Young individuals, aged <40 years, represent 7% of all patients with early breast cancer (EBC), most of whom receive chemotherapy. Preserving future fertility in these patients has become a major ...concern. This prospective study assessed ovarian function during and after chemotherapy according to patient and tumor characteristics and evaluated the outcome of controlled ovarian hyperstimulation (COH). Ovarian reserve was evaluated in terms of amenorrhea duration and by longitudinal serum anti‐Müllerian hormone (AMH) level variations measured at study entry, during treatment and until 24 months thereafter. COH has been proposed for patients receiving adjuvant chemotherapy. We studied the association between clinical factors and ovarian function using Cox models and logistic regression. In this young population (age < 38 years, median = 32), 85 of 90 evaluable patients (94%) experienced chemo‐induced amenorrhea, including six persistent amenorrhea and one chemotherapy‐induced definitive ovarian failure. Overall, 33% of patients still had undetectable AMH values 12 months after the end of chemotherapy, although most had recovered spontaneous and regular menstrual function. No specific factor was associated with clinical or biological late ovarian dysfunction, except for age and baseline AMH value. Overall, 58 patients underwent COH. The mean number of total retrieved oocytes and metaphase II oocytes were of 11.7 and 6.9, respectively. Thus, our study confirms the importance of fertility preservation in young patients with EBC. Our findings indicate that sequential chemotherapy is associated with a higher risk of persistent amenorrhea. There was no significant association between tumor characteristics, fertility preservation or recovery of ovarian reserve.
What's new?
Serum anti‐Müllerian hormone (AMH) is a marker of ovarian follicular content and a real‐time indicator of both follicular depletion and ovarian recovery in patients with cancer. This prospective study describes the menstrual function and dynamics of serum AMH variations during and after chemotherapy in premenopausal patients treated for breast cancer. The findings indicate that sequential chemotherapy is associated with a higher risk of persistent amenorrhea. There was no significant association between tumor characteristics, fertility preservation with controlled ovarian hyperstimulation or recovery of the ovarian reserve. The study underlines the necessity of fertility preservation before commencing chemotherapy.
Abstract Background The most appropriate design of Phase-II trials evaluating new therapies in osteosarcoma remains poorly defined. Objective To study consistency in phase-II clinical trials ...evaluating new therapies for osteosarcoma recurrences with respect to eligibility criteria, response assessment, end-points, statistical design and reported results. Methods Systematic review of clinical trials registered on clinicaltrials.gov , clinicaltrialsregister.eu and French National Cancer Institute website or referenced in PubMed and American Society of Clinical Oncology websites, between 2003 and 2016, using the following criteria: (osteosarcoma OR bone sarcoma) AND (Phase-II). Results Among the 99 trials identified, 80 were Phase-II, 17 I/II and 2 II/III, evaluating mostly targeted therapy (n = 40), and chemotherapy alone (n = 26). Results were fully (n = 28) or partially (abstract, n = 6) published. Twenty-four trials were dedicated to osteosarcoma, 22 had an osteosarcoma stratum. Twenty-eight out of 99 trials refer to the age range observed at recurrence (28%). Overall, 65 trials were run in multicentre settings, including 17 international trials. Only 9 trials were randomised. The primary end-point was tumour response in 71 trials (response rate, n = 40 or best response, n = 31), with various definitions (complete + partial ± minor response and stable disease), mainly evaluated with RECIST criteria (n = 69); it was progression-free survival in 24 trials and OS in 3. In single-arm trials evaluating response rate, the null hypothesis tested (when available, n = 12) varied from 5% to 25%. Conclusion No robust historical data can currently be derived from past efficacy Phase-II trials. There is an urgent need to develop international randomised Phase-II trials across all age ranges with standardised primary end-point.
In most countries, reference chemotherapy for osteosarcoma is MAP regimen (M = high-dose methotrexate, AP = doxorubicin-cisplatinum). In France, the standard preoperative chemotherapy for ...children/adolescents combines M and etoposide-ifosfamide (EI), based on the OS94-trial. We report the safety and efficacy results of patients ≤25 years treated with preoperative M-EI regimen enroled in the French OS2006-study, between 2007 and 2014.
