Systemic Cancer Treatment Research Articles

Development and validation of the NCC-BC-A scale to assess patient-reported outcomes for breast cancer patients in China.

The commonly used international patient-reported outcome scales for breast cancer were developed before the advent of multiple targeted therapies and immunotherapies, rendering them potentially insufficient for current clinical practices. Therefore, it is necessary to develop a specific patient-reported outcome scale tailored for breast cancer patients in China to optimize the management model for these patients. A comprehensive literature search was performed in the PubMed, Embase, Wanfang, and CNKI databases to extract dimensions and items for a potential patient-reported outcome scale. The Delphi method was used to modify, add, subtract, and adjust the language of items until the experts reached a consensus on the first draft. This draft was further refined using a cognitive test and a presurvey. The optimized scale was used for a formal survey, and the items were further analyzed and screened using metrics such as the coefficient of variation, correlation coefficient, internal item consistency, factor analysis, reliability, and validity. A total of 10,954 articles were analyzed, and 237 were used to create a pool of 277 patient-reported outcome items. Through two rounds of Delphi expert consultation, the experts' authority coefficients were 0.739 and 0.826. After a cognitive test, several items were adjusted to enhance understanding. Further adjustments were made following a presurvey of 200 advanced breast cancer patients, resulting in a 38-item patient-reported outcomes scale, termed NCC-BC-A. In the national formal survey, 588 advanced breast cancer patients participated. Principal component analysis showed good consistency among the items and sufficient difference between the dimensions. The results were normally distributed with good variation. The Cronbach's α coefficient of the scale was 0.925 and the test-retest reliability was 0.9041. The NCC-BC-A scale has high validity and reliability. It comprehensively considered the characteristics of systemic treatment for breast cancer, and the specific context within China. Its implementation may help clinicians to pay more attention to quality of life of breast cancer patients and to optimize the system for managing this condition.

Differences in Health Care Expenditures by Cancer Patients During Their Last Year of Life: A Registry-Based Study.

During the last year of life, persons with cancer should probably have similar care needs and costs, but studies suggest otherwise. A study of direct medical costs (excluding costs for expensive prescription drugs) was performed based on registry data in Stockholm County, which covers 2.4 million inhabitants, for all deceased persons with cancer during 2015-2021. The data were mainly analyzed with the aid of multiple regression models, including Generalized Linear Models (GLMs). In a population of 20,431 deceased persons with cancer, the costs increased month by month (p < 0.0001). Higher costs were mainly associated with lower age (p < 0.0001), higher risk of frailty, as measured by the Hospital Frailty Risk Scale (p < 0.0001), and having a hematological malignancy. In a separate model, where those 5% with the highest costs were identified, these variables were strengthened. Sex and socio-economic groups on an area level had little or no significance. Systemic cancer treatments during the last month of life and acute hospitals as place of death had only a moderate impact on costs in adjusted models. Higher costs are mainly related to lower age, higher frailty risk and having a hematological malignancy, and the effects are both statistically and clinically significant despite the fact that expensive drugs were not included. On the other hand, the costs were mainly comparable in regard to sex or socio-economic factors, indicating equal care.

Expectations concerning cancer treatment: perspectives of medical oncologists and patients on advanced, unresectable lung carcinoma.

This study seeks to compare expectations regarding systemic cancer treatment for advanced lung cancer from the perspectives of both patient and medical oncologist. A cross-sectional study involving 17 medical oncologists from 13 Spanish hospitals between 2021 and 2022. Patients with advanced, unresectable lung cancer were recruited prior to initiating systemic cancer treatment. Both patients and oncologists completed the NEOetic-EIT and the STAR. Seventeen medical oncologists specializing in lung cancer participated, with a mean age of 36.2 years (range 28-56); 65% were female. The study included 298 patients with advanced, unresectable lung cancer, predominantly non-small cell type (72%), and most at stage IV (77%). Most patients were retired or unemployed (71%), and married or partnered (77%). Treatment approaches varied, with 44% based on biomarkers. Oncologists had greater expectations of positive outcomes for participants with better baseline prognosis, such as ECOG 0, newly diagnosed, locally advanced, unresectable non-small cell lung cancer, and those receiving biomarker-based treatments. In contrast, patients' treatment expectations did not vary based on sociodemographic or clinical factors. Generally, patients had high expectations of cure, in contrast to oncologists' lower expectations, though both anticipated similar quality-of-life improvements. Patients anticipated more side effects than oncologists. Among oncologists, expectations varied by gender and decreased with age and experience, with no differences detected among patients based on gender, age, or doctor-patient relationship. This study reveals the complex expectations of patients and oncologists in advanced lung cancer treatment. It underscores the need for effective communication in oncology to align patient expectations with clinical realities.

