International Journal of Clinical Oncology最新文献

Background: Appearance care enables cancer patients to maintain social connections during treatment, but it remains an unmet need in Japan. We surveyed healthcare professionals in Japan to collect information on their awareness of appearance care and their institutions' appearance care systems.

Methods: From November 1 to December 13, 2022, we performed an online survey of 16,838 members of the Japan Society of Clinical Oncology.

Results: We received responses from 807 members (671(83%) physicians; 65(8%) pharmacists; 45(6%) nurses; 22(3%) dentists; and 4(0.5%) others), 72% of whom were men and 28%, women. Among respondents, 93% (n = 749//807) had been asked by patients about appearance care, and 46% (n = 318/693) of the physicians and dentists had refused to perform treatment or changed it because of its effects on physical appearance. Only 59% (n = 410) of physicians and dentists were familiar with the term appearance care, but 100% (n = 45) of nurses and 97% (n = 63) of pharmacists were. Among all respondents, 26% reported that their institution had a specialized department and specific personnel for appearance care. In some cases, physicians and dentists had difficulty communicating correct information to patients, and other healthcare professionals compensated for this deficit.

Conclusion: The survey revealed that physicians have low awareness of appearance care. It was suggested that communication and a team approach between physicians and other healthcare professionals is recommended. Each medical facility may be encouraged to establish a sustainable system for providing information on appearance care in that patients or medical personnel themselves can easily consult. Activities are also needed to raise awareness about appearance care among physicians.

Background: Precision medicine is a promising therapeutic strategy for pancreatic cancer. However, only a few patients are eligible for genotype-matched treatments because of the low detection rate of actionable genomic alterations, and the clinical application of comprehensive genomic profiling (CGP) in pancreatic cancer has not been completely investigated. CGP provides considerable information, including the prognosis and eligibility of patients for genotype-matched treatments, which can guide physicians' treatment strategies. This study aimed to investigate the contribution of CGP to patient outcomes.

Methods: This single-center retrospective cohort study enrolled patients with recurrent or metastatic pancreatic cancer with adenocarcinoma or adenosquamous carcinoma who underwent systemic chemotherapy between April 2018 and April 2022. We reviewed the medical records for patient characteristics, survival, and genomic information. We compared overall survival (OS) between patients who received CGP (CGP group) and those who did not (non-CGP group).

Results: Of 111 eligible patients, 59 underwent CGP. Median OS was significantly longer in the CGP than the non-CGP group (25.2 vs. 11.8 months; hazard ratio, 0.49; P = 0.0013). Six patients (10.2%) underwent genotype-matched treatments, with a median OS of 35.5 months, compared to 17.0 months for those who did not. The CGP group demonstrated a higher transition rate to subsequent chemotherapy than did the non-CGP group (76.3% vs. 48.1%, P = 0.0030).

Conclusions: OS was prolonged in patients with pancreatic cancer who underwent CGP, probably due to its influence on physicians' treatment strategies. These findings highlight the importance of the proactive and timely implementation of CGP in patients with pancreatic cancer.

Background: Axitinib is a widely used tyrosine kinase inhibitor (TKI) in metastatic renal cell carcinoma (mRCC) treatment. Here, we analyzed the characteristics of patients who did not respond to axitinib and evaluated alternative options for their treatment.

Methods: We retrospectively analyzed data for 449 patients with mRCC who were administered axitinib following another TKI as initial therapy. Patients with progressive disease (PD) at their first assessment were defined as showing early-PD. We analyzed the characteristics of patients at risk of early-PD and evaluated the relationship between the treatment following axitinib and their prognosis.

Results: Early-PD was diagnosed in 102 patients, and was more common in those who had not undergone nephrectomy (p < 0.001), those treated with a TKI for a short period (p < 0.001), and those in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) poor risk category for mRCC (p < 0.001). Multivariate analysis showed that these were independent risk factors for early-PD (all p < 0.001). Of those with early-PD, 52 changed to next-line treatment. The progression-free survival periods were 5.5 (95% confidence interval (CI) 2.4-8.6) months for patients administered TKIs, 4.2 (95% CI 0.3-8.1) months for those on nivolumab, and 2.2 (1.8-2.6) months for those on mammalian target of rapamycin inhibitors (p = 0.030).

