Adjuvant Treatment For Patients Research Articles

Accuracy of pre-operative tumor size assessment compared to final pathology and frequency of adjuvant treatment in patients with FIGO 2018 stage IB2 cervical cancer

ObjectiveThe primary aim of our study was to compare tumor size assessment by pre-operative evaluation (physical examination and/or imaging) with tumor size on final pathology. As a secondary outcome, we...

Efficacy of cisplatin-gemcitabine-durvalumab in patients with advanced biliary tract cancer experiencing early vs late disease relapse after surgery: a large real-life worldwide population.

In the TOPAZ-1, patients with biliary tract cancers (BTC) and recurrence within 6 months after surgery were excluded, even if this event is frequently observed in clinical practice. Our study aimed to assess if the efficacy of cisplatin-gemcitabine-durvalumab (CGD) in this population is comparable to that reported in the phase 3 trial. The study cohort included patients with BTC who underwent surgery on the primary tumor, experienced disease recurrence occurring ≤6 months or >6 months after surgery or after the end of adjuvant therapy and started CGD. The primary objectives were overall survival (OS) and progression free survival (PFS). A total of 178 patients were enrolled. No significant differences were observed between early and late relapse groups in OS (23.4 months vs not reached; HR 1.26; 95% CI, 0.67-2.37; P = .45) and PFS [7.0 months vs 9.8 months; HR 1.3(95% CI, 0.9-2.1) P = .13]. Overall response rate and disease control rate (P = .33 and P = .62) were comparable between the 2 groups, as the overall safety profile. In addition, we compared survival outcomes between the selected population and a historical cohort of patients with BTC treated with cisplatin-gemcitabine (CG) and found that despite the absence of statistical significance, CGD showed an outcome trend compared with CG regardless of the time of recurrence after surgery or adjuvant chemotherapy [(CG ≤ 6 vs CGD ≤ 6 months: HR 0.59, 95%CI, 0.35-1.01, P = .05; HR 0.70; 95%CI, 0.46-1.06, P = .09, OS and PFS, respectively) and (CG > 6 vs. CGD > 6 months: HR 0.50; 95%CI, 0.29-0.88, P = 0.0165; HR 0.54; 95%CI, 0.35-0.84, P = .0068, OS and PFS, respectively)]. Our analysis suggests that CGD retains its efficacy independently of the timing of relapse after surgery or completion of adjuvant treatment in patients with advanced BTC.

Cost-effectiveness of pembrolizumab as an adjuvant treatment of renal cell carcinoma post-nephrectomy in Switzerland

Aims Pembrolizumab has demonstrated significantly prolonged disease-free survival and overall survival (OS) among adult patients post-nephrectomy who have an intermediate-high risk, high-risk, or M1 stage with no evidence of disease (M1 NED) renal cell carcinoma (RCC) with clear cell component. The aim of this study was to evaluate the cost-effectiveness of pembrolizumab for patients with RCC post-nephrectomy versus observation in Switzerland. Materials and methods A previously published Markov model was adapted for the Swiss setting to estimate the cost-effectiveness of adjuvant pembrolizumab versus observation from the Swiss statutory health insurance perspective. Transition probabilities between model states were estimated using survival curves from KEYNOTE-564 (data cut-off: 14 June 2021). Outcomes included costs (2022 Swiss francs [CHF]), quality-adjusted life-years (QALYs), and life-years (LYs), measured over a lifetime horizon. Costs included drug acquisition and administration for adjuvant and subsequent therapy. Both costs and effectiveness were discounted at 3.0% annually. Cost-effectiveness was evaluated at a hypothetical willingness-to-pay (WTP) threshold of CHF 100,000. Sensitivity was assessed through scenario analyses as well as deterministic and probabilistic sensitivity analyses. Results Over a lifetime horizon, the total incremental cost for pembrolizumab versus observation was CHF 59,089, providing incremental gains of 0.90 QALYs (1.07 LYs); the incremental cost-effectiveness ratio was CHF 65,299/QALY. Pembrolizumab was deemed cost-effective versus observation, with a 69.9% probability of cost-effectiveness. Limitations A more recent interim analysis data cut from KEYNOTE-564 with median follow up of 57.2 months has since been published; however, these were not available at the time of analysis. It would likely have minimal impact on transition probabilities from disease-free, and the current approach remains conservative for predicting OS for pembrolizumab. Conclusions As an adjuvant treatment of RCC post-nephrectomy, pembrolizumab was found to be cost-effective versus observation in Switzerland at a WTP threshold of CHF 100,000/QALY. Policy makers should consider pembrolizumab as an adjuvant treatment for patients with RCC post-nephrectomy when making decisions regarding resource allocation.

