Current Status and Issues of Collaboration Between Physicians and Pharmacists in Fertility Preservation.

Purpose: This study addresses the critical issue of fertility preservation among young patients with cancer in Japan, recognizing the brief decision-making window and the need for comprehensive support. Pharmacists, well-versed in the side effects of anticancer drugs, can play a vital role in this support process. However, the extent of pharmacists' involvement in fertility preservation remains unclear. We aimed to investigate pharmacists' roles in addressing cancer treatment-induced fertility concerns and their collaboration with physicians, offering insights into enhancing pharmacist participation in fertility preservation. Methods: A survey conducted between April and July 2022 targeted doctors and pharmacists at cancer treatment hospitals, along with pharmacists affiliated with the Japanese Society of Pharmaceutical Health Care and Sciences. Results: Our findings indicated that although pharmacists had limited knowledge about gonadotoxicity and fertility, they expressed readiness to conduct research and provide information when consulted. Approximately 10%-20% of the pharmacists participated in explaining the primary disease at diagnosis. Pharmacists played a more prominent role after establishing chemotherapy regimens, with less involvement in its formulation. Notably, treatment decision case conferences emerged as crucial forums for gathering patient data, confirming treatment plans, and identifying those in need for fertility preservation information. Roughly half of the pharmacists attended these conferences, suggesting a need for increased participation. Conclusion: Enhancing physician-pharmacist collaboration could be pivotal for effective fertility preservation. This requires augmenting the knowledge and awareness of both professions and encouraging greater participation in case conferences to create a conducive environment for addressing this critical aspect of cancer care.

Patient Preference for Surgical Methods for Ipsilateral Breast Tumor Recurrence.

BACKGROUND: Mastectomy has been the standard surgical treatment for ipsilateral breast tumor recurrence (IBTR). Recently, there has been growing interest in repeat breast-conserving surgery (rBCS) for IBTR among breast surgeons; however, there is currently little information regarding patient preferences for surgical procedure for IBTR. The purpose of this study was to evaluate preference for surgical procedure (mastectomy vs. rBCS) among breast cancer patients who had undergone salvage surgery for IBTR. METHODS: Overall, 100 breast cancer patients who had undergone salvage surgery for IBTR were asked about their preferred surgical methods for IBTR and the reason. The association of patient preference and the reasons related to various clinical and pathological factors were assessed. RESULTS: Of the 100 respondents, only 11 patients (11%) preferred rBCS. Patients who had undergone rBCS and radiotherapy for IBTR were significantly more likely to prefer to undergo rBCS than other groups (p = 0.030). The most frequent reason for choosing rBCS was the patient's desire to minimize breast deformity and surgical wounds. CONCLUSIONS: Our study revealed that there is a low rate of patients who opt to undergo rBCS among patients who had undergone salvage surgery for IBTR. Discrepancies in perceptions regarding the surgical procedure for IBTR between patients and their surgeons may exist.

Optimizing smartphone psychotherapy for depressive symptoms in patients with cancer: Multiphase optimization strategy using a decentralized multicenter randomized clinical trial (J-SUPPORT 2001 Study).

AIM: Patients with cancer experience various forms of psychological distress, including depressive symptoms, which can impact quality of life, elevate morbidity risk, and increase medical costs. Psychotherapy and pharmacotherapy are effective for reducing depressive symptoms among patients with cancer, but most patients prefer psychotherapy. This study aimed to develop an efficient and effective smartphone psychotherapy component to address depressive symptom. METHODS: This was a decentralized, parallel-group, multicenter, open, individually randomized, fully factorial trial. Patients aged ≥20 years with cancer were randomized by the presence/absence of three cognitive-behavioral therapy (CBT) skills (behavioral activation [BA], assertiveness training [AT], and problem-solving [PS]) on a smartphone app. All participants received psychoeducation (PE). The primary outcome was change in the patient health questionnaire-9 (PHQ-9) total score between baseline and week 8. Secondary outcomes included anxiety. RESULTS: In total, 359 participants were randomized. Primary outcome data at week 8 were obtained for 355 participants (99%). The week 8 PHQ-9 total score was significantly reduced from baseline for all participants by -1.41 points (95% confidence interval [CI] -1.89, -0.92), but between-group differences in change scores were not significant (BA: -0.04, 95% CI -0.75, 0.67; AT: -0.16, 95% CI -0.87, 0.55; PS: -0.19, 95% CI -0.90, 0.52). CONCLUSION: As the presence of any of the three intervention components did not contribute to a significant additive reduction of depressive symptoms, we cannot make evidence-based recommendations regarding the use of specific smartphone psychotherapy.

