Oncologist最新文献

Background: Both hyperthermic intraperitoneal chemotherapy (HIPEC) and conventional intraperitoneal chemotherapy (IP) have shown survival benefits in ovarian cancer (OC), but direct comparisons between the two perfusion modalities are lacking. This study aimed to compare effectiveness and safety between HIPEC and conventional IP in OC.

Methods: This retrospective real-world study analyzed 606 patients with stages II-IV OC who received HIPEC or IP following cytoreductive surgery between 2013 and 2024. The primary endpoint was progression-free survival. Overall survival and adverse events were secondary endpoints. The study used inverse probability of treatment propensity-score weighting. We also conducted sensitivity analyses to evaluate result robustness and subgroup analyses to explore potential effect modification.

Results: After a median follow-up of 26 months, disease progression occurred in 40.6% of patients in the HIPEC group and 55.0% in the IP group (hazard ratio [HR] 0.79; P = .103). Mortality rates were 13.2% and 22.5%, respectively (HR 0.83; P = .434), showing no significant differences in progression and survival between the two groups. Exploratory subgroup analyses suggested a trend toward improved progression-free outcomes with HIPEC, particularly among patients with BRCA wild-type or BRCA1-mutated tumors and early postoperative perfusion. Hypoalbuminemia was the most common event in both groups (HIPEC 27.2%; IP 15.6%). HIPEC group had more abdominal distension and wound dehiscence, whereas IP patients experienced nausea and rash more frequently.

Conclusions: HIPEC did not significantly improve survival over conventional IP in the overall population, but showed greater benefit in specific subgroups, underscoring the importance of individualized intraperitoneal chemotherapy strategies in OC.

Background: Radiotherapy (RT) provides meaningful local control for hepatocellular carcinoma (HCC) but is limited by radio-resistance. Preclinical and clinical data suggest that adding programmed death receptor-1 (PD-1) blockade may enhance radiosensitivity in various malignancies. We compared outcomes of stereotactic body radiotherapy (SBRT) plus PD-1 inhibitors versus SBRT alone in unresectable HCC.

Methods: We retrospectively analyzed consecutive patients treated with SBRT (January 2019-December 2024) from three centers. Key exclusions removed confounding from recent systemic/locoregional therapies. Propensity score matching (PSM, 1:1) balanced demographics, liver function, tumor characteristics and prior therapy. Tumor responses were assessed by RECIST 1.1, while survival was estimated by Kaplan-Meier and Cox models.

Results: Of 540 eligible patients, 157 received RT+PD-1 and 383 received RT alone; after PSM, 314 patients remained (157/157). Median follow-up was 29.9 months (IQR 21-36). After matching, RT+PD-1 showed a higher objective response rate (ORR) that approached significance (48.4% vs. 37.6%, p = 0.053). Progression free survival (PFS) was significantly prolonged with RT+PD-1 (median 11.0 vs. 8.5 months; 1-year 69.9% vs. 54.1%; HR 0.75, 95% CI 0.58-0.96, p = 0.024). OS also favored RT+PD-1 (median 33.9 vs. 26.3 months; 3-year 41.9% vs. 23.0%; HR 0.74, 95% CI 0.54-1.02, p = 0.066). On multivariable analysis after PSM, RT+PD-1 independently reduced risks of progression (HR 0.69, p = 0.005) and death (HR 0.70, p = 0.029). Adverse events (AEs) were similar overall, but grade ≥3 AEs were more frequent with RT+PD-1 (15.2% vs. 7.0%, p = 0.020).

Conclusions: In unresectable HCC, adding PD-1 blockade to SBRT enhances anti-tumor activity and improves long-term survival outcomes.

Background: Despite recent advances and an improved treatment paradigm, the prognosis in patients with advanced NSCLC remains poor. Novel endpoints to evaluate antitumor activity are needed to expedite safe and effective drug development.

Methods: We performed a retrospective pooled analysis of 10,495 patients with NSCLC using radiological tumor measurements across 22 randomized clinical trials fit to a regression-growth model to derive the g value. We evaluated the g value across both type and line of therapy.

Results: The g value is inversely associated with survival. Patients receiving targeted therapy had lower g values than patients receiving immune checkpoint inhibitors or chemotherapy. Additionally, patients receiving front-line treatment had a lower g value than patients receiving later line treatment. A lower g value was associated with a higher median OS and a longer median PFS.