The efficacy and safety of CDK4/6 inhibitors combined with endocrine therapy versus endocrine therapy alone in the adjuvant treatment of patients with high-risk invasive HR+/HER2-early breast cancer: A comprehensive updated meta-analysis of randomized clinical trials

BackgroundThis paper aimed to evaluate the effectiveness of incorporating CDK 4/6 inhibitors (CDK4/6i) into ET for the adjuvant treatment of HR + HER2-resected early-stage breast cancer (ESBC) patients, employing meta-analysis. MethodsIn this paper, we compiled randomized clinical trials focusing on CDK4/6i used in the adjuvant treatment of high-risk invasive HR-positive and HER2-ESBC patients. A meta-analysis was performed in line with the PRISMA guidelines. ResultsWe identified four clinical trials that met our inclusion criteria and were published between 2020 and 2024. These trials involved a combined sample size of 17,749 patients diagnosed with breast cancer. The data obtained from the pooled analysis revealed a remarkable beneficial trend in terms of invasive disease-free survival (iDFS) for the use of ET in combination with CDK4/6i compared to the group receiving ET alone (HR = 0.81, 95 % CI: 0.67–0.98, p = 0.03). Of note, CDK4/6 inhibitors demonstrated a notably beneficial effect in both grade 2 (HR = 0.69, 95 % CI: 0.59–0.81, p < 0.001) and grade 3 (HR = 0.76, 95 % CI: 0.65–0.89, p < 0.001). Significant improvements were noted in terms of distant relapse-free survival (dRFS) in the groups treated with abemaciclib and ribociclib (HR = 0.65, 95 % CI: 0.56–0.76, p < 0.001; HR = 0.72, 95 % CI: 0.58–0.89, p = 0.003, respectively). CDK4/6i didn't yield a statistically significant difference in overall survival (OS) (HR = 0.96, 95 % CI: 0.77–1.19, p = 0.69). The use of CDK4/6i with ET was associated with an increased risk of adverse events, particularly anemia and neutropenia, compared with ET alone (OR = 9.12, 95 % CI = 5.04–16.48, p < 0.001). ConclusionThe findings of this paper demonstrate a significant improvement in iDFS when ET is combined with CDK4/6i, compared to ET alone. Specifically, treatments with abemaciclib and ribociclib showed notable enhancements in dRFS.

Postoperative Complications of Upfront Ovarian Cancer Surgery and Their Effects on Chemotherapy Delay.

Extensive surgery on advanced-stage epithelial ovarian cancer is associated with increased postoperative morbidity, which may cause a delay in or omission of chemotherapy. We examined postoperative complications and their effects on adjuvant treatment in patients undergoing primary debulking surgery (PDS). Stage IIIC-IV epithelial ovarian cancer patients who underwent PDS between January 2013 and December 2020 were included. Patients were divided into two groups according to the radicality of the operation, i.e., extensive or standard surgery, and their outcomes were compared. In total, 172 patients were included; 119 underwent extensive surgery, and 53 had standard surgery. Clavien-Dindo grade 3-5 (CDC 3+) complications were detected in 41.2% of patients after extensive operations and in 17% after standard surgery (p = 0.002). The most common CDC 3+ complication was pleural effusion. Despite the difference in the complication rates, the delay in chemotherapy did not differ between the extensive and standard groups (p = 0.98). Complications are common after PDS. Extensive surgery increases the complication rate, but most complications can be treated effectively; therefore, a delay in adjuvant treatment is rare.

Real-world evaluation of nivolumab utilization in adjuvant treatment of localized muscle-invasive urothelial carcinoma

IntroductionIn 2022, nivolumab was granted marketing authorization for adjuvant treatment in patients at high-risk of recurrence following surgery for localized invasive muscle urothelial carcinoma, who express PD-L1 on the operative specimen. We aimed to investigate its real-world utilization. Materials and methodsOur bicentric real-world study, conducted at Foch Hospital and Georges-Pompidou European Hospital between July 2022 and January 2024, included patients who underwent surgery for urothelial carcinoma or were referred for adjuvant nivolumab treatment at these centers. ResultsA total of 200 patients underwent surgery during the study period, of whom 70 met the high-risk criteria, with 46% of these patients not receiving adjuvant treatment due to ineligibility. Our survival outcomes among patients treated by nivolumab are consistent with the results of the CheckMate 274 study (Bajorin et al. N Engl J Med. 2021). Our study population was older and frailer than that of the study cohort, with a mean age of 69years. Significant PD-L1 expression was observed in 66% of the tested patients. The median disease-free survival was 11.34months in patients who received neoadjuvant chemotherapy followed by surgery and adjuvant nivolumab. Nivolumab was generally well-tolerated, but 25% of patients discontinued it due to toxicity. Our initial data on treatments for recurrence after adjuvant nivolumab highlighted the effectiveness of conventional chemotherapy (cisplatin or carboplatin combined with gemcitabine) and targeted chemotherapy (enfortumab vedotin). ConclusionOur real-world data align with existing literature regarding adjuvant nivolumab in localized invasive muscle urothelial carcinoma. Level of evidence3.

Cost-Utility Analysis of Adjuvant Olaparib for Germline BRCA1/2-Mutated, High-Risk HER2-Negative Early Breast Cancer in Spain.

