Abstract Background Despite a high response rate to front-line therapy, prognosis of epithelial ovarian carcinoma (EOC) remains poor. Approaches that combine Cytoreductive Surgery (CRS) and ...Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with this strategy. Patients and methods A retrospective cohort multicentric study from French centres was performed. All consecutive patients with advanced and recurrent EOC treated with CRS and HIPEC were included. Results The study included 566 patients from 13 centres who underwent 607 procedures between 1991 and 2010. There were 92 patients with advanced EOC (first-line treatment), and 474 patients with recurrent EOC. A complete cytoreductive surgery was performed in 74.9% of patients. Mortality and grades 3 to 4 morbidity rates were 0.8% and 31.3%, respectively. The median overall survivals were 35.4 months and 45.7 months for advanced and recurrent EOC, respectively. There was no significant difference in overall survival between patients with chemosensitive and with chemoresistant recurrence. Peritoneal Cancer Index (PCI) that evaluated disease extent was the strongest independent prognostic factor for overall and disease-free survival in all groups. Conclusion For advanced and recurrent EOC, curative therapeutic approach combining optimal CRS and HIPEC should be considered as it may achieve long-term survival in patients with a severe prognosis disease, even in patients with chemoresistant disease. PCI should be used for patient's selection.
We present a new version of the Met Office Hadley Centre/Climatic Research Unit global surface temperature data set, HadCRUT5. HadCRUT5 presents monthly average near‐surface temperature anomalies, ...relative to the 1961–1990 period, on a regular 5° latitude by 5° longitude grid from 1850 to 2018. HadCRUT5 is a combination of sea‐surface temperature (SST) measurements over the ocean from ships and buoys and near‐surface air temperature measurements from weather stations over the land surface. These data have been sourced from updated compilations and the adjustments applied to mitigate the impact of changes in SST measurement methods have been revised. Two variants of HadCRUT5 have been produced for use in different applications. The first represents temperature anomaly data on a grid for locations where measurement data are available. The second, more spatially complete, variant uses a Gaussian process based statistical method to make better use of the available observations, extending temperature anomaly estimates into regions for which the underlying measurements are informative. Each is provided as a 200‐member ensemble accompanied by additional uncertainty information. The combination of revised input data sets and statistical analysis results in greater warming of the global average over the course of the whole record. In recent years, increased warming results from an improved representation of Arctic warming and a better understanding of evolving biases in SST measurements from ships. These updates result in greater consistency with other independent global surface temperature data sets, despite their different approaches to data set construction, and further increase confidence in our understanding of changes seen.
Plain Language Summary
We have produced a new version of a data set that measures changes of near‐surface temperature across the globe from 1850 to 2018, called HadCRUT5. We have included an improved data set of sea‐surface temperature, which better accounts for the effects of changes through time in how measurement were made from ships and buoys at sea. We have also included an expanded compilation of measurements made at weather stations on land. There are two variations of HadCRUT5, produced for different uses. The first, the “HadCRUT5 noninfilled data set,” maps temperature changes on a grid for locations close to where we have measurements. The second, the “HadCRUT5 analysis,” extends our estimates to locations further from the available measurements using a statistical technique that makes use of the spatial connectedness of temperature patterns. This improves the representation of less well observed regions in estimates of global, hemispheric and regional temperature change. Together, these updates and improvements reveal a slightly greater rise in near‐surface temperature since the nineteenth century, especially in the Northern Hemisphere, which is more consistent with other data sets. This increases our confidence in our understanding of global surface temperature changes since the mid‐19th century.
Key Points
We have created a new version of the Met Office Hadley Centre and Climatic Research Unit global surface temperature data set for 1850–2018
The new data set better represents sparsely observed regions of the globe and incorporates an improved sea‐surface temperature data set
This data set shows increased global average warming since the mid‐19th century and in recent years, consistent with other analyses
Abstract
STUDY QUESTION
How efficacious is transplantation of ovarian cortex previously exposed to chemotherapy?
SUMMARY ANSWER
Prior exposure to chemotherapy did not disrupt the function of ...cryopreserved ovarian tissue after transplantation.
