Effectiveness and safety of primary prophylaxis with G-CSF during chemotherapy for invasive breast cancer: a systematic review and meta-analysis from Clinical Practice Guidelines for the Use of G-CSF 2022.

INTRODUCTION: Chemotherapy for breast cancer can cause neutropenia, increasing the risk of febrile neutropenia (FN) and serious infections. The use of granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis has been explored to mitigate these risks. To evaluate the efficacy and safety of primary G-CSF prophylaxis in patients with invasive breast cancer undergoing chemotherapy. METHODS: A systematic literature 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 using G-CSF as primary prophylaxis in invasive breast cancer were included. The primary outcomes were overall survival (OS) and FN incidence. Meta-analyses were performed for outcomes with sufficient data. RESULTS: Eight RCTs were included in the qualitative analysis, and five RCTs were meta-analyzed for FN incidence. The meta-analysis showed a significant reduction in FN incidence with primary G-CSF prophylaxis (risk difference [RD] = 0.22, 95% CI: 0.01-0.43, p = 0.04). Evidence for improvement in OS with G-CSF was inconclusive. Four RCTs suggested a tendency for increased pain with G-CSF, but statistical significance was not reported. CONCLUSIONS: Primary prophylactic use of G-CSF is strongly recommended for breast cancer patients undergoing chemotherapy, as it has been shown to reduce the incidence of FN. While the impact on OS is unclear, the benefits of reducing FN are considered to outweigh the potential harm of increased pain.

Clinical benefit of post-trastuzumab deruxtecan treatment in patients with HER 2-positive unresectable or metastatic breast cancer: A single-institution retrospective observational study.

PURPOSE: Trastuzumab deruxtecan (T-DXd) can improve the prognosis of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). However, data on treatment recommendations after T-DXd are lacking. Thus, this study aimed to evaluate the treatment options after T-DXd and their effectiveness. METHODS: Patients with HER2-positive MBC were included in this study. Data from clinical records were retrospectively analyzed. The primary outcome was time to treatment failure (TTF). Secondary endpoints were TTF of each treatment and first-line treatment after interstitial lung disease (ILD) and overall survival (OS). RESULTS: A total of 29 patients were included. Among them, 18 (62%) were hormone receptor-positive. All patients had a median TTF (mTTF) of 3.5 months (95% confidence interval (CI) 2.1-10.03). The mTTF of each treatment, including HER2 tyrosine kinase inhibitor (HER2 TKI), other anti-HER2 treatments, and other treatments, was 2.6, 8.8, and 3.8 months, respectively. No significant differences were observed between treatments, but regimens that include trastuzumab showed a longer TTF than TKI. However, the mTTF among patients who developed T-DXd-related ILD was 2.33 months (95% CI 0.7-not reached), which was shorter than that among those who did not develop ILD (3.83 months, 95% CI 2.1-10.03, hazard ratio: 2.046, 95% CI 0.760-5.507, p = 0.258). The median OS was 14.9 months (95% CI 11.07-29.17). CONCLUSION: Treatments after T-DXd showed a shorter mTTF. Regimens that include trastuzumab may be more effective post-T-DXd treatment than HER2 TKI. Further data are needed to establish the best sequential treatment after T-DXd.

Comparison between a single dose of PEG G-CSF and multiple doses of non-PEG G-CSF: a systematic review and meta-analysis from Clinical Practice Guidelines for the use of G-CSF 2022.

BACKGROUD: Granulocyte colony-stimulating factor (G-CSF) is widely used for the primary prophylaxis of febrile neutropenia (FN). Two types of G-CSF are available in Japan, namely G-CSF chemically bound to polyethylene glycol (PEG G-CSF), which provides long-lasting effects with a single dose, and non-polyethylene glycol-bound G-CSF (non-PEG G-CSF), which must be sequentially administrated for several days. METHODS: This current study investigated the utility of these treatments for the primary prophylaxis of FN through a systematic review of the literature. A detailed literature search for related studies was performed using PubMed, Ichushi-Web, and the Cochrane Library. Data were independently extracted and assessed by two reviewers. A qualitative analysis or meta-analysis was conducted to evaluate six outcomes. RESULTS: Through the first and second screenings, 23 and 18 articles were extracted for qualitative synthesis and meta-analysis, respectively. The incidence of FN was significantly lower in the PEG G-CSF group than in the non-PEG G-CSF group with a strong quality/certainty of evidence. The differences in other outcomes, such as overall survival, infection-related mortality, the duration of neutropenia (less than 500/µL), quality of life, and pain, were not apparent. CONCLUSIONS: A single dose of PEG G-CSF is strongly recommended over multiple-dose non-PEG G-CSF therapy for the primary prophylaxis of FN.

