Multidisciplinary management of adolescents and young adults (AYA) sarcoma: A successful effort of an adult high-volume cancer center.

INTRODUCTION: The aim of this retrospective study was to investigate the clinicopathological characteristics of AYA sarcomas and their clinical outcomes at a high-volume single center. METHODS: Demographic, clinicopathological data on the diagnosis, treatment and follow-up of all sarcoma patients aged 16-39 years (ys) observed at our Institute between January 2010 and December 2021 were retrospectively collected, including diagnostic (TTD) and treatment delay(TTT), clinical outcomes (OS and PFS), and late-treatment effects. RESULTS: We identified 228 AYA patients, median age 30 years, 29% ≤ 25 years, 57% males, 88% soft tissue sarcomas (STS), and 12% bone sarcomas (BS). Among STSs, 13% were small round cell tumors (SRCT), 52% intermediate-high-grade, 24% low-grade STSs. Among BS, 32% were high-grade. Median TTD and TTT were 120 (0-8255) and 7 days (0-83), respectively. Surgery was performed in 83%, radiotherapy in 29%, and systemic therapy in 27%. Median follow-up was 72.9 months(1.6-145), 5-year and 10-year OS were 78.5% and 62%, respectively. Kaplan-Meyer analysis showed a significantly better 5-year OS and PFS for patients with >92 days of TTD (OS 85.7% vs. 66.7%, p = 0.001, PFS 50.2% vs. 24.9%, p = 0.009). According to age (≤25 years vs. > 25 years), 5-year OS was 69.8% versus 82.2%, respectively (p = 0.047). CONCLUSION: Our analysis confirmed previous data on sarcoma AYA patients followed in a referral center. Unexpectedly, diagnostic delay was not associated with poor OS and PFS. Patients <25 years showed a poorer prognosis due to the higher incidence of SRCT.

Why are they not coming back? A single-center follow-up study on oncological women oocyte's storing for fertility preservation.

Introduction: Oocyte cryopreservation is a valid option for female cancer patients to preserve fertility. The number of patients undergoing fertility preservation (FP) cycles has increased over the past years. Nevertheless, the rates of patients returning to use their cryopreserved material have shown to be considerably low, ranging from 5-8%, but significant data regarding the reasons of such low return rates are scarce. Methods: This study is a single-center follow-up retrospective study evaluating the return rate of oncological women who underwent FP at a tertiary care Fertility Center and assessing the reasons influencing the patients who did not return. Data about patients who returned to attempt pregnancy were retrieved from internal registries. Non-returned patients were assessed with a standardized phone survey investigating health condition, marital status and family projects, spontaneous conceptions, and the reasons why they had not returned to use their gametes. A univariate analysis between returned and non-returned patients was performed. Results: Of the 397 patients who received counseling about FP, 171 (43.1%) underwent oocyte cryopreservation between 2001 and 2017. Nine (5%) died, and 17 (10%) were lost at follow-up. A total of 20 patients (11.7%) returned and 125 did not. In the non-returned group, 37 (29.6%) did not have a partner, 10 (8%) had a previous spontaneous conception, and 15 (12%) had recurrent malignancy at the time of follow-up. In the univariate analysis, younger age at freezing (31.8±6.2 vs. 35.2±4.7; p 0.018), lack of a partner (p 0.002), type of cancer (other than breast cancer; p 0.024) were the significant factors in the non-returned group. As for the personal reason for not coming back, patients mainly answered as follows: lack of a partner (29, 23.2%), the desire for spontaneous motherhood (24, 19.2%), previous spontaneous pregnancies after FP procedures (16, 12.8%), and still ongoing hormonal therapy for breast cancer (13, 10.4%). All patients confirmed their will to keep the storage of their oocytes. Discussion: The impact of a cancer diagnosis on a woman's maternal desire, sentimental status and life priorities should be studied more thoroughly. Studies investigating hormonal therapy suppression in breast cancer patients seeking pregnancy should be encouraged. Clinical trial registration: https://clinicaltrials.gov, identifier NCT05223764.

