Progression-free Survival In Patients Research Articles

Abstract IA26: Exploring breast cancer vulnerabilities through apoptotic pathways

Abstract Combined CDK4/6 inhibitor and endocrine therapy has rapidly become standard therapy for patients with early line relapsed estrogen receptor (ER)-positive, HER2-negative breast cancer. Although this combination has been shown to significantly improve progression free and overall survival, relapse is virtually inevitable. This may in part be due to the profound cytostatic effect of CDK4/6 inhibitors on tumors, which is associated with reduced apoptotic cell death. It seems likely that growth arrested and/or senescent tumor cells acquire resistance to therapy, leading to relapse. BH3 mimetics are an emerging class of drug that target pro-survival proteins such as BCL2, BCL-xL and MCL1. Venetoclax, a BH3 mimetic that has potent and specific activity against BCL2, has shown considerable promise in hematopoietic tumors such as CLL, but has yet to be fully explored in solid tumors. We have previously demonstrated safety and efficacy of combining tamoxifen with venetoclax for patients with metastatic ER-positive BCL2-positive disease using pre-clinical PDX models and a dose-finding phase 1 study [mBEP study, ISRCTN98335443], where most patients were CDK4/6 inhibitor therapy-naïve. In the post-CDK4/6 inhibitor setting, however, venetoclax did not improve clinical benefit rate or progression free survival when added to fulvestrant in the phase 2 study VERONICA [NCT03584009]. In that study a minority of tumours exhibited strong BCL2 expression and exploratory biomarker analysis revealed a trend towards improved progression free survival for patients with tumors exhibiting high BCL2 expression (IHC 3+), a BCL2:BCL-xL Histoscore ratio ≥1, or with PIK3CA wild-type status. Using pre-clinical models including patient derived xenografts of ER-positive breast cancer, we have shown that the addition of venetoclax to dual therapy comprising fulvestrant and the CDK4/6 inhibitor palbociclib elicits a superior and more durable tumor response, accompanied by increased apoptosis. These findings have formed the basis of a phase 1 clinical trial of palbociclib, letrozole and venetoclax [PALVEN, NCT03900884] in patients with early line relapsed ER and BCL2-positive metastatic breast cancer. In parallel, pre-clinical studies are underway to determine the effect of dual targeting BCL-xL and MCL1, as well as dual targeting of AKT and with a BH3 mimetic in CDK4/6 inhibitor refractory breast cancer cells. Citation Format: James R Whittle, François Vaillant, Elliot Surgenor, Luuk Heitink, Christine Muttiah, Jane E Visvader, Geoffrey J Lindeman. Exploring breast cancer vulnerabilities through apoptotic pathways [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr IA26.

Effect of dipeptidyl protease 4 (DPP4) inhibitors on progression-free survival in patients with metastatic renal cell carcinoma: A single-center retrospective analysis.

Effect of dipeptidyl protease 4 (DPP4) inhibitors on progression-free survival in patients with metastatic renal cell carcinoma: A single-center retrospective analysis.

Total and anatomically contextualized quantitative 18F-DCFPyL PET at biochemical recurrence to predict subsequent biochemical progression-free survival in patients with prostate cancer.

33 Background: PSMA PET has been shown to detect more metastasis and alter management at biochemical recurrence (BCR), but it remains to be determined that it changes oncologic outcome. We assessed the quantitative parameters on 18F-DCFPyL PET at BCR and evaluated their association with tumor volume, metastatic locations with the subsequent biochemical progression free survival (bPFS). Methods: This is a retrospective image analysis and longitudinal follow up of a prospective study evaluating 18F-DCFPyL PET in BCR. Patients were treated with androgen deprivation therapy (ADT) and/or metastatic directed therapy (MDT) based on imaging findings. The 18F-DCFPyL PET images were quantitatively analyzed by the aPROMISE application, a semi-automated software for comprehensive analysis and structured reporting of PSMA PET/CT. aPROMISE uses deep learning to segment detailed anatomical information from the CT images and uses this information in combination with the PET image to detect and quantify candidates for prostate cancer lesions. The reader works in tandem with the software to vet the final list of lesions, from which the quantitative assessments and final report is created automatically. Based on the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria. SUV mean, PSMA positive total tumor volume (PSMAttv) and aPSMA scores, a quantitative score for tumor burden measuring the interaction of tumor volume and uptake stratified by local tumors (aPSMA-miT), regional lymph nodes (aPSMA-miN) and distant metastases (aPSMA-miMa for extrapelvic metastases, miMb for bone metastases and miMc for other organ metastases) were obtained based on the miTNM classification. The association of these quantitative parameters with the subsequent bPFS was evaluated. Results: 143 patients (age 70.5 ± 7.9, range 50 -93 years; median PSA 2.8, range 0.12 – 1125.9 ng/mL) were included in the quantitative image analysis. 80 of 143 patients (56%) had nodal metastases 51/143 patients (36%) had bone metastases, only 16 of 143 patients (11%) had visceral metastases. With median follow up of 40 months, 82 of 143 patients (57%) have progressed again biochemically after MDT. The median bPFS was 26.9 months. Quantitative analysis of 18F-DCFPyL PET found that the subsequent bPFS is significantly associated with aPSMA-miMb ( P = 0.003), aPSMA-miN ( P = 0.005), aPSMA-miT ( P < 0.001), and PSMAttv ( P = 0.006), but not with SUVmean, SUVmax or aPSMA-miMc. Conclusions: Quantitative image analysis of 18F-DCFPyL PET at BCR may be useful in predicting the subsequent bPFS. Given many patients were treated with MDT and/or ADT, clinical implication of the findings remains to be elucidated to guide treatment intensification based on findings on 18F-DCFPyL PET.

