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Impact of a Reproductive Health Survivorship Care Plan on Fertility, Pregnancy Concerns, and Accessing Reproductive Healthcare Among Young Nulliparous Breast Cancer Survivors.
No full textBackground: Young patients with breast cancer frequently receive chemotherapy and/or endocrine therapy that adversely affect ovarian function, leading to fertility, pregnancy, and other reproductive health concerns. Despite available evidence-based management strategies, dissemination to survivors and healthcare providers remains limited, resulting in substantial unmet informational and care needs. Web-based survivorship care plans may offer an effective approach to address these gaps.
Aims: To evaluate the effect of a web-based Reproductive Health Survivorship Care Plan (SCP-R) on reproductive concerns and reproductive healthcare access among nulliparous young breast cancer survivors (YBCS).
Methods and results: This is a secondary analysis of a 24-week randomized controlled trial on the effectiveness of a web-based SCP-R addressing unmet informational and clinical management needs for breast cancer survivors aged 18-50 years. The current analysis is restricted to nulliparous participants ages 18-40. The primary outcomes are improvement in fertility and pregnancy health concerns, as measured by the Reproductive Concerns After Cancer (RCAC) scale. The secondary outcome is fertility specialist access measured by referral, consultation, or treatment by a fertility specialist. Among 182 study participants from the parent trial, 47 met the inclusion criteria for the current study (17 in the intervention and 30 in the attention control). Mean age at diagnosis was 30.7 (SD = 3.5) years, and mean age at study participation was 34.0 (SD = 3.8) years. Fertility potential and pregnancy concerns improved in 35.3% of participants randomized to the intervention arm compared to 10.0% in the control arm (RR = 3.5, 95% CI = 1.01-12.34, p = 0.05). Intervention arm participants were significantly more likely to receive a fertility specialist referral, schedule a fertility consult, or undergo fertility treatment (37.5% in the intervention arm vs. 6.7% in the control arm; RR = 5.6, 95% CI = 1.28-24.73, p = 0.02).
Conclusions: The web-based SCP-R intervention led to improvements in fertility potential and pregnancy concerns over time and resulted in more YBCS accessing fertility specialists, highlighting the importance of age- and parity-specific survivorship care interventions to address reproductive health concerns
Oncological outcomes with and without axillary lymph node dissection in patients with residual micrometastases after neoadjuvant chemotherapy (OPBC-07/microNAC): an international, retrospective cohort study.
No full textBACKGROUND: Despite the paucity of outcome data, axillary lymph node dissection (ALND) is increasingly being omitted in patients with positive sentinel lymph nodes after neoadjuvant chemotherapy, particularly in those with low-volume residual disease. We investigated oncological outcomes in patients with breast cancer and residual micrometastases in the sentinel lymph nodes treated with or without ALND.
METHODS: OPBC-07/microNAC was a retrospective cohort study, using data obtained from the institutional databases of 84 cancer centres in 30 countries. Patients aged 18 years or older with clinical T1-4, N0-3 breast cancer at diagnosis treated with neoadjuvant chemotherapy followed by surgery between Jan 1, 2013, and May 31, 2023, who were found to have residual micrometastases (metastasis measuring \u3e0·2 mm or \u3e200 cells, not exceeding 2·0 mm in size) on frozen section or on final paraffin sections as determined by sentinel lymph node biopsy, targeted axillary dissection (sentinel lymph node biopsy with single or dual-tracer mapping plus image-guided localisation of the initially biopsy-proven and clipped node), or the marking axillary lymph nodes with radioactive iodine seeds (MARI) procedure were eligible for inclusion. The primary endpoint was the 5-year rate of any axillary recurrence (isolated or combined with local or distant recurrence) stratified by type of axillary surgery. Given the median follow-up, here we report 3-year rates and exploratory 5-year estimates. This study was registered with ClinicalTrials.gov, NCT06529302.
