Japanese journal of clinical oncology最新文献

Background: Pazopanib is used to treat relapsed and refractory sarcomas. Pazopanib's role in pediatric, adolescent, and young adult populations remains unestablished.

Methods: To assess pazopanib's utility, we analyzed retrospectively collected data from pediatric (0-14 years) and adolescent and young adult (15-39 years) patients diagnosed with relapsed or refractory sarcomas who received pazopanib.

Results: We assessed data from 21 patients (10 pediatric, 11 adolescent, and young adult). Their diagnoses included osteosarcoma (n = 11), rhabdomyosarcoma (n = 4), alveolar soft part sarcoma (n = 5), and leiomyosarcoma (n = 1). Thirteen (62%) patients presented with metastatic disease at the initial diagnosis. Patients had received a median of three prior chemotherapy regimens (range: 0-6). The median duration of pazopanib treatment was 3.5 months (range: 1-12) for pediatric patients and 4 months (range: 1-83) for adolescents and young adults. Nine patients (five adolescents and young adults) discontinued pazopanib owing to disease progression, and two discontinued owing to adverse events (pneumothorax). We observed seven cases of stable disease (four adolescents and young adults) and 12 of progressive disease (six adolescents and young adults) after ~3 months. The median survival following pazopanib initiation was 7.8, 4.8, and 12.4 months for overall, pediatric, and adolescent and young adult patients, respectively.

Conclusions: In a small cohort of children and adolescent and young adult patients with heavily pretreated relapsed or refractory sarcoma, pazopanib may be a feasible option. Further research on optimal therapeutic timing and the target population for pazopanib's indication is required.

Objectives: This article aims to describe the newly developed Japanese practice guidelines for psychological distress of adult individuals with cancer who have elevated levels of psychological distress.

Methods: We conducted systematic reviews and Delphi consensus rounds to determine the levels of certainty of evidence and strength of recommendation.

Results: In our proposed flow of care, all individuals with cancer should initially be provided with general support, comprising supportive communication, detection of psychological distress, attendance to their needs, and differentiating physical conditions that mimic psychological distress. If a patient still has significant psychological distress despite such support, more specific care for psychological distress should be considered. Collaborative care has strong evidence base and is strongly recommended. Evidence for psychotherapy for psychological distress and fear of cancer recurrence is moderate to strong, however, recommendations for these interventions were weakened because of the heterogeneity of interventions and lack of formal training system. Evidence of pharmacotherapy was weak. Thus, anxiolytics are weakly recommended only for short term and should be accompanied with psychosocial support. Antidepressants are weakly recommended when a patient is diagnosed with depression. Early specialized palliative care, care for caregivers and peer support are not recommended as a sole means to alleviate psychological distress, due to the scarce supporting evidence. Provision of these interventions is not hindered when they aim to improve the outcomes other than psychological distress, such as quality of life, symptom burden and self-efficacy.

Discussion: New practice guidelines for psychological distress of adult individuals with cancer have been developed.

Background: Olfactory neuroblastoma (ONB) is a rare malignant tumor of the nasal cavity and paranasal sinuses. In this study, we aimed to analyze ONB cases registered in the nationwide Head and Neck Cancer Registry of Japan.

Methods: Among 90 885 head and neck cancer registrations (2011-19), we identified 346 patients with ONB. We summarized demographics, tumor-node-metastasis (TNM) classification, and treatment modalities (surgery, radiotherapy, chemotherapy) and compared patterns between an early (2011-15) and a late (2016-19) period. Survival was analyzed in 95 patients with standardized 5-year outcomes available.

Results: T4 lesions were frequent, and 234 patients (67.6%) received surgery-based treatment, typically combined with postoperative radiotherapy. Over time, endoscopic approaches increased markedly and became predominant over open skull base surgery. Among the 95 patients with evaluable follow-up, the 5-year overall survival (OS) and 5-year recurrence-free survival (RFS) were 85.1% and 62.7%, respectively. Patients <60 years old and female patients exhibited better OS compared to younger patients and males. Postoperative radiotherapy was associated with improved RFS but not OS. Chemotherapy was used more often with open skull base surgery than with other surgical approaches.

Conclusions: Endoscopic surgery for ONB rose substantially, while younger age and female sex were associated with better OS, and postoperative radiotherapy was correlated with improved RFS.

Messenger RNA (mRNA) offers a powerful platform for therapeutic cancer vaccines. Several clinical trials targeting tumor-associated antigens and neoantigens have demonstrated promising immunological and clinical responses. For effective cancer vaccination, technologies for in vivo mRNA delivery and mRNA molecular design are essential. mRNA delivery systems, typically based on synthetic nanoparticles, are designed to protect mRNA from enzymatic degradation, facilitate its delivery to lymphoid organs and antigen-presenting cells, and stimulate innate immune responses to serve as adjuvants. To maximize the potential of these delivery systems, molecular design of the delivered mRNA is also critical. Strategies such as nucleoside modification, self-amplifying RNA, circular RNA, and hybridization-based mRNA engineering are employed to modulate the immunostimulatory properties of mRNA, extend the duration of antigen presentation, and introduce additional functionalities to the delivery systems. While technological advances in these areas have significantly contributed to the recent progress of mRNA cancer vaccines, current formulations, including widely used lipid nanoparticles (iLNPs), still have considerable room for improvement in terms of safety and efficacy. This has prompted vigorous research efforts to redesign iLNPs and explore non-lipid-based approaches. In this context, this review outlines the established foundational technologies and highlights ongoing research in mRNA delivery and engineering, with a focus on their biological and functional aspects.