Prognostic value of artificial intelligence (AI) –driven tumor estimation of PSMA PET total tumor burden (TTB) in newly diagnosed high-volume metastatic hormone-sensitive prostate cancer (mHSPC).

47 Background: Prostate cancer represents a significant economic burden for health systems; the identification of risk factors that allows the identification of subgroups of patients that require closer follow-up or more intense therapeutic regimens has a direct impact on the prognosis and expenses for the patient, there is currently great interest in patients with high-volume mHSPC, this group is defined according to the number of lesions and their location, this could represent a challenge in decision making due to the variety of presentations regarding tumor burden, currently with the development of AI algorithms it is possible to estimate the PSMA TTB by identifying patients who are candidates for specific therapies without exposing them to comorbidities associated to aggressive regimens. Methods: Baseline PSMA PET scans of patients with histopathological corroborated diagnosis of prostate cancer and considered as high volume according to 68Ga PSMA PET/CT imaging in the period from October 2017 to June 2020 were retrospectively analyzed using an automated algorithm to estimate PSMA TTB, the median follow-up was of 44 +/- 9.7 months. These patients were divided into two groups according to the optimal cutoff values of PSMA TTB and estimate progression-free survival after initial therapy with Kaplan-Meier curves and correlation index between tumor burden and prostatic specific antigen. Results: 53 patients with a mean age of 71 years (+/- 5.1) were included, 17 with Gleason 7 (4+3/3+4), 18; G8 (4+4), 15; G9 (5+4/4+5) and 3; G10 (5+5), ISUP group 3 (n=17), group 4 (n=18) group 5 (n=18), the mean PSA value at diagnosis was 62.1 ng/dL (range 25.2- 201.5). PSMA TTB mean was 100.1cm3 (range 21cm3- 518.8 cm3). Log-rank test revealed that PSMA TTB lower than 45 cm3 (n=21) presented higher time of progression-free survival in comparison with patients with PSMA TTB higher than 45 cm3 (n=32) (31.1 mo vs 47.8 mo, p <0.003). TTB and PSA demonstrated a significant correlation (Pearson r= 0.526, p< 0.0001). There was no difference between groups of low and high PSMA TTB and ISUP groups or Gleason score. Sites of visceral disease were lung (n=11), (pleura=9) liver (n=9), adrenal, (n=5) brain, (n=2), and sites of extra spinal and pelvic disease were ribs (n=24) femur (n=16), skull (n=8), scapula (n=7), humerus (n=7). All patients had one or more lesions at previously described sites. Conclusions: PSMA TTB has great value in predicting progression-free survival of patients with newly diagnosed high-volume metastatic hormone-sensitive prostate cancer and has a strong correlation with PSA, strengthening the role of next-generation molecular imaging with PSMA PET as an invaluable tool in initial diagnosis and potentially in follow-up by providing information on the biological behavior of the disease in a systemic way.

Active surveillance for clinical complete responders after chemoradiotherapy for oesophageal squamous cell carcinoma.