Optimal timing of prophylactic pegylated G-CSF after chemotherapy administration for patients with cancer: a systematic review and meta-analysis from Clinical Practice Guidelines for the use of G-CSF 2022.

INTRODUCTION: The timing of prophylactic pegylated granulocyte colony-stimulating factor (G-CSF) administration during cancer chemotherapy varies, with Day 2 and Days 3-5 being the most common schedules. Optimal timing remains uncertain, affecting efficacy and adverse events. This systematic review sought to evaluate the available evidence on the timing of prophylactic pegylated G-CSF administration. METHODS: Based on the Minds Handbook for Clinical Practice Guideline Development, we searched the PubMed, Ichushi-Web, and Cochrane Library databases for literature published from January 1990 to December 2019. The inclusion criteria included studies among the adult population using pegfilgrastim. The search strategy focused on timing-related keywords. Two reviewers independently extracted and assessed the data. RESULTS: Among 300 initial search results, only four articles met the inclusion criteria. A meta-analysis for febrile neutropenia incidence suggested a potential higher incidence when pegylated G-CSF was administered on Days 3-5 than on Day 2 (odds ratio: 1.27, 95% CI 0.66-2.46, p = 0.47), with a moderate certainty of evidence. No significant difference in overall survival or mortality due to infections was observed. The trend of severe adverse events was lower on Days 3-5, without statistical significance (odds ratio: 0.72, 95% CI 0.14-3.67, p = 0.69) and with a moderate certainty of evidence. Data on pain were inconclusive. CONCLUSIONS: Both Day 2 and Days 3-5 were weakly recommended for pegylated G-CSF administration post-chemotherapy in patients with cancer. The limited evidence highlights the need for further research to refine recommendations.

Decreased liver B vitamin-related enzymes as a metabolic hallmark of cancer cachexia.

Cancer cachexia is a complex metabolic disorder accounting for ~20% of cancer-related deaths, yet its metabolic landscape remains unexplored. Here, we report a decrease in B vitamin-related liver enzymes as a hallmark of systemic metabolic changes occurring in cancer cachexia. Metabolomics of multiple mouse models highlights cachexia-associated reductions of niacin, vitamin B6, and a glycine-related subset of one-carbon (C1) metabolites in the liver. Integration of proteomics and metabolomics reveals that liver enzymes related to niacin, vitamin B6, and glycine-related C1 enzymes dependent on B vitamins decrease linearly with their associated metabolites, likely reflecting stoichiometric cofactor-enzyme interactions. The decrease of B vitamin-related enzymes is also found to depend on protein abundance and cofactor subtype. These metabolic/proteomic changes and decreased protein malonylation, another cachexia feature identified by protein post-translational modification analysis, are reflected in blood samples from mouse models and gastric cancer patients with cachexia, underscoring the clinical relevance of our findings.

Fact-Checking Cancer Information on Social Media in Japan: Retrospective Study Using Twitter.

