ABSTRACT
What is this summary about? Dostarlimab, also known by the brand name JEMPERLI, is a medicine that uses a patient's own immune system to treat endometrial cancer. Dostarlimab is a type of medicine called an immunotherapy. Immunotherapies help the immune system find and attack cancer cells. Dostarlimab stops cancer cells from being able to hide from the immune system, which allows the patient to have a boosted immune response against their cancer.The RUBY study is a phase 3 clinical study of primary advanced (cancer that has spread outside the uterus) or recurrent (cancer that has come back) endometrial cancer. A phase 3 clinical study looks at how well a new treatment works compared to the standard, or usual, treatment in a large patient population. The RUBY study is testing how well dostarlimab given with chemotherapy, followed by dostarlimab alone, works at delaying primary advanced or recurrent endometrial cancer from getting worse and preventing patients from dying, compared to chemotherapy given alone (the current standard treatment for primary advanced or recurrent endometrial cancer).What were the results? When dostarlimab was given with chemotherapy, this combination was found to delay primary advanced or recurrent endometrial cancer from getting worse and to prevent patients from dying, compared with chemotherapy given alone (without dostarlimab). Patients in the study who received dostarlimab with chemotherapy had a 36% lower risk of dying or having their cancer get worse.What do the results mean? The results from this study contributed to the approval of dostarlimab with chemotherapy as a new treatment option for patients with mismatch repair deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer. As of the publication of this plain language summary of publication (PLSP), this combination of dostarlimab with chemotherapy has been approved in the United States of America, the United Kingdom, the European Union and Hong Kong.Clinical Trial Registration: NCT03981796 (RUBY).
ABSTRACT
Cyanobacteria play a key role in primary production in both oceans and fresh waters and hold great potential for sustainable production of a large number of commodities. During their life, cyanobacteria cells need to acclimate to a multitude of challenges, including shifts in intensity and quality of incident light. Despite our increasing understanding of metabolic regulation under various light regimes, detailed insight into fitness advantages and limitations under shifting light quality remains underexplored. Here, we study photo-physiological acclimation in the cyanobacterium Synechocystis sp. PCC 6803 throughout the photosynthetically active radiation (PAR) range. Using light emitting diodes (LEDs) with qualitatively different narrow spectra, we describe wavelength dependence of light capture, electron transport and energy transduction to main cellular pools. In addition, we describe processes that fine-tune light capture, such as state transitions, or the efficiency of energy transfer from phycobilisomes to photosystems (PS). We show that growth was the most limited under blue light due to inefficient light harvesting, and that many cellular processes are tightly linked to the redox state of the plastoquinone (PQ) pool, which was the most reduced under red light. The PSI-to-PSII ratio was low under blue photons, however, it was not the main growth-limiting factor, since it was even more reduced under violet and near far-red lights, where Synechocystis grew faster compared to blue light. Our results provide insight into the spectral dependence of phototrophic growth and can provide the foundation for future studies of molecular mechanisms underlying light acclimation in cyanobacteria, leading to light optimization in controlled cultivations.
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Background: Second-generation oral H1-antihistamines, including bilastine, represent the emerging treatments of allergic rhinitis (including rhinoconjunctivitis) and chronic urticaria in both adults and children. This study analyses available evidence supporting the use of bilastine amongst second-generation antihistamines for the symptomatic treatment of allergic rhinitis and urticaria in adults and children. Methods: Consensus amongst experts from 17 countries on the ideal treatment of rhinitis and urticaria, and the specific role of bilastine was measured by means of a modified Delphi process. A total of 12 statements were voted on by the experts using a five-point Likert scale (1 = strongly disagree; 2 = disagree; 3 = undecided; 4 = agree; 5 = strongly agree). The definition of consensus was set at a minimum of 80% concordance for 4+5 scores (agree or strongly agree). Results: All proposed statements reached consensus, with a concordance of ≥98% for five statements and ≥96% for seven. Conclusions: The wide consensus obtained for the proposed statements suggests a prominent role for bilastine in the management of allergic rhinitis and urticaria.
