International Journal of Clinical Oncology最新文献

Introduction: Uterine carcinosarcoma (UCS) and uterine sarcomas (US) are rare but aggressive cancer with poor prognoses. The prognostic value of systemic inflammatory response (SIR) indicators, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), in predicting outcomes of UCS and US remains unclear. This study investigated the prognostic significance of SIR indicators for UCS and US.

Materials and methods: Clinicopathological data from 237 patients diagnosed with UCS or US across 14 hospitals from January 2008 to December 2017 were retrospectively analyzed. NLR, PLR, and MLR values were calculated from preoperative blood counts. Prognostic impact was evaluated using Kaplan-Meier survival analysis, Cox regression models, and receiver operating characteristic (ROC) curve analysis.

Results: Elevated NLR, PLR, and MLR were associated with poorer progression-free survival (PFS) in UCS. Additionally, a high NLR also indicated worse overall survival (OS) in UCS. In patients with US, only PLR was significantly associated with poorer PFS. Combining SIR indicators provided a stronger prognostic prediction for UCS compared to individual indicators. Multivariate analysis revealed that high levels of SIR indicators were an independent poor prognostic factor for both PFS and OS in UCS.

Conclusion: SIR indicators, particularly when combined, are valuable prognostic markers in UCS, reflecting the inflammatory status and aiding in stratifying patients for tailored therapeutic strategies. These findings support the incorporation of SIR indicators into clinical practice for better management of patients with UCS.

Background: Enfortumab vedotin (EV) is a novel treatment for metastatic urothelial carcinoma (mUC) that progresses after platinum-based chemotherapy and PD-1/PD-L1 inhibitor therapy. This study aimed to compare the efficacy of EV with that of paclitaxel plus carboplatin therapy (TC), which was commonly used as late-line therapy.

Methods: This retrospective study included patients with mUC who progressed after platinum-based chemotherapy and PD-1/PD-L1 inhibitor therapy. Patients were classified into two groups: those who were initiated on EV (EV group) and those who received TC as the next-line treatment (TC group). Therapeutic efficacy and adverse events (AEs) were investigated.

Results: A total of 55 patients were included in this study (20 in the TC group and 35 in the EV group). The EV group had significantly better progression-free survival (PFS) (p = 0.0013) and overall survival (OS) (p = 0.0279) than the TC group. The most frequent AEs were neutropenia (70.0%), febrile neutropenia (20.0%), and peripheral neuropathy (20.0%) in the TC group and pruritus (45.7%) and maculopapular rash (37.1%) in the EV group. Patients who progressed after EV administration were classified into two groups: those who received TC (the TC group) and those who were shifted to best supportive care (the BSC group). The TC group had significantly better OS (p = 0.0084).

Conclusions: EV was associated with significantly better PFS and OS than TC in patients with mUC who progressed after platinum-based chemotherapy and PD-1/PD-L1 inhibitor therapy. TC is beneficial for certain patients, even in cases of progression after EV administration.

Background: JCOG1212 is a dose-finding and efficacy confirmatory study of concurrent superselective intra-arterial infusion of cisplatin and radiotherapy (RADPLAT) for locally advanced primary squamous cell carcinoma of the maxillary sinus (cT4a,bN0M0). In this study, we report the results of the final analysis of the efficacy confirmation phase for the T4a cohort with 5-year follow-up data to evaluate the late adverse events and long-term efficacy.

Methods: Based on the results of the dose-finding phase, the efficacy confirmation phase consisted of seven weekly intra-arterial infusions of cisplatin 100 mg/m² combined with radiotherapy (70 Gy). The 5-year prognosis and late adverse events were evaluated.

Results: Between April 2014 and August 2018, 64 patients were included in the analysis (one ineligible patient was excluded); 31 patients were treated with three-dimensional conformal radiation therapy (3D-CRT) and 33 with intensity modulated radiation therapy (IMRT). The 5-year overall survival, event-free survival, and local event-free survival was 71.9, 54.7, and 57.5%, respectively. In terms of late adverse events, grade 3 or higher non-hematologic toxicity was observed in 42.9% of 63 patients (retinopathy: 12, cataract: 10, osteonecrosis of mandible: 4, etc.). Grade 3 and 4 cataracts of affected side appeared in 22.6% (7/31) of the 3D-CRT group compared to 3.1% (1/32) in the IMRT group. Twenty-one patients had died, with 15 from the primary disease, 5 from other causes, and 1 from treatment-related cause.

Conclusion: The prognosis of RADPLAT was favorable after 5-year follow-up with acceptable late adverse events and low proportion of treatment related death.

Background: The quality of life (QOL) of ovarian cancer patients is often impaired by refractory ascites. Cell-free and concentrated ascites reinfusion therapy (CART) is a palliative treatment for refractory ascites, but adverse events, such as fever, are problematic. Several cytokines have been suggested to be responsible for the adverse events, but they have not been investigated in detail. Thus, we comprehensively analyzed cytokines in ascites fluid (AF) and serum before and after CART to determine the influence of cytokines on the safety and efficacy of CART.