BACKGROUND: The widespread use of social media has made it easier for patients to access cancer information. However, a large amount of misinformation and harmful information that could negatively impact patients' decision-making is also disseminated on social media platforms. OBJECTIVE: We aimed to determine the actual amount of misinformation and harmful information as well as trends in the dissemination of cancer-related information on Twitter, a representative social media platform. Our findings can support decision-making among Japanese patients with cancer. METHODS: Using the Twitter app programming interface, we extracted tweets containing the term "cancer" in Japanese that were posted between August and September of 2022. The eligibility criteria were the cancer-related tweets with the following information: (1) reference to the occurrence or prognosis of cancer, (2) recommendation or nonrecommendation of actions, (3) reference to the course of cancer treatment or adverse events, (4) results of cancer research, and (5) other cancer-related knowledge and information. Finally, we selected the top 100 tweets with the highest number of "likes." For each tweet, 2 independent reviewers evaluated whether the information was factual or misinformation, and whether it was harmful or safe with the reasons for the decisions on the misinformation and harmful tweets. Additionally, we examined the frequency of information dissemination using the number of retweets for the top 100 tweets and investigated trends in the dissemination of information. RESULTS: The extracted tweets totaled 69,875. Of the top 100 cancer-related tweets with the most "likes" that met the eligibility criteria, 44 (44%) contained misinformation, 31 (31%) contained harmful information, and 30 (30%) contained both misinformation and harmful information. Misinformation was described as Unproven (29/94, 40.4%), Disproven (19/94, 20.2%), Inappropriate application (4/94, 4.3%), Strength of evidence mischaracterized (14/94, 14.9%), Misleading (18/94, 18%), and Other misinformation (1/94, 1.1%). Harmful action was described as Harmful action (9/59, 15.2%), Harmful inaction (43/59, 72.9%), Harmful interactions (3/59, 5.1%), Economic harm (3/59, 5.1%), and Other harmful information (1/59, 1.7%). Harmful information was liked more often than safe information (median 95, IQR 43-1919 vs 75.0 IQR 43-10,747; P=.04). The median number of retweets for the leading 100 tweets was 13.5 (IQR 0-2197). Misinformation was retweeted significantly more often than factual information (median 29.0, IQR 0-502 vs 7.5, IQR 0-2197; P=.01); harmful information was also retweeted significantly more often than safe information (median 35.0, IQR 0-502 vs 8.0, IQR 0-2197; P=.002). CONCLUSIONS: It is evident that there is a prevalence of misinformation and harmful information related to cancer on Twitter in Japan and it is crucial to increase health literacy and awareness regarding this issue. Furthermore, we believe that it is important for government agencies and health care professionals to continue providing accurate medical information to support patients and their families in making informed decisions.

Chapter 3: Management of kidney injury caused by cancer drug therapy, from clinical practice guidelines for the management of kidney injury during anticancer drug therapy 2022.

Cisplatin should be administered with diuretics and Magnesium supplementation under adequate hydration to avoid renal impairment. Patients should be evaluated for eGFR (estimated glomerular filtration rate) during the treatment with pemetrexed, as kidney injury has been reported. Pemetrexed should be administered with caution in patients with a CCr (creatinine clearance) < 45 mL/min. Mesna is used to prevent hemorrhagic cystitis in patients receiving ifosfamide. Febuxostat is effective in avoiding hyperuricemia induced by TLS (tumor lysis syndrome). Preventative rasburicase is recommended in high-risk cases of TLS. Thrombotic microangiopathy could be triggered by anticancer drugs and there is no evidence of efficacy of plasma exchange therapy. When proteinuria occurs during treatment with anti-angiogenic agents or multi-kinase inhibitors, dose reductions or interruptions based on grading should be considered. Grade 3 proteinuria and renal dysfunction require urgent intervention, including drug interruption or withdrawal, and referral to a nephrologist should be considered. The first-line drugs used for blood pressure elevation due to anti-angiogenic agents are ACE (angiotensin-converting enzyme) inhibitors and ARBs (angiotensin receptor blockers). The protein binding of drugs and their pharmacokinetics are considerably altered in patients with hypoalbuminemia. The clearance of rituximab is increased in patients with proteinuria, and the correlation with urinary IgG suggests similar pharmacokinetic changes when using other antibody drugs. AIN (acute interstitial nephritis) is the most common cause of ICI (immune checkpoint inhibitor)-related kidney injury that is often treated with steroids. The need for renal biopsy in patients with kidney injury that occurs during treatment with ICI remains controversial.

Single-dose trastuzumab monotherapy achieved pathological complete response (pCR) in a patient with HER2-positive breast cancer: a case report.

