Psychosocial experiences regarding potential fertility loss and pregnancy failure after treatment in cancer survivors of reproductive age to identify psychosocial care needs: a systematic review.

PURPOSE: The challenges of fertility loss owing to cancer treatment persist long after treatment. However, psychosocial care for fertility among cancer survivors who have completed cancer treatment is insufficient. This systematic review examined psychosocial experiences related to the potential loss of fertility and unsuccessful pregnancy after treatment in cancer survivors of reproductive age to identify psychosocial care needs. METHODS: A systematic review was conducted using the online databases PubMed, Cochrane Library, PsycINFO, CINAHL, and Ichushi-Web between August and December 2022 to identify studies that addressed psychosocial experiences after fertility loss or failure to conceive among young cancer survivors. Study quality was assessed using the Mixed Methods Appraisal Tool. RESULTS: Forty studies were included, revealing psychosocial experiences across five categories: subjective fear of (potential) fertility loss, impact on romantic relationships, alternative methods for family building, reliance on social support, and specialized care. Only one study addressed the psychosocial aspects after complete loss of fertility in young cancer survivors. CONCLUSIONS: The possibility and uncertainty of fertility loss led to stress and depression, loss of identity, decreased opportunities to meet a new partner, and damaged relationships established before diagnosis. The needs encompass fertility preservation, sexuality, approaches to building a family, partner communication, and other diverse needs.

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.

Survey of Transitional Care Between Pediatrics and Obstetrics/Gynecology in Japan.

Purpose: This study's aim was to determine the actual status of transitional care for patients with pediatric cancer (PPCs) in Japan by surveying obstetricians/gynecologists. Methods: A questionnaire survey on transitional medicine was conducted in the form of an online questionnaire at 579 major training facilities nationwide, which were registered with the Japanese Society of Obstetrics and Gynecology. Results: While 40% of the facilities had received referrals for PPCs, only 13% provided transitional care specifically for PPCs. The most common problems with referrals were related to "insufficient explanation." In addition, at facilities with no experience treating PPCs, many respondents commented that they did not know how to follow the progression of the disease. Regarding the necessity of obstetrics/gynecology visits for PPCs, more than half of the respondents at facilities with experience treating PPCs answered that such visits were "necessary"; only 1% answered that they were "unnecessary." On the other hand, 37% of the facilities that had no experience treating PPCs answered that it was "necessary," whereas 4% answered that it was "unnecessary." Conclusions: This survey of the actual status of transitional care between pediatrics and obstetrics/gynecology in Japan identified issues to be addressed for the spread of transitional care. The results suggest that, in the future, health care professionals need education to increase their knowledge, and that patient education that leads to patients' awareness of their own self-management is necessary.

Differences Between Cancer Survivors and Healthy Subjects in Factors that Facilitate and Obstruct the Use of the Foster Parent System and Special Adoption System: A Nationwide Cross-Sectional Study in Japan.

Purpose: To investigate factors that obstruct and facilitate the use of the foster parent and special adoption systems (i.e., foster systems) by cancer survivors, and examine how to effectively provide information. Methods: This was a cross-sectional study that compared the results of a questionnaire survey of foster parents and adoptive parents (i.e., foster parents) who were and were not cancer survivors belonging to foster parent associations in 33 locations in Japan. This study was supported by a 2022 Ministry of Health, Labor, and Welfare Grant-in-Aid for Scientific Research (Grant No. 20EA1004). Results: "Lack of information," an obstructive factor and "Sympathetic understanding and cooperation from my partner and family," a facilitative factor were the highest score in both groups. Significant differences between the two groups were found in "Support from government agencies and others for foster parents," a facilitative factor, which was lower in the cancer survivors' group. There were no other significant differences between both the groups. Conclusion: This study found that when considering the use of the foster systems, a lack of information was the biggest obstructive factor and family understanding was the most helpful for both cancer survivors and noncancer groups. It was thought that stronger government support for cancer survivors might encourage cancer survivors to consider becoming foster parents. It would be effective for cancer treatment facilities, reproductive medical facilities, the government, and foster parent associations to work together to provide information carefully to cancer survivors.

Survey on the implementation status and reproductive outcomes of oocyte and ovarian tissue cryopreservation in Japan: Historical comparison with nationwide surveys.