Ectopic Breast Cancer Arising within an Axillary Lymph Node.

We report our experience with the diagnosis and treatment of an ectopic breast cancer arising within an axillary lymph node. The patient was a 65-year-old woman diagnosed breast cancer and axillary lymph node metastasis. We performed a partial mastectomy and axillary lymph node dissection. Postoperative pathology revealed no malignant lesions in the breast; however, a nodule in one of axillary lymph nodes had mixed benign and malignant components, leading to a diagnosis of invasive ductal carcinoma derived from ectopic mammary tissue. This case represents a very rare form of breast cancer, and the malignancy was difficult to distinguish from metastasis.

Prospective analysis of patient-reported outcomes and physician-reported outcomes with gynecologic cancer chemotherapy.

OBJECTIVE: Gynecologic cancer chemotherapy impacts the quality of life (QOL) of patients, with lasting adverse events that may require treatment adjustments or discontinuation. Consequently, real-time symptom monitoring before outpatient visits has resulted in improved QOL for patients and extended survival times. This study investigated whether there are differences between electronic patient-reported outcomes (e-PRO-CTCAE) and physician-assessed outcomes (NCI-CTCAE) evaluated in an outpatient setting in gynecologic cancer chemotherapy. METHODS: The study was conducted on 50 patients who received their first chemotherapy treatment at St. Marianna University Hospital Obstetrics and Gynecology from July 1, 2021 to December 31, 2022. PRO-CTCAE and NCI-CTCAE were evaluated at each instance of chemotherapy and 2 weeks after. The PRO-CTCAE was additionally collected weekly using e-PRO. RESULTS: The values for "Joint Pain," "Nausea," "Taste Disturbance," "Constipation," "Insomnia," "Fatigue," "Limb Edema," and "Concentration Impairment" were consistently higher in PRO-CTCAE than in NCI-CTCAE, indicating that physicians underestimated the severity of adverse events. In contrast, there was no significant difference in "Peripheral Neuropathy," demonstrating that physicians had a good understanding of this condition in patients. The weekly responses obtained from e-PRO revealed that symptom exacerbations peaked outside of clinic visits. CONCLUSIONS: This study demonstrated physicians tend to underestimate most adverse events. Moreover, the responses using e-PRO revealed peak symptom deterioration occurred outside of outpatient visits. This suggested that e-PRO and actions taken in response to them can improve patients' QOL.

Factors associated with financial toxicity in patients with breast cancer in Japan: a comparison of patient and physician perspectives.

BACKGROUND: Financial toxicity (FT) is a notable concern for patients with breast cancer worldwide. The situation regarding FT in Japan, however, has not been well explored. This study examined FT in patients with breast cancer in Japan and presented an overview of the group study's overall findings. METHODS: The survey used the Questant application and primarily targeted patients with breast cancer attending research facilities and physicians who are members of the Japanese Breast Cancer Society. The Japanese version of the Comprehensive Score for FT (COST) was used to quantify patients' FT. Multiple regression analysis was used to identify factors related to FT in patients with breast cancer in Japan and evaluate the sufficiency of information support level (ISL) for medical expenses. RESULTS: We collected 1558 responses from patients and 825 from physicians. In terms of factors affecting FT, recent payments had the highest impact, followed by stage, and related departments positively affecting FT. Conversely, factors such as income, age, and family support were found to negatively affect FT. A significant discrepancy was identified between patients and physicians in perceived information support, with patients frequently feeling unsupported and physicians believing that they have provided adequate support. Furthermore, differences in the frequency of explanations and opportunities to ask questions about medical costs across FT grades were found. The analysis also showed that physicians with a better understanding of information support needs and greater knowledge of medical costs tended to provide more support that is comprehensive. CONCLUSION: This study emphasizes the importance of addressing FT in patients with breast cancer in Japan and highlights the need for enhanced information support, deeper understanding by physicians, and collaborative efforts among professionals to mitigate financial burden and provide personalized, tailored support for individual needs.