Here we estimate the cost-effectiveness of olaparib in the Spanish National Health Service (SNHS) as adjuvant treatment of early germline mutations in the BRCA1/2 genes (gBRCAm) HER2-negative (HER2neg) breast cancer (BC) with high risk of recurrence. A semi-Markov model was adapted to the Spanish healthcare setting, using the perspective of the SNHS, and a lifetime horizon. Two scenarios were compared: receiving olaparib versus standard of care (SoC) treatment. The model comprised five health states and included the clinical results of the OlympiA trial, along with the direct healthcare costs associated with the use of early BC and subsequent treatment resources (€2023). A discount rate of 3% was applied for future cost and quality-of-life outcomes. A probabilistic sensitivity analysis (PSA) was carried out. The introduction of olaparib as adjuvant treatment for patients with early gBRCAm HER2neg BC with high risk of recurrence could involve an incremental cost of €44,273 and €50,164, with an improvement of 1.14 and 1.28 quality-adjusted life years (QALYs) for hormone receptor-positive (HR+) and triple-negative (TN) patients, respectively. Therefore, adjuvant olaparib could be cost-effective for early gBRCAm HER2neg BC, with an incremental cost-effectiveness ratio of €38,839/QALY and €39,084/QALY for HR+ and TN patients, respectively. The results from the PSA showed that 75.7% and 82.2% of the simulations fell below the €60,000/QALY threshold. Olaparib as adjuvant treatment could be cost-effective in gBRCAm patients with early HER2neg BC in Spain.

Trastuzumab emtansine induced hyponatremia in breast cancer - A case report.

Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), approved for use as an adjuvant treatment for patients with residual disease after neoadjuvant chemotherapy and antihuman epidermal growth factor receptor 2 (HER-2) therapy and in metastatic HER-2-positive breast cancer. Previous studies have shown that T-DM1 has a favorable safety profile, with few high-grade toxicities reported so far. We describe a patient who developed profound hyponatremia-which has not been reported previously-following treatment with adjuvant T-DM1 for HER-2+ breast cancer.

Redefining Recovery: The Transformative Impact of the ALINA Trial on Adjuvant Therapy for ALK-Positive Non-Small Cell Lung Cancer.

On April 18, 2024, the Food and Drug Administration approved alectinib as an adjuvant treatment for patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) after tumor resection. This approval was grounded in the outcomes of the ALINA trial, which demonstrated that alectinib significantly enhances disease-free survival compared to traditional platinum-based chemotherapy in the adjuvant setting. The ALINA trial is notable not just for advancing ALK tyrosine kinase inhibitors (TKIs) into the adjuvant setting but also for its innovative approach of comparing them to adjuvant chemotherapy, distinguishing it from other landmark trials.

Health and Economic Outcomes of Pembrolizumab in the Treatment of Metastatic Non-small Cell Lung Cancer (mNSCLC) and Melanoma in Italy.

In Italy, the management of metastatic non-small cell lung cancer and melanoma leads to significant healthcare challenges, necessitating cost-effective treatment strategies and offering valuable insights for healthcare policymakers and stakeholders. This study was designed to assess the costs, quality-adjusted life-years (QALYs) and disability-adjusted life-years (DALYs) associated with the health and economic outcomes of (1) pembrolizumab-combined chemotherapy administered as a first-line treatment for metastatic non-squamous and squamous non-small cell lung cancer (NSCLC) where the tumour presents with a programmed death-ligand 1 expression level <50% and of (2) adjuvant pembrolizumab treatment for stage III melanoma. Three cost-effectiveness models developed by MSD were investigated for each treatment indication. A unique model was built to assess the overall effect of pembrolizumab versus chemotherapy or watchful waiting in patients with lung cancer or melanoma, respectively. Theoretical cohorts of patients with metastatic squamous and non-squamous NSCLC were followed over time using a partitioned survival model with weekly cycles. A weekly cycle Markov model was employed for melanoma. The analysis was conducted from the Italian National Health Service perspective, considering a time horizon of 40 years (lifetime). A single closed cohort of treatable patients was followed over time for each indication (4000, 7000 and 900 for NSCLC squamous, non-squamous and melanoma, respectively). The costs evaluated included those for adverse drug events, non-drug disease management, subsequent treatment and terminal care. Drug acquisition and administration costs were excluded. For each treatment indication assessed, pembrolizumab produced downstream direct cost offsets (- €122,498,568, -€133,369,076 and -€32,993,242 for NSCLC squamous, non-squamous and melanoma indications, respectively), increased quality of life (+2088, +5317 and +2307 QALYs for NSCLC squamous, non-squamous and melanoma indications, respectively) and reduced disability (-2658, -7202 and -3029 DALYs for NSCLC squamous, non-squamous and melanoma indications, respectively). Across indications, the total cost offsets of pembrolizumab were -€288,860,885, with 9712 QALYs gained and 12,889 DALYs avoided. The analysis demonstrated that, compared with chemotherapy, pembrolizumab is more cost effective in Italy as a first-line treatment in patients with metastatic squamous or non-squamous NSCLC and, if compared with watchful waiting, as adjuvant treatment in patients with stage III melanoma. The present analysis suggested that pembrolizumab use could lead to important health benefits for patients while offsetting a portion of cancer care costs.