Conclusion: Patients who have not undergone nephrectomy, those previously treated with another TKI for a short period, and those in the IMDC poor risk category are more likely to experience early-PD when taking axitinib. Furthermore, TKIs are the best treatment for patients with early-PD who have previously been administered axitinib.

Background: In early-stage breast cancer, dose-dense chemotherapy, which involves the administration of standard doses at shorter intervals, is safer when administered with granulocyte colony-stimulating factor (G-CSF) to mitigate chemotherapy-induced neutropenia. This study aimed to thoroughly evaluate the advantages and disadvantages of dose-dense regimens based on the use of G-CSF.

Methods: A systematic review was conducted according to the "Minds Handbook for Clinical Practice Guideline Development" using PubMed, Ichushi-Web, and the Cochrane Library databases. Randomized controlled trials (RCTs) and cohort studies assessing dose-dense chemotherapy with prophylactic pegfilgrastim administration in early-stage breast cancer were included. Outcomes included overall survival, event-free survival, incidence of febrile neutropenia, quality of life (QOL), and pain. Meta-analyses were performed on outcomes with sufficient data.

Results: Our literature search identified 23 RCTs. Overall survival and event-free survival showed a trend favoring dose-dense therapy (hazard ratio, 0.90, 0.90; 95% confidence interval [CI] 0.78 - 1.03, 0.80 - 1.01; p = 0.13; 0.07, respectively). The incidence of febrile neutropenia was similar between the groups (odds ratio, 0.90; 95% CI 0.58 - 1.40; p = 0.65). Mortality due to infection could not be compared owing to the small number of events. Pain increased with dose-dense therapy (odds ratio 2.57; 95% CI 1.00 - 6.62; p = 0.05), likely from G-CSF-induced bone pain. Only one study examined QOL, showing a decline with chemotherapy that recovered after treatment.

Conclusions: Dose-dense chemotherapy trended toward improved survival outcomes without increasing the risk of infection, although pain increased. Further research should identify the specific subgroups that most benefit from dose-dense regimens. More data are needed on the impact on QOL.

Background: Intraductal Carcinoma of the Prostate (IDC-P) is a significant prognostic indicator for prostate cancer, which demonstrates significant associations with homologous recombination repair gene mutations (HRRm) and alterations in tumor suppressor genes. However, no study in Japan has investigated the association between IDC-P and genetic mutations in men with metastatic castration-sensitive prostate cancer (mCSPC).

Methods: This prospective observational study enrolled 102 de novo mCSPC (LATITUDE high-risk) patients diagnosed between 2018 and 2021, with subsequent monitoring of survival outcomes. A single genitourinary pathologist evaluated all needle biopsy slides. Genetic analyses were performed using the Myriad myChoice HRD plus™. These genetic analyses covered 108 genetic loci, including 15 HRRm genes, with a success rate of 91%.

Results: Genetic alterations were observed in 79 patients (77.5%), with 20 exhibiting HRRm (19.6%). Common genetic alterations included FOXA1 (29.4%) and TP53 (17.6%) mutations; BRCA (9.8%) mutations were the most frequent HRRm (BRCA1:2 cases, BRCA2:8 cases, including 6 biallelic). IDC-P-positive patients demonstrated a significantly higher frequency of genetic aberrations (82.6% vs. 50%, p = 0.0082). Patients with biallelic BRCA2, TP53, and PTEN mutations exhibited significantly poorer cancer-specific survival. Multivariate analysis identified lactate dehydrogenase (LDH) (HR 1.005, p = 0.035), TP53 mutations (HR 5.196, p < 0.001), biallelic BRCA2 mutations (HR 10.686, p = 0.005), and IDC-P as independent predictors of poor cancer-specific survival. No cancer-related deaths occurred in IDC-P-negative cases.