9183 Pituitary Metastasis Of Lung Adenocarcinoma Presenting As Anterior Pituitary Dysfunction

Abstract Disclosure: O. faour: None. M. Kinaan: None. S.K. Suryanarayanan: None. Introduction: The pituitary should not be overlooked as a site for metastasis and can be the first presentation of neoplastic disease in some patients. Most common presenting symptoms: headache, ophthalmoplegia, visual field defect and Arginine Vasopressin Deficiency (AVP-D). We present a case of pituitary metastasis of lung adenocarcinoma presenting as anterior Pituitary dysfunction that also showed partial AVP-D unmasked after starting steroids. Case Description: A 63-year-old male with history of tobacco use, COPD, and hypertension presented with syncope. He reported a 30lbs weight loss within prior 2 months, low energy, increased thirst, and polyuria. Physical exam was significant for cachexia, normal visual field on confrontation, and vital signs of BP 100/61, HR 83, and Weighing 180 lbs. Since he had syncope, Cortisol checked was undetectable and Free T4 was low, He was started on hydrocortisone and levothyroxine. CTA chest revealed a right hilar mass measuring 2.7 x 3 cm. Endobronchial biopsy was consistent with lung adenocarcinoma. MRI of pituitary gland revealed solid hypointense lesion with glandular thickening and diffuse heterogeneity involving most of the pituitary gland measuring up to 16 mm. No cavernous sinus invasion. Pituitary infundibulum showed diffuse thickening and enhancement of the pituitary stalk throughout with Intact posterior pituitary bright spot. Labs showed low LH, cortisol, ACTH, GH, TSH, and ADH. Initially, the patient was able to maintain a euvolemic status through increased water intake; however, he was later found to have partial central AVP-D when steroids were introduced. He responded to the use of Desmopressin, developed hyponatremia after 3 doses. He was started on a combination of carboplatin/pemetrexed/pembrolizumab but had no response and was transferred to palliative care/hospice and passed away within 7months after diagnosis.Discussion:Pituitary metastasis is rare and most commonly occurs in lung and breast cancers. Unfortunately, they are associated with poor prognosis. MRI findings of loss of posterior pituitary bright spot, thickening of the stalk, and dumbbell shape can be helpful in distinguishing between primary pituitary tumors and metastases. PET-FDG scan has limited value. Pituitary metastasis commonly presents with posterior pituitary dysfunction due to direct blood supply. Unmasking or worsening of AVP-D can happen with steroid replacement in patients requiring initiation or intensification of Desmopressin therapy. Treatment involves combination of surgery, radiation therapy, and systemic treatment for the primary cancer which can improve symptoms only but does not improve mortality. Presentation: 6/1/2024

Emerging Claudin18.2-targeting Therapy for Systemic Treatment of Gastric Cancer: Seeking Nobility Amidst Danger.

Gastric cancer in advanced stages lacked effective treatment options. claudin18.2 (CLDN18.2) is a membrane protein that is crucial for close junctions in the differentiated epithelial cells of the gastric mucosa, playing a vital role in barrier function, and can be hardly recognized by immune cells due to its polarity pattern. As the polarity of gastric tumor cells changes, claudin18.2 is exposed on the cell surface， resulting in immune system recognition, and making it an ideal target. In this review, we summarized the expression regulation mechanism of claudin18.2 both in normal cells and malignant tumor cells. Besides, we analyzed the available clinical results and potential areas for future research on claudin18.2-positive gastric cancer and claudin18.2-targeting therapy. In conclusion, claudin18.2 is an ideal target for gastric cancer treatment, and the claudin18.2-targeting therapy has changed the treatment pattern of gastric cancer.