WHAT IS KNOWN ALREADY
Ovarian tissue cryopreservation (OTC) followed by ovarian tissue transplantation (OTT) is an efficacious technique for restoration of female fertility. At least 130 children have been born following this procedure. To date, little is known about the efficacy of OTT in patients exposed to cancer chemotherapy prior to OTC.
STUDY DESIGN, SIZE, DURATION
This study evaluates the recovery of ovarian function and fertility in 31 consecutive patients who had received OTT, between 2005 and 2015.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Thirty one patients, wanting children, were transplanted with autologous ovarian cortex, among which 22 patients (71%) had been exposed to chemotherapy before OTC. Recovery of ovarian function was considered total once menstruation occurred. Ovarian function recovery (OFR), ovarian graft survival, and incidence of pregnancy were related to previous chemotherapy exposure, type of chemotherapy and graft characteristics (number of grafted fragments and follicular density).
MAIN RESULTS AND ROLE OF CHANCE
The amount of ovarian tissue collected was the only parameter to show any significant change between patients with versus without previous chemotherapy. At 1 year after OTT, the cumulative incidence of OFR was 83% (93% in patients exposed to chemotherapy and 67% in others (P = 0.14)). A low follicular density (<0.3 foll/mm2) in the transplant and a low number of grafted fragments (<16) were significantly associated with a delayed OFR. Graft survival at 2 years after OTT was 77%. It was significantly lower in patients exposed to bifunctional alkylating agents before ovarian cryopreservation and in patients with a low follicular density. The proportion of women who succeeded in having at least one live birth was 23% in the total population, 0% (0/9) in the group ‘no previous chemotherapy’, and 32% (7/22) in the group ‘previous chemotherapy’. The cumulative incidence of pregnancy (Kaplan–Meier) at 3 years after OTT was 36% overall and 49% in case of previous chemotherapy, with no difference related to previous chemotherapy exposure. In total there were 13 pregnancies and 8 births in 7 patients.
LIMITATIONS, REASONS FOR CAUTION
The pathology in the two groups of patients was not comparable. In the group of patients who had chemotherapy before OTC, there were 95% of hematological malignancies. In the group of patients who did not have chemotherapy before OTC only 1 out of 9 patients had a malignant hematological disease while 44% had some pathology affecting the ovaries. Few women are available for study and only large changes are likely to have statistical significance.
WIDER IMPLICATIONS OF THE FINDINGS
These results suggest that prior cancer chemotherapy should no longer be considered a limitation to cryopreservation of ovarian tissue and current recommendations in this regard should be revised.
STUDY FUNDING/COMPETING INTEREST(S)
This study was supported by the Agence de la Biomédecine (France’s biomedical office). There are no competing interests to report.
TRIAL REGISTRATION NUMBER
NCT02184806.
Since dose escalation allowed by image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer (LACC), local relapses have become a rare event. Only scarce data are available on the ...outcome of patients experiencing a local relapse after IGABT.
Between 2004 and 2016, all consecutive patients treated at Gustave Roussy Institute for LACC and receiving concomitant chemoradiation and IGABT were analysed. Clinical and treatment-related prognostic factors for survival after local relapse were searched, in order to potentially identify patients requiring salvage treatment.
Two hundred and fifty-nine patients were treated during this period. With a median follow-up of 4.1 years, 10.8% (n = 28) had a local relapse. Among these patients, 53.6% had synchronous lymph nodes or distant metastatic relapse and only 13 patients (5% of all patients) had isolated local relapse. After local relapse, median survival was 47 months and three patients were alive at last follow-up. Only three patients with local relapse could receive salvage surgery (10.7%). Metastases occurrence and pelvic wall involvement were the main contraindications (67.9%) for salvage surgery. Among the three patients treated with surgery, two are still alive at last follow-up without significant complication. Improved survival was observed among the two patients who could have surgery (p = .02). Local progression led to serious symptoms in 75% of patients. Only the time interval between brachytherapy and relapse (<1 year) was prognostic for 2-year overall survival (p = .005).