BACKGROUND: With advances in breast cancer treatment, the importance of de-escalation therapy to reduce harm during the treatment of elderly patients has attracted attention in recent years. Certain patient populations are expected to have a superior response to anti-HER2 drugs, particularly those with human epidermal growth factor receptor type 2 (HER2)-positive breast cancer. In this report, we describe our experience of dramatic anti-HER2 drug response in a patient who achieved pathological complete response (pCR) with a single dose of trastuzumab. CASE PRESENTATION: An 88-year-old woman presented with a 2-cm palpable mass in the left breast. Vacuum-assisted breast biopsy, ultrasonography, and positron emission tomography-computed tomography revealed estrogen receptor-negative and HER2-positive, T1N0M0, stage I breast cancer. Mastectomy was scheduled within 2 months of the initial visit; however, the patient was anxious about the length of the waiting period and requested medication in the interim. Therefore, prior to surgery, one cycle of trastuzumab monotherapy was administered at the discretion of the attending physician. Postoperative pathology showed no remnant of invasive carcinoma and pCR with only a 0.2-mm ductal carcinoma in situ remnant. The patient refused further medication after surgery because of severe diarrhea after trastuzumab administration. Postoperative treatment was limited to follow-up, and no recurrence was observed at 1 year and 6 months postoperatively. CONCLUSION: This case suggests that trastuzumab monotherapy may be effective in certain patients with HER2-positive breast cancer. In the future, identifying patients who are more likely to respond to trastuzumab, as in this case, will allow for more options regarding de-escalation therapy without chemotherapy, particularly in elderly patients who are concerned about the side effects of chemotherapy.

Evaluation of the Role of Axillary Lymph Node Fine-Needle Aspiration Cytology in Early Breast Cancer With or Without Neoadjuvant Chemotherapy.

PURPOSE: Fine-needle aspiration cytology (FNAC) of axillary lymph nodes (AxLNs) is performed to diagnose nodal metastasis in patients with breast cancer. Although the sensitivity of ultrasound-guided FNAC for identifying AxLN metastasis is in the range of 36%-99%, whether sentinel lymph node biopsy (SLNB) should be performed for neoadjuvant chemotherapy (NAC) patients with negative FNAC results is uncertain. This study aimed to determine the role of FNAC before NAC in the evaluation and management of AxLN in early breast cancer patients. METHODS: We retrospectively analyzed 3,810 clinically node-negative (a lymph node with no clinical metastasis without FNAC or radiological suspicion of metastasis with negative FNAC results) patients with breast cancer who underwent SLNB between 2008 and 2019. We compared the positivity rate of sentinel lymph nodes (SLNs) between patients who received and those who did not receive NAC with negative FNAC results or without FNAC and axillary recurrence rate in the neoadjuvant group with negative SLNB results. RESULTS: In the non-neoadjuvant (primary surgery) group, the positivity rate of SLNs in patients with negative FNAC results was higher than that in patients without FNAC (33.2% vs. 12.9%; p < 0.001). However, the SLN positivity rate of patients with negative FNAC results (false-negative rate for FNAC) in the neoadjuvant group was lower than that in the primary surgery group (3.0% vs. 33.2%; p < 0.001). After a median follow-up of 3 years, one axillary nodal recurrence was observed, which was a case from the neoadjuvant non-FNAC group. None of the patients in the neoadjuvant group with negative FNAC results had axillary recurrence. CONCLUSION: The false-negative rate for FNAC in the primary surgery group was high; however, SLNB was the proper axillary staging procedure for NAC patients who have clinically suspicious AxLN metastases on radiologic examination but negative FNAC results.

Multicentre, randomised, double-blind, placebo-controlled phase II study of prophylactic olanzapine for patients with metastatic breast cancer receiving T-DXd treatment: protocol for the ERICA study (WJOG14320B).

INTRODUCTION: The antibody-drug conjugate trastuzumab deruxtecan (T-DXd) has led to a change in the clinical management of breast cancer. Nausea and vomiting are the most common adverse events of T-DXd, which cannot be completely alleviated by standard prophylactic regimens. Olanzapine is particularly effective in preventing delayed nausea caused by chemotherapy. In this study, we will evaluate the efficacy of olanzapine in managing persistent nausea and vomiting during T-DXd treatment. METHODS AND ANALYSIS: The ERICA study is a multicentre, placebo-controlled, double-blind, randomised phase II study with the aim to evaluate the antiemetic effects of the prophylactic olanzapine (5 mg orally, on days 1-6) or placebo combined with a 1,5-hydroxytryptamine-3 (5-HT3)-receptor antagonist and dexamethasone in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer undergoing T-DXd treatment. For a period of 22 days from the day of T-DXd treatment, patients will document their experience in an electronic symptom diary daily during observational periods. The primary endpoint is the complete response rate, defined as no vomiting and no rescue medications during the 'delayed phase' of 24-120 hours post-T-DXd administration. In addition, we define 120-504 hour as the 'persistent phase' and 0-504 hours as the 'overall phase' for secondary endpoint analysis. We have estimated that a total sample size of at least 156 patients is needed to allow a power of 80% at a one-sided significance level of 20% in this study. The target sample size is set to 166 to account for possible case exclusions. ETHICS AND DISSEMINATION: The study protocol is approved by the West Japan Oncology Group protocol review committee and the SHOWA University Clinical Research Review Board. The study results will be presented at international conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCTs031210410.

