International Journal of Clinical Oncology最新文献

The efficacy of molecularly targeted agents has been established in advanced lung cancer, and their indications have recently expanded to include perioperative treatment of resectable lung cancer. For epidermal growth factor receptor (EGFR) mutation-positive patients, postoperative adjuvant therapy with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) is available in Japan following the results of the ADAURA trial. In addition to EGFR-TKIs, postoperative adjuvant therapy with TKIs targeting anaplastic lymphoma kinase (ALK) and rearranged during transfection (RET) is expected to be established. On the other hand, because adjuvant chemotherapy is ineffective in patients who have been completely cured of cancer through surgery alone, the balance between efficacy and adverse effects must be considered, and further studies will be needed to determine the necessary and sufficient dosage and the appropriate duration of administration. In addition, the cost of adjuvant chemotherapy has recently become an issue that cannot be overlooked. Therefore, it will be imperative to develop biomarkers to effectively narrow down the patients who benefit from adjuvant chemotherapy.

Background: Lung adenocarcinoma (LUAD) causes leading death worldwide. Mitophagy and lactate metabolism accumulation are distinctive features of LUAD. We aimed to identify lactate-related genes (LRGs) signatures based on mitophagy for predicting prognosis and immune response in LUAD.

Methods: The gene expression and clinical data were downloaded from TCGA and GEO database. First, the subtype analysis was analyzed based on 29 mitophagy genes. Survival, immune, and function differences between the different subtypes were analyzed. Then, based on mitophagy genes and 14 LRGs, the best LRGs were screened to construct a risk score model and combined with clinical factors to establish a nomogram for predicting patient survival. Finally, the expression level and molecular function of the key candidate gene OGDH were verified by in vitro experiments.

Results: All the LUAD samples were divided into 2 subtypes: sub1 and sub2. The sub2 possessed worse survival. Immune score, immune checkpoint genes, and human leucocyte antigen genes in sub1 were higher than in sub2. Six optimal mitophagy-related LRGs were used to construct a risk score model. A high-risk score indicates poorer survival, higher tumor mutation burden, and higher drug sensitivity. The nomogram was robust in predicting LUAD survival. The experiments in vitro showed that knockdown of OGDH inhibited the proliferation, migration and invasion in LUAD cells.

Conclusions: A nomogram based on the construction of the mitophagy-related lactate genes predicts prognosis and immune response in LUAD. These results could help with risk stratification and targeted therapy for LUAD.

Background: For prostate cancer (PCa) in the elderly, including patients ≥ 80 years, the safety of robot-assisted radical prostatectomy (RARP) is controversial. We aimed to evaluate the effect of aging on the postoperative complication rates after RARP.

Methods: This cohort study used a database of patients who had undergone RARP at 25 different institutes. We divided the cohort into four age groups (< 70, 70-74, 75-79, and ≥ 80 years). The complication rates after RARP in the 70-74, 75-79, and ≥ 80 year group were compared using the < 70 year group serving as the control group by applying the inverse probability of treatment weighting (IPTW)-adjusted regression analysis.

Results: A total of 8055 patients were evaluated. The postoperative complication rates were 8.8%, 9.7%, 9.6%, and 10.0% in the < 70, 71-74, 75-79, and ≥ 80 age groups, respectively. In IPTW-adjusted analyses, the risk of overall complications (< 70 vs. 70-74 year group: OR = 1.09 [95% CI 0.92-1.29]; < 70 vs. 75-79 year group: OR = 1.09 [95% CI 0.88-1.37], and < 70 vs. ≥ 80 year group: OR = 2.21 [95% CI 0.92-5.32]) did not change with increasing age. There was no significant increase in risk for any complication category, such as bowel dysfunction, symptomatic lymphocele, or bacterial infection, between the < 70 and ≥ 80 age groups.

Conclusion: Our findings showed that, in appropriately selected patients, the risk of complications after RARP did not increase with age, even at 75 or 80 years.

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: Osteosarcoma, the most common primary bone malignancy, has a complex genetic basis and two incidence peaks. In younger patients, the standard treatment involves wide surgical resection combined with adjuvant chemotherapy; however, the role of chemotherapy in elderly patients remains controversial. The aims of this study were to investigate genetic differences between younger and elderly patients with osteosarcoma and to identify genetic signatures associated with chemotherapy response.

Methods: Genetic alterations were analyzed using cancer genome profiling data for 204 patients with osteosarcoma obtained from the Center for Cancer Genomics and Advanced Therapeutics.

Results: The mutation spectrum was consistent with previous results for osteosarcoma. CCNE1, MCL1, MYC, and RB1 alterations were significantly associated with a younger age, while CDK4, CDKN2A, CDKN2B, H3F3A, KMT2D, MDM2, RAC1, and SETD2 alterations were significantly associated with an older age. Age, unsupervised clustering of gene alterations, and MYC amplifications were significantly associated with the response to ifosfamide. Notably, both clustered mutation signatures and MYC amplification were correlated with age.

Conclusions: These findings suggest that distinct oncogenic mechanisms contribute to differential sensitivity to chemotherapy in younger and elderly patients. Cancer genome profiling may aid in chemotherapy selection, and its early implementation is recommended to optimize treatment strategies.

Background: This systematic review and meta-analysis aimed to investigate the association between health-related quality of life (HRQOL) as measured with the Short Form 36 Health Survey (SF-36) or Short Form 12 Health Survey (SF-12) and mortality risk in patients with diverse types of cancer.