PURPOSE: To clarify the reproductive outcomes of fertility preservation (FP) treatment. METHODS: We conducted a mailed-in questionnaire survey at institutions certified by the Japan Society of Obstetrics and Gynecology to investigate the number of oocyte cryopreservations (OC) and ovarian tissue cryopreservations (OTC) performed from December 2016 to the end of 2020. And, we conducted a detailed investigation of cases in which frozen specimens were used during the investigation period, and made historical comparisons with previous nationwide studies. RESULTS: Responses were received from 114 out of 150 facilities (response rate: 76.0%) for OC and 43 out of 51 for OTC (response rate: 84.3%). Breast cancer was the most common disease among patients whose FP specimens were used. During the study period, 1237 OCs and 198 OTCs were performed. In addition, 57 cycles of embryo transfer (ET) using cryopreserved oocytes and 12 cases of ovarian tissue transplantation (OTT) were performed. The mean age of patients who underwent ET using cryopreserved oocytes was 34.8 (±5.8) years, with a median age of 36 years. The pregnancy rate per ET using cryopreserved oocytes was 26.3% and the live birth rate (LBR) was 17.5%. Further, the LBR per patient was 43.3%, and the pregnancy rate following OTTs was 33.3%. Also, controlled ovarian stimulation using the random start method or the combination of aromatase inhibitors had no effect on pregnancy outcome. CONCLUSION: Implementation of both OCs and OTCs have markedly increased over time in Japan, with comparable reproductive outcomes as other reports.

Challenges to Widespread Use of Fertility Preservation Facilities for Pediatric Cancer Patients in Japan.

Purpose: Although fertility preservation for pediatric cancer patients is becoming more widespread in Japan, some facilities do not provide sufficient information regarding fertility. This study aimed to elucidate the problems pertaining to the lack of information about fertility among patients. Methods: Based on a 2020 survey, seminars addressing fertility preservation were held from the Designated Pediatric Cancer Care Hospitals in each of the seven blocks in Japan to their partner hospital (pediatric cancer hospitals). The seminar consisted of lectures and group discussions, and a questionnaire was also administered after each seminar. Results: In the group discussions, a lack of explanations to patients and explanatory materials for children were cited as issues by many facilities. The survey results revealed a lack of material explaining fertility preservation and a lack of knowledge among health care providers. There were also many requests to use the patient explanation videos presented at the seminar. Conclusion: The results indicate that further education for health care providers by seminar and other sources and enhancement of explanatory materials are important for fertility preservation in pediatric cancer hospitals in Japan.

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.

The study of the efficiency of in vitro maturation of ovarian tissue oocytes in pediatric patients.

PURPOSE: Although recent in vitro maturation (IVM) studies in pediatric patients have demonstrated successful retrieval and maturation of oocytes, the studies included only a small number of premenarchal patients. In the present study, we examined the potential use of oocyte retrieval and maturation for pediatric patients who undergo ovarian tissue cryopreservation (OTC). METHODS: We retrospectively examined the clinical records of pediatric patients who underwent OTC at our institution between October 2015 and December 2022. Data on the age, primary disease, menstrual history, pre-procedure chemotherapy, anti-Müllerian hormone (AMH) level, number of oocytes collected ex vivo from ovarian tissue, and number of mature oocytes from IVM were examined. RESULTS: Data of 60 pediatric patients (aged 1 to 17 years) were included for analysis. Oocytes were retrieved from 36 patients; the oocytes of 18 of these patients could be cryopreserved. The IVM rate was significantly lower in the premenarchal patients than in the postmenarchal patients. The number of mature oocytes retrieved from IVM was higher in the no-chemotherapy group than in the chemotherapy group. A significant positive correlation was observed between the AMH level and the IVM outcomes. CONCLUSION: Oocyte retrieval and maturation in pediatric patients undergoing OTC is particularly useful in those not receiving chemotherapy. In patients receiving chemotherapy, the AMH level may be useful for predicting the IVM outcome. Activation of the oocyte maturation process in vivo in pediatric patients and better understanding of the major regulators of oocyte maturation are necessary to improve the utility of the IVM procedure.

Investigation of an efficient method of oocyte retrieval by dual stimulation for patients with cancer.