Treatment comprised preoperative chemotherapy with the 7 M-courses and 2 EI-courses, then surgery and postoperative chemotherapy assigned by risk's groups: standard-risk (good histological response without metastases) received 12 M-courses, 3 EI-courses; high-risk (poor histologic response, initial metastases or unresectable primary) received 5 M-courses alternated with 5 AP-courses. 253 patients were randomised to receive (n = 128) or not (n = 125) zoledronate.
409/522 patients enroled in the OS2006 study who received preoperative M-EI were analysed. Median age was 14.3 years (4.7–24.5), with 55 patients aged 18–25 years. Primary tumour location was limb in 383 patients (94%) and 85 (21%) presented metastases. Median chemotherapy duration was 37.4 weeks. 381 (96%) patients underwent surgery, 258 patients (65%) had a good histologic response. 187/324 patients (58%) with localised disease did not receive doxorubicin nor cisplatinum. Toxicity was evaluated in the randomised study: most patients experienced ≥1 severe toxicity (grade IV haematological or grade III/IV extra-haematological). Median follow-up was 4.8 years, and 168 patients had events. Five-year event-free survival was 56% (95% CI, 51–62%) and overall survival 71% (66–76%).
M-EI regimen/strategy was feasible for patient aged ≤25 years with survival rates are comparable to those obtained with MAP regimen.
•Paediatric and young adult methotrexate-based chemotherapy regimen of OS2006 protocol.•Event-free survival and overall survival rates were similar to those with standard Methotrexate-Doxorubicin-Cisplatinum (MAP) regimen used worldwide.•First-line treatment with doxorubicin and cisplatinum was avoided in 58% patients with localised tumours.
Chronic postsurgical pain (CPSP) occurs in 20%-30% of patients who undergo total mastectomy (TM) performed under general anesthesia alone and significantly affects the quality of life. Pectoserratus ...and interpectoral plane block have been reportedly combined with general anesthesia to control immediate postoperative pain after TM. Our prospective cohort study aimed to evaluate the incidence of CPSP after TM when pectoserratus and interpectoral plane block were combined with general anesthesia.
We recruited adult women scheduled to undergo TM for breast cancer. Patients planned for TM with flap surgery, those who underwent breast surgery in the past 5 years, or those presenting with residual chronic pain after prior breast surgery were excluded. After general anesthesia induction, an anesthesiologist performed pectoserratus and interpectoral plane block with a ropivacaine (3.75 mg/mL) and clonidine (3.75 µg/mL) in 40 mL of 0.9% sodium chloride. The primary endpoint was the occurrence of CPSP-defined as pain with a Numeric Rating Scale Score of ≥3, either at the breast surgical site and/or at axilla, without other identifiable causes-evaluated during a pain medicine consultation at 6 months post TM.
Overall, 43/164 study participants had CPSP (26.2%; 95% CI: 19.7 to 33.6); of these, 23 had neuropathic type of pain (53.5%), 19 had nociceptive (44.2%), and 1 had mixed (2.3%) type of pain.
Although postoperative analgesia has significantly improved in the last decade, there is still need for improvement to reduce CPSP after oncologic breast surgery.
NCT03023007.
Objective Pelvic magnetic resonance imaging (MRI) is a key exam used for the initial assessment of loco-regional involvement of cervical cancer. In patients with locally advanced cervical cancer, MRI ...is used to evaluate the early response to radiochemotherapy before image-guided brachytherapy, the prognostic impact of which we aimed to study. Methods Patients with locally advanced cervical cancer treated using concomitant radiochemotherapy followed by closure treatment between January 2010 and December 2015 were included in this study. Clinical, anatomopathological, radiological, therapeutic, and follow-up data were evaluated. Results After applying the inclusion and exclusion criteria to the initially chosen 310 patients, 232 were included for evaluation (median follow-up period, 5.3 years). The median age was 50 years (range, 25–83 years), and the median tumor size was 47.5 mm (range, 0–105 mm). Based on the International Federation of Gynaecology and Obstetrics classification system, 9 patients were in stage IB2; 20, IB3; 2, IIA; 63, IIB; 4, IIIA; 7, IIIB; and 127, IIIC1 or higher. The re-evaluation MRI was performed at the median dose of 55.5 Gy, and median reduction in tumor size was 55.2% (range, −20–100%). There was a difference between the disease-free and overall survival rates of the patients with a tumor response greater or lesser than 50%. The risk of recurrence or death reduced by 39% in patients with a tumor size reduction >50%. The overall 5-year survival rate of patients with a response greater and lesser than 50% were 77.7% and 61.5%, respectively. The 5-year disease-free survival rate for these two groups of patients were 68.8% and 51.5%, respectively. Conclusion Our study confirms the prognostic impact of tumor size reduction using MRI data obtained after radiochemotherapy in patients with locally advanced cervical cancer.
