International Journal of Clinical Oncology最新文献

The Intraperitoneal Carboplatin for Ovarian Cancer (iPocc) trial demonstrated that intraperitoneal (IP) administration of carboplatin is more effective than intravenous (IV) administration for advanced ovarian cancer, especially in cases with large residual tumors, challenging previous assumptions that IP chemotherapy is only beneficial for small residual tumors. Additionally, the iPocc trial showed that IP chemotherapy has a comparable safety profile to IV chemotherapy, with the exception of port-related toxicities. This review summarizes the principles, development, and significance of IP chemotherapy and discusses its future potential in light of recent studies. Notably, the iPocc trial, conducted under Japan's new clinical trial regulations, achieving regulatory approval based on investigator-initiated results. The iPocc regimen offers a viable treatment option for patients with advanced ovarian cancer (stages II-IV). However, bevacizumab is recommended for later-line treatments rather than combining it with IP chemotherapy until further trials support such combinations. Future studies are needed to identify biomarkers that predict response to the iPocc regimen. The trial's success underscores the dedication of patients and families who contributed to this groundbreaking research.

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.

In Japan, high-quality cancer statistics are collected through cancer registries. However, these data are rarely summarized or reported in research articles. We compiled statistical data on lung cancer in Japan including the COVID-19 pandemic. In 2019, the number of cases of lung cancer in Japan was 126,548. The age-adjusted incidence rate of lung cancer increased from 23.2/100,000 to 42.4/100,000 in males and from 7.2/100,000 to 18.3/100,000 in females between 1975 and 2019. The age-adjusted mortality rate of lung cancer in Japan increased since 2000, after which it decreased. This trend was similar in both males and females. We also investigated statistics on lung cancer worldwide (Australia, Sweden, England, and the United States [USA]). The age-adjusted incidence rate of lung cancer in the data standardized to the world population for males has increased only in Japan; for females, it has decreased only in the USA. Global age-adjusted lung cancer mortality rates have been declining in all countries. In addition, the COVID-19 pandemic has not affected the age-adjusted mortality rate of lung cancer. On the other hand, the number of individuals undergoing lung cancer screening in Japan decreased from 7.92 million in 2019 to 6.59 million in 2020. The COVID-19 pandemic may have affected individuals undergoing lung cancer screening, and its impact on lung cancer needs to be continuously monitored in the future.

Background: In 2018, the International Federation of Gynecology and Obstetrics (FIGO) revised its cervical cancer staging system to enhance clinical relevance, notably by categorizing lymph node metastases (LNM) as an independent stage IIIC. This multicenter study evaluates the prognostic implications of the FIGO 2018 classification within a Japanese cohort.

Methods: This study included 1468 patients with cervical cancer. Initial FIGO 2009 stages were restaged under FIGO 2018. Stage IIIC was further compared based on the location of LNM (pelvic or para-aortic, i.e., IIIC1 and IIIC2, respectively), local tumor stage, and histology.

Results: A total of 345 cases (27.4%) were upstaged to stage IIIC, which exhibited a poorer prognosis compared to stage II (HR, 2.12; 95% CI 1.29 - 3.48; p = 0.004) and better than stage IIIAB (HR, 0.46; 95% CI 0.27 - 0.78; p = 0.004). Notably, stage IIIC2 showed a significantly worse prognosis than IIIC1 (HR, 2.32; 95% CI 1.37 - 3.93; p = 0.003). Subdivisions of stage IIIC1 (T1, T2, and T3AB) displayed significantly varied prognoses, with the prognosis for IIIC1-T3AB similar to that of stage IIIAB. In contrast, all subdivisions of IIIC2 showed uniformly poor outcomes. Multivariate analysis of stage IIIC patients revealed that para-aortic LNM, adenocarcinoma and adenosquamous carcinoma histology, and local T3AB tumor remained significant.

Conclusions: The classification of para-aortic LNM as stage IIIC2 has proven to be of critical relevance in the Japanese cohort. However, the prognostic impact of stage IIIC1 remains influenced by local tumor factors and histological subtypes.

Background: The purpose of this study was to compare outcomes and adverse events between three-dimensional conformal radiation therapy (3D-CRT) and intensity-modulated radiation therapy (IMRT) in patients undergoing long-course neoadjuvant radiation therapy (NA-RT) for locally advanced rectal adenocarcinoma (LARC).

Methods: We retrospectively analyzed a total of 47 consecutive patients who received NA-RT for LARC between January 2011 and September 2022. Seven and 40 patients were diagnosed with clinical stages II and III, respectively. The prescribed dose per fraction was 1.8 Gy for total doses of 45 or 50.4 Gy. Seventeen and 30 patients received 3D-CRT and IMRT, respectively. NA-RT was delivered with concurrent chemotherapy of oral administration of S-1.