Purpose: To examine the optimal timing of second ovarian stimulation using the dual stimulation method for good ovarian responders with cancer undergoing oocyte retrieval for fertility preservation. Methods: A retrospective analysis was conducted using data from 69 patients with cancer who underwent oocyte retrieval for fertility preservation at four Japanese institutions during 2010-2021. Twenty-two patients underwent two oocyte retrievals for fertility preservation. We studied the relationship between the initial number of oocytes retrieved via dual stimulation and risk of ovarian enlargement as well as the appropriate waiting interval between the end of the first ovarian stimulation and beginning of the second ovarian stimulation. Results: The risk of ovarian enlargement was high when the initial number of oocytes retrieved via dual stimulation was ≥5. An 8-day waiting interval may be more effective for performing a second ovarian stimulation oocyte retrieval in these cases, although the difference was not significant. Conclusions: This study provides one policy for effectively managing ovarian enlargement and timing of second ovarian stimulation during oocyte retrieval via the dual stimulation method for patients with cancer undergoing fertility preservation. If more facilities implement this procedure, more oocytes may be obtained in a short period for fertility preservation purposes.

Oral-malodor measurement and intention to quit smoking in men: A before-after study.

INTRODUCTION: Few studies have examined the effect of feedback based on oral-malodor measurements on the motivation to quit smoking. Therefore, this study examined whether oral-malodor measurements were associated with the intention to quit smoking. METHODS: This retrospective, uncontrolled before-after study invited smokers to a workplace health event in 2019 and 2020 to motivate them to quit smoking. They attended seminars on oral health and smoking cessation aids, and then underwent respiratory function and oral-malodor measurements using exhaled and oral cavity air, respectively. Intention to quit smoking was evaluated by answers to questions regarding the intention to quit in the next 1 or 6 months in questionnaires collected before and after the event. This study analyzed 241 men aged 20-54 years (mean: 33.2 ± 10.5) to examine factors associated with the intention to quit in multivariable logistic regression analyses for age, tobacco type (cigarettes and heated-tobacco products), and category of tobacco consumption. RESULTS: Before the event, 8.7%, 17.0%, and 74.3% of smokers had intended to quit in the next month, the next six months, or had no intention to quit, respectively. After the event, the respective percentages were 17.8%, 26.6%, and 55.6%. A higher methyl mercaptan concentration, a volatile sulfide component of oral malodor, was significantly associated with the intention to quit in the next month (adjusted odds ratio, AOR=4.24; 95% CI: 1.52-11.8, p=0.006). The participants with higher daily tobacco consumption were less likely to acquire the intention to quit in the next six months (AOR=0.37; 95% CI: 0.15-0.92, p=0.032). Other variables, such as lung age deficit, exhaled CO concentration, and hydrogen sulfide concentration (another component of oral malodor), were not significantly associated. CONCLUSIONS: Oral-malodor measurement feedback may help motivate men to quit smoking in the next 1 month rather than in the next six months.

Effect of a web-based fertility preservation training program for medical professionals in Japan.

BACKGROUND: Our web-based training program called "Educating Medical Professionals about Reproductive Issues in Cancer Healthcare" aims to help healthcare professionals communicate promptly with patients and survivors who are adolescents and young adults, with information pertinent to reproductive health issues such as the risk of infertility and fertility preservation. METHODS: The study participants were professional healthcare providers, including physicians, nurses, pharmacists, social workers, midwives, psychologists, laboratory technicians, genetic counselors, and dieticians. Pre- and post- and 3-month follow-up tests consisting of 41 questions were administered to measure changes in knowledge and confidence. The participants also received a follow-up survey that covered confidence, communication techniques, and practice habits. A total of 820 healthcare providers participated in this program. RESULTS: The mean total score from the pre-test to the post-test grew significantly (p < 0.01), and participants' self-confidence increased. In addition, there was a change in the behavior of healthcare providers, who began asking about patients' marital status and parity. CONCLUSION: Our web-based fertility preservation training program improved knowledge and self-confidence regarding fertility preservation issues among healthcare providers caring for adolescents and young adult cancer patients and survivors.

Investigation of Fertility Preservation Education Videos for Pediatric Patients Based on International and Historical Survey.

Purpose: Recently, direct communication with children about cancer seems to have shifted, but little is known about communication regarding discussions of future infertility risk due to cancer therapy. This study conducted cross-cultural comparisons between Japan and the United States to clarify communication patterns about cancer notification and develop appropriate information about fertility issues. Methods: An online survey was distributed to members of the Japanese Society of Pediatric Hematology/Oncology in July 2019 and the American Society of Pediatric Hematology/Oncology in July 2020. Based on the results from the survey, we developed three types of educational videos: a prepubertal version A, B, and a pubertal version. Next, we conducted a survey to assess whether these were appropriate for clinical practice. Results: We analyzed 325 physicians in Japan and 46 in the United States. In Japan, 80.5%, 91.7%, and 92.1% of the physicians notified patients aged 7-9, 10-14, and 15-17 years of their cancer diagnosis directly, respectively, compared within the United States, where the rate was 100%, regardless of age. Further, 9% and 45% of physicians in Japan and the United States, respectively, discuss fertility issues directly with patients aged 7-9 years. In the survey to assess the educational videos, 85% of the physicians preferred to use the educational videos in clinical practice. Conclusion: This is the first step in bringing concordance to communication patters for emerging cancer care around the globe and that this study and its intervention arm provide guidance in ways that ensure global equity in care.