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OBJECTIVE: Fertility-sparing surgery (FSS) aims to achieve oncological outcomes that are non-inferior to radical treatment while preserving fertility and optimizing reproductive results. This study assesses in vitro fertilization (IVF) outcomes in early-stage cervical cancer survivors following FSS, comparing radical and non-radical approaches. METHODS: This retrospective analysis used data from Hungary's National Health Insurance Fund (2004-2022) on patients who underwent IVF treatment following FSS for early-stage cervical cancer at ten Hungarian fertility clinics. Patients were classified into radical and non-radical surgical groups, with the uterine arteries being spared in the non-radical procedures. RStudio (R software version: 4.2.2) was used for statistical analysis. Student's t-test was used to compare group means, and Fisher's exact test was applied to assess independence and distributions between categorical variables, and to estimate odds. RESULTS: The study analyzed data from 122 IVF treatment cycles involving 36 patients. The non-radical group had a significantly higher live birth rate (83%, 5/6 compared to the radical group (17%, 5/30). Additionally, the non-radical group had a significantly higher implantation rate and cumulative live birth rate per oocyte retrieval (37%, 7/19 and 55%, 6/11 respectively) compared to the radical group (8%, 12/148 and 6%, 5/80 respectively). CONCLUSION: This is the largest study to evaluate IVF outcomes in young cervical cancer survivors who have undergone FSS. The findings suggest that less radical procedures are associated with significantly better IVF outcomes. These results emphasize the importance of considering oncological safety and reproductive outcomes together when choosing FSS for early-stage cervical cancer patients. It also highlights the reproductive benefits of performing less radical surgery.
Subject(s)
Fertility Preservation , Fertilization in Vitro , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/surgery , Uterine Cervical Neoplasms/pathology , Retrospective Studies , Adult , Fertility Preservation/methods , Fertility Preservation/statistics & numerical data , Pregnancy , Fertilization in Vitro/methods , Neoplasm Staging , Hungary , Organ Sparing Treatments/methods , Organ Sparing Treatments/statistics & numerical dataABSTRACT
We developed a visible-light-driven photochemical transformation in which activated primary, secondary, and tertiary alkylcarboxylic acids were converted into the corresponding boronic esters in the absence of catechol and any added photocatalyst. The procedure relies on the utilization of hypoboric acid and redox-active esters of alkylcarboxylic acids to ensure a simple and economic procedure. Quantum chemical calculations and mechanistic considerations provide deeper insights into the mechanism of photochemical borylation reactions.
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An international joint statement about the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer was published in 2016, warning about the uncritical use of HIPEC outside controlled studies. This statement has now been updated after the most recent literature was reviewed by the participating study groups and societies. HIPEC became a treatment option in patients with advanced colon cancer after positive results of a randomized trial comparing surgery and HIPEC versus palliative treatment alone. Although this trial did not compare the added value of HIPEC to surgery alone, HIPEC for the treatment of peritoneal metastases was in the subsequent years generalized to many other cancer types associated with peritoneal carcinomatosis including epithelial ovarian cancer (EOC). In the meantime, new evidence from prospective randomized trials specifically for EOC-patients emerged, with however contradicting results and several quality aspects that made the interpretation of their findings critical. Moreover, three additional trials in colorectal cancer failed to confirm the previously presumed survival benefit through the implementation of HIPEC in peritoneally disseminated colorectal cancers. Based on a still unclear and inconsistent landscape, the authors conclude that HIPEC should remain within the remit of clinical trials for EOC-patients. Available evidence is not yet sufficient to justify its broad endorsement into the routine clinical practice.
Subject(s)
Hyperthermia, Induced , Ovarian Neoplasms , Humans , Female , Carcinoma, Ovarian Epithelial/pathology , Hyperthermic Intraperitoneal Chemotherapy , Prospective Studies , Austria , Switzerland , Hyperthermia, Induced/methods , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Combined Modality Therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
PURPOSE: Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS: This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS: Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION: Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer.
Subject(s)
Antibodies, Monoclonal , Antineoplastic Agents , Endometrial Neoplasms , Phthalazines , Piperazines , Female , Humans , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin , Endometrial Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Paclitaxel , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Double-Blind MethodABSTRACT
Herein, we report a modular regioselective alkene difunctionalization strategy based on the use of hydrofluoroolefin (HFO) gas as fluorous feedstock material. The transformation of the HFO gas to iodonium salt creates vicinal electrophilic sites readily available for a broad range of nucleophiles.