Guidelines on the treatment of oesophageal squamous cell carcinoma (SCC) recommend neoadjuvant chemoradiotherapy plus surgery or definitive chemoradiotherapy. The aim of this study was to evaluate the outcome of patients with a cCR after chemoradiotherapy who underwent active surveillance. Patients with oesophageal SCC who were treated with chemoradiotherapy between January 2016 and June 2022 were identified from an institutional database. Survival and recurrence of patients with a cCR who underwent active surveillance were compared with those of patients who underwent planned surgery. Survival was calculated according to the Kaplan-Meier method and compared between groups using the log rank test. The 37 patients who underwent active surveillance were older and tumours were more often located in the middle/upper-third of the oesophagus than in the surgery group of 57 patients. Median follow-up was 28.1 (i.q.r. 17.2-47.1) months for the active surveillance group and 20 (12.9-39.1) months for the surgery group. Overall survival was comparable between the two groups, with 3-year survival rates of 50 (95% c.i. 31 to 67) and 59 (40 to 73)% for the active surveillance and surgery groups respectively (P = 0.55). Three-year progression-free survival for patients who underwent active surveillance was better than in the surgery group: 70 (43 to 85) versus 58 (40 to 72)% (P = 0.02). Overall and progression-free survival was comparable between patients in the active surveillance group and 23 patients in the surgery group who had a pCR (ypT0 N0). The overall recurrence rate was comparable between the groups: 7 of 37 (19.4%) in active surveillance group versus 16 of 49 (32.6%) in surgery group (P = 0.26). Locoregional recurrence was noted more often in the active surveillance group and systemic recurrence in the surgery group. Active surveillance is feasible and safe for patients with oesophageal SCC who have a cCR after chemoradiotherapy.

Very good partial remission predicts progression-free survival in patients with multiple myeloma

Aim. To examine the role of very good partial response or better (VGPR+) as a surrogate predictor of progression-free survival (PFS) in multiple myeloma (MM) patients.Materials and methods. A systematic literature review of MEDLINE database (2010–2023) and materials presented at hematology and cancer congresses (2020–2022) was performed to identify studies reporting median progressionfree survival (PFS) and the rate of very good partial response (VGPR+). The study used Spearman’s weighted correlation and linear regression methods to analyze the association between median PFS and VGPR+. A total of 34,443 patients were involved in 182 original studies that included real-world clinical practice data.Results. Based on the number of patients or year of publication, the correlation between VGPR+ and median PFS was statistically significant (Spearman coefficient r = 0.61), but low. For refractory/recurrent MM (r = 0.69) and for monoclonal antibody therapy (r = 0.81), the correlation between VGPR+ and PFS was stronger. In addition to achieving VGPR+, the line of therapy and autologous stem cell transplantation also played an important role in determining PFS. Based on these factors, an increase of one percentage point in VGPR+ predicted a 0.21‑month increase in median PFS in the final adjusted linear regression model.Conclusion. In this study, VGPR+ was found to predict PFS, making it a universal early point of reference for MM prognosis regardless of the treatment type.

Factors associated with prolonged progression-free survival of patients treated with first-line afatinib for advanced epidermal growth factor receptor-mutated non-small cell lung cancer.

This study aimed to investigate the factors associated with prolonged progression-free survival (PFS) (>36 months) of advanced non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations treated with first-line afatinib. We performed a retrospective analysis of data of patients with advanced EGFR-mutated NSCLC receiving first-line afatinib at two tertiary care referral centers, Linkou and Kaohsiung Chang Gung Memorial Hospital, in Taiwan between June 2014 and April 2022. The data of 546 treatment-naïve EGFR-mutated advanced NSCLC patients were analyzed. Median PFS and overall survival were 14.5 months and 27.2 months, respectively. The PFS of 462 patients (84.6%) was less than 36 months and of 84 patients (15.4%) was more than 36 months. The PFS > 36 months group had a significantly higher percentage of patients with uncommon mutations (p = 0.002). The PFS ≤36 months group had significantly higher incidences of bone, liver, and adrenal metastases (all p < 0.05) and a higher rate of multiple distant metastases. Multivariate logistic regression analysis showed that liver metastasis was negatively and independently associated with prolonged PFS (adjusted odds ratio = 0.246 [95% CI: 0.067-0.908], p = 0.035). The median overall survival of the PFS >36 months group was 46.0 months and that of the PFS ≤36 months group was 22.9 months (log-rank test, p < 0.001). We found that EGFR-mutated NSCLC patients receiving first-line afatinib were prone to shorter PFS if they had distant organ metastasis, especially liver metastasis.