Updates in Systemic Treatment of Hormone Receptor-Positive Early-Stage Breast Cancer.

Hormone-receptor positive (HR +) and human epidermal growth factor receptor 2 (HER2) negative early breast cancer (eBC) is a heterogeneous disease with several contributing factors for increased risk of recurrence, including tumor features, individual biomarkers, and genomic risk. The current standard approach in the management of HR + /HER2neg eBC includes chemotherapy and endocrine therapy (ET), and additional therapies based on risk profile, menopausal status, and genetics are sometimes appropriate. The risk of recurrence is more pronounced in patients with high-risk eBC including large tumor size, nodal involvement, high proliferative index, and genetic predisposition. In premenopausal patients with high-risk eBC, ovarian function suppression in combination with adjuvant ET improves survival. In postmenopausal patients, extended aromatase inhibitor (AI) therapy can be considered. Recent trials have identified novel treatment approaches to reduce the risk of recurrence in high-risk HR + /HER2neg eBC including the addition of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to adjuvant ET. For patients with germline BRCA1/BRCA2 mutations, adjuvant poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have been shown to improve overall survival (OS). However, despite these recent advances, the risk of recurrence remains substantial, highlighting an area of unmet need. There are several ongoing clinical trials further investigating the role of CDK 4/6 inhibitors and immunotherapy in high-risk HR + /HER2neg eBC.

SY30-3 Current status and future development of second-line or later systemic treatment for advanced biliary tract cancer

SY30-3 Current status and future development of second-line or later systemic treatment for advanced biliary tract cancer

Immunotherapy in Stage III-IV Colon Cancer: A Propensity Score-Matched Analysis of the National Cancer Database.

Immunotherapy for the systemic treatment of cancer offers new treatment possibilities for advanced malignancies. Despite promising initial results, evidence on efficacy of immunotherapy for colon cancer is lacking. Thus, we aimed to assess short-term and long-term outcomes of immunotherapy in patients with advanced colon cancer. A US National Cancer Database was searched for patients with stage III-IV colonic adenocarcinoma between 2010 and 2019. Propensity score matching was used to classify the cohort into 2 groups: patients who received immunotherapy and controls. Main outcome measures were primary outcome was overall survival (OS). A total of 23,778 patients with stage III-IV colonic adenocarcinoma were treated with immunotherapy during the study period compared to 114,753 controls. Immunotherapy treated patients were younger (median age 61 vs. 67 y; P <0.001), more often male (57.3% vs. 50.7%, P <0.001), had more private insurance (44.1% vs. 33.7%; P <0.001), had more left-sided tumors (49.5% vs. 39.1%; P <0.001) and liver metastasis (80.2% vs. 61.7%; P <0.001) than controls. Immunotherapy patients received more standard chemotherapy (49.8% vs. 41.6%; P <0.001). After propensity-score matching, mean OS was significantly shorter in the immunotherapy group compared with controls (34.7 vs. 36.2 mo; P =0.008). Cox regression analysis demonstrated that immunotherapy was associated with increased risk for mortality (HR: 1.1; 95% CI: 1.02-1.18; P =0.005). Patients who received immunotherapy had lower 90-day mortality rates compared with controls (2.3% vs. 3.6%; P =0.004), but the groups had equivalent 30-day mortality rates (0.7% vs. 0.8%; P =0.76). Immunotherapy showed no improvement in OS in patients with stage III-IV colon cancer.

Effect of streamlining prior authorization processes for systemic cancer treatments on efficiency and financial losses.