Oncofertility-related psycho-educational therapy for young adult patients with breast cancer and their partners: Randomized controlled trial.

BACKGROUND: A couples' psycho-educational program called Oncofertility! Psycho-Education and Couple Enrichment (O!PEACE) therapy was created and its effect when provided before cancer treatment was examined. METHODS: This multicenter randomized controlled trial with nonmasking, parallel two-group comparison enrolled women aged 20 to 39 years with early-stage breast cancer and their partners. They were randomly assigned to receive O!PEACE (37 couples) or usual care (37 couples). Primary end points were cancer-related posttraumatic stress symptoms, symptoms of depression, and anxiety. Secondary end points were stress-coping strategies, resilience, and marital relationship. RESULTS: Women receiving psycho-educational therapy had significantly reduced Impact of Event Scale-revised version for Japanese scores (p = .011, ηp 2  =  = .089). For patients with Impact of Event Scale-revised version for Japanese scores at baseline ≥18.27, O!PEACE therapy improved these scores when compared with usual care (U = 172.80, p = .027, r = 0.258). A >5-point reduction was present in 59.3% and 30% of women in the O!PEACE therapy and usual-care groups, respectively. For partners, O!PEACE therapy significantly improved stress-coping strategies (95% CI, -0.60 to -0.05; p = .018, ηp 2  =  = .074) and escape-avoidance marital communication (95% CI, -0.33 to -0.08; p = .001, ηp 2  = .136). O!PEACE therapy significantly improved the partners' support (95% CI, 0.10-0.50; p = .001, ηp 2  = .127), the rate of receiving fertility preservation consultations, and knowledge levels. CONCLUSIONS: O!PEACE therapy before cancer treatment can improve posttraumatic stress symptoms, stress-coping behavior, and marital relationships. Larger sample sizes and longer term follow-up are required. PLAIN LANGUAGE SUMMARY: A psycho-educational program, the Oncofertility! Psycho-Education and Couple Enrichment (O!PEACE) therapy program was developed and evaluated for women diagnosed with breast cancer and their partners. A multicenter randomized controlled trial showed that the O!PEACE psycho-educational therapy, with only two precancer treatment sessions, can reduce cancer-related posttraumatic stress symptoms and improve oncofertility knowledge and marital relationships in young adult patients with breast cancer. The therapy could also improve stress-coping strategies in marital communications with their partners. Couples may use O!PEACE psycho-educational therapy to consider fertility preservation and improve their psychosocial aspects.

Comparison of older and younger patients with ovarian cancer: A post hoc study (JGOG3016-A3) of the treatment strength and prognostic outcomes of conventional or dose-dense chemotherapy.

AIM: To evaluate changes of treatment strength and its impact on prognosis in older patients with ovarian cancer. METHODS: We compared relative dose intensity (RDI) as a representative of treatment strength, prognosis, and other features between older (≥65 years) and younger patients (<65 years) retrospectively. Seventy-seven older patients of 301 who received dose-dense-paclitaxel-carboplatin (dTC) and 93 older patients of 304 who received conventional-paclitaxel-carboplatin (cTC) from the Japanese Gynecologic Oncology Group (JGOG) 3016 clinical trial were analyzed. RESULTS: The RDI of older patients was lower than that of younger patients in cTC (87.4% vs. 90.8%, p = 0.009) but not in dTC (79.0% vs. 81.2%, p = 0.205). In both regimens, older patients had worse overall survival than younger patients: hazard ratio [HR] = 1.80; 95% confidence interval [CI]: 1.25-2.59; p = 0.001 for dTC, and HR = 1.59; 95% CI: 1.15-2.19; p = 0.04 for cTC. However, the RDI was not determined as a prognostic factor statistically. The prognostic factors identified by multivariate analysis for both regimens were clinical stage and residual disease; for dTC were age, performance status, and serum albumin; and for cTC was white blood cell count. There was no difference in neutropenia observed between age groups in either regimen. CONCLUSIONS: The RDI of older patients varies according to the administered schedule and is not always lower than that of younger patients. Older patients with comparable treatment strength to younger patients in the dTC group did not accomplish the same level of prognosis as younger patients. Other biologic factors attributable to aging may affect prognosis.