Subject(s)
Fertility Preservation , Neoplasms , Adult , Humans , Male , Testis , Neoplasms/therapy , CryopreservationABSTRACT
Climate change threatens surface waters worldwide, especially shallow lakes where one of the expected consequences is a sharp increase in their water temperatures. Phytobenthos is an essential, but still less studied component of aquatic ecosystems, and it would be important to learn more about how global warming will affect this community in shallow lakes. In this research, the effects of different climate change scenarios (SSP2-4.5 and SSP5-8.5, as intermediate and high emission scenarios) on the structure and function of the entire phytobenthos community using species- and trait-based approaches were experimentally investigated in an outdoor mesocosm system. Our results show that the forecasted 3 °C increase in temperature will already exert significant impacts on the benthic algal community by (1) altering its species and (2) trait composition (smaller cell size, lower abundance of colonial and higher of filamentous forms); (3) decreasing Shannon diversity; and (4) enhancing the variability of the community. Higher increase in the temperature (+5 °C) will imply more drastic alterations in freshwater phytobenthos by (1) inducing very high variability in species composition and compositional changes even in phylum level (towards higher abundance of Cyanobacteria and Chlorophyta at the expense of Bacillariophyta); (2) continuing shift in trait composition (benefits for smaller cell volume, filamentous life-forms, non-motile and weakly attached taxa); (3) further reducing the functional diversity; (4) increasing biofilm thickness (1.4 µm/°C) and (5) decreasing maximum quantum yield of photosystem II. In conclusion, already the intermediate emission scenario will predictably induce high risk in biodiversity issues, the high emission scenario will imply drastic impacts on the benthic algae endangering even the function of the ecosystem.
Subject(s)
Climate Change , Lakes , Ecosystem , Global Warming , BiodiversityABSTRACT
In Hungary, an average of 2066 women under the age of 40 are diagnosed with cancer each year according to data from the National Cancer Registry. Approximately two-thirds of these patients require gonadotoxic treatment for their disease, which could potentially reduce their chances of future conception and childbirth. Currently, there are no professional guidelines on fertility preservation in Hungary, however, it is important to inform patients about their options. In our previous paper, we presented the gonadotoxic effects of oncotherapies and the currently available fertility preservation techniques. This second paper provides current treatment methods and recommends fertility preservation techniques in different cancer types. The success of an oncofertility program relies heavily on the effective communication and collaboration between oncologists and reproductive specialists involved in fertility preservation. This paper may be the first step in elaborating a guideline towards improving access to oncofertility services and ultimately improving the quality of life for young cancer survivors in Hungary. Orv Hetil. 2023; 164(29): 1134-1145.
Subject(s)
Fertility Preservation , Neoplasms , Pregnancy , Humans , Female , Fertility Preservation/methods , Quality of Life , Neoplasms/complications , Neoplasms/therapy , Parturition , ReproductionABSTRACT
The incidence of cancer increases with age and as family planning is being delayed, there is a growing number of cancer patients whose fertility may be affected by oncological treatments. International guidelines recommend that all reproductive age cancer patients, including adolescent patients, should be referred for fertility preservation consultation, and if necessary, fertility preservation procedures should be performed. Fertility preservation enables cancer survivors to offer a chance for biological parenthood after recovery. In this review, the gonadotoxic effects of oncological therapies and the fertility preservation possibilities for female cancer patients based on international recommendations and literature are discussed. Our next review will provide detailed information on the special fertility preservation possibilities for different cancer types. The two reviews may help to elaborate a national guidance. Orv Hetil. 2023; 164(28): 1094-1101.