Methods: Thirteen ovarian cancer patients with refractory malignant ascites who underwent CART were enrolled. We comprehensively analyzed 27 cytokines in AF and serum before and after CART. Simultaneously, vital measurements, blood tests, adverse event recordings, and QOL assessments were performed to examine the relationships between the cytokines in AF and serum.

Results: Interleukin (IL)-5, IL-6, IL-10, and monocyte chemoattractant protein-1 levels were increased in the concentrated AF and in the serum immediately after reinfusion, but they decreased after 24 h. Body temperature also increased immediately after reinfusion, and decreased after 24 h. The CRP level at 24 h after reinfusion was increased, and was positively correlated with the IL-6 level. A QOL assessment using the Cancer Fatigue Scale revealed significantly lower scores after CART.

Conclusions: The results indicate that the cytokine-induced fever and increased inflammatory response after CART were temporary, and that CART is safe. Additionally, QOL improved after CART. Thus, CART appears safe and effective for treating patients with refractory cancerous ascites.

Background: While R-CHOP has been one of the standard therapies for untreated high-tumor-burden (HTB) follicular lymphoma (FL) for over 2 decades, obinutuzumab plus bendamustine (OB) is also currently regarded as the standard of care since its approval in 2018 in Japan; however, the long-term efficacy and safety of OB in the daily clinical practice has not been thoroughly evaluated.

Methods: We conducted a multicenter retrospective study for the clinical outcome of 53 patients with HTB FL treated by OB as the frontline therapy between 2018 and 2021 in the Kyoto Hematology Clinical Study Group (KOTOSG). All patients had at least 2-year follow-up period.

Results: The median age was 67, and 60.4% were classified as high risk according to the Follicular Lymphoma International Prognostic Index. The overall and complete response rates after induction therapy with OB were 98% and 83%, respectively. With a median follow-up of 38.5 months, the 3-year progression-free survival (PFS) and overall survival (OS) were 77.3% and 91.2%, respectively. Grade 3-4 hematological adverse events (AEs) were common, including neutropenia (58.5%) and lymphopenia (98.1%). Non-hematological AEs included infections, such as lung infections, coronavirus disease 2019, and sepsis, with two cases (3.8%) being fatal. Finally, propensity score-matched analysis showed no significant difference in PFS between 46 FL patients treated by the frontline OB and 46 FL patients treated by R-CHOP between 2001 and 2019 in KOTOSG.

Conclusion: This study highlighted the need for careful treatment selection based on patient background and disease condition in real-world practice with more elderly patients.

Purpose: Recent improvements in cancer prognosis have highlighted the need for patients to balance social interactions with their therapeutic regimens. Central to this balance is managing the physical changes induced by cancer treatments. This study aimed to examine patients' reactions to these changes and to identify their needs related to appearance care.

Methods: We conducted a survey among 800 patients undergoing systemic therapy to investigate the actual impact of changes and to determine the specific care needs across 45 appearance-related items. The survey using the original questionnaire was an online self-reported.

Results: Of the surveyed patients, 202 responded. The median age was 58 years (ranging from 30 to 81), comprising 144 women and 58 men. Hair loss was experienced by 157 (78%) patients, with 109 (70%) of them purchasing wigs. The demand for information and consultation was highest for alopecia, reported by over 60% of respondents, followed by needs related to skin care and wigs. In addition, 26 items had unmet needs affecting more than 50% of the participants, with 24 of these items pursued by fewer than half of the patients. In female patients who experienced hair loss, patients with breast cancer more frequently sought information and consultation and had higher levels of unmet needs compared with those with non-breast cancer.

Conclusions: The findings underscore the substantial and diverse appearance-related needs among cancer patients, with many experiencing significant unmet needs. These results suggest that comprehensive support systems are essential to address the varied and individualized needs of patients undergoing contemporary cancer treatments.

Cervical cancer is the third most common malignant tumor in women worldwide in terms of both incidence and mortality. The field of cervical cancer treatment is rapidly evolving, and various combination therapies are being explored to enhance the efficacy of immune checkpoint inhibitors (ICI) and provide new treatment options for patients at different disease stages. Clinical trials involving immune checkpoint inhibitors are now being conducted following a phase 3 trial with cemiplimab, an ICI, which demonstrated a significant improvement in prognosis in advanced or metastatic cervical cancer patients. These trials include monotherapy and combination therapy with other immune therapies, chemotherapy, or radiation therapy. Furthermore, other approaches for controlling tumors via the immune system, such as therapeutic vaccination for specific tumor antigens or immune cell therapy including chimeric antigen receptor (CAR)-T cell therapy and tumor-infiltrating lymphocytes are being investigated. Ongoing trials will continue to illuminate the optimal strategies for combining these therapies and addressing challenges associated with immune checkpoint failure in cervical cancer. Herein, we conducted a review of articles related to immunotherapy for cervical cancer and describe current treatment strategies for cervical cancer via immunotherapy.