412 Background: Prior authorizations (PAs) for systemic cancer treatments are a barrier to timely quality cancer care delivery. The high administrative burden to complete peer to peer’s (P2P) and appeals leads to care delays and revenue losses. At our tertiary academic cancer center, in partnership with our cancer registry and Epic teams, we shifted the clerical work required for PAs from clinicians to certified tumor registrars (CTRs) to increase authorization efficiency and decrease financial losses from denials. Methods: Clinicians place the treatment plan order which goes to the CTR work queue. We leveraged the Epic staging smart form to consolidate and auto-populate common elements needed for PA. The CTRs then complete and validate the form prior to the authorization specialists obtaining the PA. We compared the pre (1/2022-9/2022) and post-implementation (11/2022-4/2024) periods on our primary outcomes: average monthly number of PAs pending review (including P2P, appeals and authorizations requiring clarifying clinical documentation), average monthly denial rate and average time spent on PAs by the authorization specialists. We compared the financial losses from denied PAs from calendar year 2022 to 2023. Analyses were conducted using descriptive statistics. Results: There was a 1.4% reduction in the average monthly number of PA’s pending review (350 vs 345). The average monthly authorized rate was steady from the beginning of the intervention (94%) to present time (95%). The average monthly denial rate was 2.9% at the beginning of the intervention and 0.9% at present time. There was a consistent decrease in the average time a PA was spent in pending review status: 118 hours in 2022, 102 hours in 2023 and 79 hours in quarter 1 of 2024. Despite the overall increase in volume of authorizations submitted, there was an overall cost savings of $27,392,894 from 2022 ($49,964,703) to 2023 ($22,571,809) from the decrease in denials. In 2022, 6.2% of total approved charges were denied and this decreased to 2.7% in 2023. Conclusions: By leveraging the EHR and optimizing existing non-clinical staff workflows, we maintained sustained average authorized and denial rates despite overall volume going up due to improved authorization efficiency and reduced financial losses due to denials. Additionally, there were overall cost savings for the institution due to the decreased percent of denials of total approved charges. Future work will include further refinement of treatment and disease specific optimizations.

Immunotherapy at the end of life.

188 Background: It is well established in the literature that cancer treatment administered at the end of life (EOL) does not improve either quality of life or survival rates. Patients undergoing systemic cancer treatments at near the EOL often have reduced access to hospice services and an increased likelihood of acute medical interventions, including emergency department visits, intensive care unit admissions, and in-hospital deaths. The development of immune checkpoint inhibitors (ICIs) has revolutionized cancer care over the past decade, demonstrating the ability to extend progression-free survival and overall survival in patients with various cancers. Furthermore, ICIs may represent a promising therapeutic option for adults with impaired performance status (PS) due to their relatively favorable side-effect profile when compared to conventional chemotherapy. While numerous studies have examined chemotherapy at the end of life, research specifically focusing on the administration of immunotherapy during this period is scarce. Methods: We conducted a retrospective chart review using the electronic medical record database at Scripps clinic focusing on cancer patients undergoing immunotherapy who passed away between June 1, 2017, and August 30, 2023, comprising a cohort of 641 individuals. Our investigation was designed to provide a retrospective overview of patient characteristics and outcomes, with a specific emphasis on factors at EOL. Results: The most prevalent tumor types were lung (34%), GI (21%), skin (13%), GU (12.6%) and others (19.4%). On average, no patients received immunotherapy in the last 30 days of their lives. Among the different cancer types, breast cancer patients had the longest interval between last treatment and death, averaging 259 days. This was followed by patients with head and neck cancer (207 days), skin cancer (199 days), genitourinary (GU) cancers (177 days), lung cancer (140 days), gynecological (GYN) cancers (135 days), and gastrointestinal (GI) cancers (134 days). 19 patients died from immune-related adverse events (IrAEs). These patients had the shortest interval between their last treatment and death, with a mean of 34 days. This was followed by those who died due to cancer progression, with an average interval of 148 days. Conclusions: The decision to administer anticancer therapies near the EOL is increasingly complex. Oncologists must carefully discuss immunotherapy with patients, monitor for IrAEs, and consider discontinuing treatment if there is disease progression, worsening PS or after two years of treatment.

Adherence to pretreatment hepatitis B virus (HBV) screening in patients with cancer after implementation of built-in order set.