Patterns of failure after radiosurgery for WHO grade 1 or imaging defined meningiomas: Long-term outcomes and implications for management

BackgroundWe analyzed long-term control and patterns of failure in patients with World Health Organization Grade 1 meningiomas treated with definitive or postoperative stereotactic radiosurgery at the authors’ affiliated institution. Methods96 patients were treated between 2004 and 2019 with definitive (n = 57) or postoperative (n = 39) stereotactic radiosurgery. Of the postoperative patients, 17 were treated adjuvantly following subtotal resection and 22 were treated as salvage at time of progression. Patients were treated to the gross tumor alone without margin or coverage of the dural tail to a median dose of 15 Gy. Median follow up was 7.4 years (inter-quartile range 4.8–11.3). Local control, marginal control, regional control, and progression-free survival were analyzed. ResultsLocal control at 5 and 10 years was 97 % and 95 %. PFS at 5 and 10 years was 94 % and 90 % with no failures reported after 6 years. Definitive and postoperative local control were similar at 5 (95 % [82–99 %] vs. 100 %) and 10 years (92 % [82–99 %] vs. 100 %). Patients treated with postoperative SRS did not have an increased marginal failure rate (p = 0.83) and only 2/39 (5 %) experienced recurrence elsewhere in the cavity. ConclusionsStereotactic radiosurgery targeting the gross tumor alone provides excellent local control and progression free survival in patients treated definitively and postoperatively. As in the definitive setting, patients treated postoperatively can be treated to gross tumor alone without need for additional margin or dural tail coverage.

Survival and progression-free survival in patients undergoing curative resection for intrahepatic cholangiocarcinoma.

562 Background: Intrahepatic cholangiocarcinoma (iCCA) is a relatively rare but increasingly prevalent form of primary liver cancer. Surgical resection with negative margins is the mainstay of the treatment for patients with resectable-iCCA. However, given the rarity of iCCA and its low resectability rate, well-defined prognostic markers and outcomes for patients undergoing curative hepatectomy are lacking. We aimed to analyze the characteristics and outcomes of patients undergoing liver resection for iCCA. Methods: All consecutive patients with confirmed iCCA who underwent hepatectomy between 7/2006-3/2023 at our institution were included. Patients who received neoadjuvant therapy were excluded. Demographic, clinical, radiological, histopathological, recurrence, and survival data were collected. Overall survival was calculated from the date of liver resection to the date of death or last clinical encounter. Continuous variables are reported as median and interquartile range (IQR) 1 and IQR3, and categorical variables as counts and percentages. Results: A total of 83 patients (43 male, 40 female) were included in the final analysis. The median age at resection was 67 years (58.0-74.0). Histologically proven liver disease was present in 30.12% and liver cirrhosis was present in 9.63% of patients. Among all patients, hypertension was present in 61.44%, diabetes mellitus in 25.30%, inflammatory bowel disease in 7.22%. The median tumor size was 4.4 cm (3.0-6.2). Tumor histologic grade was 55.42% moderately differentiated tumor, 37.3% poorly differentiated tumor, and 7.22% well differentiated tumor. Of all patients, 37.66% had lymph node invasion, 35.61% had perineural invasion, and 30.76% had vascular invasion on liver histology. Positive surgical margins were present in 20.73% of patients. The duration from liver resection to the last follow-up or death was 1.6 years (0.80-3.20). The 1-, 3-, and 5-year recurrence-free survival rates were 72.78, 34.95, and 15.88% respectively. The 1-, 3-, and 5-year overall survival rates were 90.9%, 65.9, 44.2%, respectively. Advanced iCCA stage at diagnosis ( p&lt;0.001), presence of lymph node metastasis ( p=0.03), vascular invasion ( p=0.02), and age&lt;50 ( p=0.01) were associated with significantly worse overall survival. There was no statistically significant survival difference between patients with concurrent liver disease and those without (6.88 vs 4.35 years, p=0.46.). Conclusions: Our results demonstrate that iCCA carries a substantial risk of recurrence despite curative resection. The presence of advanced stage at diagnosis, lymph node involvement, vascular invasion, and age&lt;50 were associated with significantly worse overall survival. Liver disease had no significant effect on the survival outcomes. Predictive markers of recurrence and survival in patients vary in the literature and remain to be validated.

Intratumoral and peritumoral CT radiomics in predicting prognosis in patients with chondrosarcoma: a multicenter study

