Clinical oncology最新文献

Aims: Programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors have shown limited effectiveness in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Combining anti-angiogenesis inhibitors with PD-1 inhibitors has the potential to reverse the immunosuppressive tumour microenvironment, synergistically enhancing the anti-tumour immune response in MSS mCRC. The goal is to present real-world data that prove the clinical efficacy and safety of fruquintinib combined with PD-1 inhibitors in MSS mCRC.

Materials and methods: We conducted a real-world retrospective study in patients with MSS mCRC who received treatment with fruquintinib combined with PD-1 inhibitors between May 2019 and March 2023 in our centre.

Results: Seventy seven patients with MSS mCRC received fruquintinib combined with PD-1 inhibitors. In total, 5.2% of patients (4/77) achieved a partial response (PR), while 50.6% (39/77) had a stable disease (SD). Notably, three lesions achieving PR were all lung metastases and the overall disease control rate (DCR) reached 55.8% (43/77). Median progression-free survival (PFS) and overall survival (OS) reached 5.1 months (95% CI: 3.6-6.7) and 14.6 months (95% CI: 9.6-15.6), respectively. Multivariate Cox analysis showed that prior treatment without vascular endothelial growth factor (VEGF) inhibitors was significantly associated with PFS and OS (p < 0.05). Further analysis indicated that total- or polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) significantly decreased after treatment (P = 0.039), especially in the PR/SD group (P = 0.003). Most adverse events included abdominal pain, rash, oedema, diarrhoea, and immunotherapy-associated hypothyroidism, yet symptoms were controllable.

Conclusion: Our results provided additional evidence that patients with MSS mCRC could benefit from the combination of fruquintinib and PD-1 inhibitors, especially those with lung metastases or without prior treatment with VEGF inhibitors. The detection of MDSCs may be an immune indicator for predicting of the combined therapy.

Aims: To analyze the long-term results of a prospective phase II trial testing intensified total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC).

Materials and methods: Patients with histologically confirmed LARC adenocarcinoma were enrolled. Intensified TNT consisted of targeted agent (bevacizumab or panitumumab/cetuximab) plus FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) induction chemotherapy followed by intensified (oxaliplatin and 5-fluorouracil) chemoradiotherapy (CRT) and surgical resection. Follow-up data were collected for all patients included in the trial. Survival outcomes were calculated using the Kaplan-Meier method and curves were compared by the log-rank test.

Results: Between October 2015 and September 2019, 28 LARC patients were enrolled. Follow-up data were available for all included patients. In total, 11 (39.3%) patients had a complete response (CR). At 6.3 years (median follow-up), 5-year overall survival (OS) and DFS were 74.6% and 57.1%, respectively. Five-year OS was 80.8% for CR patients and 70.1% for no-CR patients (p-value 0.07). Those patients with CR after TNT treatment had a 5-year DFS of 81.8% versus 41.2% for those with no CR (p-value 0.015).

Conclusion: The addition of a targeted agent to induction FOLFOXIRI and oxaliplatin to 5-fluorouracil-based CRT, with the doses and intensities used in this study, resulted in high CR rates. Patients who achieve a CR demonstrate superior DFS compared to patients without CR. Intensified TNT may have the potential to increase survival outcomes. Further research on TNT strategies in LARC is encouraged.

Aims: Cancer staging is routinely done in a multidisciplinary team meeting (MDM). There is however no established quality assurance (QA) for MDM-recorded cancer staging. Conversely, radiotherapy peer review is a recommended QA process. This study aimed to compare the cancer staging of the multiprofessional radiotherapy peer review (with radiologists) against the referring MDMs.

Materials and methods: All head and neck intensity-modulated radiotherapy (IMRT) cases discussed in peer review between May 2023 to April 2024 were prospectively evaluated. Any radiological disease progression (PD) on IMRT-planning scan since the diagnostic scans, and patients' cancer staging, were prospectively recorded. These were compared with the MDM-recorded outcomes data.

Results: A total of 235 IMRT cases were peer-reviewed: 166 definitive, 63 post-operative and 6 palliatives. Of the analysable definitive cases, 44/150 (29%) were found to have PD, with a mean interval from diagnostic to IMRT-planning scan of 51 days (Standard Deviation SD = 25), compared to 38 days (SD = 21) in the cohort without PD (p < 0.01). After the exclusion of 28 patients with the most advanced non-metastatic stage, 35 (30%) were upstaged with a mean interval from diagnostic to IMRT-planning of 49 days (SD = 26), compared to 39 days (SD = 23) in the cohort without upstage (p = 0.05). Twenty (57%) upstaged patients had evidence of PD, while the other 15 (43%) were upstaged despite the absence of PD. Two MDM-recorded T3-category larynx cancers were subsequently recommended for a primary laryngectomy due to T4a-category at peer review, and both were proven T4a pathologically. Three upstaged patients were recommended concomitant chemotherapy. The peer review recommended IMRT volume changes to 156 (66%) patients.

Conclusion: Discrepancies in MDM staging can occur, and a protracted diagnosis and treatment pathway too can affect final cancer staging. Routine radiologist input in peer review can provide crucial post-MDM outcome assurance and the recommended clinical management.

Aims: Treatment with stereotactic radiosurgery/radiotherapy (SRS/SRT) is standard practice in selected patients with small numbers of brain metastases (BMs). It is less accepted in those with ≥5 BMs, due to the lack of a prospective evidence base. While randomised trials are ongoing, we present the experience of a single UK cancer centre in using SRS/SRT for patients with 5 or more BMs without whole brain radiotherapy (WBRT).

Materials and methods: Patients undergoing treatment at a single centre between 2014 and 2019 were prospectively identified. All follow-up imaging was reviewed to identify any evidence of local failure or distant brain progression, which was analysed using a death-censored approach.

Results: A total of N = 88 patients were included, with a median of seven BMs (range: 5-37). Post-SRS/SRT toxicity events occurred in 42%, most commonly reliance on steroids for ≥4 weeks (36% of the cohort). Median survival was 10 months, with median freedom from local failure and distant brain progression of 12 and 8 months, respectively; none of these outcomes differed significantly by the number of BMs. Brain-directed salvage treatment was required after a median of 21 months, and was not significantly associated with the number of BMs.

Conclusion: SRS/SRT alone may have a role in the management of selected patients with multiple BMs. Since the number of BMs were not significantly associated with overall survival or disease control, the National Health Service (NHS) commissioning criteria should continue to be based on tumour volume.