Conclusion: The g value, as a volumetric measurement of tumor growth rate, may provide an additional or supplementary approach to assess the potential clinical activity of an agent. Prospective studies are needed to further assess the association of the g value derived from early tumor measurements with long-term outcomes in patients.

Implications for practice: Characterization of the growth rate may provide additional information regarding the potential clinical activity of a drug, which could aid in the selection of therapies for further drug development. While the g value has the potential to provide an early assessment of new therapies in a clinical trial before a time-to-event endpoint is reached, further evaluation through prospective studies and meta-analyses is needed to assess the association of g value with long-term outcomes, such as PFS and OS.

Background: Second-line FOLFOX-bevacizumab treatment is effective in metastatic colorectal cancer (mCRC) treatment after irinotecan-based chemotherapy failure. First- or second-line raltitrexed-oxaliplatin (TOMOX) treatment has an acceptable toxicity profile in mCRC. The aim of study was to evaluated TOMOX- bevacizumab combination as a second-line treatment.

Methods: The BEVATOMOX study was a non-comparative, prospective, randomized, open-label, multicentric phase II trial. Patients with histologically proven unresectable mCRC and progressive metastatic disease after irinotecan-based chemotherapy were randomized (1:2) to receive mFOLFOX6-bevacizumab (control arm, bevacizumab 5 mg/kg, mFOLFOX6 D1 = D15, 12 cycles) or TOMOX-bevacizumab (experimental arm, bevacizumab 7.5 mg/kg, raltitrexed 3 mg/m2 based on creatinine clearance, oxaliplatin 130 mg/m2, D1 = D21, 8 cycles). The primary endpoint was six-month progression-free survival (6PFS). Target enrollment was 30 and 62 patients in the control and experimental arms, respectively.

Results: Eighty-three patients (median age 66 (48-82) years, 63.9% male, 54.2% KRAS mt) were included: 33 in the control and 50 in the experimental arms. The 6PFS rate and median overall survival were 51.5% (95%CI 36-67) and 11.1 months (9.5-16.4) in the control arm vs. 38% (95%CI 26-51) and 9.3 (5.7-11.6) months in the experimental arm. In the experimental arm, left-sided tumors had a longer overall survival vs. right-sided (11.6 vs. 4.6 months, p < 0.001). Grade 3-4 toxicities (mucositis, neutropenia, febrile neutropenia, paresthesia, hand-foot syndrome) were similar between arms.

Conclusion: The TOMOX-Bev combination is a feasible second-line mCRC treatment with an acceptable toxicity profile. Recruitment failure prevents efficacy conclusions, but TOMOX-Bev may be an alternative if fluropyrimidines are contraindicated.

Trial registration number: ClinicalTrials.gov, NCT01532804.

Background: The optimal first-line treatment for RASwild-type metastatic colorectal cancer remains undetermined. Several studies have compared the efficacy of different first-line regimens, including doublet- or triplet-chemotherapy(CT) alone or in combination with targeted therapies (anti-EGFR/anti-VEGF), without conclusive results.

Methods: We conducted a systematic review and meta-analysis of phase II/III randomized clinical trials(RCT) comparing triplet-CT+anti-EGFRs with alternative first-line regimens in RASwild-type patients. Pairwise- and network-meta-analyses were performed to assess ORR. Furthermore, we evaluated PFS and OS with pairwise-metanalyses.

Results: A total of 1,283 patients across seven RCT were included. Four treatment arms were analyzed: Arm A (triplet-CT+anti-EGFR), Arm B (doublet-CT+anti-EGFR), Arm C (triplet alone), and Arm D (triplet+anti-VEGF). Arms A, B e D demonstrated higher ORR compared to Arm C, while no significant differences were found among Arms A, B, and D (OR 1.05, 95% CI 0.73-1.49; p = 0.804, for Arm B in comparison to Arm A; OR 0.80, 95% CI 0.52-1.25; p = 0.328, for Arm D in comparison to Arm A). Pairwise-meta-analysis revealed significantly lower ORR for Arm C compared to Arm A (OR 4.23,95% CI 2.06-8.68, p = 0.002). P-scores ranked Arm B highest for effectiveness (0.808), followed by Arm A (0.746), then Arm D (0.444) and lastly Arm C (0.002) The pooled HR for OS demonstrated a superiority for arm A (0.82, 95% CI 0.70-0.97, p = 0.022).