The impact of combined PD-L1 positive score on clinical response to nivolumab in patients with advanced esophageal squamous cell carcinoma.

BACKGROUND: Nivolumab is recommended for patients with advanced esophageal squamous cell carcinoma (aESCC) refractory or intolerant to fluoropyrimidine- and platinum-based chemotherapy regardless of the tumor proportion score (TPS). However, the role of combined positive score (CPS) in predicting nivolumab efficacy remains unclear. We aimed to study whether TPS or CPS is a more suitable biomarker for predicting nivolumab efficacy in these patients. METHODS: We retrospectively collected data from patients with aESCC treated with fluoropyrimidines and platinum and subsequently received nivolumab monotherapy between January 1, 2014 and September 15, 2020. Next, we evaluated the efficiencies of TPS and CPS in predicting the clinical response to nivolumab using PD-L1 IHC 22C3 pharmDx assay. RESULTS: This study included 50 patients (CPS groups: ≥ 10/1-10/ < 1, n = 24/18/8, respectively; TPS groups, ≥ 10%/1%-10%/ < 1%, n = 17/8/25, respectively). The median progression-free survival was 3.2, 2.5, and 1.5 months in the ≥ 10, 1-10 [hazard ratio (HR) vs. CPS of ≥ 10 group, 1.01; p = 0.98; adjusted HR, 1.33; p = 0.56], and < 1 CPS groups (HR vs. CPS of ≥ 10 group, 3.44; p = 0.006; adjusted HR, 1.67; p = 0.41), respectively. For the patients with CPS of ≥ 10/1-10/ < 1 and TPS of ≥ 10%/1%-10%/ < 1%, the objective response rate was 30%/25%/0% and 36%/0%/19% and the disease control rate was 60%/50%/12% (p = 0.06) and 65%/40%/38% (p = 0.30), respectively. CONCLUSIONS: This study suggests that a CPS of < 1 is not a strong predictor of efficacy but can predict the absence of response to nivolumab in patients with aESCC.

Impact of omitting fluorouracil from FOLFIRI plus bevacizumab as second-line chemotherapy for patients with metastatic colorectal cancer.

PURPOSE: Fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab is the standard second-line chemotherapy for patients with metastatic colorectal cancer (mCRC) who are refractory or intolerant to fluoropyrimidines and oxaliplatin. However, the benefits of incorporating fluoropyrimidines into second-line chemotherapy for patients with mCRC who are refractory to fluoropyrimidines are unknown. METHODS: We retrospectively evaluated patients with mCRC who were administered irinotecan plus bevacizumab or FOLFIRI plus bevacizumab as second-line chemotherapy at a single institution from January 2010 to April 2020. We compared the efficacy and safety of irinotecan plus bevacizumab (IRI group) with those of FOLFIRI plus bevacizumab (FOLFIRI group). RESULTS: Of the 255 enrolled patients, 107 (IRI/FOLFIRI group, 31/76 patients) were eligible for analysis. After a median follow-up of 13.1 months (range 1.2-48.4) and 14.3 months (range 0.9-46.5) for the IRI and FOLFIRI groups, respectively, the median progression-free survival was 6.4 months and 5.8 months [adjusted hazard ratio (aHR), 0.82; 95% confidence interval (CI) 0.50-1.34, p = 0.44] and the median overall survival was 16.6 months and 16.5 months (aHR, 1.01; 95% CI 0.59-1.69; p = 0.97) in the IRI and FOLFIRI groups, respectively. All-grade nausea, stomatitis, neutropenia, thrombocytopenia, Grade 3/4 neutropenia, and febrile neutropenia occurred more frequently in the FOLFIRI group than in the IRI group. CONCLUSION: Our study suggests omitting fluorouracil from FOLFIRI plus bevacizumab as the second-line chemotherapy decreases adverse events without affecting the treatment efficacy in patients with mCRC who are refractory to fluoropyrimidines. Further randomized prospective studies are warranted to validate our result.