Conclusion: Our study emphasizes the significant association between IDC-P and an elevated incidence of genetic alterations in Japanese mCSPC patients, emphasizing the need for early genetic testing to guide therapeutic decision-making.

Background: Human epidermal growth factor receptor 3 (HER3), a tyrosine kinase belonging to the HER family, is a known target for cancer therapy; recently, an anti-HER3 antibody-drug conjugate (ADC) is developing. To understand HER3 expression in epithelial ovarian cancer (EOC), this study was conducted.

Methods: We investigated the expression of HER3 in 202 patients with EOC using immunohistochemistry (IHC), and the association between HER3 expression, clinicopathological features, prognosis, and treatment timing.

Results: Of all the cases, 55.4% had a HER3 IHC score ≥ 1 + . In particular, 78.0% of the patients with clear cell carcinoma (CCC) and 87.9% of the patients with mucinous carcinoma (MC) had a HER3 IHC score ≥ 1 + . Regarding clinicopathological features, early disease stage, feasibility of primary debulking surgery, no residual tumor, and low CA125 levels were more frequently observed in patients with a HER3 IHC score ≥ 1 + . Furthermore, a HER3 no-expression showed a significant association with a relatively short progression-free survival (PFS). And, for patients with mucinous carcinoma, those with a HER3 IHC score ≥ 1 + had poorer PFS and overall survival than those with a HER3 no-expression (no statistically significant difference). In addition, we analyzed HER3 expression at primary tumor and recurrence tumor in same patients. Thus, we observed the HER3 IHC score tended to change from 0 to ≥ 1 + in recurrence cases compared with primary cases.

Conclusions: These observations suggested that patients with MC, CCC and recurrence of all histological type may potentially benefit from future clinical trials of HER3-directed therapies.

Background: Immune checkpoint inhibitors (ICIs) have recently emerged as a promising strategy for the treatment of pleural mesothelioma (PM).

Methods: This retrospective study evaluated treatment efficacy and safety in Japanese patients with PM treated with nivolumab and ipilimumab (N + I group: 41 patients) as first-line therapy and nivolumab monotherapy (N group: 33 patients) as second- or later-line treatment.

Results: The median overall survival (OS) and progression-free survival (PFS) were not reached and 10.4 months in the N + I group, and 8.6 months and 3.5 months in the N group, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 68.3% of the N + I group and 72.7% of the N group, with grade 3-4 TRAEs in 19.5% and 12.1% of patients, respectively. Patients with an ECOG PS 0-1 had significantly better OS and PFS in both treatment groups (p < 0.001). In the N + I group, OS was significantly better in patients with TRAEs (p = 0.020) and in those with the epithelioid subtype (p = 0.047), although PFS was not significantly different (p = 0.138 and p = 0.154, respectively). In the N group, both OS (p = 0.007) and PFS (p = 0.048) were significantly longer in patients with TRAEs.

Conclusion: This study provides valuable real-world clinical evidence of the efficacy and safety of nivolumab plus ipilimumab and nivolumab monotherapy in Japanese patients with PM. These results support the use of ICIs as a viable treatment option for advanced or relapsed disease.

Background: Avelumab + axitinib was approved for the treatment of advanced renal cell carcinoma (aRCC) in Japan in December 2019. We report long-term real-world subgroup analyses with first-line avelumab + axitinib in patients with aRCC by International Metastatic RCC Database Consortium (IMDC) risk classification from the J-DART2 study in Japan.

Methods: J-DART2 was a multicenter, noninterventional, retrospective study examining characteristics, treatment patterns, and outcomes in patients with aRCC who started first-line avelumab + axitinib in Japan between December 2019 and October 2022.

Results: Data from 150 patients across 19 sites were analyzed. IMDC risk was favorable in 39 patients (26.0%), intermediate (1 risk factor) in 46 (30.7%), intermediate (2 risk factors) in 36 (24.0%), and poor in 29 (19.3%). Baseline characteristics were generally consistent across IMDC risk subgroups. In subgroups with favorable, intermediate (1 risk factor), intermediate (2 risk factors), and poor risk, median progression-free survival was 31.0, 15.3, 16.4, and 8.1 months; median overall survival (OS) was not reached, but 24-month OS rates were 95.2%, 91.3%, 85.3%, and 57.6%, respectively. Objective response rates were 54.5%, 56.8%, 47.1%, and 54.2%, respectively. High-dose corticosteroid treatment for immune-related adverse events was administered in 5.1%, 8.7%, 8.3%, and 6.9% of patients, respectively.