Evaluating the Prognostic Role of the PAM50 Signature and Selected Immune-Related Signatures for Recurrence in Patients With T1abN0 Breast Cancer

BackgroundDe-escalation of adjuvant treatment in patients with T1abN0 breast cancer is discussed internationally. Identification of new prognostic factors in these patients may assist this de-escalation. The PAM50 signature and tumor inflammation signature (TIS), Programmed Cell Death Protein 1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) signatures are possible prognostic factors for recurrence. Materials and MethodsDanish patients with T1abN0 breast cancer diagnosed between 2007-2016 were identified, the NanoString Breast Cancer 360 Panel was performed on tissue samples from cases with recurrence matched 1:1 with controls without recurrence (n = 234). The association between gene signatures and recurrence was analyzed with conditional logistic regression. ResultsPatients with the basal-like subtype had higher values of TIS, PD-1 and PD-L1 scores compared with other subtypes. Patients with higher PD-L1 score had significantly lower odds of recurrence (odds ratio [OR] 0.61, P = .01). Likewise, an increased TIS score was associated to lower, but nonsignificant odds of recurrence (OR 0.76, P = .07). Patients with human epidermal growth factor receptor 2 (HER2)-enriched subtype had significantly higher odds of recurrence compared with patients with luminal A subtype (OR 4.8, P = .03). DiscussionPAM50 and immune-related signatures provide important prognostic information in patients with T1abN0 breast cancer, which may refine the risk assessment in these patients.

Personalized neoantigen-pulsed autologous dendritic cells vaccine as an adjuvant treatment for patients with newly-diagnosed glioblastoma multiforme: A phase I trial.

e14025 Background: Glioblastoma Multiforme (GBM) is the most common and aggressive primary brain malignancy in adults. We herein report a phase I trial using personalized neoantigen-pulsed autologous dendritic cells (nDC) vaccine as an adjuvant treatment for patients with newly-diagnosed GBM. Methods: It is a single-center, single-arm phase I trial, enrolling patients aged 18-75 years old, with newly-diagnosed GBM and tumor resection extent ≥90%. Tumor specimens were sequenced for identification of personalized neoantigens. A total of 3-10 neoantigen peptides were loaded into DC to generate the nDC vaccine. The vaccine was administered subcutaneously for 5-6 doses at 1×10^7 cells following concomitant radiotherapy plus temozolomide. The primary objective is safety. Secondary objectives include survival outcomes and T cell immune response against the neoantigens. Results: As of Dec. 31, 2023, eleven patients completed at least one dose of vaccination and were included in the safety analysis; eight patients completed planned doses and were included in the efficacy analysis. All the patients reported Treatment-emergent adverse events (TEAEs). Most TEAEs were grade 1 or 2. One patient reported two grade 3 TEAEs: decreased white blood cell count and decreased lymphocyte count. Pyrexia was considered as treatment-related adverse event (TRAE) that was reported in two (18.2%) patients. No treatment-related deaths occurred. Among eight efficacy-assessable patients, seven (87.5%) patients kept progression-free for at least 5.4-27.3 months; one patient progressed at 10.2 months after surgery and achieved complete remission after receiving anti-PD1 plus bevacizumab therapy; compared to the baseline level, a median 15-fold (3 to 506-fold) increase of neoantigen-specific cytotoxic T cells was detected in their peripheral blood samples post-vaccination, indicating strong anti-tumor T cell responses elicited by the nDC vaccine. Conclusions: The nDC vaccine, combined with the standard treatments for GBM, was well tolerated. Initial results from this ongoing study have exhibited encouraging survival outcome of the nDC vaccine for patients with newly-diagnosed GBMs. Clinical trial information: NCT04968366 . [Table: see text]

Clinical profile and response to adjuvant treatments in patients with follicular dendritic cell sarcoma in the United States: Insights from SEER analysis.