330 Background: Patients with a history of HBV exposure are at risk of reactivation when receiving treatments that affect the immune system, such as cancer-directed therapies. ASCO guidelines recommend universal HBV screening prior to initiation of cancer-directed therapies to prevent hepatic dysfunction and delays in cancer care. However, significant variation remains in clinical practice. Improving HBV screening is of special interest at our institution, given that we serve a large proportion of Asian immigrants at high risk of prior HBV exposure. With our institution’s transition to EPIC on Apr 1, 2022, the HBV serology order set was incorporated into the pre-treatment checklist of every cancer therapy plan. We studied the rates of HBV screening before and after implementing this change. Methods: We identified patients with cancer starting systemic cancer treatment at our institution between Oct 1, 2021 – Mar 31, 2022 (pre-EPIC period), and Oct 1, 2023 – Mar 31, 2023 (post-EPIC period). Patients who received only endocrine therapy, transferred care, or lost to follow-up prior to treatment initiation were excluded. To select a random sample from each time-period of interest, patients were assigned a random number, sorted based on this random number, and then reviewed in order. All data was collected retrospectively by manual chart review. Results: We randomly selected and reviewed 69 patients from pre-EPIC period, and 75 from post-EPIC period. Their demographic, disease, and treatment characteristics are summarized in the table. HBV screening rates were 42% and 80% in the pre-and post-EPIC periods, respectively (p&lt;0.001). Twenty-one (14.6%) patients screened positive for HBV core antibody, among whom six (5.1%) had negative surface antibodies. Conclusions: The built-in HBV serology order set significantly improved rates of hepatitis B screening prior to starting systemic cancer-directed treatment. It is a low-cost and highly effective intervention. Our next steps are to determine how a higher adherence to HBV screening guidelines impacted the management of patients with prior HBV exposure. Pre-EPIC:Oct 1, 2021 - Mar 31, 2022 (N=69) Post-EPIC: Oct 1, 2022 – Mar 31, 2023 (N=75) P values Age at diagnosis (years), mean (SD) 62.1 (1.4) 65.2 (1.6) 0.15 Female (%) 40 (58.0) 35 (46.7) 0.18 Race (%): 0.051 White 51 (73.9) 49 (65.3) Asian 8 (11.6) 20 (26.7) Other 10 (14.5) 6 (8.0) Cancer type (%): 0.39 Hematological Malignancies 19 (27.5) 16 (21.3) Solid Tumor 50 (72.7) 59 (78.7) Metastatic Disease (%) 24 (34.8) 25 (33.3) 0.95 Treatment Type (%): 0.13 CD20 mAb+/- other 3 (4.4) 9 (12.0) Chemotherapy+/-other 52 (75.4) 57 (76.0) Other 14 (20.3) 9 (12.0) mAb: monoclonal antibody.

Prediction of undetectable circulating tumor DNA by comprehensive genomic profiling assay in metastatic prostate cancer: the SCRUM-Japan MONSTAR SCREEN project.

Undetectable circulating tumor DNA (ctDNA) is an obstacle to performing comprehensive genomic profiling in daily practice to identify genomic alterations. We investigated the associations between clinicopathological factors and undetectable ctDNA using a commercially available comprehensive genomic profiling assay in metastatic prostate cancer. Patients treated with systemic treatment for metastatic prostate cancer were included. ctDNA was analyzed by FoundationOne®Liquid CDx at enrollment. The associations between clinicopathological characteristics and ctDNA detection were analyzed. The number of bone metastasis was associated with ctDNA detection (odds ratio [95% confidence interval], 13.6 [1.71-108], P = 0.014). An algorithm predicting ctDNA detection using clinicopathological parameters was created. If ≥ 4 bone metastases were observed, ctDNA detection was estimated to be 98.9%. Among the patients with < 4 bone metastases, if two or three features among ISUP grade group 5, PSA level ≥ 10ng/ml, and castration resistance were present, the ctDNA detection rate was 96.7% while the ctDNA detection rate was 86.3% if no or only one feature was present. An algorithm created in this study is helpful in determining when to undertake comprehensive genomic profiling assay using blood.