Conclusion: Subgroup analyses from J-DART2 confirm the long-term real-world effectiveness of first-line avelumab + axitinib across IMDC risk groups in patients with aRCC in Japan. Our findings were consistent with previous analyses by IMDC risk and support the favorable benefit-risk profile of avelumab + axitinib in clinical practice in Japan.

Background: A BRAF inhibitor, encorafenib, combined with a MEK inhibitor, binimetinib, was approved in Japan in early 2019 for the treatment of BRAF V600-mutant, unresectable malignant melanoma based on results of the global phase III trial, COLUMBUS, conducted in various countries including Japan. This post-marketing surveillance (PMS) assessed the combination in real-world clinical practice in Japan.

Methods: We performed a prospective, multicentre, 12-month PMS of the safety and effectiveness of encorafenib plus binimetinib for radically unresectable, BRAF-mutant malignant melanoma in Japan.

Results: Among 174 survey forms collected from 85 centres between February 2019 and August 2020, 172 were included for safety and effectiveness analysis. Patients (male [52.3%], median age 62.0 years) had Eastern Cooperative Oncology Group Performance Status 0 or 1 (91.8%) and comorbidities (55.2%). Respective encorafenib and binimetinib median dosages were 450 mg/day and 90 mg/day; median treatment duration, 24.1 and 24.2 weeks, and discontinuation, 71.5% for each, primarily for disease progression (56.9%) and adverse drug reactions (ADRs, 38.2%). Safety assessment ADRs occurred in 99 patients (57.6%), including eye disorders (40.7%), hepatic dysfunction (20.3%), rhabdomyolysis (4.7%), haemorrhage (2.3%), palmar-plantar erythrodysaesthesia syndrome (1.7%), and hypertension (1.7%); 19.8% were grade ≥ 3, none were grade 5, most resolved with/without treatment modification. At 12 months, the objective response rate was 48.8% (95% CI 41.2, 56.6; complete [19.2%], partial [29.7%]), overall survival was 40.1%.

Conclusion: The safety and effectiveness of encorafenib plus binimetinib in Japanese patients with BRAF-mutant malignant melanoma were similar to data reported in COLUMBUS; no new safety concerns were identified.

Objectives: Prostate cancer patients receiving androgen deprivation therapy (ADT) have increased risks of decreased bone mineral density (BMD). However, there are no established guidelines for assessing BMD in patients with bone metastases. The aim of this study was to assess the effects of ADT on bone health by comparing longitudinal changes in BMD between prostate cancer patients with and without bone metastases.

Methods: A single-center observational study was conducted from February 2020 to January 2023 at Kobe University Hospital. BMD at the lumbar vertebrae, total hip, and femoral neck was measured at baseline, 6, and 12 months using dual-energy X-ray absorptiometry. Bones were classified into Metastatic Site (with metastases), Non-metastatic Sites (from patients with bone metastases), and Control (patients without metastases) groups. All patients received luteinizing hormone-releasing hormone antagonists or agonists plus oral ARSI or bicalutamide for 1 year.

Results: Among the 78 patients, 35, 110, and 245 bones were classified into the Metastatic Site group, Non-metastatic Sites group, and Control group, respectively. The Metastatic Site group exhibited significantly higher T-scores compared with the other groups (P < 0.001). Repeated measures analysis revealed a statistically significant reduction in T-scores over time across all groups (P < 0.001). However, no significant interaction was observed between group classification and time (P = 0.817).

Conclusion: The present study demonstrates that BMD changes at non-metastatic sites in patients with bone metastases are similar to those in patients without metastases. Monitoring BMD at non-metastatic sites may provide valuable insights into ADT's effects on bone health in prostate cancer patients.