e23537 Background: Follicular Dendritic Cell Sarcoma (FDCS) is a rare, indolent, low-grade sarcoma known for local recurrences managed primarily by surgery. The role for adjuvant therapy has not been established for either radiation or chemotherapy. We aimed to comprehensively analyze clinical and epidemiological profiles and responses to treatment in these patients. Methods: This is a retrospective study using the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Result (SEER) database. Cases of FDCS between 2001 to 2022 were identified utilizing the International Classification of Diseases for Oncology edition 3 (ICD-O-3) code 9758/3. Only adults &gt; 18 years of age and diagnosed by positive histology or cytology were included. Descriptive statistics were used to describe demographic and tumor characteristics. Logistic regression was used to identify the factors influencing survival. Kaplan-Meier method was used to plot survival based on different treatment regimens and stages. Results: A total of 168 patients with FDCS were identified, with more than 50% of the patients ≥ 50 years of age. The mean age at diagnosis was 52.6 years, 56% were female, and 74.4% were white. Most of the patients had localized disease (63.7%), 17.9% had distant disease, and the remaining had unknown stages. About 90% of the patients underwent surgery, with 41% receiving local tumor excision. In Univariate analysis, older age, and distant disease were found to have poor outcomes. Surgery, irrespective of stage, was found to improve overall Survival (Table 1). While chemotherapy and distant disease had poor outcomes in univariate analysis, they were not statistically significant in multivariate analysis. The majority of the patients who received chemotherapy alone without surgical intervention had distant disease, explaining the poor outcome seen in univariate analysis. Among 107 patients with localized disease, 41 patients (41.1%) underwent only surgery and 43 patients (40.1%) received adjuvant therapy (either chemotherapy or radiation vs both) along with surgery. 5-year overall survival was significantly lower in patients who received adjuvant therapy. (88.4% vs 68.4%, p = 0.001). Conclusions: In conclusion, FDCS has a fair overall 5-year survival with surgery alone. Patients with localized disease, who received adjuvant therapies had poor survival outcomes as compared to the surgery-only group owing to disease burden. Large prospective studies are required to properly evaluate the benefit of adding chemotherapy or radiotherapy in resectable disease.

Analysis of the sensitivity to endocrine therapy (SET) assay in the PALLAS adjuvant trial of palbociclib in HR+/HER2- breast cancer (ABCSG-42/AFT-05/BIG-14-13).

538 Background: The phase 3 PALLAS trial compared 2 years of the CDK4/6 inhibitor palbociclib with endocrine therapy of provider choice, versus endocrine therapy alone, as adjuvant treatment for patients (pts) with Stage II-III hormone receptor-positive HER2-negative (HR+/HER2-) breast cancer. The SET2,3 index adjusts the measurement of SETER/PR index of endocrine receptor-related transcriptional activity with a baseline prognostic index (BPI) derived from tumor size (T), number of involved lymph nodes (N) and gene expression levels of ESR1, PGR, ERBB2 and AURKA (RNA4 subtype score). High SET2,3 (index ≥ 2.10) represents high endocrine sensitivity with favorable prognosis. Clinical outcome results from PALLAS were previously published, and the trial now has 5-year median follow-up. Methods: Participants in PALLAS provided a tumor tissue block prior to randomization. RNA was extracted from samples with sufficient tumor tissue and cellularity (&gt;25mm2 with ≥20% cancer nuclei). SET2,3 index was measured from 300ng total RNA using the QuantiGene Plex platform (ThermoFisher, Waltham, MA) following the manufacturer’s protocol and using pre-defined quality control (QC) parameters and cut point. Results from primary tumor samples prior to systemic therapy were analyzed. Invasive disease-free survival (iDFS) was summarized with Kaplan-Meier plots using log-rank test. Cox models were adjusted for treatment arm assignment, with a treatment arm by SET index value interaction term to test for prediction of palbociclib benefit. The pre-defined level of significance was a two-sided 0.05. Results: There were 4075 pts from the total PALLAS population (N=5796) who provided a primary tumor sample that met pre-analytical requirements to perform the SET assay, from which 3388 (83%) results passed quality control, including 3093 from a sample obtained prior to receiving systemic therapy (1559 in palbociclib arm and 1534 in the control arm). SET2,3 index could not be calculated for 12 pts due to missing tumor or nodal information. There was no evidence of an interaction between treatment arm and SET indices (continuous) for iDFS: SET2,3 index interaction p=0.12 and SETER/PR index interaction p=0.92. Estimated 5-year iDFS was superior for those with high SET2,3: iDFS was 91.4% (95%CI 89.9–92.8) in 1719 (55.8%) pts with high SET2,3, versus 78.5% (95%CI 76.0–80.8) in 1362 (44.2%) pts with low SET2,3 (HR 0.38, 95%CI 0.31–0.47, p&lt;0.0001). The SETER/PR index was also significantly associated with iDFS (HR 0.70 per 0.5 units, 95%CI 0.65–0.77, p&lt;0.0001). Conclusions: There was no evidence that the SET2,3 or SETER/PR index of endocrine-related transcriptional activity predicts benefit from palbociclib treatment. SET2,3 index was strongly prognostic for pts with Stage II-III breast cancer, with excellent 5-year IDFS for pts classified as SET2,3 high. Clinical trial information: NCT02513394 .

Health-related quality of life (HRQoL) results for adjuvant alectinib vs chemotherapy in patients with resected ALK+ non-small cell lung cancer (NSCLC): Data from ALINA.