Optimization of smartphone psychotherapy for depression and anxiety among patients with cancer using the multiphase optimization strategy (MOST) framework and decentralized clinical trial system (SMartphone Intervention to LEssen depression/Anxiety and GAIN resilience: SMILE AGAIN project): a protocol for a randomized controlled trial.

BACKGROUND: Cancer patients experience various forms of psychological distress. Their distress, mainly in the form of depression and anxiety, leads to poor quality of life, increased medical spending due to frequent visits, and decrease in treatment adherence. It is estimated that 30-50% among them would require support from mental health professionals: in reality, much less actually receive such support partly due to a shortage of qualified professionals and also due to psychological barriers in seeking such help. The purpose of the present study is to develop the easily accessible and the most efficient and effective smartphone psychotherapy package to alleviate depression and anxiety in cancer patients. METHODS: Based on the multiphase optimization strategy (MOST) framework, the SMartphone Intervention to LEssen depression/Anxiety and GAIN resilience project (SMILE-AGAIN project) is a parallel-group, multicenter, open, stratified block randomized, fully factorial trial with four experimental components: psychosocial education (PE), behavioral activation (BA), assertion training (AT), and problem-solving therapy (PS). The allocation sequences are maintained centrally. All participants receive PE and then are randomized to the presence/absence of the remaining three components. The primary outcome of this study is the Patient Health Questionnaire-9 (PHQ-9) total score, which will be administered as an electronic patient-reported outcome on the patients' smartphones after 8 weeks. The protocol was approved by the Institutional Review Board of Nagoya City University on July 15, 2020 (ID: 46-20-0005). The randomized trial, which commenced in March 2021, is currently enrolling participants. The estimated end date for this study is March 2023. DISCUSSION: The highly efficient experimental design will allow for the identification of the most effective components and the most efficient combinations among the four components of the smartphone psychotherapy package for cancer patients. Given that many cancer patients face significant psychological hurdles in seeing mental health professionals, easily accessible therapeutic interventions without hospital visits may offer benefits. If an effective combination of psychotherapy is determined in this study, it can be provided using smartphones to patients who cannot easily access hospitals or clinics. TRIAL REGISTRATION: UMIN000041536, CTR. Registered on 1 November 2020  https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000047301 .

Preferences Regarding Breast Surgery Omission Among Patients With Breast Cancer Who Receive Neoadjuvant Chemotherapy.

BACKGROUND/AIM: Currently, several ongoing prospective studies are investigating the safety of breast surgery omission in patients with breast cancer who are exceptional responders to neoadjuvant chemotherapy. However, there is little information about the preferences of these patients regarding omission of breast surgery. PATIENTS AND METHODS: We conducted a questionnaire survey to assess preferences regarding omission of breast surgery among patients with breast cancer who had human epidermal growth factor receptor 2-positive or estrogen receptor-negative tumors and good clinical response after neoadjuvant chemotherapy. Patients' estimation of the risk of ipsilateral breast tumor recurrence (IBTR) after definitive surgery or breast surgery omission was also assessed. RESULTS: Of 93 patients, only 22 (23.7%) said they would omit breast surgery. Under the scenario of omitting breast surgery, the 5-year IBTR rate estimated by patients who said they would omit breast surgery was significantly lower (median, 10%) than the rate estimated by patients who preferred undergoing definitive surgery (median, 30%) (p=0.017). CONCLUSION: The proportion of our surveyed patients who were willing to omit breast surgery was low. Patients who said they preferred to omit breast surgery overestimated the 5-year IBTR risk.

Patient-reported outcome and quality of life research policy: Japan Clinical Oncology Group (JCOG) policy.