Arthralgia induced by endocrine therapy with or without cyclin-dependent kinase 4/6 inhibitors in breast cancer: A systematic review and meta-analysis.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) have been approved for breast cancer (BC) treatment. Several trials suggested that arthralgia was reduced in patients treated with ET plus CDK4/6i compared with that in those with ET-alone. We aimed to compare arthralgia rates in BC patients treated with/without CDK4/6i. We reviewed randomized controlled phase II/III trials investigating CDK4/6i with ET in hormone receptor-positive and epidermal growth factor 2-negative BC. Publications were retrieved from PubMed from January 2014 to April 2021. We compared arthralgia rates between patients who were administered ET plus CDK4/6i (CDK4/6i group) and those treated with ET-alone (control group). We reviewed 12 trials that reported data on adverse effects for arthralgia. These trials included 17,440 patients (9255 in the CDK4/6i group and 8185 in the control group). The arthralgia rate in the CDK4/6i group was significantly lower than that in the control group (27.6% vs. 34.8%, p < .001), especially in early BC (28.8% vs. 37.3%, p < .001). These suggested that the arthralgia rate in patients treated with ET plus CDK4/6i was lower than that in patients treated with ET-alone and that CDK4/6i may decrease the arthralgia rate in BC patients treated with ET, especially in early BC.

Satisfaction survey on a preoperative explanation method using three-dimensional breast imaging for breast cancer patients considering breast-conserving surgery.

PURPOSE: Although one of the essential factors in surgical shared decision-making is the body image, the breast morphology after breast-conserving surgery is particularly difficult to explain in a uniform manner due to large individual differences. METHODS: Patients with breast cancer eligible for breast-conserving surgery (BCS) were recruited between June 2020 and October 2021. We surveyed the patients' satisfaction with our method of explaining the likely breast morphology after BCS using three-dimensional (3D) breast imaging in the form of a questionnaire. RESULTS: A total of 162 patients were enrolled, and 137 (84.6%) answered the questionnaire. One hundred and sixteen patients (84.6%) answered that they were very satisfied or satisfied with our explanation method, and 100 (73.0%) patients were very satisfied or satisfied with the 3D breast imaging. Some patients answered that 3D breast imaging helped them prepare for BCS, or on the contrary, made them choose mastectomy with breast reconstruction because the deformation likely with BCS was considered unacceptable. Only a few patients who underwent BCS felt that their postoperative morphology was more deformed than the preoperatively imagined one. CONCLUSION: Our results suggest that our preoperative explanation method using 3D breast imaging was useful for shared decision-making.

Use of Anticancer Therapies and Economic Burden Near the End of Life in Japan: Results From Claims Database.

PURPOSE: In patients with cancer, aggressive treatment near the end of life (EOL) may decrease quality of life and increase medical costs. In this study, we examined the use of anticancer therapies near the EOL in Japan. METHODS: We used a commercial database of health insurance claims in Japan, to examine patient data on cancer and death until August 2020. We assessed the proportion of patients using anticancer therapies within 14 days of death, associated factors, and medical costs from the payer's perspective. RESULTS: The database documented 5,759 patients with cancer who died between December 2013 and August 2020. Among them, 4.8% of patients and 3.9% of age-adjusted patients received anticancer therapy within 14 days of death. Patients age < 60 years were associated with a high probability of receiving anticancer therapy near the EOL. The estimated annual anticancer therapy and related costs were Japanese yen 1,296 million (US dollars 12.6 million). CONCLUSION: We found the percentage of patients receiving anticancer therapies within 14 days of death in Japan, its associated factors, and economic burden. Our findings can serve as a benchmark for optimizing EOL care.

Time to Chemotherapy for Patients With Estrogen Receptor-Positive Breast Cancer and Cyclin-Dependent Kinase 4 and 6 Inhibitor Use.

