Oncologic outcomes after MRI-assisted image-guided brachytherapy with hybrid interstitial and intra-cavitary applicators under moderate sedation for locally advanced cervix cancer.

Purpose: To report outcomes of using image-guided hybrid intra-cavitary/interstitial applicators under moderate sedation for locally advanced cervical cancer patients in our institution. Material and methods: A total of 69 fractions of brachytherapy with hybrid applicators were performed in 33 patients from January 2017 to April 2021. All patients underwent MRI pelvis 1 week pre-brachytherapy to determine suitability for interstitial brachytherapy and pre-plan needle placement. All insertion of applicators were performed under moderate sedation with midazolam and/or fentanyl. Fifty-eight (84.1%) fractions were planned with CT alone. Clinical outcomes, dose volume parameters, and toxicities were analyzed. Results: The median follow-up was 28 months. A total of 320 needles (median, 5 needles per fraction) were implanted, with a median insertion depth of 3 cm (range, 1.5-4 cm). The median high-risk clinical target volume (HR-CTV) during initial brachytherapy was 34.5 cc (range, 17.8-74.7 cc). The median total EQD2 D2cc of the rectum, bladder, sigmoid, and small intestine colon was 71.8 Gy, 81.5 Gy, 69 Gy, and 58.3 Gy, respectively. The 2-year local control and overall survival were 80.7% and 77.7%, respectively. Larger volume HR-CTV was significantly associated with worse local control (HR = 1.08, p = 0.005) and overall survival (HR = 1.04, p = 0.015). None of the patients required in-patient admission or blood transfusion post-procedure. Late grade 3 gastrointestinal and genitourinary toxicities were observed in 4 patients (12.2%). Conclusions: Hybrid applicators inserted under moderate sedation are feasible and safe. Image-guided interstitial brachytherapy with CT planning aided by MRI performed 1 week pre-brachytherapy is associated with favorable outcomes and modest toxicities.

Minimizing transmission of COVID-19 while delivering optimal cancer care in a National Cancer Centre.

The COVID-19 pandemic has disrupted current models of healthcare and adaptations will likely continue. With the gradual easing of lockdown measures worldwide, cancer centres must be prepared to implement novel means to prevent repeated waves of infection. There are two limitations unique to oncology - a higher susceptibility of patients to COVID-19 and the multidisciplinary approach required of cancer management. We describe the measures implemented in the largest cancer centre in Singapore to continue optimal cancer care in spite of the ongoing pandemic, with no nosocomial infections reported in our centre to date. We adopted a multipronged approach, with an overall committee supervising the entire COVID-19 management effort. A screening clinic was setup to triage patients prior to entry to the centre. Each Oncology Division within the cancer centre designed solutions tailored to the specific needs of their discipline. We explore in detail the screening criteria and workflow of the screening clinic, as well as modifications by individual divisions to reduce infection risk to patients and healthcare professionals. This approach can be modelled by other cancer centres during this prolonged COVID-19 pandemic.

Stereotactic body radiotherapy for early stage lung cancer-historical developments and future strategies.

The application of radiosurgery dose escalation extra-cranially in a moving target, surrounded by critical normal tissue, presents unique dosimetric and clinical challenges. Building on a strong foundation of robust technological advancements and well-planned clinical studies, lung stereotactic body radiotherapy (SBRT) has firmly established its place in the management of early stage non-small cell lung cancer (NSCLC). Nevertheless, favourable outcomes and long-term survival still evade a substantial proportion of patients, especially for central and larger peripheral lung tumours. In this review, we will document the historical developments of lung SBRT over the past decades, highlighting key studies, which have shaped current clinical practice. At the same time, we will address some of the recent advancements in radiation technology, molecular profiling and immunotherapy, and discuss how these important developments can lead to combinatorial strategies, which we hope will form the backbone of new clinical trials and drive better cure rates.

In the secretory endometria of women, luminal epithelia exhibit gene and protein expressions that differ from those of glandular epithelia.

OBJECTIVE: To characterize the transcriptome of luminal epithelia (LE) of fertile secretory endometria and compare the results with those from glandular epithelia (GE). DESIGN: Endometrial samples were collected at 2 and 7 days after initial blood LH surge in separate menstrual cycles. LE were obtained with the use of laser microdissection. mRNA was amplified with the use of linear polymerase chain reaction and hybridized to Agilent 4×44 microarrays. Gene analysis was used to identify differentially expressed mRNAs. Immunohistochemistry was used to assess nine proteins. SETTING: One IVF clinic. PATIENT(S): Seven Caucasian fertile cycling women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cycle dating with the use of blood endocrinologic markers, microarrays of laser-microdissected LE, immunohistochemical analysis. RESULT(S): One hundred sixty-one (of 401) differentially expressed mRNAs in LE were identified from the metabolism pathway. Increased selective protein expression in LE at 7 days after initial LH surge was observed. LE mRNA expression was the converse of that in GE. The two cell types each had a different significant biologic pathway identified. CONCLUSION(S): Our results introduce a new concept that LE differentially expressed mRNAs are in the converse direction to that of GE, indicating different biologic processes despite the GE being continuous with the luminal monolayer. This probable distinction of biologic roles has not been noted previously. Further investigations must take cognizance of this observation.