Results: Planned NA-RT was completed without any treatment interruption in 43 of the 47 patients. Two patients experienced treatment interruption, and two patients discontinued due to grade ≥ 3 toxicities. No significant differences were observed between patients receiving 3D-CRT and IMRT in local control, progression-free survival, and overall survival (P = 0.488, 0.259, and 0.636, respectively). Patients receiving IMRT showed significantly fewer non-hematological grade ≥ 2 acute toxicities than those receiving 3D-CRT (33.3% vs. 70.6%, P = 0.018). In addition, patients who received IMRT tended to have less intestinal toxicity of grade ≥ 2 than those who received 3D-CRT (P = 0.057).

Conclusion: IMRT significantly reduced grade ≥ 2 acute toxicities without compromising oncologic outcomes compared to 3D-CRT. Therefore, IMRT may be considered as a current standard treatment in the total neoadjuvant therapy era.

Doxorubicin + cisplatin and paclitaxel + carboplatin are standard chemotherapy regimens for endometrial cancer. The development of PD-1 and PDL-1 antibody drugs has led to the use of these agents for endometrial cancer in other countries. The KEYNOTE-775 trial for advanced or recurrent endometrial cancer demonstrated the benefits of pembrolizumab and lenvatinib combination therapy, and the results of this trial led to the approval of its coverage for recurrent cancer by the Japanese health insurance system. Currently, treatment with immune checkpoint inhibitors is transitioning from second-line to first-line therapy. In a global randomized phase III study, the drugs dostarlimab, durvalumab, and atezolizumab, which are not yet approved in Japan, showed better results in the study arms than in the control arm. Additionally, biomarkers have been developed for endometrial cancer, enabling gynecologists to pursue treatment options based on the biomarkers detected for better treatment outcomes. In this article, we review the clinical trials of immune checkpoint inhibitors for advanced or recurrent endometrial cancer.

Background: Nivolumab is the standard treatment for platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (R/M-HNSCC). Several studies have reported the efficacy of paclitaxel plus cetuximab (PC) combination therapy in this patient population.

Methods: We conducted a retrospective analysis of patients with platinum-refractory R/M-HNSCC treated with nivolumab or PC at our institution between January 2015 and March 2022. Eligibility criteria included histologically confirmed HNSCC, ECOG performance status (PS) 0-2, with platinum-refractory R/M disease, defined as recurrence or disease progression within 6 months after platinum-based definitive chemoradiotherapy.

Results: The baseline characteristics of the 56 patients (21 PC/35 nivolumab) were ECOG PS 1-2 (76/54%), metastatic sites ≥ 2 (33/46%), local recurrence (62/23%), and median tumor size (43.2/26.2 mm). Median progression-free survival (mPFS) tended to favor PC over nivolumab (4.3/2.7 months, hazard ratio [HR]: 0.7, p = 0.41), and median overall survival tended to be inferior for PC (8.0/23.2 months, HR: 1.58, p = 0.20). Similar results were obtained after adjusting for several relevant factors. The objective response rate was numerically higher with PC (31/19%). Grade 3/4 adverse events were more frequent with PC (29/6%), and the most prevalent were leukopenia (19%) for PC and liver dysfunction (6%) for nivolumab. Subsequent treatment with PC and nivolumab was administered to 75% and 72% of patients, respectively; the mPFS of these patients was significantly lower with PC (1.6/9.2 months, HR: 9.9, p < 0.001).

Conclusion: Both PC and nivolumab are viable treatment options for platinum-refractory R/M-HNSCC, though their efficacy and safety profiles should be carefully considered.

Early cancer detection substantially improves the rate of patient survival; however, conventional screening methods are directed at single anatomical sites and focus primarily on a limited number of cancers, such as gastric, colorectal, lung, breast, and cervical cancer. Additionally, several cancers are inadequately screened, hindering early detection of 45.5% cases. In contrast, Multi-Cancer Early Detection (MCED) assays offer simultaneous screening of multiple cancers from a single liquid biopsy and identify molecular changes before symptom onset. These tests assess DNA mutations, abnormal DNA methylation patterns, fragmented DNA, and other tumor-derived biomarkers, indicating the presence of cancer and predicting its origin. Moreover, MCED assays concurrently detect multiple cancers without recommended screening protocols, potentially revolutionizing cancer screening and management. Large trials have reported promising results, achieving 50-95% sensitivity and 89-99% specificity for multiple cancer types. However, challenges, regarding improving accuracy, addressing ethical issues (e.g., psychosocial impact assessment), and integrating MCED into healthcare systems, must be addressed to achieve widespread adoption. Furthermore, prospective multi-institutional studies are crucial for demonstrating the clinical benefits in diverse populations. This review provides an overview of the principles, development status, and clinical significance of MCED tests, and discusses their potential and challenges.

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.