ObjectiveTo evaluate the efficacy of the CT-based intratumoral, peritumoral, and combined radiomics signatures in predicting progression-free survival (PFS) of patients with chondrosarcoma (CS).MethodsIn this study, patients diagnosed with CS between January 2009 and January 2022 were retrospectively screened, and 214 patients with CS from two centers were respectively enrolled into the training cohorts (institution 1, n = 113) and test cohorts (institution 2, n = 101). The intratumoral and peritumoral radiomics features were extracted from CT images. The intratumoral, peritumoral, and combined radiomics signatures were constructed respectively, and their radiomics scores (Rad-score) were calculated. The performance of intratumoral, peritumoral, and combined radiomics signatures in PFS prediction in patients with CS was evaluated by C-index, time-dependent area under the receiver operating characteristics curve (time-AUC), and time-dependent C-index (time C-index).ResultsEleven, 7, and 16 features were used to construct the intratumoral, peritumoral, and combined radiomics signatures, respectively. The combined radiomics signature showed the best prediction ability in the training cohort (C-index, 0.835; 95%; confidence interval [CI], 0.764–0.905) and the test cohort (C-index, 0.800; 95% CI, 0.681–0.920). Time-AUC and time C-index showed that the combined signature outperformed the intratumoral and peritumoral radiomics signatures in the prediction of PFS.ConclusionThe CT-based combined signature incorporating intratumoral and peritumoral radiomics features can predict PFS in patients with CS, which might assist clinicians in selecting individualized surveillance and treatment plans for CS patients.Critical relevance statementDevelop and validate CT-based intratumoral, peritumoral, and combined radiomics signatures to evaluate the efficacy in predicting prognosis of patients with CS.Key points• Reliable prognostic models for preoperative chondrosarcoma are lacking.• Combined radiomics signature incorporating intratumoral and peritumoral features can predict progression-free survival in patients with chondrosarcoma.• Combined radiomics signature may facilitate individualized stratification and management of patients with chondrosarcoma.Graphical

Applying the en-bloc technique in corpus callosum glioblastoma surgery contributes to maximal resection and better prognosis: a retrospective study.

Corpus callosum glioblastoma (ccGBM) is a specific type of GBM and has worse outcomes than other non-ccGBMs. We sought to identify whether en-bloc resection of ccGBMs based on T2-FLAIR imaging contributes to clinical outcomes and can achieve a satisfactory balance between maximal resection and preservation of neurological function. A total of 106 adult ccGBM patients (including astrocytoma, WHO grade 4, IDH mutation, and glioblastoma) were obtained from the Department of Neurosurgery in Nanfang Hospital between January 2008 and December 2018. The clinical data, including gender, age, symptoms, location of tumor, involvement of eloquent areas, extent of resection (EOR), pre- and postoperative Karnofsky Performance Status (KPS) scales, and National Institute of Health stroke scale (NIHSS) scores were collected. Propensity score matching (PSM) analysis was applied to control the confounders for analyzing the relationship between the en-bloc technique and EOR, and the change in the postoperative KPS scales and NIHSS scores. Applying the en-bloc technique did not negatively affect the postoperative KPS scales compared to no-en-bloc resection (P = 0.851 for PSM analysis) but had a positive effect on preserving or improving the postoperative NIHSS scores (P = 0.004 for PSM analysis). A positive correlation between EOR and the en-bloc technique was identified (r = 0.483, P < 0.001; r = 0.720, P < 0.001 for PSM analysis), indicating that applying the en-bloc technique could contribute to enlarged maximal resection. Further survival analysis confirmed that applying the en-bloc technique and achieving supramaximal resection could significantly prolong OS and PFS, and multivariate analysis suggested that tumor location, pathology, EOR and the en-bloc technique could be regarded as independent prognostic indicators for OS in patients with ccGBMs, and pathology, EOR and the en-bloc technique were independently correlated with patient's PFS. Interestingly, the en-bloc technique also provided a marked reduction in the risk of tumor recurrence compared with the no-en-bloc technique in tumors undergoing TR, indicating that the essential role of the en-bloc technique in ccGBM surgery (HR: 0.712; 95% CI: 0.535-0.947; P = 0.02). The en-bloc technique could contribute to achieving an enlarged maximal resection and could significantly prolong overall survival and progression-free survival in patients with ccGBMs.

Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial

No prospective data were available prior to 2021 to inform selection between combination BRAF and MEK inhibition versus dual blockade of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) as first-line treatment options for BRAFV600-mutant melanoma. SECOMBIT (NCT02631447) was a randomized, three-arm, noncomparative phase II trial in which patients were randomized to one of two sequences with immunotherapy or targeted therapy first, with a third arm in which an 8-week induction course of targeted therapy followed by a planned switch to immunotherapy was the first treatment. BRAF/MEK inhibitors were encorafenib plus binimetinib and checkpoint inhibitors ipilimumab plus nivolumab. Primary outcome of overall survival was previously reported, demonstrating improved survival with immunotherapy administered until progression and followed by BRAF/MEK inhibition. Here we report 4-year survival outcomes, confirming long-term benefit with first-line immunotherapy. We also describe preliminary results of predefined biomarkers analyses that identify a trend toward improved 4-year overall survival and total progression-free survival in patients with loss-of-function mutations affecting JAK or low baseline levels of serum interferon gamma (IFNy). These long-term survival outcomes confirm immunotherapy as the preferred first-line treatment approach for most patients with BRAFV600-mutant metastatic melanoma, and the biomarker analyses are hypothesis-generating for future investigations of predictors of durable benefit with dual checkpoint blockade and targeted therapy.