Salvage surgery is feasible in a very low number of highly selected patients with local relapse following IGABT. Local failure is a major cause of severe local symptoms, confirming that every effort should be done to achieve long-term local control through dose escalation.
•In locally advanced cervical cancer, local relapse is a rare event due to dose escalation allowed by brachytherapy.•Feasibility of salvage surgery is uncertain and is feasible in a low number of highly selected patients.•Salvage surgery, however, appears to improve overall survival without significant complication.
The aim of this study was to evaluate prognostic factors for recurrence after conservative treatment of a large series of ‘apparent’ stage I serous borderline ovarian tumors (SBOTs).
A review of 119 ...patients treated conservatively between 2000 and 2009 with follow-up data. All pathological slides were reviewed by the same expert pathologist. Prognostic factors for recurrence were studied (age, histological subtypes and surgical procedure).
Conservative surgical procedures were: unilateral cystectomy (n = 43, 36%); unilateral adnexectomy (UA; n = 50, 42%); bilateral cystectomies (n = 11, 9%) and UA + contralateral cystectomy (n = 15, 13%). Stromal microinvasion and/or a micropapillary pattern was present in 21 (18%) and 13 (11%) patients, respectively. With a median follow-up of 45 months, 38 (32%) patients relapsed (10 also had peritoneal disease in the form of noninvasive implants at the first recurrence). In 2 of these 38 patients, progression-to-invasive disease occurred at the second and third relapse (one patient died to the recurrence). Three prognostic factors for recurrence were identified in the univariate analysis: a young age (< or >30 years old), the type of conservative treatment (adnexectomy versus cystectomy) and tumor bilaterality. In the multivariate analysis, only age remained statistically significant.
In this series (the largest reported, to date, on recurrences after the conservative management of stage I SBOT), the risk of relapse was not related to tumor histological subtypes (micropapillary and stromal microinvasion) nor to the use of complete staging surgery. Invasive recurrences were very rare in stage I SBOT, but did occur. A young age, tumor bilaterality and the use of a cystectomy were identified as risk factors for recurrence, suggesting that management of fertility preservation (particularly in very young patients) should be associated with a meticulously conducted follow-up.
The overall prognosis of stage I borderline ovarian tumors (BOT) is excellent but a small percentage of patients die to their disease. The prognostic factors for such a rare event are still not ...clearly defined. The aim of this study was to determine these factors for recurrence per se and recurrence in the form of invasive carcinoma in a large series of stage I tumors.
A retrospective review of patients with BOT. Three inclusion criteria were defined: (i) a centralized histological review; (ii) macroscopic stage I tumors; (iii) exclusion of metastatic disease to the ovaries.
From 2000 to 2010, 254 patients fulfilled inclusion criteria 140 had mucinous BOT (MBOT) and 114 a serous BOT (SBOT), and 191 had undergone conservative management. After a median follow-up of 45 months, 43 patients had developed recurrences (31 borderline and 12 invasive).
The risks of recurrences were statistically increased after conservative treatment, particularly after a cystectomy, in patients with stage IB and among patients with incompletely staged tumors. In the subgroup of conservatively treated patients (representing 75% of our population), the risks of recurrences were statistically increased in patients affected by a SBOT, in patients who had undergone a cystectomy, in patients with stage IB disease and in patients with a micropapillary pattern (MPP). MBOT and the presence of a MPP were identified as prognostic factors for invasive disease.
In the present series of BOT with the largest number of patients treated conservatively to date, the presence of a MPP and the mucinous subtype were associated with a higher rate of progression to carcinoma after conservative management. These important results suggest that MBOT belong to a ‘high-risk’ group likely to develop an invasive recurrence after fertility-sparing surgery in stage I BOT.
The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 ...June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.
•46 participants from 15 countries across Europe, Asia and the USA contributed to the ESGO–ESMO–ESP consensus conference.•Recommendations cover diagnosis and management of early, advanced and recurrent ovarian cancers.•Recommendations are based on available data and/or the experts’ collective, multidisciplinary opinions and experience.•The results, including questions, recommendations and supporting evidence for each recommendation, are detailed here.