Advanced recurrent endometrial cancer (EC) has a poor prognosis and new treatment options are needed. In 2013, EC was classified by genomic analysis into four groups: the POLE ultra-mutated group, the MSI-high hypermutated group (MSI-H), the copy number low group, and the copy number high group. The prognosis differs based on the classification, which should enable the individualization of treatment. The MSI-H and POLE types can induce PD-L1 expression in cancer cells. Among the gynecological cancers, EC exhibits the highest levels of PD-1 and PD-L1 expression and has the highest proportion of MSI-H. Thus, an immune checkpoint inhibitor (ICI) is expected to be effective. The first ICI to show efficacy in recurrent EC was the anti-PD1 antibody pembrolizumab, which exhibited efficacy in MSI-H EC. The combination of pembrolizumab and the multi-kinase inhibitor lenvatinib significantly prolongs OS/PFS compared with single-agent chemotherapy in previously treated recurrent EC, regardless of MSI status. ICIs are now moving from second-line and beyond to first-line treatment regimens. The efficacy of paclitaxel plus carboplatin (TC) and ICI combinations compared with TC have been demonstrated, including an ongoing Phase III trial comparing chemotherapy with the combination of pembrolizumab and lenvatinib. Although ICIs are becoming the mainstay of EC, they cause systemic inflammatory side effects known as irAEs. The incidence of irAEs is higher for combination therapy with CT or lenvatinib compared with ICI therapy alone. Even though they are rarely fatal, irAEs should be addressed promptly.

Background: FOLFOXIRI plus bevacizumab (BEV) is an option for first-line treatment of metastatic colorectal cancer (mCRC). However, there is no consensus on the optimal treatment strategy when disease progresses. The EFFORT open-label, multicenter, single-arm phase II study investigated whether FOLFIRI plus aflibercept retains activity after progression of FOLFOXIRI plus BEV treatment.

Methods: The patients with unresectable mCRC who failed first-line FOLFOXIRI plus BEV received FOLFIRI plus aflibercept. The primary endpoint was progression-free survival (PFS) in the full analysis set (FAS). Angiogenic biomarkers were measured before treatment initiation.

Results: From April 2019 to May 2021, 35 patients were enrolled and 34 were analysed in the FAS population (men, 18; median age, 63 years [range: 32-78]). The primary tumor was left-sided in most cases (23/34), 23 patients were RAS mutant, 3 patients had BRAF V600E mutation and 27 patients had liver metastases. The primary end-point was met with a median PFS of 4.3 months [80% confidence interval [CI] 3.7-5.1]. Median overall survival was 15.2 months [95% CI 8.9-22.7]. Per RECIST, there were 1 complete response, 4 partial responses, 21 stable diseases and 8 disease progressions. Overall response rate was 14.7% [95% CI 5.0-31.1], and disease control rate was 76.5% [95% CI 58.8-89.3]. Responses were more common in patients with high VEGF-C, low VEGF-D and low PlGF levels before treatment.

Conclusion: FOLFIRI plus aflibercept, administered after failure of FOLFOXIRI plus BEV, is effective and has a manageable safety profile. This regimen may be a useful second-line treatment option for these patients.

Background: This study investigated the characteristics of prostate-specific antigen (PSA) dynamics when androgen receptor signaling inhibitor (ARSI), or vintage agent (bicalutamide) was used for patients with metastatic hormone-sensitive prostate cancer (mHSPC).

Patients and methods: A total of 213 mHSPC patients from each of the ARSI and bicalutamide groups treated between 2015 and 2022 were selected from multiple institutions using propensity score-matched analysis to align backgrounds. PSA progression-free survival (PFS) and overall survival (OS) were assessed. PSA level at 3 months, PSA nadir level, and time to PSA nadir were examined to analyze of PSA kinetics.

Results: ARSI treatment significantly improved PSA PFS compared to bicalutamide (P = 0.0063), although no significant difference in OS was seen (P = 0.3134). No significant differences were observed between treatment groups in median PSA levels at 3 months (1.47 vs 0.52 ng/ml, P = 0.3042) or PSA nadir levels (0.263 vs 0.1345 ng/ml, P = 0.1228). Bicalutamide treatment demonstrated longer time to nadir than ARSI in progression-free cases (median: 243 vs 213.5 days, P = 0.0003). Survival tree analysis found that PSA nadir ≤ 1.5 ng/ml and time to nadir ≥ 145 days were the optimal cut-offs for best stratifying OS with bicalutamide, while PSA nadir ≤ 0.45 ng/ml and time to nadir ≥ 70 days were optimal with ARSI.

Conclusion: No significant differences in PSA response was seen between groups; however, distinct optimal cut-offs were demonstrated for PSA nadir and time to nadir. The present findings will be useful for optimal PSA monitoring for mHSPC patients and for early identification of poor-prognosis populations.