Subject(s)
Fertility Preservation , Neoplasms , Adolescent , Humans , Female , Fertility Preservation/methods , Cryopreservation/methods , Neoplasms/complications , Neoplasms/therapy , Fertility , ReproductionABSTRACT
OBJECTIVES: To analyze the impact of perioperative characteristics on the risk of recurrence in patients with uterine leiomyosarcomas. METHODS: A sub-analysis of the SARComa of the UTerus (SARCUT) study, which is a multicentric cross-sectional pan-European study that included 390 patients diagnosed with leiomyosarcoma, between 2001 and 2007. Perioperative factors related to risk of recurrence and survival were analyzed. RESULTS: The 5-year and 10-year disease-free survivals (DFS) were 46% and 55%, respectively. Overall survival at 5 and 10 years was 34% and 47%, respectively. The most important factors related to global recurrence were the incomplete cytoreduction (hazard ratio [HR] 2.87; 95% confidence interval [CI] 1.91-4.31); performing bilateral adnexectomy (HR 2.71; 95% CI 1.23-5.93); tumor persistence after any treatment (HR 2.38; 95% CI 1.39-4.06); and adjuvant chemotherapy administration (HR 2.55; 95% CI 1.82-3.58) or adjuvant radiotherapy (HR 2.26; 95% CI 1.53-3.32). The major factors significantly associated with pelvic relapse were tumor persistence after any treatment (HR 3.63; 95% CI 1.83-7.20) and adjuvant radiotherapy (HR 2.74; 95% CI 1.44-5.20). Incomplete cytoreduction was the most important factor associated with distant relapse (HR 1.91; 95% CI 1.22-2.97). The most important factors related to overall survival were tumor persistence after any treatment (HR 4.59; 95% CI 2.51-8.40), incomplete cytoreduction (HR 3.68; 95% CI 2.44-5.56), tumor margin involvement (HR 2.41; 95% CI 1.64-3.55) and adjuvant chemotherapy (HR 1.91; 95% CI 1.31-2.78). CONCLUSIONS: Complete cytoreduction is the main prognosis factor impacting the DFS and overall survival of patients with uterine leiomyosarcoma. Adjuvant chemotherapy administration was associated with decreased rates of DFS and overall survival. The adjuvant radiotherapy was associated with a higher risk of global recurrence.
Subject(s)
Leiomyosarcoma , Sarcoma , Uterine Neoplasms , Female , Humans , Leiomyosarcoma/surgery , Prognosis , Cross-Sectional Studies , Neoplasm Recurrence, Local/epidemiology , Sarcoma/pathology , Uterine Neoplasms/surgery , Uterine Neoplasms/drug therapy , Chemotherapy, Adjuvant , Recurrence , Retrospective Studies , Neoplasm StagingABSTRACT
Synthesis and applications of fluoroalkyl and fluoroalkenyliodonium salts are summarized in this account article, focusing preferably to the reagents designed in our laboratory in the last decade. Among these reagents trifluoroethyl(aryl)iodonium salts have been used most frequently to build carbon-carbon and carbon-heteroatom bonds in simple nucleophilic substitutions and through transition metal catalyzed coupling reactions. Iodonium salts equipped with unsaturated fluorinated function showed diverse reactivity due to their electron deficient character, and these molecular motifs enable cycloadditions and nucleophilic additions to prepare fluorinated carbo- and heterocyclic molecules. Beyond the overview of existing transformations, with the presented collection, we aim to inspire future developments of iodonium reagents and their application in organic synthesis.
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BACKGROUND: Dostarlimab is an immune-checkpoint inhibitor that targets the programmed cell death 1 receptor. The combination of chemotherapy and immunotherapy may have synergistic effects in the treatment of endometrial cancer. METHODS: We conducted a phase 3, global, double-blind, randomized, placebo-controlled trial. Eligible patients with primary advanced stage III or IV or first recurrent endometrial cancer were randomly assigned in a 1:1 ratio to receive either dostarlimab (500 mg) or placebo, plus carboplatin (area under the concentration-time curve, 5 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area), every 3 weeks (six cycles), followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. The primary end points were progression-free survival as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, and overall survival. Safety was also assessed. RESULTS: Of the 494 patients who underwent randomization, 118 (23.9%) had mismatch repair-deficient (dMMR), microsatellite instability-high (MSI-H) tumors. In the dMMR-MSI-H population, estimated progression-free survival at 24 months was 61.4% (95% confidence interval [CI], 46.3 to 73.4) in the dostarlimab group and 15.7% (95% CI, 7.2 to 27.0) in the placebo group (hazard ratio for progression or death, 0.28; 95% CI, 0.16 to 0.50; P<0.001). In the overall population, progression-free survival at 24 months was 36.1% (95% CI, 29.3 to 42.9) in the dostarlimab group and 18.1% (95% CI, 13.0 to 23.9) in the placebo group (hazard ratio, 0.64; 95% CI, 0.51 to 0.80; P<0.001). Overall survival at 24 months was 71.3% (95% CI, 64.5 to 77.1) with dostarlimab and 56.0% (95% CI, 48.9 to 62.5) with placebo (hazard ratio for death, 0.64; 95% CI, 0.46 to 0.87). The most common adverse events that occurred or worsened during treatment were nausea (53.9% of the patients in the dostarlimab group and 45.9% of those in the placebo group), alopecia (53.5% and 50.0%), and fatigue (51.9% and 54.5%). Severe and serious adverse events were more frequent in the dostarlimab group than in the placebo group. CONCLUSIONS: Dostarlimab plus carboplatin-paclitaxel significantly increased progression-free survival among patients with primary advanced or recurrent endometrial cancer, with a substantial benefit in the dMMR-MSI-H population. (Funded by GSK; RUBY ClinicalTrials.gov number, NCT03981796.).