Multi-parameter MRI radiomic features may contribute to predict progression-free survival in patients with WHO grade II meningiomas.

This study aims to investigate the potential value of radiomic features from multi-parameter MRI in predicting progression-free survival (PFS) of patients with WHO grade II meningiomas. Kaplan-Meier survival curves were used for survival analysis of clinical features. A total of 851 radiomic features were extracted based on tumor region segmentation from each sequence, and Max-Relevance and Min-Redundancy (mRMR) algorithm was applied to filter and select radiomic features. Bagged AdaBoost, Stochastic Gradient Boosting, Random Forest, and Neural Network models were built based on selected features. Discriminative abilities of models were evaluated using receiver operating characteristics (ROC) and area under the curve (AUC). Our study enrolled 164 patients with WHO grade II meningiomas. Female gender (p=0.023), gross total resection (GTR) (p<0.001), age <68 years old (p=0.023), and edema index <2.3 (p=0.006) are protective factors for PFS in these patients. Both the Bagged AdaBoost model and the Neural Network model achieved the best performance on test set with an AUC of 0.927 (95% CI, Bagged AdaBoost: 0.834-1.000; Neural Network: 0.836-1.000). The Bagged AdaBoost model and the Neural Network model based on radiomic features demonstrated decent predictive ability for PFS in patients with WHO grade II meningiomas who underwent operation using preoperative multi-parameter MR images, thus bringing benefit for patient prognosis prediction in clinical practice. Our study emphasizes the importance of utilizing advanced imaging techniques such as radiomics to improve personalized treatment strategies for meningiomas by providing more accurate prognostic information that can guide clinicians toward better decision-making processes when treating their patients' conditions effectively while minimizing risks associated with unnecessary interventions or treatments that may not be beneficial.

Effect of the thyroid transcription factor 1 expression and treatment discontinuation due to adverse events on progression-free survival in patients with advanced non-squamous non-small cell lung cancer treated with pembrolizumab plus pemetrexed and platinum chemotherapy: a Japanese four-hospital, retrospective study.

Although a significant improvement in progression-free survival (PFS) has been reported in the thyroid transcription factor 1 (TTF-1) positive patients under treatment for non-squamous non-small cell lung cancer (NS-NSCLC), including immune checkpoint inhibitor therapy, the association between TTF-1 expression and adverse event occurrence remains unclear. Therefore, this study investigated the impact of TTF-1 and its adverse events on PFS during pembrolizumab plus pemetrexed and platinum chemotherapy for NS-NSCLC. Patients who received the pembrolizumab plus pemetrexed and platinum chemotherapy from 1/1/2018 to 12/31/2022 and whose TTF-1 expression was measured were included in the study. This was a retrospective study conducted using electronic medical records. The mean age of the 79 patients was 67.5 ± 8.4 years, with 75.95% patients being male. Among them, 59.49% were TTF-1 positive. PFS comparison between TTF-1-positive and -negative patients showed a trend toward longer PFS for TTF-1 positive patients, though the results were statistically insignificant (P = 0.190). Proportional hazards analysis indicated significant PFS extension from treatment interruption, as adverse events related to cancer therapy stopped (hazard ratio [HR] = 0.32, P = 0.005) and the number of anticancer agents used (HR = 0.01, P < 0.001). Additionally, pembrolizumab plus pemetrexed and platinum chemotherapy for TTF-1-positive NS-NSCLC significantly extended PFS after treatment discontinuation as related adverse events stopped (827 vs. 210 days, P = 0.021). Measurement of TTF-1 may accordingly serve as a predictor of treatment response to the pembrolizumab plus pemetrexed and platinum chemotherapy. It may also be a predictor of patient prognosis when treatment is discontinued due to related adverse events.

Tyrosine kinase inhibitors in patients with neuroendocrine neoplasms: a systematic literature review.