8006 Background: ALINA (NCT03456076) is a global, open-label, phase 3, randomized trial evaluating the efficacy and safety of adjuvant alectinib versus chemotherapy in patients with resected stage IB (≥4 cm)–IIIA, ALK+ NSCLC. A significant disease-free survival benefit was observed with alectinib vs chemotherapy (HR 0.24, 95% CI: 0.13–0.43, p&lt;0.0001; N=257 patients in the ITT). In the adjuvant setting, where patients have received surgery with curative intent, the impact of treatment on HRQoL is an important clinical consideration. We report HRQoL results from ALINA. Methods: Patients ≥18 years old with ECOG PS 0/1 and completely resected, stage IB–IIIA, ALK+ NSCLC (UICC/AJCC 7th edition) were randomized 1:1 to receive oral 600 mg alectinib twice-daily for 2 years, or four 21-day cycles of platinum-based chemotherapy. HRQoL was an exploratory endpoint measured using the Short Form-36 version 2 (SF-36v2) health survey, which assesses functional health and well-being across 8 domains and 2 aggregated summary scores: the physical (PCS) and mental (MCS) component summary scores. Patients completed the SF-36v2 at baseline, every 3 weeks to Week 12, then every 12 weeks until disease recurrence, withdrawal of consent, death, or Week 96 (or equivalent post-chemotherapy follow-up visit). SF-36v2 was scored using norm-based scoring relative to the 2009 US general population (mean ± standard deviation: 50 ± 10), with higher scores indicating better health. Within-group minimal important differences (MIDs) were used as benchmarks for each domain, MCS and PCS. Data cut-off: 26 June 2023. Results: Completion rates were generally high (&gt;90%) throughout the study. At baseline, most mean scores were low (&lt;50) and were similar between study arms. With alectinib, mean scores were ≥50 for the Bodily Pain, Mental Health and Vitality domains by Week 96, suggesting that patients functioned as well as the general population on these aspects. The mean change from baseline met or exceeded MIDs for 5 domains and MCS by Week 12, and exceeded MIDs for 6 domains, MCS and PCS by Week 96. In the chemotherapy arm, mean scores were low during treatment; mean change from baseline for General Health and Vitality exceeded negative MIDs, indicating worsening in these domains. Mean scores improved in the post-chemotherapy period; in the final assessment, mean scores were ≥50 for the Bodily Pain, Mental Health and Vitality domains, and MIDs were met or exceeded for MCS, PCS and 5 domains. Conclusions: Alectinib demonstrated an improvement in most domains of HRQoL by Week 12, followed by maintenance of HRQoL on all 8 domains, MCS and PCS to Week 96. With chemotherapy, HRQoL was low during treatment, but improved in the post-chemotherapy period. Together with the DFS benefit seen in ALINA, these data support alectinib as an important new adjuvant treatment for patients with resected ALK+ NSCLC. Clinical trial information: NCT03456076 .

Anthocyanins as Adjuvant Treatment for Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Recent studies suggest a role for anthocyanins in the treatment of non-alcoholic fatty liver disease (NAFLD). The purpose of the present review was to assess the effect of anthocyanins as an adjuvant treatment in patients with NAFLD. The literature search was conducted on MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), the Web of Science, and Scopus without language or time limits up to March 27, 2024. The primary outcomes included the severity of liver fibrosis and the level of liver transaminases. Secondary outcomes included obesity and lipid profile assessments. Standardized mean differences (SMDs) with 95% CIs were calculated for numerical outcomes. Five studies were included. The pooled effect sizes showed lower levels of liver fibrosis and liver transaminases in the anthocyanin group, but the difference was nonsignificant and small in size. The same result was obtained with anthropometric measurements of total cholesterol, low-density lipoprotein, and serum triglycerides, where effect sizes ranged from negligible to medium in magnitude but were all nonsignificant. The anthocyanin group showed a significantly lower body fat percentage (SMD = -0.41 (95%CI: -0.76; -0.06), P = 0.021). Currently, no evidence is available on the efficacy of anthocyanins in improving liver fibrosis or dyslipidemia in patients with NAFLD. There is limited evidence that anthocyanins can lower body fat percentages, but the effect was not reflected in the pooled results of other obesity indices. The few available clinical trials showed several limitations and variations regarding the doses of anthocyanins. Future clinical trials should avoid the limitations of the current studies and provide evidence supporting or refuting the use of anthocyanins in NAFLD patients.

A phase 3, randomized study of adjuvant rilvegostomig plus chemotherapy in resected biliary tract cancer: ARTEMIDE-Biliary01.