PURPOSE: Safely postponing the use of chemotherapy is important for quality of life maintenance in patients with hormone receptor-positive advanced breast cancer. In previous studies, a combination of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) and fulvestrant prolonged the time to chemotherapy (TTC). In this study, we used real-world data to evaluate TTC in the context of CDK4/6i therapy. METHODS: We performed a retrospective chart review of women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer treated at the Aichi Cancer Center Hospital. The patients were categorized into having received CDK4/6i therapy first (n = 41), second (n = 33), and none at all (n = 67). The change in TTC among the groups was examined. RESULTS: The median follow-up time was 13.8, 27.5, and 30.3 months in the CDK4/6i (first), CDK4/6i (second), and non-CDK4/6i groups, respectively. The median progression-free survival (PFS) with first-line therapy for metastasis was 30.0, 11.9, and 13.0 months, respectively (CDK4/6i [first] vs. non-CDK4/6i; p = 0.018, CDK4/6i [second] vs. non-CDK4/6i; p = 0.383). The median TTC was not reached in the CDK4/6i (first) group, was 39.1 months in the CDK4/6i (second) group, and was 44.2 months in the non-CDK4/6i group (CDK4/6i [first] vs. non-CDK4/6i; p = 0.880; CDK4/6i [second] vs. non-CDK4/6i; p = 0.407). The non-CDK4/6i group with TTC ≥ 60 months included more cases of secondary endocrine therapy resistance (p = 0.017), no perioperative chemotherapy (p = 0.021), and a longer disease-free interval (p = 0.093). CONCLUSION: Although PFS was significantly longer in the CDK4/6i (first) group than in the non-CDK4/6i group, TTC did not significantly differ among the three groups in real-world data. The non-CDK4/6i group showed a long TTC in patients with late recurrence and low risk at the primary lesion site, who benefited greatly from hormone monotherapy.

Impact of Tumor Progression on Survival During Neoadjuvant Chemotherapy in Breast Cancer: A Cohort Study.

BACKGROUND/AIM: Few patients with breast cancer experience tumor progression during neoadjuvant systemic therapy (NST), but their poor outcome is similar to that of patients who fail to achieve a pathological complete response (pCR). No previous reports have compared patients with pCR, non-pCR, and progression during NST to determine the survival outcomes. PATIENTS AND METHODS: This retrospective chart review of patients with stage I-III breast cancer was conducted between January 2001 and December 2018. pCR was defined as no invasive cancer or in situ residuals in the breast and lymph nodes (ypT0 ypN0). Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier methods. RESULTS: Of the 595 patients who received NST, 167 (28.1%) had pCR (pCR group), 404 (67.9%) did not attain pCR (non-pCR group), and 24 (4.0%) experienced tumor progression during NST (PD group). The median DFS was 6.0 months, 154.0 months, and not reached in the PD, non-pCR, and pCR groups, respectively. The PD group had significantly shorter DFS than patients without tumor progression in the pCR and non-pCR groups [hazard ratio (HR)=13.0, 95%CI=8.1-21.0, p<0.01]. The median OS was 13.6 months (95%CI=10.4-35.5) in the PD group and was not reached in the pCR and non-pCR (non-PD) groups. The OS was significantly poorer in the PD group than in the non-PD groups (HR=15.8, 95%CI=9.2-27.1, p<0.01). CONCLUSION: The PD group had the poorest survival outcome even after recurrence, thus warranting new treatment strategies.

Association between bevacizumab with cancer drug therapies and drug-induced interstitial lung disease in patients with solid tumor: A systematic review and meta-analysis of randomized clinical trials.

PURPOSE: This study aimed to determine interstitial lung disease (ILD) incidences in patients receiving cancer drug therapies with or without bevacizumab treatment. METHODS: Systematic searches of PubMed, Embase, and Cochrane Library were conducted in January 2021. The main inclusion criteria were randomized clinical trials that compared bevacizumab with standard treatment in patients with solid tumors. Cochrane Collaboration's Tool was used for assessing risk-of-bias. RESULTS: Thirteen records involving 7201 patients were included in the meta-analysis. There were 42 ILD events in bevacizumab groups and 72 in control groups. In bevacizumab groups, the odds ratio for ILD was 0.62 (95% CI 0.42-0.92; p = 0.02), which was a significantly lower incidence than the control. This tendency was shown in targeted therapy groups but not in the cytotoxic agent groups. CONCLUSION: Our data suggest that bevacizumab may reduce the incidence of ILD.