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Endometrial Neoplasms , Neoplasm Recurrence, Local , Female , Humans , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/administration & dosage , Carboplatin/adverse effects , DNA Mismatch Repair , Double-Blind Method , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/genetics , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Immune Checkpoint Inhibitors/administration & dosage , Immune Checkpoint Inhibitors/adverse effects , Microsatellite Instability , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/etiology , Paclitaxel/administration & dosage , Paclitaxel/adverse effectsABSTRACT
BACKGROUND: Fertility-sparing treatment in patients with cervical cancer should, in principle, follow identical algorithms to that in patients without future reproductive plans. In recent years, a trend toward nonradical procedures, such as conization or simple trachelectomy, has become apparent in medical literature, because of their associations with better pregnancy outcomes. However, the published reports included small numbers of patients and heterogenous treatment strategies to ascertain the safety of such approaches. OBJECTIVE: This study aimed to collect multi-institutional data regarding the oncological outcomes after fertility-sparing treatment in patients with cervical cancer and to identify prognostic risk factors, including the influence of the radicality of individual cervical procedures. STUDY DESIGN: Patients aged 18 to 40 years with International Federation of Gynecology and Obstetrics 2018 stage IA1 with positive lymphovascular space invasion or ≥IA2 cervical cancer who underwent any type of fertility-sparing procedure were eligible for this retrospective observational study, regardless of their histotype, tumor grade, and history of neoadjuvant chemotherapy. Associations between disease- and treatment-related characteristics with the risk of recurrence were analyzed. RESULTS: A total of 733 patients from 44 institutions across 13 countries were included in this study. Almost half of the patients had stage IB1 cervical cancer (49%), and two-thirds of patients were nulliparous (66%). After a median follow-up of 72 months, 51 patients (7%) experienced recurrence, of whom 19 (2.6%) died because of the disease. The most common sites of recurrence were the cervix (53%) and pelvic nodes (22%). The risk of recurrence was 3 times higher in patients with tumors >2 cm in size than in patients with smaller tumors, irrespective of the treatment radicality (19.4% vs 5.7%; hazard ratio, 2.982; 95% confidence interval, 1.383-6.431; P=.005). The recurrence risk in patients with tumors ≤2 cm in size did not differ between patients who underwent radical trachelectomy and patients who underwent nonradical (conization and simple trachelectomy) cervical procedures (P=.957), regardless of tumor size subcategory (<1 or 1-2 cm) or lymphovascular space invasion. CONCLUSION: Nonradical fertility-sparing cervical procedures were not associated with an increased risk of recurrence compared with radical procedures in patients with tumors ≤2 cm in size in this large, multicenter retrospective study. The risk of recurrence after any type of fertility-sparing procedure was significantly greater in patients with tumors >2 cm in size.
Subject(s)
Fertility Preservation , Uterine Cervical Neoplasms , Pregnancy , Female , Humans , Uterine Cervical Neoplasms/surgery , Uterine Cervical Neoplasms/pathology , Retrospective Studies , Cervix Uteri/surgery , Cervix Uteri/pathology , Fertility Preservation/methods , Pregnancy Outcome , Risk Factors , Neoplasm StagingABSTRACT
In Hungary, there is no actual ovarian cancer guideline, despite this disease being the most lethal gynaecologic cancer. An expert panel was created by the Hungarian Society of Gynaecologic Oncologists to prepare a recommendation for the reatment of ovarian cancer patients. This multidisciplinary expert group worked together during the first trimester of 2022 using the guidelines and recommendations of the European Society of Gynaecologic Oncologists (ESGO) and the European Society for Medical Oncology (ESMO) and created the updated recommendations. This paper presents the recommended surgical and medical treatment of early, advanced stage and recurrent ovarian cancer.