Assessments of patient-reported outcomes and health-related quality of life in cancer clinical trials have been increasingly emphasized recently because patient and public involvement in cancer treatment development has been promoted by regulatory authorities and academic societies. To assess patient experiences during and after cancer treatment, there is interest in implementing patient-reported outcome and health-related quality of life assessments into cancer clinical trials. The Japan Clinical Oncology Group quality of life ad hoc committee previously created a version of the Quality of Life Assessment Policy in 2006. Recently, there has been increasing demand from Japan Clinical Oncology Group researchers to assess patient-reported outcome/health-related quality of life in clinical trials. Although guidelines are available regarding planning and reporting clinical trials that include patient-reported outcome/health-related quality of life as an endpoint, there are still issues regarding the lack of consensus on standardized methods for analysing and interpreting the results. Hence, it was considered necessary to reorganize the Japan Clinical Oncology Group patient-reported outcome/quality of life research committee and to revise the former patient-reported outcome/quality of life research policy to promote patient-reported outcome/health-related quality of life research in future Japan Clinical Oncology Group trials. The purpose of this Japan Clinical Oncology Group patient-reported outcome/quality of life research policy is to define patient-reported outcome/health-related quality of life research and provide guidelines for including patient-reported outcome/health-related quality of life as an endpoint in Japan Clinical Oncology Group trials.

Surgical site infections in thyroid and parathyroid surgery in Japan: An analysis of the Japan Nosocomial Infections Surveillance database from 2013 to 2020.

Surgical site infections (SSIs) after thyroid surgery are rare complications, with incidence rates of 0.3%-1.6%. Using a Japanese database, we conducted exploratory analyses on the incidence of SSIs, investigated the incidence of SSIs by the National Nosocomial Infections Surveillance risk index, and identified the causative bacteria of SSIs. SSIs occurred in 50 (0.7%) of 7388 thyroid surgery cases. Risk index-0 patients had the lowest incidence rate of SSIs (0.41%). The incidence of SSIs in risk index-1 patients was 3.05 times the incidence of SSIs in risk index-0 patients. The rate of SSI occurrence for risk index-2 patients was 4.22 times the rate of SSI occurrence for risk index-0 patients. Thirty-one bacterial species were identified as the cause of SSIs in thyroid surgery cases, of which 12 (38.7%) SSIs were caused by Staphylococcus aureus and Staphylococcus epidermidis. Of the nine SSIs caused by Staphylococcus aureus, 55.6% (five cases) were attributed to methicillin-resistant Staphylococcus aureus. Therefore, routine prophylactic antibiotic administration should be avoided, while the target for administration should be narrowed, according to the SSI risk. Administration of prophylactic antibiotics, such as 2 g piperacillin or 1 g cefazolin, is considered appropriate.

A Case of Brachial Lymph Node Recurrences after the Resection of Locally Advanced Breast Cancer.

We present a case of two recurrences in the brachial lymph nodes after initial resection, which was performed for radical cure. A 66-year-old woman was diagnosed with left breast cancer T4bN3cM0 Stage IIIC and an immunohistochemistry assay showed estrogen receptor (ER) positivity (5%), progesterone-receptor (PgR) positivity (1%), human epidermal growth factor receptor-2 (HER2) positivity (3+), and low Ki-67 (15%). After four courses of adriamycin and cyclophosphamide, followed by four courses of trastuzumab plus docetaxel, the patient underwent left mastectomy and axillary dissection. Postoperatively, she was diagnosed with breast cancer ypT1cN0M0, and trastuzumab and anastrozole were started. Postoperative irradiation was performed. Three years and 5 months after the initial breast cancer surgery, she had left brachial lymph node recurrence. It was resected, and tamoxifen was administered postoperatively. One year and 9 months after, she had another left brachial lymph node recurrence, and it was resected. She received radiation therapy to her upper limb and started taking exemestane. After 1 year and 3 months since the second recurrence surgery, there has been no recurrence. Our case suggests that the replacement of regional lymph nodes with tumor cells may result in the reconstruction of lymph flow to the upper arm and the development of brachial lymph node metastasis. There are no reports of resection of the recurrent tumor in the brachial lymph node for curative treatment. Therefore, careful follow-up is important in the future.

Pathologic method for extracting good prognosis group in triple-negative breast cancer after neoadjuvant chemotherapy.