Methods: A literature search was conducted using CINAHL, PubMed/MEDLINE, and Scopus databases to collect articles published before December 2022. Of these, observational studies that examined the association between HRQOL and mortality risk in patients with various cancer types were extracted. A subgroup analysis with a focus on the timing when HRQOL assessment was performed.

Results: Nineteen studies were included in the final analysis. Through overall analysis of the timing of HRQOL measurements, most domains were found to be significantly associated with the mortality risk, irrespective of the timing of assessment, but HRQOL assessed in pre-treatment and palliative phases had particularly strong association.

Conclusions: In the present review, the physical functioning domain of HRQOL was found to be associated with mortality risk in a diverse group of cancer patients. This suggests the need for supportive care to improve HRQOL in cancer patients.

Background: Biweekly irinotecan plus cisplatin combination therapy (BIRIP) and irinotecan monotherapy (IRI) are both expectable second-line chemotherapy (SLC) options for treating advanced gastric cancer (AGC). Although many patients receiving SLC have undergone gastrectomy, the impact of gastrectomy on SLC remains unclear, and the impact of gastrectomy may vary from regimen to regimen.

Patients and methods: A total of 290 eligible patients registered in two randomized phase III trials evaluating BIRIP (IRI, 60 mg/m²; CDDP, 30 mg/m², q2w) or IRI (150 mg/m², q2w) for patients with AGC was classified into the prior gastrectomy subgroup (PGG) or the no gastrectomy subgroup (NGG). We performed a subgroup analysis to evaluate the impact of gastrectomy on second-line BIRIP and IRI.

Results: The BIRIP demonstrated significantly longer OS (11.1 vs. 6.8 months; HR 0.64; P = 0.026) and PFS (3.7 vs. 2.3 months; HR 0.54; P = 0.003) than the IRI, as well as better ORR (23.5% vs. 7.1%, P = 0.046) and DCR (74.5% vs. 47.6%, P = 0.010) in NGG. Although in PGG, the BIRIP failed to demonstrate differences in OS (13.8 vs. 13.8 months; HR 0.94; P = 0.722), PFS (4.9 vs. 4.5 months; HR 0.82; P = 0.194), ORR (18.3% vs. 20.5%) and DCR (70.4% vs. 65.1%). The incidence of grade 3 or worse adverse events did not differ except for a high incidence of anemia in the BIRIP group in PGG.

Conclusions: BIRIP was an effective treatment option that may improve survival outcomes among patients with AGC without previous gastrectomy.

Clinical trial registration: UMIN000025367.

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.

Background and objective: Lymph node metastasis (LNM) in soft tissue sarcoma (STS) of the extremities is relatively rare. We aimed to evaluate the prognosis and the survival of patients with LNM and correlate them to the pattern of metastasis.

Methods: A retrospective study of patients diagnosed with STS of the extremities from 2015 to 2019.

Results: 111/1506 patients (7.4%) had LNM. Nodal metastasis was correlated significantly with old age, advanced tumor stages, high-grade tumors, presence of Lymphovascular invasion (LVI), and resection margins <  = 2 cm. Metachronous LNM was documented in 96 patients (86.5%) and synchronous LNM in 15 patients (13.5%). The 6-year overall survival (OS) was 36.3% for those with LNM and 52.9% for those without LNM. The 6-year disease-free survival (DFS) was 5.7% for those with LNM and 32.6% for those without LNM. Metachronus pattern of LNM showed a significantly poorer outcome regarding 6-year OS and DFS than the synchronous pattern.

Conclusions: LNM significantly negatively predicts OS and DFS in the extremities' STS. In particular, the metachronous pattern of LNM indicates a grave prognosis as these patients are supposed to harbor an occult LNM at presentation and were not subjected to lymphadenectomy at their initial primary treatment surgery. Therefore, seeking a valid noninvasive diagnostic tool such as sentinel lymph node biopsy to detect nodal metastasis is necessary.

Background: Treatment-related skin reactions (TRSRs) induced by enfortumab vedotin (EV) targeting nectin-4 are among the most common adverse events. However, their association with survival and treatment response is poorly understood.

Methods: We retrospectively identified patients who received EV from December 2021 to April 2023 at Nagoya University Hospital and its affiliated facilities and extracted clinical data from their medical records. We evaluated cancer-specific survival (CSS) and progression-free survival (PFS) as survival outcomes and overall response rate (ORR) and disease control rate (DCR) as treatment responses between patients with and without TRSRs.

Results: In total, 67 eligible patients were identified. Thirty-four patients experienced TRSRs, and the remaining 33 did not experience TRSRs. The median follow-up period was 8 months. Patients in the TRSRs group demonstrated significantly longer median CSS (15 vs. 8 months; p = 0.003) and median PFS (10 vs. 5 months; p < 0.001) than the non-TRSRs. Regarding treatment response, the patients in the TRSRs group showed a favorable, albeit nonsignificant, treatment response trend compared with those in the non-TRSRs group (ORR, 73.5% vs. 51.5%; p = 0.107; DCR, 91.2 % vs. 81.8%; p = 0.444).

Conclusions: Patients with TRSRs demonstrated more prolonged survival and superior treatment responses to EV treatment. The role of TRSR as a surrogate marker of EV's efficacy should be further explored in prospective and sufficiently powered studies.