Gene and protein expression signature of endometrial glandular and stromal compartments during the window of implantation.

OBJECTIVE: To map the changes in messenger RNA (mRNA) and protein abundance during the window of implantation in specifically endometrial stromal and glandular epithelial cells obtained using laser microdissection microscopy (LDM). DESIGN: Endometrial samples were collected from two menstrual cycles at 2 and 7 days after first significant rise in blood LH, and separate cell populations were obtained using LDM. A new generation linear polymerase chain reaction (PCR) amplified the mRNA, which were hybridized to both Affymetrix U133 Plus2 and Agilent 4x44K microarrays followed by gene set analysis. Immunohistochemistry assessed protein expression between the two collection times. SETTING: In vitro fertilization clinic. PATIENT(S): Nine Caucasian, fertile, cycling women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cycle dating using blood markers; microarrays on laser microdissected glands and stroma; dual platform microarray confirmation; immunohistochemical analysis of cell cycle proteins. RESULT(S): The two microarray platforms showed concordance. During the window of implantation, a statistically significant network of 22 mRNA associated with the cell cycle was down-regulated. Immunohistochemistry identified altered localization in stroma. CONCLUSION(S): Microarrays demonstrated glands and stroma have distinct mRNA signatures, each dependent on the day of the cycle. We characterized two compartments of the receptive endometrium with a transcriptomic signature identifying regulation of only the cell cycle. Immunohistochemical analysis of cell cycle proteins identified a signature staining pattern of nuclear relocalization of a group of cyclins of stromal cells, which may be clinically applicable.

Vascular endothelial growth factor and leptin: regulation in human cumulus cells and in follicles.

BACKGROUND: The factors that determine oocyte competency are poorly understood. It is believed that angiogenic factors are crucial. Modulation of these factors is therefore a central consideration. The adjacent association of cumulus cells to oocytes gives these cells a particular importance in relation to oocyte behavior. We report the effects of gonadotropins on the secretion of VEGF and leptin from cumulus cells; and the concentrations of the proteins in follicular fluid and their relationship to fertilization of oocytes in vitro. METHODS: The subjects were women undergoing intracytoplasmic sperm injection (ICSI). Oocytes and follicular fluid were collected. Leptin and vascular endothelial growth factor (VEGF) concentrations in incubation supernatants and follicular fluid and leptin in cell lysates were measured. Fertilization of corresponding oocytes were noted. In the present study, cells from individual follicles were incubated, as well as pooled cells from a woman. RESULTS: For the first time we demonstrated that VEGF release by human cumulus cells was modulated by gonadotropins in a dose-related, time-dependent manner, but no leptin was detected in either the supernatants after cumulus cell incubations or in cell lysates. Mean leptin levels were similar whether from follicles associated with eggs that were fertilized (14.4 +/- 1.1 ng/ml, mean +/- SEM) or not (12.4 +/- 1.1 ng/ml). Mean VEGF levels were also similar (11.1 +/- 1.2 ng/ml; 12.8 +/- 1.3 ng/ml). A greater proportion of VEGF in follicles was derived from follicular activities, compared with transfer from other physiological compartments, than leptin. CONCLUSIONS: Whereas it is possible that VEGF is part of the gonadotropin-mediated network that regulates development of the oocyte, leptin may not be produced in significant quantities by cumulus cells or be related to oocyte competency.

Absence of association of androgen receptor trinucleotide expansion and poor semen quality.

This study investigated the relationship between variation in the polymorphic CAG trinucleotide repeat (TNR) region of the human androgen receptor (AR) gene and semen quality in a Caucasian sample population. These men were patients attending the New Zealand Centre for Reproductive Medicine in Christchurch. The AR TNR region was amplified by polymerase chain reaction and then DNA sequenced to determine exact numbers of CAG repeats for each sample. In addition, the samples were screened for microdeletions within the AZFc region of the Y-chromosome. A total of 105 men with poor semen quality were compared with a group of 93 men with normal semen quality. Men with poor semen quality had similar CAG repeat number to men with normal semen quality (21.46 +/- 0.30 vs. 20.99 +/- 0.28, p = 0.126). Y-chromosome microdeletions were only detected in men with suboptimal semen parameters (7.4%). However, the presence of a deletion was not related to CAG repeat number. The CAG repeat number in the men with normal semen quality in the present study is similar to the Australian and German samples, but lower than those reported for the Swedes, Dutch and Danes. These results are contrary to the hypothesis that higher CAG repeats are associated with infertility in men, but strongly suggest that different populations may show different numbers of CAG repeats in addition to racial variation reported in previous studies.