Objective: Despite standard induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT), locoregionally advanced nasopharyngeal carcinoma (LANPC) continues to relapse and metastasize at high rates. Recent advances suggest that integrating immunotherapy and target agents may improve outcomes. This study aimed to evaluate the short-term efficacy and safety of combining PD-1 inhibitor and nimotuzumab with induction chemotherapy in LANPC patients.

Methods: We retrospectively analyzed 197 patients with LANPC treated at our institution between January 2022 and December 2023. Patients received either induction chemotherapy (IC) alone or IC plus PD-1 inhibitor and nimotuzumab (ICIT), followed by CCRT. Propensity score matching yielded 90 IC and 45 ICIT patients for analysis. Efficacy, adverse events, and survival outcomes were evaluated after induction and full course.

Results: The median follow-up duration was 22.8 months. Induction best overall response was higher with ICIT than with IC alone (95.6% vs. 80.0%, P = .03), driven by a marked reduction in stable disease. Subgroup analysis showed pronounced benefit in males, patients with advanced N stage, and those with high epidermal growth factor receptor expression. The ICIT group showed a trend toward improved early tumor shrinkage, with no locoregional failures observed. Hematologic toxicities were similar between groups, while the ICIT group experienced higher rates of grade 3 mucositis and hepatic toxicity.

Conclusions: Adding PD-1 inhibitor plus nimotuzumab to induction chemotherapy improved early tumor shrinkage while maintaining an acceptable safety profile. These encouraging early data reinforce the need for ongoing prospective trials to confirm long-term benefit and to refine patient selection.

The ARASENS trial demonstrated a significant overall survival (OS) benefit for a triplet regimen in metastatic castration-sensitive prostate cancer (mCSPC). We aimed to determine whether this benefit is synergistic or additive. Using a mathematical model of independent drug action and published data from the ARASENS and ARANOTE, we compared the observed OS of the triplet regimen to a predicted OS curve. Reconstructed individual patient data were compared using a Cox model. The observed OS was statistically superior to the predicted OS (hazard ratio [HR] 0.82, 95% CI 0.68-0.99; P = .047), indicating a clinical benefit ~18% greater than the expected additive effect. To address confounding by subsequent therapies, we analyzed time to initial subsequent anticancer therapy, which showed an even more pronounced greater-than-additive benefit (HR 0.57, 95% CI 0.44-0.74; P < .001). These findings suggest the triplet regimen provides an early therapeutic advantage that exceeds additive expectations, supporting an upfront combination strategy in mCSPC.

Objective: To identify pretreatment factors associated with developing primary resistance to nivolumab plus ipilimumab therapy in patients with advanced renal cell carcinoma (RCC).

Methods: We retrospectively reviewed the clinical characteristics, laboratory data, and tumor-related factors in patients with advanced RCC who initiated nivolumab plus ipilimumab as first-line therapy between January 2018 and July 2021. Primary resistance was defined as radiographic or clinical progression within 3 months of treatment initiation. Cases with suspected pseudoprogression were excluded.

Results: Eighty-nine patients met the inclusion criteria; 23 exhibited primary resistance. Univariate analysis identified the following significant predictive factors: body mass index (P = .006), lymph node metastasis (P = .021), sarcomatoid differentiation (P = .035), solitary metastatic organ (P = .051), liver metastasis (P = .056), and serum lactate dehydrogenase (LDH) (P = .094). Receiver operating characteristic curve analysis determined an LDH cutoff value of 174 U/L, which was significantly associated with primary resistance (P = .029). Considering the number of primary resistance cases, multivariable analysis incorporated three candidate variables (lymph node metastasis, sarcomatoid differentiation, and LDH ≥ 174 U/L) and identified sarcomatoid differentiation (odds ratio, 4.264; 95% confidence interval (CI), 1.299-14.825; P = .017) and LDH ≥ 174 U/L (odds ratio, 3.634; 95% CI, 1.143-13.770; P = .028) as independent predictors of primary resistance.

Conclusions: Sarcomatoid differentiation on pretreatment biopsy or elevated serum LDH before treatment initiation may predict primary resistance to nivolumab plus ipilimumab therapy in patients with advanced RCC. Alternative regimens should be considered in such cases, particularly for patients who are likely to experience rapid disease progression or for whom the occurrence of P-res is not clinically acceptable.

Background: Extended waiting periods between cancer diagnosis and treatment initiation may impact patients' quality of life and prognosis. However, few studies have examined the current situation in Japan and the factors influencing these waiting periods.

Methods: This study included individuals with gastric cancer (n = 1956), colorectal cancer (n = 2843), lung cancer (n = 3309), and female breast cancer (n = 3172) diagnosed in 2016-17 at 19 facilities in the Hokushin region of Japan. The proportion of patients who waited over 30 days for each cancer type was calculated. Multilevel logistic regression analysis was used to examine the association between waiting over 30 days and patient and facility characteristics.

Results: The proportions of patients who waited over 30 days were 53.7% for gastric cancer, 42.8% for colorectal cancer, 50.5% for lung cancer, and 75.7% for female breast cancer. Among lung cancer patients, elderly patients showed a higher proportion of waiting over 30 days compared to younger patients. Patients at medical institutions with a large number of hospital beds showed higher proportions of waiting over 30 days across multiple cancer types.

Conclusion: In the Hokushin region, patients who waited over 30 days are prevalent among female patients with breast cancer compared to other cancer types, and among older adults with lung cancer compared to younger lung cancer patients, as well as in medical institutions with a large number of hospital beds across cancer types. Hence, efforts to reduce this number are needed.