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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: 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.

Choice of oncologist by patients with pancreatic cancer is a complex personal decision. We conducted a retrospective analysis of the Pancreatic Cancer Action Network registry to explore whether age, gender, disease status, feelings of trust and comfort, and the opportunity for clinical trial participation influenced patient choice. Of 110 participants who completed the "Information about Choosing an Oncologist Survey," 68 (61.8%) reported visiting another oncologist. Feeling comfortable and trusting their first oncologist decreased the likelihood of seeking a second opinion (OR: 0.08; CI: 0.01-0.42; P = .005). Patients with resectable disease were also less likely to visit another oncologist compared to patients with borderline resectable or locally advanced disease (OR: 0.28; CI: 0.08-0.95; P = .042). Age, gender, and the opportunity for clinical trial participation did not influence patient choice. Most patients who saw additional oncologists did so because of recommendations from friends or family members. This analysis leveraged patient-reported outcomes to highlight determinants of patient decision-making.

Background: Breast cancer survival rates in sub-Saharan Africa are low. In a prospective, multi-center cohort study, we estimated 5-year overall survival rates, overall survival determinants, and mediating effects between socioeconomic status on overall survival among South African women diagnosed with invasive BC.

Patients and methods: Patients from 4 public hospitals were enrolled between July 1, 2015 and January 31, 2019. Survival determinants were assessed using Cox proportional hazard models adjusted for age, background mortality, and treatments. Socioeconomic pathway effects on overall survival were determined through generalized structural equation models.

Results: Of 2838 participants, 58% had advanced-stage (III/IV) disease. Five-year crude overall survival was 44.3% (95% CI 42.5-46.2). Significant mortality risks were late stage at diagnosis (hazard ratio [HR] = 2.31 [95% CI 1.99-2.69] [stage III]; 4.79 [95% CI 3.96-5.80] [stage IV]), HIV-positive status (HR = 1.45 [95% CI 1.25-1.67]), unemployment HR = 1.25 [95% CI 1.09-1.44], and low education HR 1.19 [95% CI 1.04-1.37]). Age and treatment-adjusted socioeconomic status effects on overall survival were mediated through HIV status (81.7% of the effect) and stage at diagnosis (81.7%), both P < .001. Poor breast cancer knowledge had an indirect effect on overall survival, accounting for 77.6% of the total effect (P = .001), fully mediated by late-stage presentation. Socioeconomic status had no significant direct path to mortality after accounting for these mediators.

Conclusion: Interventions should prioritize early breast cancer detection. For patients with low socioeconomic status, particularly those with comorbid HIV, we must mitigate multifaceted barriers to healthcare access, including limited awareness and knowledge of breast cancer.

Background: Metastatic urothelial carcinoma (mUC) remains highly lethal despite advances in treatment. There is limited data surrounding the efficacy and toxicity of immune checkpoint inhibitors in treating elderly patients due to the high bar of clinical trial participation. The Geriatric 8 (G8) screening tool is a quick, 8-item questionnaire designed to assess frailty in older adults. This study evaluates the G8 tool's utility in predicting overall survival (OS) and progression-free survival (PFS) in patients with mUC treated with immune checkpoint inhibitors.

Materials and methods: A retrospective analysis was conducted on 48 mUC patients treated with ICI monotherapy at Winship Cancer Institute between 2016 and 2019. Baseline G8 scores were calculated from clinical notes. Primary outcomes included OS and PFS, analyzed using Kaplan-Meier, Cox proportional hazards models, and multivariate analysis adjusted for demographic and clinical variables.

Results: An impaired baseline G8 score predicted worse OS but not PFS. The incidence of immune-related adverse events was lower but not statistically significant in patients with impaired G8 scores (HR, 0.31; OR, 0.09-1.14; P = .077).

Conclusion: The G8 screening tool effectively predicts OS in older mUC patients treated with ICIs, highlighting its potential utility in clinical decision-making. Frail patients, as identified by the G8, had significantly worse survival outcomes, underscoring the need for tailored therapeutic approaches in this vulnerable population. Further studies are warranted to validate these findings and explore interventions that may improve outcomes for frail, older patients with mUC.

Background: Febrile neutropenia (FN) is a common complication with myelosuppressive chemotherapy regimens, significantly affecting patients with breast cancer (BC) receiving docetaxel and cyclophosphamide (TC). Treatment with granulocyte colony-stimulating factor (G-CSF) is established for prophylactic and therapeutic use to reduce risk of FN. Eflapegrastim-xnst, a novel long-acting G-CSF, has a favorable safety profile and is effective in reducing neutropenia risk in patients with early-stage BC receiving TC, when administered 24 h after chemotherapy. The benefits of eflapegrastim-xnst given same day as TC have not been evaluated in a randomized controlled trial.

Patients and methods: This phase 1, multicenter, open-label trial evaluated efficacy and safety of eflapegrastim-xnst administered 0.5 h post-TC chemotherapy for four cycles in patients with early-stage BC. The primary end point was time to recovery of absolute neutrophil count (ANC) from nadir to ≥1.5 × 109/L in cycle 1. Secondary end points included safety, duration of severe neutropenia, incidence of FN, and neutropenic complications.

Results: Of 53 patients enrolled, 49 completed the study. Mean time to ANC recovery in cycle 1, the primary end point, was 1.8 days. Only 1 patient (2%) experienced an FN episode in cycle 1 (1 episode/228 cycles received [0.4%]). Incidence of severe neutropenia decreased from 42.9% (cycle 1) to 27.3% (cycle 4). Eflapegrastim-xnst was well tolerated; common treatment-emergent adverse events included fatigue, nausea, alopecia, and bone pain.

Conclusions: Eflapegrastim-xnst, administered same day as TC chemotherapy was effective and well tolerated evidenced by short time to neutrophil recovery and low incidence of FN, with an adverse event profile similar to that of next-day dosing.

Background: Young women with breast cancer (YWBC) face medical and psychosocial challenges that are inconsistently addressed by healthcare frameworks. This study evaluated whether a patient navigation (PN) program for YWBC facilitates access to specialty and supportive care through structured patient needs assessments and referrals.

Patients and methods: Within 3 months of diagnosis, ≤40-year-old patients were prospectively enrolled into a PN program in which a navigator systematically administered needs detection surveys and provided referrals to required services at baseline, 3 months (m), and 6 m. Attendance to referrals at baseline and 3 m was assessed at the next timepoint.

Results: Among 189 participants, 85% required >2 referrals at any timepoint. At baseline and 3 m, referrals were mostly to nutrition (66% and 46%), support groups (65% and 24%), and psychology (56% and 36%); and at 6 m, to nutrition (32%), sexology (31%), and psychology (19%). From baseline-to-3 m, attendance was highest for support groups (99%), genetic cancer risk assessment (88%), and external breast prosthesis providers (82%); from 3 m-to-6 m, for support groups (100%), sexology (91%), and external breast prosthesis (86%). Nearly none attended >2 referrals and receiving more referrals was associated with higher absence rates (P < .001).

Conclusion: This PN program enabled structured identification of patients' needs and referral to required services, highlighting the relevance of nutrition, support groups, and psychology needs during early assessments, as well as sexology counseling during later follow-ups. The high absence rates observed suggest that individualized selection of specific referrals prioritizing patients' needs and preferences at different timepoints in their cancer trajectory could improve attendance while avoiding patient and health-system oversaturation.