Testicular sperm extraction and intracytoplasmic sperm injection outcome in cancer survivors with no available cryopreserved sperm.

OBJECTIVE: To assess rates of successful testicular sperm retrieval and intracytoplasmic sperm injection (ICSI) outcome in cancer survivors affected by non-obstructive azoospermia (NOA) or retrograde ejaculation (RE)/failure of emission (FOE). METHODS: A retrospective analysis of cancer survivors who did not cryopreserve sperm prior to treatment undergoing testicular sperm extraction (TESE). Non-cancer NOA patients and neurologic RE/FOE were the control group. RESULTS: A total of 97 cancer survivors were offered TESE and 88 (91%) accepted. Sperm was retrieved and cryopreserved in 34/67 patients with NOA (50.7%) and in 21/21 patients affected by RE/FOE (100%). Sperm retrieval rates were similar in the control group (44.9% in NOA and 100% in RE/FOE). The ICSI cumulative pregnancy rate (60%) and live birth rate (40%) per couple in 30 NOA men did not differ from controls (50.0 and 46.5%, respectively; p = 0.399/0.670). The cumulative pregnancy rate (66.7%) and live birth rate (55.6%) in 18 RE/FOE men did not differ from the control group (38.9 and 33.3%, respectively; p = 0.181/0.315). The cancer type and the resulting infertility disorder (NOA or RE/FOE) were not associated with ICSI outcomes. Female partner age was inversely related to the cumulative live birth rate, being fourfold lower (11.5%) in women ≥ 40 years and 48.8% in younger women (p = 0.0037). CONCLUSIONS: The rate of successful TESE and the ICSI outcome in cancer survivors with NOA and RE/FOE is the same as non-cancer azoospermic patients. Female partner age (older than 40 years) was associated with a significant reduction in live birth rates after TESE-ICSI procedures.

Oocyte Cryopreservation in Oncological Patients: Eighteen Years Experience of a Tertiary Care Referral Center.

Objective: The aim of the present study is to report our experience on elective women fertility preservation before cancer treatment. Study Design: This is a single-center retrospective observational study, including all patients who underwent elective fertility preservation before oncological treatment between January 2001 and March 2019 at our Institute. Results: Of a total of 568 women who received fertility counseling, 244 (42.9%) underwent 252 oocyte retrieval cycles after controlled ovarian stimulation for cryopreservation. The majority of patients were diagnosed with breast cancer (59.9%), followed by women affected by Hodgkin's and non-Hodgkin's lymphoma (27.4%). A minority comprised patients diagnosed with other malignancies that affected soft tissues (2.8%), ovary borderline type (2.4%), digestive system (1.6%), leukemia (1.6%), uterine cervix (1.2%). The remaining 3.1% were affected by other cancer types. The mean age of the cohort was 31.3 ± 6.4 years and the mean oocyte retrieval was 13.5± 8.4. Of 11 women who returned to attempt a pregnancy, three performed two thawed cycles. We obtained four pregnancies from 24 embryo transfers (Pregnancy Rate 36.4% for couple): two miscarriages and two live births. Overall, 95.7% of oocytes are still in storage. Conclusions: A close collaboration between Cancer and Fertility Center in a tertiary care hospital is essential to provide a good health service in oncological patients. Offering fertility preservation is no longer considered optional and must be included in every therapeutic program for women who receive an oncological diagnosis in their reproductive age. Oocyte cryopreservation appears to be a good opportunity for fertility preservation. Our results, although they are obtained in a small sample, are encouraging, even if only 4.5% of patients returned to use their gametes.

Persistent organochlorine compounds in fetal and maternal tissues: evaluation of their potential influence on several indicators of fetal growth and health.