Conclusions: Triplet-CT+anti-EGFR demonstrated no clear ORR advantage over other targeted regimens but was superior to triplet-CT alone. Preliminary data indicate a potential OS benefit. Due to increased toxicity, routine use of triplet-CT+anti-EGFR should be carefully evaluated.

Background: The age-specific distribution of frailty and its domain-level characteristics remain poorly understood across the adult population of patients with cancer. We aimed to quantify the frailty prevalence and geriatric assessment (GA) impairment patterns in adults and to examine their prognostic relevance in newly diagnosed patients with cancer.

Material and methods: This multicenter, cross-sectional cohort enrolled 2,501 adults (≥20 years) before therapy in 2021-2023. GA covered eight domains (function, comorbidity, cognition, mood, nutrition, polypharmacy, falls, and social support). Patients were grouped into six age bands (20-39 to ≥ 80) and labeled fit (0 deficits), prefrail (1), or frail (≥2). We analyzed age-specific geriatric impairment patterns and overall survival (OS).

Results: The mean number of GA deficits increased significantly across the six ordered age bands. Frailty was common and increased with age: 40.0% (20-39), 42.3% (40-49), 56.2% (70-79), and 74.4% (≥80). Malnutrition was the most frequent deficit (59.1% overall), affecting 51% of patients aged 20-39 years, peaking at 63.8% in the 70-79-year cohort. Older age groups showed steeper increases in comorbidities, cognitive impairment, and functional decline. Polypharmacy and depressed mood were frequent, but varied less with age; inadequate social support was uniformly low. In multivariable models, prefrailty and frailty predicted worse OS. Age-stratified analyses of 40-49, 50-59, and 70-79-year cohorts showed similar associations.

Conclusion: Frailty is prevalent across adults of all ages with distinct, age-associated GA profiles. Nutritional deficits were the most prevalent impairment even among younger adults, whereas functional, comorbidity, and cognitive burdens escalate in older patients with cancer. Routine pretreatment GA for all adults can identify vulnerabilities and enable age-tailored supportive interventions.

Background: Despite successes in other malignancies, immune checkpoint blockade (ICB) has not demonstrated reproducible efficacy in mismatch repair-proficient (pMMR) colorectal cancer (CRC). Preclinical studies indicate that multitargeted combination immunotherapy may sensitize resistant tumors to immune-mediated killing. This trial was designed to test this hypothesis by combining agents to induce and augment an immune response in pMMR CRC.

Methods: In this single-center, phase 1/2 trial, eligible patients had pMMR, RECIST v1.1-measurable metastatic CRC, ≥2 prior lines of therapy and no prior immunotherapy. The primary endpoint was objective response rate. Patients received triplet therapy: CV-301 (CEA/MUC-1 vaccine), N-803 (IL-15 receptor superagonist), bintrafusp alfa (bifunctional anti-PD-L1/TGFβ "trap") or quadruplet therapy (adding PDS01ADC [tumor-targeted IL-12 immunocytokine]).

Results: Between September 2020 and September 2022, 32 patients enrolled to triplet (n = 12) and quadruplet (n = 20) therapy. The combinations had toxicity profiles consistent with each individual agent included. One complete response durable for 29+ months occurred in a patient with RAS wild-type CRC metastatic to lymph nodes who received quadruplet therapy.

Conclusion: Quadruplet therapy produced one objective response in unselected mCRC patients (n = 20). There were no responses with triplet therapy (n = 12). The role of ICB-based combination immunotherapy in pMMR CRC remains unclear. NCT04491955.

Patients and methods: we retrospectively collected data of patients with HR+/HER2- advanced breast cancer (ABC) treated with endocrine therapy (ET) and a CDK4/6 inhibitor (CDK4/6i) aiming to describe the patterns of post-progression outcomes.

Results: Among 452 evaluable patients 325 were treated in the first-line setting. Median progression free-survival (mPFS) was 22.8 months overall and 29.7 months in patients treated in first-line setting. Factors associated with outcomes in multivariate analysis were the line of CDK4/6i therapy, de novo vs recurrent disease, visceral vs bone-only metastases, and primary endocrine resistance.A total of 300 patients progressed and 250 overall and 156 in the first-line cohort received a subsequent treatment. Visceral progression and CDK4/6i duration <12 months were associated with a higher likelihood of receiving anthracycline or taxanes (AT) as compared to ET ±everolimus (EET). Post-progression PFS (PPFS) and post-progression OS (PPOS) were statistically significantly better with EET and capecitabine (C) arms over AT overall and in patients with visceral progression. Multivariate analysis confirmed a significant advantage for EET and C, while visceral progression retained a significant impact only on PPOS. After progression to the 1st post-CDK4/6i treatment C obtained a significant better PPOS as compared to other treatments.