Subject(s)
Oncologists , Ovarian Neoplasms , Female , Humans , Hungary , Medical Oncology , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/therapyABSTRACT
[1,2]-shift of atoms in alkyl fragments belongs to the class of dyotropic rearrangements. Various atoms, including halogens can be involved in the migration, however participation of iodine is unprecedented. Herein, we report our experimental and DFT studies on the oxidation triggered dyotropic rearrangement of iodo and chloro functions via butterfly-type transition state to demonstrate the migrating ability of λ3 -iodane centre. With the exploitation of dyotropic rearrangement we designed and synthesized a novel fluoroalkyl iodonium reagent from industrial feedstock gas HFO-1234yf. We demonstrated that the hypervalent reagent serves as an excellent fluoroalkylation agent for various amines and nitrogen heterocycles.
ABSTRACT
INTRODUCTION: High-risk human papilloma virus (HPV)-associated cervical cancer is the fourth most common cancer in women worldwide. Current treatments of high-grade squamous intraepithelial lesion (HSIL) of the cervix are based on invasive surgical interventions, compromising cervical competence and functionality. APRICITY is a multicentre, prospective, double-blind, randomised controlled phase 3 study further evaluating the efficacy and safety of Cevira, an integrated drug-delivery and light-delivery device for hexaminolevulinate photodynamic therapy, which shows promise as a novel, non-invasive outpatient therapy for women with HSIL. METHODS AND ANALYSIS: Patients with biopsy-confirmed HSIL histology are invited to participate in the study planned to be conducted at 47 sites in China and 25 sites in Ukraine, Russia and the European Union. The aim is to include at least 384 patients, which will be randomised to either Cevira or placebo group (2:1). All patients will be assessed 3 months after first treatment and a second treatment will be administered in patients who are HPV positive or have at least low-grade squamous intraepithelial lesion. Primary endpoint is the proportion of the responders 6 months after first treatment. Secondary efficacy and safety endpoints will be assessed at 6 months, and data for secondary performance endpoints of the Cevira device will be collected at 3 months and 6 months, in case second treatment was administered. All patients in the Cevira group will be enrolled in an open, long-term extension study for 6 months to collect additional efficacy and safety data (study extension endpoints). ETHICS AND DISSEMINATION: The study was approved by the ethics committee of the Peking Union Medical College Hospital and Hannover Medical University, Germany. Findings will be disseminated through peer review publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04484415; clinicaltrials.gov.
Subject(s)
Carcinoma in Situ , Papillomavirus Infections , Photochemotherapy , Squamous Intraepithelial Lesions , Uterine Cervical Neoplasms , Aminolevulinic Acid/analogs & derivatives , Clinical Trials, Phase III as Topic , Female , Humans , Multicenter Studies as Topic , Papillomavirus Infections/complications , Photochemotherapy/methods , Prospective Studies , Randomized Controlled Trials as Topic , Uterine Cervical Neoplasms/pathologyABSTRACT
Introduction: Fertility preservation or oncofertility is a relatively new interdisciplinary field dealing with the preservation of female and male reproductive functions before the administration of gonadotoxic therapy. Despite recommendations from different international scientific bodies, Hungary still does not have a national fertility preservation network, patient referral is unorganised. Objective: As the first step towards establishing a national fertility preservation program, a study was designed to evaluate the Hungarian oncologists' knowledge, attitudes and practice in the field of oncofertility. Method: A national online survey was sent to the physician members of the Hungarian Society of Clinical Oncology between November 2020 and February 2021. The survey was completed by 94 physicians and the results were analysed statistically. Results: The majority of the oncologists (77%) discusses reproductive health issues before starting gonadotoxic therapy. However, almost half of these physicians do not refer patients for fertility preservation consultation or treatment. Physicians report lack of organised fertility preservation network, lack of knowledge and clinical practice guidelines as major barriers in referring their patients for fertility preservation. The majority (86%) proposes that a better col-laboration between cancer and fertility centers needs to be organized in Hungary. Conclusion: This study is the first nationwide survey to assess oncologists' attitude, knowledge and practice in the field of oncofertility in Hungary. It highlights the need for more education and increased collaboration between oncologists and reproductive specialists. This is an important step towards the establishment of a national fertility preservation network which is our ultimate goal.