Some organochlorine compounds, such as polychlorinated biphenyls (PCBs), have a tendency to bioaccumulate in humans and predators at the top of the food chain. We have recently confirmed the transplacental transfer of these compounds and the present study has been designed on the same material with the aim of investigating their potential health effects on newborns from 70 pregnant women, resident in a Northern Italy industrial town. Organochlorine compounds [namely, p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT), p,p'-dichlorodiphenyldichloroethene (p,p'-DDE), hexachlorobenzene (HCB), and PCBs] have been analyzed both in cord and maternal serum, placenta, and maternal subcutaneous adipose tissue by GC-MSD. p,p'-DDT levels in the adipose tissue resulted significantly (p<0.05) related to birth length. Mothers of neonates born by preterm programmed caesarean delivery showed significantly (p<0.005 for both) higher serum p,p'-DDE serum concentrations and p,p'-DDT levels in the adipose tissue, as compared to mothers delivering at term.

Distribution of persistent organochlorine pollutants in maternal and foetal tissues: data from an Italian polluted urban area.

This study was designed to evaluate both levels and distributions of organochlorine pollutants in placenta and other maternal-foetal tissues, from women resident in an Italian highly industrialized urban area with demonstrated PCB pollution. To this end, 30 polychlorinated biphenyl congeners (PCBs), p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT), p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB), were determined in placenta, both maternal and cord blood serum and adipose tissue of Caucasian pregnant women (n=70) undergoing to programmed caesarean delivery. Median placental concentrations of PCBs, p,p'-DDE and HCB (0.89 ng g(-1), 0.63 ng g(-1) and 0.19 ng g(-1) on wet tissue weight basis, respectively), were lower than previously published data. p,p'-DDT could be detected in most of adipose tissue samples, but very rarely in the other compartments. Distributions of investigated compounds in biological matrices showed significant relationships, confirming their transplacental transfer. It is worthy of note that HCB tended to be transferred more easily from maternal to foetal tissues. Maternal serum levels of these pollutants can allow a reliable estimation of organochlorine compound body burden, and can be useful markers of prenatal exposure, given their relationships with placental and umbilical cord serum levels.

Leptin in functional hypothalamic amenorrhoea.

BACKGROUND: Leptin, body weight, body mass index (BMI) and other hormones in women with functional hypothalamic amenorrhoea (FHA) were investigated and the hypothesis proposed that energy imbalance is the predominant mechanism for leptin reduction in patients with FHA. METHODS: Eighty-eight women with FHA and 65 age- and weight-matched controls were divided into homogeneous groups on the basis of their BMI: women with different degrees of underweight (BMI 15-16, 17-18 kg/m(2)) and of normal weight (BMI 19-21, 22-24 kg/m(2)). Hormone and carrier protein assays were measured in all groups. RESULTS: In each BMI group of patients with FHA, gononadotrophins, prolactin, insulin, free tri-iodothyronine and leptin levels were significantly lower than those of the respective controls, whereas cortisol and insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) were higher. We found significant linear positive correlations between leptin and body weight, BMI, LH, peptide-C, insulin, IGF-1 values and negative correlations with cortisol and IGFBP-1. CONCLUSIONS: Leptin values in women with FHA are significantly lower than controls, even in the group of patients having normal body weight and BMI. Leptin profile is different between patients with FHA and controls: it is suggested that energy balance can interfere with the ratio of body weight/leptin and BMI/leptin in FHA.

Long-term follow-up of functional hypothalamic amenorrhea and prognostic factors.

This study evaluated the prognosis of functional hypothalamic amenorrhea (FHA) and the predictive factors of recovery, through a long-term follow-up. Ninety-three women affected by FHA underwent a follow-up for an average period of 8.1 yr (range 7-9 yr). At the end of the follow-up, 65 (70.7%) patients recovered. Statistical analysis showed that there was no association between recovery and anamnestic causes of FHA or with the echographic ovarian morphology but identified the predictive factors of recovery as the basal body mass index (BMI), the basal cortisol, and androstenedione plasma levels. A higher basal BMI and A, and lower cortisol values are positive prognostic factors for the recovery. Also the BMI, acquired during the follow-up, is important for FHA resolution: in fact, in recovered women the BMI increased or remained stable, whereas in nonrecovered women it decreased or remained stable. At the end of the follow-up, 52 (74.3%) patients treated with hormone replacement therapy and 8 (80%) with no therapy recovered, but only 5 (41.7%) with oral contraceptive pills recovered.