The Adenosinergic Pathway in Non-Small Cell Lung Cancer.

Immune checkpoint inhibitors (ICIs) targeting PD-(L)1 and CTLA-4 have revolutionized the systemic treatment of non-small cell lung cancer (NSCLC), achieving impressive results. However, long-term clinical benefits are only seen in a minority of patients. Extensive research is being conducted on novel potential immune checkpoints and the mechanisms underlying ICI resistance. The tumor microenvironment (TME) plays a critical role in modulating the immune response and influencing the efficacy of ICIs. The adenosinergic pathway and extracellular adenosine (eADO) are potential targets to improve the response to ICIs in NSCLC patients. First, this review delves into the adenosinergic pathway and the impact of adenosine within the TME. Second, we provide an overview of relevant preclinical and clinical data on molecules targeting this pathway, particularly focusing on NSCLC.

At the Crossroads of Local and Systemic Treatment of Operable Non-Small Cell Lung Cancer.

At the Crossroads of Local and Systemic Treatment of Operable Non-Small Cell Lung Cancer.

The impact of inter-cycle treatment delays on overall survival in patients with advanced-stage ovarian cancer.

Chemotherapy forms the cornerstone of systemic treatment for advanced ovarian cancer, extending overall survival; however, drug-related toxicity can lead to treatment delays, potentially diminishing treatment efficacy. This study evaluated the impact of treatment delays on all-cause mortality of patients with ovarian cancer, to better inform decisions on patient management. This retrospective, population-based cohort study included 1517 women with advanced-stage ovarian cancer, receiving first-line adjuvant or neoadjuvant chemotherapy in 2014 and 2015. The frequency of inter-cycle delays >7 dayswas calculated using drug administration dates. Kaplan-Meier estimates were used to compare 2-year overall survival (OS) between patients who were delayed and those treated to schedule. Cox proportional hazards regression was used to investigate the impact of treatment delay on all-cause mortality. Inverse probability of treatment weighting propensity scores were used to adjust for confounding variables. Delays >7 days occurred in 35.3% of patients. Two-year OS probability was 62.7% in patients who experienced treatment delays >7 days (95% CI, 58.7-66.9) compared to 69.1% in those treated to schedule (95% CI, 66.2-72.0). Delays were not significantly associated with all-cause mortality when adjusted for confounders (HR 1.00 95% CI, 0.83-1.20, P = .9). Delays to chemotherapy treatment were not significantly associated with worsened survival in patients with advanced-stage ovarian cancer. These results can inform clinical decision making that prioritize toxicity management and quality of life for those treated with chemotherapy.

Bilateral breast metastases from anaplastic lymphoma kinase-positive lung cancer in a male: a case report

BackgroundDistant metastases from lung cancer are commonly found in the brain, bone, and liver. Metastases to the breast from non-mammary malignancies are extremely rare, and their clinical presentations remain unclear.Case presentationWe herein report a case of bilateral breast metastases from anaplastic lymphoma kinase-positive advanced lung cancer in a 51-year-old Japanese male patient. During the course of systemic treatment for advanced lung cancer, computed tomography revealed bilateral breast enlargement without contrast enhancement, a finding consistent with gynecomastia. While other metastatic lesions responded to chemotherapy, both breast masses grew vertically like nodules. The breast masses were immunohistochemically diagnosed as metastases from lung cancer and were removed surgically. Simultaneous bilateral breast metastases from malignancies of other organs, like ones in this case, have rarely been described.ConclusionsIt is important to keep in mind that breast metastases from nonmammary malignancies are a possible explanation for unusual breast findings in a patient with a history of malignancies.