Conclusion: we showed in a large real-world series that most patients with HR+/HER2- ABC failing CDK4/6i and ET unselected for the occurrence of molecular mutations retain endocrine sensitivity and may benefit of a subsequent ET ± a targeted therapy delaying the need for chemotherapy regardless of site of progression and prior CDK4/6i therapy duration.

Background: Biliary tract cancers (BTCs), including gallbladder cancer (GBC) and cholangiocarcinoma (CCA), are rare but aggressive malignancies with distinct molecular landscapes and poor prognosis. Genomic profiling has revealed significant molecular alterations, but the genomic landscape of BTC in the Indian population remains underexplored. This study aims to comprehensively characterize the mutation landscape of BTC in the Indian population.

Methods: A total of 154 BTC cases, including 69 CCA and 85 GBC, were retrospectively analyzed using data collected from various targeted sequencing panels. Somatic mutations, copy number variations (CNVs), and gene fusions in key oncogenic and tumor suppressor genes were identified from these panel reports. Downstream analyses were performed to derive key biological insights, including pathway enrichment and mutual exclusivity and co-occurrence analyses of genomic alterations.

Results: TP53 was the most frequently mutated gene (53%), followed by KRAS (18%), ARID1A (9%), IDH1 (7%), and PIK3CA (7%). Recurrent amplifications were observed in MYC (12%) and ERBB2 (9%). Pathway enrichment analysis revealed significant dysregulation in the PI3K-AKT-mTOR, Notch, and Wnt/β-catenin signaling pathways. Notably, IDH1 mutations were primarily observed in CCA, while STK11 mutations were exclusive to GBC, highlighting distinct molecular characteristics between the two subtypes. PD-L1-negative tumors exhibited distinct genomic alterations, notably SMAD4 mutations, which were associated with reduced PD-L1 expression. This loss of SMAD4, involved in TGF-β signaling, could impair immune response regulation and facilitate immune evasion.

Conclusions: This study provides a comprehensive molecular profiling of BTCs in the Indian population, revealing key genomic alterations, subtype-specific differences, and associations with immune features. The findings underscore the importance of molecular profiling in guiding personalized treatment strategies.

Background: Chemotherapy-induced nausea and vomiting (CINV) significantly impact the patients' quality of life. Whether the granisetron transdermal delivery system (GTDS) offers better protection than palonosetron against long-delayed (120-168 h) CINV after highly or moderately emetogenic chemotherapy (HEC/MEC) had not been prospectively tested.

Methods: A multicenter, randomized clinical study was conducted in China. Patients scheduled to receive either HEC or MEC were randomly assigned (1:1) to GTDS or palonosetron, each in combination with a neurokinin-1 receptor antagonist (NK1-RA) and dexamethasone. The primary endpoint was the complete response (CR; no vomiting and no rescue medication) rate during the long-delayed phase (120-168 hours), stratified by HEC and MEC categories, to demonstrate the superiority of GTDS over palonosetron.

Results: Overall, 150 patients received either GTDS or palonosetron respectively. We found that the GTDS group demonstrated a significantly higher long-delayed CR rate (97.3%) than the palonosetron group (92%) (p = 0.04). This advantage was driven predominantly by the HEC subgroup (GTDS 97.5% vs palonosetron 90.8%, p = 0.028). No significant differences were observed between the groups for the acute (0-24 h, 92.7% vs 90.0%; p = 0.412), delayed (24-120 h, 80.0% vs 76.0%; p = 0.403), extended-delayed (24-168 h, 80.7% vs 75.3%; p = 0.265), or overall (0-168 h, 78.0% vs 74.0%; p = 0.417) phases.

Conclusion: A GTDS-based triple antiemetic regimen can effectively control CINV associated with HEC or MEC. It provides a convenient alternative route for delivering granisetron for up to 7 days, with superior efficacy in controlling long-delayed CINV.

Trial registration: clinicaltrials.gov identifier: NCT04912271 (in-house ethic number: YBCSG-21-04).