Several tyrosine kinase receptors inhibitors (TKIs) have demonstrated antiproliferative effects in well-differentiated neuroendocrine tumors (NETs). We aimed to summarize and appraise the current evidence of the efficacy of TKIs in patients with different types of NETs. We performed a systematic review of clinical trials of TKIs in patients with advanced gastroenteropancreatic or lung NETs (PROSPERO registration number: CRD42024507379). Population characteristics, efficacy, and safety results were summarized by type of NET. Twenty-eight studies were eligible, totaling 2284 patients. While sunitinib remains the only Food and Drug Administration-approved TKI in patients with NETs (for patients with pancreatic well-differentiated NETs), recent placebo-controlled randomized trials have demonstrated improved response rates and progression-free survival for patients with progressive and pre-treated well-differentiated pancreatic (cabozantinib or surufatinib) or gastrointestinal (GI) NETs (pazopanib, cabozantinib, or surufatinib). There is limited evidence to support the use of a TKI in patients with lung or grade 3 NETs. The toxicity associated with TKIs follows a class effect, with a significant proportion of patients experiencing fatigue, hypertension, and hand-foot skin reactions. TKIs are effective therapies in patients with pancreatic or GI well-differentiated NETs and should be part of the therapeutical sequencing of these patients.

Clinical and pathological characteristics and expression of related molecules in patients with airway disseminated lung adenocarcinoma

Abstract Objective Lung adenocarcinoma exhibits diverse genetic and morphological backgrounds, in addition to considerable differences in clinical pathology and molecular biological characteristics. Among these, the phenomenon of spread through air space (STAS), a distinct mode of lung cancer infiltration, has rarely been reported. Therefore, this study aimed to explore the relationship between STAS tumor cells and the clinical and molecular characteristics of patients with lung adenocarcinoma, as well as their impact on prognosis. Methods This study included 147 patients who were diagnosed with lung adenocarcinoma at the Inner Mongolia Autonomous Region Cancer Institute between January 2014 and December 2017. Surgical resection specimens were retrospectively analyzed. Using univariate and multivariate Cox analyses, we assessed the association between STAS and the clinicopathological features and molecular characteristics of patients with lung adenocarcinoma. Furthermore, we investigated the effects on patient prognosis. In addition, we developed a column–line plot prediction model and performed internal validation. Results Patients with positive STAS had a significantly higher proportion of tumors with a diameter ≥2 cm, with infiltration around the pleura, blood vessels, and nerves, and a pathological stage &gt;IIB than in STAS-negative patients (P &lt; 0.05). Cox multivariate survival analysis revealed that clinical stage, STAS status, tumor size, and visceral pleural invasion were independent prognostic factors influencing the 5-year progression-free survival in patients with lung adenocarcinoma. The predictive values and P values from the Hosmer-Lemeshow test were 0.8 and 0.2, respectively, indicating no statistical difference. Receiver operating characteristic curve analysis demonstrated areas under the curve of 0.884 and 0.872 for the training and validation groups, respectively. The nomogram model exhibited the best fit with a value of 192.09. Conclusions Clinical stage, pleural invasion, vascular invasion, peripheral nerve invasion, tumor size, and necrosis are independent prognostic factors for patients with STAS-positive lung adenocarcinoma. The nomogram based on the clinical stage, pleural invasion, vascular invasion, peripheral nerve invasion, tumor size, and necrosis showed good accuracy, differentiation, and clinical practicality.

INFLUENCE OF THE METABOLIC SYNDROME ON THE QUALITY AND LIFETIME OF PROSTATE CANCER PATIENTS WITH THE DEVELOPMENT OF BONE MEATSTASES

Summary. Aim: to determine the quality of life, progression-free (PFS) and overall survival (OS) of patients with localized prostate cancer (PC) with existing metabolic syndrome (MS) and the development of bone metastases (BM) after radical prostatectomy (RP). Objects and methods: а retrospective clinical study diagnosed in 35 patients with localized PC and development of BM. Patients with a moderate (Grade group 2.3) and high (Grade group 4.5) risk of disease progression are divided into subgroups based on the presence and absence of MS. Analyzed indicators of recurrence-free and overall survival; the quality of life of patients was assessed using the QLQ-C30 questionnaire. Results: among 35 study participants after RP with the development of BM – 27 (77.1%) have MS, 8 (22.9%) haven’t features of MS. MS was found in 25.9% of patients with GG 2.3 and 74.1% of GG 4.5; the absence of MS was observed in 62.5 and 37.5% of patients, respectively. The median progression-free survival of patients with РС GG 2.3 and existing MS was 13.3% lower compared to the rate of patients without MS; in patients with PС GG 4.5 – by 10.5%. They also noted a decrease in the median overall survival of patients with MS compared to the rate of patients without MS by 6.4 (GG 2.3) and by 23.9% (GG 4.5). The data of the study demonstrate a decrease in the general health status of patients before RP and at the time of development of BM with existing MS by 27.6%, without MS by 5.5%. Decrease in quality-of-life indicators was noted in the following indicators: social status, fatigue, lack of appetite and the presence of financial difficulties. Conclusion: the investigation analysis showed that presence of metabolic syndrome influence on decreasing quality of life, progression-free survival and overall survival rates in patients with prostate cancer.