559P Early changes in circulating tumor DNA (ctDNA) and outcome during systemic palliative treatment for metastatic colorectal cancer: A systematic review and meta-analysis — An initiative under the ctDNA RECIST program

559P Early changes in circulating tumor DNA (ctDNA) and outcome during systemic palliative treatment for metastatic colorectal cancer: A systematic review and meta-analysis — An initiative under the ctDNA RECIST program

Research Progress of Neoadjuvant Chemotherapy in Advanced Bladder Cancer

Systemic treatment, commonly referred to as chemotherapy, is a fundamental approach for treating muscle-invasive bladder cancer (MIBC) and metastatic bladder cancer. Neoadjuvant chemotherapy has recently become a standard treatment for MIBC, significantly reducing tumor recurrence rates and improving patient outcomes. Patients may receive adjuvant chemotherapy involving various drug combinations to improve prognosis following surgery. MIBC patients who are unwilling or unable to undergo radical cystectomy and instead opt for bladder-sparing surgery may benefit from systemic chemotherapy combined with radiotherapy, wherein chemotherapy proves more impactful than radiotherapy. Over the past 30 years, cisplatin-based chemotherapy has been the main approach for treating metastatic bladder cancer. Recent advancements in the molecular understanding of bladder cancer have led to the use of targeted therapies, which have shown promising results. Immunotherapy for MIBC has only recently emerged, with clinical trial results indicating that immunotherapy offers better efficacy and fewer side effects for metastatic bladder cancer. In recent years, basic research on bladder cancer has been burgeoning, and clinical treatment methods have been improving accordingly. This article reviews the development of systemic treatment for bladder cancer.

Psychological impact of exceptional response in people with advanced cancer: a qualitative exploration.

In the cancer context, exceptional response incorporates unusual or unexpected response to anti-cancer treatment. For this study, exceptionally 'good' responses are defined as progression-free survival of more than three times the median from comparable trials. We aimed to explore how people meeting the definition of exceptional response to systemic cancer treatment experience adjust to their unexpected survivorship. Individuals with 'exceptional response' to anti-cancer therapy nationally were referred by their treating clinicians to the Exceptional Responders Program. We conducted a qualitative sub-study involving semi-structured interviews with purposively selected participants. Those eligible had metastatic cancer, had survived at least 3 times the expected time since diagnosis, spoke English, and were aged > 18years. Interviews were audiorecorded, transcribed and analysed thematically; and continued until thematic saturation was achieved. Twenty participants were interviewed. Thirteen were male (65%) with a median age of 63years. Median time since cancer diagnosis was 6.5years (range 3-18); survival times ranged between 3 and 10 times that expected. We identified four themes which varied in importance between individuals and over time. Exceptional responders may benefit from routine screening of distress and unmet needs to provide psychosocial support. Clinical services must focus on first capturing and then tailoring care to meet the diverse needs of this growing cohort. Adjustment to a diagnosis of advanced cancer and subsequent unexpected long-term survival is an often isolating experience and is common amongst exceptional responders. Seeking psychological and social support may assist with adjustment.

Menstrual Blood Stem Cells-Derived Exosomes as Promising Therapeutic Tools in Premature Ovarian Insufficiency Induced by Gonadotoxic Systemic Anticancer Treatment.

Gonadotoxicity resulting from systemic and locoregional cancer treatments significantly threatens women's reproductive health, often culminating in premature ovarian insufficiency. These therapies, particularly alkylating agents and ionizing radiation, induce DNA damage and apoptosis in ovarian follicles, leading to infertility, amenorrhea, and estrogen deficiency, which exacerbate risks of osteoporosis and cardiovascular diseases. Existing fertility preservation methods do not prevent immediate ovarian damage, underscoring the need for innovative protective strategies. Menstrual blood-derived stem cells (MenSC) and their extracellular vesicles (EV) present promising regenerative potential due to their therapeutic cargo delivery and pathway modulation capabilities. Preclinical studies demonstrate that MenSC-derived EV ameliorate premature ovarian insufficiency by inhibiting granulosa cell apoptosis, promoting angiogenesis, and activating pivotal pathways such as SMAD3/AKT/MDM2/P53. However, comprehensive research is imperative to ensure the safety, efficacy, and long-term effects of MenSC-derived EV in clinical practice. In this review, we update the current knowledge and research regarding the use of MenSC-derived EV as a novel therapeutic weapon for ovarian regeneration in the context of gonadotoxicity induced by systemic anticancer treatment.