The area of residual tumor (ART) is a prognostic factor in patients treated with neoadjuvant chemotherapy (NAC) for lung, pancreatic, and rectal cancers. This study aimed to evaluate the usefulness of ART as a method for predicting the prognosis of triple-negative breast cancer (TNBC) patients after NAC. We included 143 patients with TNBC treated with NAC. The ART at the maximum cut surface of the residual tumor was measured. We divided the patients into three groups: ART-0 (ART = 0 mm2 ), ART-low (0 mm2  < ART ≤ 136mm2 ), and ART-high (ART > 136 mm2 ), and compared their clinicopathologic factors and prognosis. There were no significant differences in either recurrence-free survival (RFS) or overall survival (OS) between ART-0 and ART-low; however, the ART-high group had significantly shorter RFS and OS than the ART-0 and ART-low groups. Multivariate analysis showed that ART-0 and -low and ypN(-) were independent favorable prognostic factors for RFS. Groups with both ART-low and ypN(-) as well as those with ART-0 and ypN(-) showed significantly longer OS and RFS than the other groups (P < .05). Moreover, there was no significant difference in the RFS and OS between the ART-0 and ypN(-) groups and the ART-low and ypN(-) groups (P = .249 and P = .554, respectively). We concluded that ART is a candidate histopathological evaluation method for predicting the prognosis of TNBC patients treated with NAC. Furthermore, postoperative chemotherapy could be omitted in patients with ART-0 and ypN(-) (pathological complete response) and those with ART-low and ypN(-).

Validation of the predictive accuracy of health-state utility values based on the Lloyd model for metastatic or recurrent breast cancer in Japan.

INTRODUCTION: Although there is a lack of data on health-state utility values (HSUVs) for calculating quality-adjusted life-years in Japan, cost-utility analysis has been introduced by the Japanese government to inform decision making in the medical field since 2016. OBJECTIVES: This study aimed to determine whether the Lloyd model which was a predictive model of HSUVs for metastatic breast cancer (MBC) patients in the UK can accurately predict actual HSUVs for Japanese patients with MBC. DESIGN: The prospective observational study followed by the validation study of the clinical predictive model. SETTING AND PARTICIPANTS: Forty-four Japanese patients with MBC were studied at 336 survey points. METHODS: This study consisted of two phases. In the first phase, we constructed a database of clinical data prospectively and HSUVs for Japanese patients with MBC to evaluate the predictive accuracy of HSUVs calculated using the Lloyd model. In the second phase, Bland-Altman analysis was used to determine how accurately predicted HSUVs (based on the Lloyd model) correlated with actual HSUVs obtained using the EuroQol 5-Dimension 5-Level questionnaire, a preference-based measure of HSUVs in patients with MBC. RESULTS: In the Bland-Altman analysis, the mean difference between HSUVs estimated by the Lloyd model and actual HSUVs, or systematic error, was -0.106. The precision was 0.165. The 95% limits of agreement ranged from -0.436 to 0.225. The t value was 4.6972, which was greater than the t value with 2 degrees of freedom at the 5% significance level (p=0.425). CONCLUSIONS: There were acceptable degrees of fixed and proportional errors associated with the prediction of HSUVs based on the Lloyd model for Japanese patients with MBC. We recommend that sensitivity analysis be performed when conducting cost-effectiveness analyses with HSUVs calculated using the Lloyd model.

Changes in Health State Utility Values in Japanese Patients with End-Stage Breast Cancer.

We aimed to determine the dynamic trends in health state utility values (HSUVs) in patients with end-stage breast cancer. We selected 181 patients comprising 137 with primary breast cancer (PBC) and 44 with metastatic breast cancer (MBC) (28 survivors and 16 patients with MBC death). HSUVs were 0.90 and 0.89 in patients with PBC and 0.83 and 0.80 in those with MBC (survivors) at 6 and 3 months, respectively, before the end of the observation period; these values were 0.73 and 0.66, respectively, in those with MBC (deceased) during the aforementioned period. The root-mean-squared error (RMSE) for the decrease in HSUVs over 3 months was 0.10, 0.096, and 0.175 for patients with PBC, MBC (survivors), and MBC (deceased), respectively. One-way analysis of variance for differences in absolute error among the groups was significant (p = 0.0102). Multiple comparisons indicated a difference of 0.068 in absolute error between patients with PBC and those with MBC (deceased) (p = 0.0082). Patients with end-stage breast cancer had well-controlled HSUVs 3 months before death, with a sharp decline in HSUVs in the 3 months leading up to death.

