific survival (DSS), local control (LC), and progression-free survival (PFS). Survival curves were drawn using the Kaplan-Meier method and predictors were analyzed using the Cox proportional hazards model. Results: Sixty-nine patients were included. The median follow-up period was 17.9 months. The 5-year OS, DSS, LC, and PFS rates were 33.2%, 49.8%, 46.2%, and 16.8%, respectively. In the multivariate Cox proportional hazard model, clinical stage was a significant predictor for OS (hazard ratio [HR]: 4.42, 95% confidence interval [CI]: 1.80 – 11.17, p = 0.001), DSS (HR: 2.08, 95% CI: 1.43 – 3.12, p = 0.0001), LC (HR: 1.86, 95% CI: 1.28 – 2.74, p = 0.001), and PFS (HR: 1.65, 95% CI: 1.25 – 2.18, p = 0.0004). Radiation dose was a significant predictor for LC (HR: 0.87, 95% CI: 0.78 – 0.97, p = 0.018) and tumor location was a significant predictor for PFS (HR: 1.55, 95% CI: 1.10 – 2.19, p = 0.018). In subgroup analysis, the 5-year OS, DSS, LC, and PFS rates for stage I were 60.0%, 80.0%, 71.9%, and 46.1%, respectively. Conclusions: Stage, radiation dose and tumor location are significant predictors for outcomes. Patients with stage I esophageal cancer can be cured by radiotherapy alone.

Safety and preliminary efficacy of pembrolizumab following trans-arterial chemoembolization for hepatocellular carcinoma: the PETAL phase Ib study.

TACE may prime adaptive immunity and enhance immunotherapy efficacy. PETAL evaluated safety, preliminary activity of TACE plus pembrolizumab and explored mechanisms of efficacy. Patients with liver-confined HCC were planned to receive up to 2 rounds of TACE followed by pembrolizumab 200 mg every 21 days commencing 30-days post-TACE until disease progression or unacceptable toxicity for up to 1 year. Primary endpoint was safety, 21-days dose-limiting toxicities (DLT) from pembrolizumab initiation. Secondary endpoints included progression-free survival (PFS) and evaluation of tumour and host determinants of response. Fifteen patients were included in the safety and efficacy population: 73% had non-viral cirrhosis, median age was 72 years. Child-Pugh (CP) class was A in 14 patients. Median tumour size was 4 cm. Ten patients (67%) received pembrolizumab after 1 TACE, 5 patients after 2 (33%). Pembrolizumab yielded no synergistic toxicity nor DLTs post-TACE. Treatment-related adverse events occurred in 93% of patients most commonly skin rash (40%), fatigue and diarrhoea (27%). After a median follow-up of 38.5 months, objective response rate (ORR) 12 weeks post-TACE was 53%. PFS rate at 12 weeks was 93% and median PFS was 8.95 months (95%CI 7.30-NA). Median duration of response was 7.3 months (95%CI: 6.3-8.3). Median OS was 33.5 months (95%CI: 11.6-NA). Dynamic changes in peripheral T-cell subsets, circulating tumour DNA, serum metabolites and in stool bacterial profiles highlight potential mechanisms of action of multi-modal therapy. TACE plus pembrolizumab was tolerable with no evidence of synergistic toxicity, encouraging further clinical development of immunotherapy alongside TACE.

Real-world efficacy and safety of BRAF-targeted therapy for patients with advanced melanoma: A single-center retrospective study in Japan.

Most clinical trials investigating targeted therapies for patients harboring BRAF V600 mutations have included mostly White patients, and data for Asian patients are scarce. Although there are several retrospective studies in Japanese patients, they have investigated only the dabrafenib + trametinib regimen, and have had a short follow-up period. We conducted a single-center retrospective study to update previous studies and compare the outcomes with those in White patients. We analyzed 89 patients who received dabrafenib + trametinib or encorafenib + binimetinib, including 11 who received both treatment regimens. The overall response rate was 79.8%, with complete response in 25 patients (28.1%) and partial response in 45 patients (51.7%). The median progression-free survival was 13.7 months, and the median overall survival was 32.9 months. The 3-year progression-free and overall survival rates were 31.8% and 47.9%, respectively. Although the two regimens showed no significant differences in efficacy, their safety profiles differed, as reported in clinical trials. Therefore, the most frequent adverse event associated with the dabrafenib + trametinib regimen was pyrexia (61.3%) and that of encorafenib + binimetinib was blurred vision (32.0%). Switching directly to another targeted therapy after progressive disease showed no clinical response; however, rechallenge followed by immune checkpoint inhibitor therapy showed a certain response. As a prognostic factor, performance status was associated with progression-free survival, and performance status, serum lactate dehydrogenase level, and dose interruption were associated with overall survival in the multivariate analysis. Real-world data on targeted therapy for patients with melanoma in Japan suggest that both dabrafenib + trametinib and encorafenib + binimetinib show similar efficacy and safety in Asian and White patients.