Japanese Journal of Cancer and Chemotherapy最新文献

Immune checkpoint inhibitors(ICIs)currently play a predominant role in the standard treatment of non-small cell lung cancer(NSCLC)across all stages. While PD-L1 positivity has traditionally been used as the sole effective biomarker, evidence suggests that certain efficacy exists even in PD-L1-negative lung cancers. Various investigations have been conducted to identify biomarkers predicting the therapeutic efficacy of ICIs, focusing on both tumor-local and host-related factors. Among indicators reflecting the host status, the gut microbiota has garnered attention, with its composition and diversity potentially influencing the efficacy of ICI therapy. The presence of specific gut microbiota has been frequently reported to enhance the effectiveness of ICI treatment. Furthermore, the use of antibiotics may diminish the effects of ICIs, while fecal microbiota transplantation has shown potential to enhance ICI therapy. In our department, analysis of the gut microbiota in patients receiving anti-PD-1 antibody treatment has been conducted, yielding promising results through the identification of specific bacterial species and the search for these species using real-time PCR, suggesting avenues for further research. Recently, attention has also been drawn to the lung microbiota and tumor microbiota in the context of lung cancer, with reports suggesting that increased diversity in these microbial communities may correlate with the efficacy of ICI therapy. However, none of these findings alone provide sufficient evidence as standalone biomarkers, necessitating future research to advance from both the host environment, including the gut microbiota, and the microenvironment of the tumor site, such as the lung and tumor microbiota.

In Japan, cancer immunotherapy using immune checkpoint inhibitors(ICIs)has become a new treatment modality in cancer chemotherapy in the 2010s, and is now widely approved for many types of cancer. Today, combination cancer immunotherapy utilizing ICIs is being developed, with many cancer types. The first approved ICI combination in Japan consists of nivolumab, an anti-PD-1 antibody, and ipilimumab, an anti-CTLA-4 antibody. In the combination therapy, ipilimumab is administered at different doses, intervals, and frequencies depending on the cancer type. ICI combination therapy has been reported to be more effective than ICI monotherapy, but also be associated with more severe adverse events. Therefore, optimal dosing strategies for ipilimumab were explored considering both treatment efficacy and adverse event profiles. In the study of 64 cases with multiple cancer, higher efficacy of ICI combined therapy was expected in cases with irAEs, and there were cases with long-lasting efficacy even after early discontinuation of ipilimumab due to irAEs. And the high dose(3 mg/kg)of ipilimumab was suggested to be an independent risk factor for CTCAE Grade 3 or higher for severe irAEs.

Background: Transitioning patients with cancer to end-of-life care settings poses psychological and operational challenges for patients, families, medical personnel, and collaborating medical institutions. However, such transitions may not always occur due to patient's deteriorating condition or death. Predicting the feasibility of these transitions is crucial for effective use of medical resources and effectuating end-of-life wishes. However, there are no reports examining the factors contributing to the discontinuation of adjustment.

Methods: We conducted a retrospective analysis of 235 patients with terminal cancer at our hospital, assessing estimated prognosis, preferred place of care, number of days of MSW intervention, number of days survived post-intervention, and completion/discontinuation of adjustment. Medical social workers(hereafter, MSW)facilitated patient transitions in FY2021. We calculated odds ratios associated with adjustment discontinuation and estimated prognosis.

Results: On average, patients received 22.9 days of intervention. Those patients completing the transition spent an average of 20.3 days at home and 28.6 days in a facility(p<0.001), with home adjustment being significantly shorter. Patients with estimated prognosis of less than 1 month were 7.1 times more likely to adjustment discontinuation than those with an estimated prognosis of 1 month or more.

Conclusion: Patients with estimated prognosis of less than 1 month were less likely to complete the adjustment. Considering the psychological and operational challenges for patients, families, and medical personnel, end-of-life care in cancer treatment hospitals must be considered. More information on the factors leading to the discontinuation of adjustments is expected to be accumulated in the future.

The research field of immunogenomics, which elucidates the detail information of immune cells and HLA based on genomic information, is becoming an essential field for understanding the pathology not only in cancer field but also in autoimmune diseases, organ transplantation, and other areas where immune responses are involved. With the comprehensive understanding of T cell receptors, B cell receptors, cancer mutational profiling, we believe that immunogenomics will greatly contribute to personalized medicine by elucidating various pathological and immunological conditions. In this article, we introduce specific examples of immunogenomics in cancer field for better understanding Immunogenomics.