Updates of primary central nervous system lymphoma.

Lymphoma occurring in the central nervous system is considered primary central nervous system lymphoma (PCNSL), usually without systematic lesions. Over the last few decades, a deep understanding of PCNSL has been lacking due to the low incidence rate, and the overall survival and progression-free survival of patients with PCNSL are lower than those with other types of non-Hodgkin lymphoma. Recently, there have been several advancements in research on PCNSL. Advances in diagnosis of the disease are primarily reflected in the promising diagnostic efficiency of novel biomarkers. Pathogenesis mainly involves abnormal activation of nuclear factor kappa-B signaling pathways, copy number variations, and DNA methylation. Novel therapies such as Bruton's tyrosine kinase inhibitors, immunomodulatory drugs, immune checkpoint inhibitors, and phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors are being evaluated as possible treatment options for PCNSL, especially for relapsed/refractory (R/R) cases. Several clinical trials also indicated the promising feasibility and efficacy of chimeric antigen receptor T-cell therapy for selected R/R PCNSL patients. This review focuses on discussing recent updates, including the diagnosis, pathogenesis, and novel therapy of PCNSL.

Cost-effectiveness analysis of continuing bevacizumab plus chemotherapy versus chemotherapy alone after first progression of metastatic colorectal cancer.

Continuation of bevacizumab plus second-line chemotherapy has significantly improved overall and progression-free survival in patients with metastatic colorectal cancer (mCRC). However, the cost-effectiveness of such high cost therapy is still uncertain in China; so this analysis was performed to evaluate the cost-effectiveness of these treatment options from the Chinese health care system perspective. A cost-effectiveness analysis was conducted using data from the ML18147 trial (ClinicalTrials.gov identifier NCT00700102) by modeling a partitioned survival model. Main evaluation indicators were quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) with a willingness to pay (WTP) threshold of $38,201 per QALY. One-way and probabilistic sensitivity analyses were conducted to assess the robustness and stability of the model. Subgroup and scenario analyses were also performed to make our study more relevant. Bevacizumab plus chemotherapy increased 0.12 QALYs and an incremental cost of $22,761.62 compared with chemotherapy, resulting in an ICER of $188,904.09 per QALY. The model was most sensitive to the utility of progression-free survival and the cost of bevacizumab. Compared with chemotherapy, bevacizumab plus chemotherapy had a 0% cost-effectiveness probability, and no cost-effectiveness in subgroups at the WTP threshold of $38,201 per QALY. The scenario analysis found that bevacizumab biosimilar gained an ICER of $126,397.38 per QALY when assuming the cost of drugs was calculated at the most affordable price. At the WTP threshold of $38,201 per QALY, continuation of bevacizumab plus chemotherapy is unlikely considered cost-effective for patients after first progression of mCRC.

Dexamethasone and overall survival and progression free survival in patients with newly diagnosed glioblastoma: a meta-analysis.

Glioblastomas, the most common primary malignant brain tumors in adults, still hold poor prognosis. Corticosteroids, such as dexamethasone, are usually prescribed to reduce peritumoral edema and limit neurological symptoms, although potential detrimental effects of these drugs have been described. The present meta-analysis aimed to explore the association of dexamethasone with overall survival (OS) and progression free survival (PFS) in patients with newly diagnosed glioblastoma. PubMed, Cochrane Library, Embase, and ClinicalTrials.gov were searched for pertinent studies following the Preferred Reporting Items of Systematic Review and Meta-Analysis checklist. Pooled multivariable-adjusted hazard ratios (HR) for OS and PFS and their associated 95% confidence intervals (CIs) were calculated using the random-effects model and the heterogeneity among studies was assessed using I2. The quality of evidence was assessed using the GRADE criteria. Seven studies were included, pooling data of 1,257 patients, with age varying from 11 to 81 years. Glioblastoma patients on pre- or peri-operative dexamethasone were associated with a significantly poorer overall survival (HR: 1.33, 95% CI: 1.15, 1.55; 7 studies; I2: 59.9%) and progression free survival (HR: 1.77, 95% CI: 1.05, 2.97; 3 studies; I2: 71.1%) compared to patients not on dexamethasone. The quality of evidence was moderate for overall survival and low for progression free survival. Dexamethasone appeared to be associated with poor survival outcomes of glioblastoma patients.