FINDINGS: 1585 female patients with ypN1mi disease were analysed, of whom 804 (50·7%) underwent ALND and 781 (49·3%) did not. Of 1585 women, 238 (15·0%) self-identified as Asian, 65 (4·1%) as Black, 200 (12·6%) as Hispanic, 968 (61·1%) as White, and 114 (7·2%) as unknown race and ethnicity. 925 (58·4%) of 1585 women had cT2 tumours, 1054 (66·5%) were node positive, and 1267 (79·9%) received nodal radiotherapy. The median follow-up was 3·1 years (IQR 1·8-5·2). The 3-year rate of any axillary recurrence (isolated or combined with local or distant recurrence) for the entire cohort was 2·0% (95% CI 1·3-2·9), with no statistical difference identified by extent of axillary surgery. However, patients with triple-negative disease who did not receive ALND had significantly higher rates of any axillary recurrence than women treated with ALND (8·7% [95% CI 4·4-15·0] vs 2·4% [95% CI 0·7-6·5], p=0·018). On multivariable analysis, triple-negative breast cancer (hazard ratio 3·83 [95% CI 1·72-8·52]) and omission of nodal radiotherapy (2·62 [1·19-5·73]) but not omission of ALND (0·86 [0·37-2·00]) were independently associated with an increased risk of any axillary recurrence.
INTERPRETATION: Overall, these results do not support ALND for all patients with ypN1mi on sentinel lymph node biopsy treated with nodal radiotherapy; however, tumour biology should be taken into account when considering ALND omission.
FUNDING: US National Institutes of Health, National Cancer Institute
Two-year real-world retrospective safety evaluation with onabotulinumtoxinA across multiple therapeutic indications: Findings from the SYNCHRONIZE study.
No full textOnabotulinumtoxinA (onabotA) is approved for the treatment of various therapeutic indications, which require retreatment. In clinical practice, many patients receive onabotA for multiple therapeutic indications concomitantly over extended time periods; however, there is limited long-term utilization and safety data for treating comorbid indications. SYNCHRONIZE, a 2-year, multicenter, retrospective observational chart review study in 10 US clinics, describes onabotA real-world utilization and safety in adults treated for ≥2 therapeutic indications within repeating 3-month periods for up to 7 treatments. This analysis assessed the long-term onabotA safety profile for multiple therapeutic indications by analyzing the incidence of treatment-emergent adverse events (TEAEs). Of 279 patients treated for ≥2 different therapeutic indications across all treatment combination groups in Period1, there was a gradual decrease to 80 patients at the last treatment period. The overall mean onabotA treatments over the study period was 9.3 (range: 2-48). Across treatment periods, most patients had a treatment interval between different indications of ≤24 h (range: 62-98 %) and received ≥200-\u3c 400U of cumulative 3-month dosages for multiple indications (range: 43 %-50 %) with a mean 3-month dose from 231.8 to 287.0 U. In total, 28.7 % of patients reported ≥1 TEAE after Period1; this proportion remained broadly constant across treatments (range: 28.3-31.8 %). Overall, the most common TEAEs across treatments were UTIs (range: 0.7-5.7 %), neck pain (range: 3.7-9.1 %), headache (range: 2.9-6.5 %), and migraine (range: 2.5-6.4 %). There was no apparent trend between TEAE incidence and treatment intervals nor cumulative 3-month dose categories for multiple indications. No patients were determined to have lack of effect based on clinical objective measurement. OnabotA showed a safety profile with no new signals in patients treated concomitantly for ≥2 therapeutic indications over repeat treatments up to 2 years. TEAEs across treatment periods were commonly related to the site of injection and were consistent with those previously reported for individual indications
Drug and single-cell gene expression integration identifies sensitive and resistant glioblastoma cell populations.
No full textGlioblastoma (GBM) remains the most common and lethal adult malignant primary brain cancer with few treatment options. A significant issue hindering GBM therapeutic development is intratumor heterogeneity and plasticity. GBM tumors contain neoplastic cells within a fluid spectrum of diverse transcriptional states. Identifying effective therapeutics requires a platform that predicts the differential sensitivity and resistance of these states to various treatments. Here, we develop scFOCAL (Single-Cell Framework for -Omics Connectivity and Analysis via L1000), to quantify the cellular drug sensitivity and resistance landscape. Using single-cell RNA sequencing of newly diagnosed and recurrent GBM tumors, we identify compounds from the LINCS L1000 database with transcriptional response signatures selectively discordant with distinct GBM cell states, and leverage this capability to predict combination synergy. We validate the significance of these findings in vitro, ex vivo, and in vivo, and identify a combination of an OLIG2 inhibitor and Depatux-M for the treatment of GBM. Our studies suggest that scFOCAL identifies cell states that are sensitive and resistant to targeted therapies in GBM using a measure of cell and drug connectivity, which can be applied to identify new synergistic combinations