Minimal residual disease detection by mutation-specific droplet digital PCR for leukemia/lymphoma.

Minimal residual disease (MRD) is usually defined as the small number of cancer cells that remain in the body after treatment. The clinical significance of MRD kinetics is well recognized in treatment of hematologic malignancies, particularly acute lymphoblastic leukemia (ALL). Real time quantitative PCR targeting immunoglobulin (Ig) or T-cell receptor (TCR) rearrangement (PCR-MRD), as well as multiparametric flow cytometric analysis targeting antigen expression, are widely used in MRD detection. In this study, we devised an alternative method to detect MRD using droplet digital PCR (ddPCR), targeting somatic single nucleotide variants (SNVs). This ddPCR-based method (ddPCR-MRD) had sensitivity up to 1E-4. We assessed ddPCR-MRD at 26 time points from eight T-ALL patients, and compared it to the results of PCR-MRD. Almost all results were concordant between the two methods, but ddPCR-MRD detected micro-residual disease that was missed by PCR-MRD in one patient. We also measured MRD in stored ovarian tissue of four pediatric cancer patients, and detected 1E-2 of submicroscopic infiltration. Considering the universality of ddPCR-MRD, the methods can be used as a complement for not only ALL, but also other malignant diseases regardless of tumor-specific Ig/TCR or surface antigen patterns.

Thyroid hormone triiodothyronine does not protect ovarian reserve from DNA damage induced by X-ray and cisplatin.

PURPOSE: Cancer therapy can induce premature ovarian insufficiency, necessitating methods for preserving fertility in female cancer patients. However, the only accepted clinical practice for doing so is cryopreservation of embryos, unfertilized ova, and ovarian tissue, despite potential options such as in vitro maturation of follicles. Therefore, considerable interest has arisen in fertoprotective agents, with research on rat ovarian granulosa cells suggesting that triiodothyronine (T3) regulates an anti-apoptosis mechanism that protects the ovarian reserve from paclitaxel-induced DNA damage. In this study, we used postnatal day 5 mouse ovary to confirm the existence of T3 thyroid hormone receptor (THR), as well as to investigate the potential protective effects of T3 against cisplatin- and X-ray-induced apoptosis. We also tested the potential anti-apoptotic effect of T3 in the breast cancer cell line MDA-MB-231. METHODS: We treated cultured mouse ovaries with varying concentration of T3 and 4 µM cisplatin and 0.2 Gy X-ray. Real-time PCR, histological analysis, immunoblot analysis, and immunofluorescence were performed to assess the potential anti-apoptotic effects of T3. RESULTS: We confirmed that THR alpha and beta are expressed in the mouse ovary. T3 (0.1, 1, 10, 100 nM, and 1 µM) does not protect ovarian reserve from cisplatin- or X-ray-induced apoptosis or DNA damage. Similarly, it does not protect mouse granulosa cells and MDA-MB-231 cells from cisplatin- or X-ray-induced apoptosis. CONCLUSION: Our findings suggest that T3 is ineffective as a fertoprotective agent, and its candidacy as a potential agent to preserve fertility should be reconsidered.

The effect of aromatase inhibitor on controlled ovarian stimulation for oocyte cryopreservation in adolescent and young cancer patients.

AIM: To determine the impact of aromatase inhibitor (AI) use in oocyte cryopreservation among Japanese adolescent and young adult (AYA) cancer patients for fertility preservation, we evaluated the oocyte cryopreservation outcomes following AI therapy in combination with the follicular phase start (FPS) and random start (RS) protocols. METHODS: This retrospective study included 81 cycles of controlled ovarian stimulation (COS) among 73 AYA patients with cancer who underwent oocyte cryopreservation to maintain fertility. The outcome measures were the total number of matured oocytes that were retrieved and cryopreserved, as well as their maturation rates. The AI (+) and AI (-) groups were compared using the RS and FPS protocols. RESULTS: Our results showed that the combined use of AI and COS decreases serum E2 levels and maintains the number of retrieved and cryopreserved mature oocytes. We also confirmed the efficacy of the RS protocol, which was found to have comparable outcomes to that of the FPS protocol in both AI (+) and AI (-) groups. CONCLUSION: The combined use of AI and COS is beneficial for oocyte cryopreservation in patients with estrogen-sensitive cancer, regardless of the menstrual cycle phase of COS initiation.