TPS4199 Background: Biliary tract cancer (BTC) is a rare but aggressive heterogenous group of gastrointestinal cancers that arise from the intra- or extrahepatic bile ducts (cholangiocarcinoma [CCA]) or the gallbladder (GBC). In early-stage disease following curative resection, adjuvant chemotherapy with a fluoropyrimidine- or gemcitabine-based regimen is usually recommended, however, recurrence rates remain high (e.g. in the BILCAP study, 5-year recurrence-free survival with adjuvant capecitabine was 34%). Immunotherapy is efficacious as adjuvant therapy in other cancer types. Results from the TOPAZ-1 and KEYNOTE-966 studies support combining immunotherapy and chemotherapy in advanced BTC, including in locally advanced non-metastatic disease. Furthermore, dual inhibition of programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) and the novel immune checkpoint, T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), has shown promising results across multiple tumor types without major increases in high-grade toxicity compared with PD-1 or PD-L1 inhibition alone. Rilvegostomig is an anti-PD-1/-TIGIT bi-specific monoclonal antibody that appears active and well tolerated in non-small-cell lung cancer. ARTEMIDE-Biliary01 will investigate the efficacy of rilvegostomig plus standard of care adjuvant chemotherapy in patients with BTC after curative intent resection. Methods: ARTEMIDE-Biliary01 (NCT06109779) is a Phase 3, randomized, double-blind, placebo-controlled, multicenter, global study to assess the efficacy and tolerability of rilvegostomig IV every three weeks versus placebo in combination with investigator's choice of chemotherapy (capecitabine, S-1 [tegafur/gimeracil/oteracil] or gemcitabine/cisplatin) as adjuvant treatment in patients with BTC after curative intent resection. This study will enroll approximately 750 adults with histologically confirmed adenocarcinoma of the biliary tract (intrahepatic or extrahepatic CCA or muscle-invasive GBC) after macroscopically complete resection (R0 or R1) and an ECOG PS of 0–1. Key exclusion criteria include locally advanced, unresectable, or metastatic disease at initial diagnosis and any anti-cancer therapy for BTC prior to surgery. The primary endpoint is recurrence-free survival, and the key secondary endpoint is overall survival. Additional endpoints include progression-free survival following recurrence, patient-reported tolerability, and safety. Enrollment has begun, and approximately 200 sites will be recruiting globally across Asia, Australia, Europe, North America, and South America. Clinical trial information: NCT06109779 .

Analysis of the fecal metagenome in pelvic radiation survivors with or without chronic gastrointestinal toxicity.

e24041 Background: Whole pelvis radiation therapy (WPRT) is often used as a definitive or adjuvant treatment in patients with genitourinary, gynecologic, and gastrointestinal (GI) malignancies. Irradiation of nearby bowel can cause acute and chronic GI symptoms, which can affect patients’ quality of life. Radiation therapy has been shown to alter the microbial flora and may select for pathogenic species, which may enhance toxicity. Characteristics of the fecal metagenome in patients with or without chronic GI toxicity is unknown. Severity of GI symptoms can vary between patients who receive a similar radiation dose to normal bowel; therefore, there is a critical need to evaluate the interaction of RT and microbial species in the development of toxicity. Methods: An institutional database was used to identify survivors that completed WPRT for prostate, gynecologic, and anal cancer within the last 5 years. Patients were excluded if they had evidence of recurrent disease requiring additional therapy. Eligible patients were asked to participate via telephone. Consenting patients provided a stool sample and completed a customized PRO-CTCAE form (scale 1-5) assessing chronic GI symptoms. Comprehensive shotgun metagenomics were performed on stool. Stool was sequenced using an Illumina NextSeq500. The fecal metagenome in patients with or without chronic GI symptoms were compared. Patients were dichotomized by PRO-CTCAE diarrhea score (0-1 [mild] vs ≥2 [moderate-severe]). Raw reads were processed with Kneaddata for trimming, Kracken2 for taxonomic profiling, and Bracken for abundance estimation for bacterial, fungal and viral genomes using sequences from the National Center for Bioinformatics to determine quantitative genus and species differences. For microbial diversity assessments, estimated inverse Simpson and Shannon indices were performed. Results: Fecal metagenome and PRO-CTCAE results were available for 13 survivors. Thirty percent (n = 4) of patients reported moderate to severe diarrhea. The mean age was 66 years, 38% were male, 46% received concurrent or adjuvant chemotherapy, and the mean time from completion of WPRT to stool analysis was 34 months (range 14-62 months). Conventional radiation bowel constraints were met for each patient. Several species were enriched in patients with mild GI toxicity. Notably, Akkermansia muciniphilia had the largest differential enrichment in patients with without chronic GI toxicity. Conclusions: In this cohort of patients, A. muciniphilia, a mucin-degrading bacteria that modulates the gut barrier integrity and mucin layer thickness, was enriched in patients with no to mild diarrhea compared to patients with moderate to severe diarrhea. A. muciniphilia supplementation has been shown to decrease systemic inflammation in Western diet-fed mice. Evaluation of A. muciniphilia as a radioprotective gut bacterium warrants further evaluation.