Genomic profiling reveals heterogeneous populations of ductal carcinoma in situ of the breast.

In a substantial number of patients, ductal carcinoma in situ (DCIS) of the breast will never progress to invasive ductal carcinoma, and these patients are often overtreated under the current clinical criteria. Although various candidate markers are available, relevant markers for delineating risk categories have not yet been established. In this study, we analyzed the clinical characteristics of 431 patients with DCIS and performed whole-exome sequencing analysis in a 21-patient discovery cohort and targeted deep sequencing analysis in a 72-patient validation cohort. We determined that age <45 years, HER2 amplification, and GATA3 mutation are possible indicators of relapse. PIK3CA mutation negativity and PgR negativity were also suggested to be risk factors. Spatial transcriptome analysis further revealed that GATA3 dysfunction upregulates epithelial-to-mesenchymal transition and angiogenesis, followed by PgR downregulation. These results reveal the existence of heterogeneous cell populations in DCIS and provide predictive markers for classifying DCIS and optimizing treatment.

Prospective observational study estimating willingness-to-pay for breast cancer treatments through contingent valuation method in Japanese breast cancer patients (JCOG1709A).

In April 2016, the Japanese government introduced health technology assessment as a response to rising medical expenses due to 'medical innovation'. This study investigates how Japanese breast cancer patients who received treatment in Japan consider the financial value (willingness-to-pay; WTP) for their life and health by using the contingent valuation method (CVM) prospectively. First, 168 patients (84 primary breast cancer patients and 84 metastatic breast cancer patients) were pre-examined their WTP with dichotomous-choice method survey form. Next, 1,596 patients (798 primary breast cancer patients and 798 metastatic breast cancer patients) will be surveyed to their WTP for hypothetical scenarios in CVM. Based on our results, we will construct an evaluation axis from the patients' viewpoint for the cost-effectiveness of clinical trials to establish standard treatments for breast cancer. We believe this research can contribute to create a meaningful healthcare system for patients, clinicians, industries, and healthcare policymakers.

Current Status of Advance Care Planning and End-of-life Communication for Patients with Advanced and Metastatic Breast Cancer.

BACKGROUND: Advance care planning (ACP) is a process that supports adults in understanding and sharing their personal values, life goals, and preferences regarding future medical care. We examined the current status of ACP and end-of-life (EOL) communication between oncologists and patients with metastatic breast cancer. MATERIALS AND METHODS: We conducted a survey among 41 institutions that specialize in oncology by using an online tool in October 2019. Participants (118 physicians) from 38 institutions completed a 39-item questionnaire that measured facility type and function; physicians' background and clinical approach, education about EOL communication, and understanding about ACP; and the current situation of ACP and EOL discussions. RESULTS: Ninety-eight responses concerning physicians' engagement in ACP with patients were obtained. Seventy-one (72%) answered that they had engaged in ACP. Among these, 23 (33%) physicians used a structured format to facilitate the conversation in their institutions, and only 6 (8%) settled triggers or sentinel events for the initiation of ACP. In the multivariable analysis, only the opportunity to learn communication skills was associated with physicians' engagement with ACP (odds ratio: 2.8, 95% confidence interval: 1.1-7.0). The frequency and timing of communication about ACP and EOL care with patients substantially varied among the oncologists. Communication about patients' life expectancy was less frequent compared with other topics. CONCLUSION: The opportunity to improve EOL communication skills promoted physicians' engagement with ACP among patients with metastatic/advanced breast cancer. However, there were still substantial variabilities in the method, frequency, and timing of ACP and EOL communication among the oncologists. IMPLICATIONS FOR PRACTICE: This study found that the opportunity to improve end-of-life (EOL) communication skills promoted physicians' engagement in advance care planning (ACP) among patients with metastatic/advanced breast cancer. All oncologists who treat said patients are encouraged to participate in effective education programs concerning EOL communication skills. In clinical practice, there are substantial variabilities in the method, frequency, and timing of ACP and EOL communication among oncologists. As recommended in several clinical guidelines, the authors suggest a system that identifies patients who require conversations about their care goals, a structured format to facilitate the conversations, and continuous measurement for improving EOL care and treatment.