Human papillomaviruses (HPV)-related gynecological cancers are a major health care issue, and a leading cause of cancer death in low- and middle-income countries (LMIC). In 2020, the World Health ...Organization launched a program aimed at cervical cancer elimination, by screening and vaccination strategies. Offering the best possible care to women diagnosed with invasive cancer is a complementary objective. Treatment of cervical cancer as per modern standards is complex and multimodal, mainly relying on surgery, external-beam radiotherapy (+/−chemotherapy) and brachytherapy. In parallel with the pivotal role of multidisciplinary discussion, international societies provide guidance to define the most effective and least toxic anti-cancer strategy, homogenize treatment protocols and provide benchmark quality indicators as a basis for accreditation processes. The challenge is to offer the appropriate diagnostic workup and treatment upfront and to avoid non- evidence-based treatment that consumes resources, impairs quality of life (QoL), and compromises oncological outcome. Various strategies may be applied for improving treatment quality: development of surgical mentorship, companion-training programs and international cooperation. The lack of radiotherapy/brachytherapy facilities is a major concern in LMIC. Reinforcing international support in terms of education, training, research and development and technical cooperation with national projects is required to increase access to minimum requirements but also introduce modern techniques, upgrade radiotherapy/brachytherapy services, and expand access to modern systemic treatments. In countries with robust economies, compliance to standards should also be increased. Integrative cancer care and multidisciplinary approaches are needed to tackle the dual challenge of increasing cure rates while minimizing QoL impairment. Appropriate dimensioning of the resources to avoid harmful treatment delays and access to expert referral centers is also a priority.
•Uterine cervical cancers are a major health care issue, especially in low- and middle-income countries.•Offering the best possible care to women diagnosed with invasive cervical cancer is a major objective.•Integrative cancer care and multidisciplinary approaches are needed to increase cure rates while minimizing quality of life impairment.•Various strategies may be applied for improving treatment quality over the world.•Appropriate dimensioning of the resources to avoid harmful treatment delays and access to expert referral centers is also a priority.
This study assessed outcomes of inoperable endometrial cancer (IEC) patients treated with definitive external beam radiation therapy (EBRT) followed by a 3D image-guided brachytherapy boost.
All ...consecutive patients treated with EBRT followed by 3D image-guided brachytherapy for IEC were retrospectively included. EBRT delivered a dose of 45Gy. Then, patients had an uterovaginal brachytherapy guided by 3D imaging. Clinical target volume (CTVBT) included the whole uterus and the initial disease extent. Gross tumour volume (GTVres) included the residual disease at time of brachytherapy.
Twenty-seven patients were identified. Causes of inoperability were comorbidities (37%) or tumour loco regional extent (63%). Including EBRT and brachytherapy, the median D90 (minimal dose delivered to 90% of the volume) was 60.7 GyEQD2 (IQR = 56.4–64.2) for the CTVBT, and was 73.6 GyEQD2 (IQR = 64.1–83.7) for the GTVres. The median overall treatment time was 50 days (IQR = 46–54). The mean follow-up was 36.5 months (SD = 30.2). The cumulative incidence of local, pelvic and distant failures was 19% (n = 5), 7% (n = 2) and 26% (n = 7), respectively. Five-year overall survival was 63% (95% CI = 43–91). Late urinary and gastro intestinal toxicities ≥ grade 2 were reported in four (15%) and two patients (7%) respectively. No vaginal toxicity ≥ grade 2 was reported.
EBRT followed by intracavitary brachytherapy seems to be an effective option for IEC. The implementation of 3D concepts at time of brachytherapy may contribute to high local control probability and low toxicity profile. Large scale retrospective or prospective data are needed to confirm these early data.
•An increasing number of patients with newly diagnosed endometrial cancer may not be surgical candidates.•It is estimated that 3–10% of early stage endometrial cancer patients are medically inoperable due to comorbidities.•Some patients with advanced disease at diagnosis may also be inoperable.•External beam radiotherapy followed by brachytherapy seems to be an effective option, with 5-year OS at 63% in this study.•Implementation of 3D concepts at time of brachytherapy may contribute to high local control probability with low toxicity.
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