In Euro‐EWING99‐R1 randomized trial, cyclophosphamide was shown to be noninferior to ifosfamide in the consolidation of standard‐risk Ewing sarcoma (SR‐EWS) after a common induction with VIDE ...(vincristine‐ifosfamide‐doxorubicin‐etoposide). We present the results of the late effects analysis of VAC (vincristine‐dactinomycin‐cyclophoshamide) vs VAI (vincristine‐dactinomycin‐ifosfamide) conducted in Euro‐EWING99‐R1 French cohort. Of 267 French randomized patients, 204 were alive and free‐of‐relapse at 5‐years including 172 with available long‐term follow‐up data concerning cardiac, renal and/or gonadal functions (sex‐ratio M/F = 1.3, median age at diagnosis = 14 years): 84 randomized in VAC (median cumulative doses: cyclophosphamide = 9.7 g/m2, ifosfamide = 59.4 g/m2) and 88 in VAI (ifosfamide = 97.1 g/m2). With a median follow‐up of 10 years (range = 5‐17), five late relapses and five second malignancies were recorded. The 10‐year event‐free survival among 5‐year free‐of‐relapse survivors was similar between VAC and VAI (93% vs 95%, P = .63). We estimated the 10‐year cumulative probabilities of cardiac and kidney toxicities at 4.4% (95% confidence interval 95% CI = 1.1%‐7.6%) and 34.8% (95% CI = 26.8%‐42.0%), respectively. Cardiac toxicity cumulative probability was similar in both arms, whereas kidney toxicity was higher in VAI (at 10 years, 43.0% vs 25.7%, P = .02), resulting from significant difference in glomerular toxicity (31.1% vs 13.1%, P < .01). At 10 years, gonadal toxicity was observed in 27% and 28% of pubertal men and women, respectively, without significant difference between VAC and VAI. Kidney and gonadal toxicities represent major issues in Euro‐EWING99‐R1, with significantly higher risk of kidney toxicities with VAI, without significant gonadal toxicity reduction. These results support the need to limit cumulative doses of both alkylating agents and to use mixed regimen as in VIDE‐VAC or VDC/IE (vincristine‐doxorubicin‐cyclophoshamide/ifosfamide‐etoposide).
What's new?
The Euro‐EWING99‐R1 trial compared the alkylating agents cyclophosphamide with ifosfamide in combination treatment for Ewing sarcoma. Here, the authors compare the late events between the two combination treatments using data from 172 patients enrolled in Euro‐EWING99‐R1. The combination containing ifosfamide carried a higher risk of kidney toxicity, but both regimens carried high rates of gonadal toxicity. Some of this toxicity could be avoided, they suggest, by using a mixed regimen to limit the dose of both alkylating agents.
Background
The objective of breast reconstruction (BR) is to erase the after-effects of total mastectomy by allowing patients to restore their breast shape. The aim of our study was to investigate ...the body map integration of different types of BR using functional magnetic resonance (fMRI).
Patients and Methods
We prospectively enrolled all women undergoing BR for breast cancer to the Remasco study (NCT02553967). Participants were categorized into four groups according to the standard of care they required: immediate BR (IBR), delayed BR (DBR), flap (autologous), or implant BR. Each patient performed sensorimotor tasks during the fMRI acquisition.
Results
Data of 38 patients were analyzed. We identified the cingulate region as the area of interest in the brain. In the case of DBR, the brain area activated during palpation of the total mastectomy scar (before BR) was different from the brain area activated during palpation of the reconstructed breast (Brodmann areas 31 versus 32). Palpation of the native breast and reconstructed breast activated the same Brodmann area 32. Comparing the brain activation signal during palpation of the native breast and the reconstructed breast did not reveal any significant difference in the overall population (
P
= 0.41) or in the groups: autologous (
P
= 0.32), implant (
P
= 0.10), IBR (
P
= 0.72), or DBR (
P
= 0.10).
Conclusions
This experimental study allowed us to describe and understand the brain plasticity processes that accompany BR. The results suggest that the reconstructed breast is integrated into the body schema, regardless of the type of BR or the timing.
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