Paternalistic decision-making continued in the past, not only in cancer care. It has since been replaced by self-determination by the patient. As the concept of advanced care planning has spread, the importance of shared decision-making between healthcare professionals and patients has been recognized. In addition, family participates in the process with Key Role in Japan. Decisions are sometimes painful, especially with advanced cancer. Families provide emotional support to the patient and participate in decision-making as an advocate when it is difficult to make decisions. Furthermore, barriers and coping with that in Japan are also mentioned. When patients have unrealistic hopes, healthcare providers can express their concerns while taking care not to deny their wishes. Patients with dementia are what they are. For patients who avoid decision-making, it is important to assess their current physical pain symptoms and emotional burden. Suffering reduces energy of the patient and can prevent thinking about the future. Future issues need to address ethical aspects and overcome clinical challenges.

Colorectal villous tumors secrete large amounts of mucus that can cause electrolyte abnormalities and dehydration, a condition known as electrolyte depletion syndrome. A woman in her 70s, who had been underweight for 10 years with a body mass index(BMI)of 16, was admitted to our hospital with electrolyte abnormalities, renal disorders, and rectal tumors. The electrolyte abnormalities and renal disorders were corrected relatively quickly with supplemental fluid therapy. Notably, 1,000 g of mucus stool per day was observed; subsequently, a lower gastrointestinal endoscopy revealed a circumferential villous tumor in the Rb of the rectum, which was biopsied and diagnosed as rectal cancer and electrolyte depletion syndrome. The patient was temporarily discharged from the hospital; however, several days later, the electrolyte abnormalities and renal disorders recurred. The patient was readmitted to the hospital and underwent robot-assisted Hartmann's surgery after improvement of the general condition of the patient. Postoperative pathology revealed papillary adenocarcinoma with SM depth, and the patient progressed without recurrence or relapse of electrolyte depletion syndrome.

Malignant psoas syndrome(MPS)is characterized by intractable pain in the region innervating the first to fourth lumbar nerves resulting from the invasion of malignant tumors into the psoas muscle. A 57-year-old man underwent a right upper lobectomy with lymph node dissection for pStage ⅠB combined small cell lung cancer(SCLC). Adjuvant chemotherapy was subsequently administered in 2022. At 9 months postoperatively, metastases to the liver and lymph nodes of the hepatic portal region were detected. After multidisciplinary treatment, the recurrent lesions were identified as progressive disease. Eight months after the recurrence, the patient complained of severe pain in the left leg. Contrast-enhanced CT showed swelling of the left psoas muscle, and the patient was diagnosed with MPS. Usually caused by cancer of the abdominal organs, MPS is uncommon in patients with lung cancer. Here we report a case of combined SCLC presenting as MPS.

A 74-year-old woman was diagnosed with invasive breast ductal carcinoma, cT2N0M1 (PUL), stage Ⅳ, and treated with abemaciclib and letrozole. The day after drug administration, the patient developed a fever of 38℃ and dyspnea upon exertion, and was diagnosed with drug-induced pneumonia. Steroid pulse therapy was administered during hospitalization, and the patient was discharged after the dose of prednisolone was gradually reduced. This case shows that, when abemaciclib is administered, drug-induced lung injury can occur within 1 week.

Programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1)axis is well known as the system resulting in the inhibition of immune responses and promotion of self-tolerance. The clinical indications for immune checkpoint inhibitors( ICIs), including the targeting of PD-1/PD-L1 axis, are dramatically expanding. However, since ICIs have been found to be ineffective or resistant in some types of cancer, the development of more effective combination therapies or predictors and biomarkers of efficacy are expected. On the other hand, we have been focusing on the tumor microenvironment(TME)as a therapeutic target, and have been analyzing the function of cancer-associated fibroblasts(CAFs), which play a central role in TME. Recently, CAFs are known to induce tumors to an immunosuppressive state, suggesting that ICIs may not be effective in such a cancer microenvironment. In this review, we demonstrated the impact of PD-L1 positivity in cancer cells and CAFs by immunohistochemistry for resected specimens. In addition, we evaluated the potential of PD-L1-positve CAFs for therapeutic target and biomarker for ICIs.