Interleukin-34 cancels anti-tumor immunity by PARP inhibitor.

OBJECTIVE: Breast cancer susceptibility gene 1 (BRCA1)-associated ovarian cancer patients have been treated with A poly (ADP-ribose) polymerase (PARP) inhibitor, extending the progression-free survival; however, they finally acquire therapeutic resistance. Interleukin (IL)-34 has been reported as a poor prognostic factor in several cancers, including ovarian cancer, and it contributes to the therapeutic resistance of chemotherapies. IL-34 may affect the therapeutic effect of PARP inhibitor through the regulation of tumor microenvironment (TME). METHODS: In this study, The Cancer Genome Atlas (TCGA) data set was used to evaluate the prognosis of IL-34 and human ovarian serous carcinoma. We also used CRISPR-Cas9 genome editing technology in a mouse model to evaluate the efficacy of PARP inhibitor therapy in the presence or absence of IL-34. RESULTS: We found that IL34 was an independent poor prognostic factor in ovarian serous carcinoma, and its high expression significantly shortens overall survival. Furthermore, in BRCA1-associated ovarian cancer, PARP inhibitor therapy contributes to anti-tumor immunity via the XCR1+ DC-CD8+ T cell axis, however, it is canceled by the presence of IL-34. CONCLUSION: These results suggest that tumor-derived IL-34 benefits tumors by creating an immunosuppressive TME and conferring PARP inhibitor therapeutic resistance. Thus, we showed the pathological effect of IL-34 and the need for it as a therapeutic target in ovarian cancer.

A Nationwide Survey Aimed at Establishing an Appropriate Long-Term Storage and Management System for Fertility Preserving Specimens in Japan.

Purpose: The demand for fertility preservation continues to grow as cancer treatment outcomes improve. The specimen storage period is longer for fertility preservation than for conventional fertility treatment; therefore, a robust management system for stored specimens is required. We conducted the first national survey in Japan on the management of cryopreserved specimens in fertility preservation facilities. Methods: Questionnaires were mailed to 130 fertility preservation facilities. Primary outcomes included the official position of the storage manager, support system in case of facility closure, disaster countermeasures, management and operating system for liquid nitrogen storage containers, preservation costs, and method to confirm the intention to continue storage. Results: The response rate was 63.8%. The facility director most commonly functioned as the storage manager (59.0%). In case of facility closure, 20.5% had an approved transfer site; 59.0% had not made any decisions. In the management of liquid nitrogen containers, 83.1% regularly replenished the liquid nitrogen, 65.1% regularly checked the amount, and 16.9% had alarm monitoring systems. Regarding disaster countermeasures, 70.9% had taken measures to protect specimens. Conclusion: This survey revealed issues such as disparities among facilities regarding long-term specimen storage systems. Accordingly, management standards for fertility preservation facilities should be established.

Current Status and Issues of the Japan Oncofertility Registry.

Purpose: Fertility preservation (FP) is becoming increasingly common among child, adolescent, and young-adult (CAYA) patients with cancer. However, Japan has long lacked definite estimates of utilization rates for FP services among CAYA patients with cancer, and little is known about disease/FP outcomes among users. Therefore, the Japan Society for Fertility Preservation (JSFP) launched the Japan Oncofertility Registry (JOFR) in 2018 and started the online registration of information regarding primary disease, FP, and data on prognosis and pregnancy outcomes. This study reports the analytical results of FP data registered in the JOFR as of 2021. Methods: Data about patients' primary disease(s), treatment courses, cancer and pregnancy outcomes, and specific procedures were extracted from the JOFR and analyzed. Results: In 2021, 1244 patients received counseling or treatment related to FP (540 males, 704 females). While the numbers of males in each age group were approximately equal, most females were aged between 31 and 40 years. In total, 490 male and 540 female patients underwent FP procedures. Leukemia, testicular cancer, and malignant lymphoma accounted for the majority of male cases seeking treatment, whereas breast cancer was the primary disease in two-thirds of the females. Since 1999, 395 patients have accumulatively experienced subsequent pregnancy. Conclusions: As of January 2022, >7000 cases from >100 fertility facilities have been registered in the JOFR. In the future, maintaining JOFR to disseminate information on cancer prognoses, pregnancy rates, and other oncofertility outcomes is expected to drive further expansion of oncofertility services in Japan.