Neoadjuvant docetaxel-cisplatin followed by concurrent chemoradiotherapy and adjuvant tislelizumab for locally advanced nasopharyngeal carcinoma: A multicenter, single-arm, phase II trial.

e18047 Background: Patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) have a high risk of distant metastasis or recurrence despite the current standard of neoadjuvant chemotherapy and concurrent chemoradiation (CCRT), indicating the need of more comprehensive treatment. Due to good compliance and convenient adverse event management, the TP (docetaxel and cisplatin) regimen is more widely accepted and commonly used as a neoadjuvant chemotherapy for LA-NPC in the real world. Immune checkpoint blockade therapy plus chemotherapy has been shown to improve the survival in recurrent or metastatic NPC. We investigated the efficacy and safety of tislelizumab, an anti-PD-1 monoclonal antibody, as adjuvant treatment in patients with LA-NPC that had the neoadjuvant TP chemotherapy and CCRT. Methods: This multicenter, open label, single arm, phase II clinical trial was done at four hospitals in China. Patients (aged 18-65 years) with histologically confirmed, LA-NPC (T4N1 and T1-4N2-3) were enrolled and treated with neoadjuvant chemotherapy for 3 cycles (docetaxel 75 mg/m2 D1, cisplatin 75 mg/m2 D1) followed by concurrent cisplatin (100mg/m2, D1 and D22) during intensity-modulated radiation (IMRT). Four weeks post-RT, tislelizumab (200 mg) was given intravenously once every 3 weeks for up to 12 cycles. By Fleming one-stage design (type I error 0.05, power 0.80, 10% drop out), planned sample size is 100. Primary endpoint is 3-year (yr) progression free survival (PFS). Secondary endpoints include safety and tolerability. Results: From June 2021 to January 2024, a total of 100 patients (median age 53y, 73.0% male) were recruited at four study sites. This protocol specified analysis included 78 subjects with &gt;12 months post-treatment follow up (median 26.2 months, 95% CI 21.3-30.1). Overall compliance rate: neoadjuvant cisplatin + docetaxel 97.5%, concurrent cisplatin 80.8%, adjuvant tislelizumab 78.2%, IMRT 99.7% (69.96 Gy). Treatment related adverse events (AEs, ≥grade 3, &gt;10%): dysphagia (30.5%), mucositis (26.2%), neutropenia(26.7%), radiation dermatitis (23.7%), anemia (16.2%). No ≥grade 4 mucositis/dermatitis. In addition, the incidence of immune-related adverse events (irAEs) of grade 3 or 4 was 5.2%, and all were thyroid toxicity and skin rash. The 2-yr PFS and 2-yr overall survival were 89.6% (95% CI 53.8 - 88.5%) and 100%, respectively. 3-yr PFS and long-term efficacy are awaited. Conclusions: Tislelizumab adjuvant therapy after neoadjuvant docetaxel -cisplatin followed by CCRT is safe with promising results for LA-NPC. However, further follow-up is needed to confirm the long-term efficacy. Clinical trial information: NCT04870905 .

A comprehensive correlation of the KI-67 proliferation index to patient´s, imaging and tumor features and its value in predicting long-term course of patients with newly diagnosed intracranial meningiomas.

To analyze the correlation of KI-67-Proliferation Index (KI-67-PI) with preoperative patients and MRI characteristics, WHO grading, histological subtype and long-term-course of patients with newly diagnosed intracranial meningiomas (IM). In this single-center retrospective study, all consecutive patients with IM were analyzed from January 2007 to August 2019. Patient´s demographics (age, sex), imaging parameters (location, volume, edema, necrosis), and tumor features (WHO grade, histology) were assessed and correlated with KI-67-PI. Long-term data were retrieved from patient's last follow-up visits. This study included 463 IM in 457 surgically treated patients. Males exhibited a higher KI-67-PI than females (7.31 ± 0.22 vs. 5.37 ± 0.53; p < 0.01, Mann-Whitney U Test). Age positively correlated with KI-67-PI in both sexes (p < 0.01, Spearman), with older patients having a higher KI-67-PI. KI-67-PI was significantly higher in convexity IM compared to frontobasal IM (7.15 ± 5.56 vs. 4.66 ± 2.94; p < 0.05, ANOVA, Tukey´s HSD), while no difference in KI-67-PI expression was found when other locations were compared to each other (Tukey´s HSD). Higher KI-67-PI was significantly correlated with larger tumor volume (p < 0.01, Spearman), larger tumor necrosis and larger peritumoral edema (p < 0.01, Kruskal-Wallis). Patients with recurrent IM had a significantly higher KI-67-PI than patients without recurrence (8.24 ± 5.88 vs. 5.14 ± 3.53; p < 0.01, ANOVA, Tukey´s HSD) during a mean follow-up period of 80.92 ± 38.1months. Atypical and anaplastic IM exhibited significantly higher KI-67-PI compared to all other WHO grade 1 histological subtypes (12.09 ± 0.73 vs. 4.51 ± 0.13; p < 0.01, Kruskal-Wallis test) and KI-67-PI was significantly higher in anaplastic IM compared to atypical meningioma (19.67 ± 1.41 vs. 11.01 ± 0.38; p < 0.01, ANOVA). Higher KI-67-PI is not only associated with atypical and anaplastic subtypes of IM, but is also significantly higher in males, positively correlates with patients age, larger tumor volume, lager peritumoral edema and necrosis on preoperative MRI and predicts tumor recurrence. Therefore, KI-67-PI may serve as a decision indicator for adjuvant treatment in patients with IM.