Olaparib (AZD2281), an orally active poly (ADP-ribose) polymerase inhibitor that induces synthetic lethality in BRCA1- or BRCA2-deficient cells, has shown promising clinical efficacy in nonrandomized ...phase II trials in patients with ovarian cancer with BRCA1 or BRCA2 deficiency. We assessed the comparative efficacy and safety of olaparib and pegylated liposomal doxorubicin (PLD) in this patient population.
In this multicenter, open-label, randomized, phase II study, patients with ovarian cancer that recurred within 12 months of prior platinum therapy and with confirmed germline BRCA1 or BRCA2 mutations were enrolled. Patients were assigned in a 1:1:1 ratio to olaparib 200 mg twice per day or 400 mg twice per day continuously or PLD 50 mg/m(2) intravenously every 28 days. The primary efficacy end point was Response Evaluation Criteria in Solid Tumors (RECIST) -assessed progression-free survival (PFS). Secondary end points included objective response rate (ORR) and safety.
Ninety-seven patients were randomly assigned. Median PFS was 6.5 months (95% CI, 5.5 to 10.1 months), 8.8 months (95% CI, 5.4 to 9.2 months), and 7.1 months (95% CI, 3.7 to 10.7 months) for the olaparib 200 mg, olaparib 400 mg, and PLD groups, respectively. There was no statistically significant difference in PFS (hazard ratio, 0.88; 95% CI, 0.51 to 1.56; P = .66) for combined olaparib doses versus PLD. RECIST-assessed ORRs were 25%, 31%, and 18% for olaparib 200 mg, olaparib 400 mg, and PLD, respectively; differences were not statistically significant. Tolerability of both treatments was as expected based on previous trials.
The efficacy of olaparib was consistent with previous studies. However, the efficacy of PLD was greater than expected. Olaparib 400 mg twice per day is a suitable dose to explore in further studies in this patient population.
Colorectal cancer (CRC) is the third most common type of cancer. One major pathway involved in the development of CRC is the serrated pathway. Colorectal polyps can be divided in benign, like small ...hyperplastic polyps and premalignant polyps, like the sessile serrated adenomas (SSA) that has a significant potential of malignant transformation. The morphological similarity between these types of polyp, not-infrequently raises diagnostic difficulties. This study aimed to morphologically differentiate between hyperplastic polyps (HP) and SSAs by using automated computerized texture analysis of Fourier transformed histological images. Thirty images of HP and 58 images of SSA were analyzed by computerized texture analysis. A fast Fourier transformation was applied to the images. The Fourier frequency plots were further transformed into gray level co-occurrence matrices and four textural variables were extracted: entropy, correlation, contrast, and homogeneity. Our study is the first to combine this type of analysis for automated classification of colonic neoplasia. The results were analyzed using statistical and neural network (NNET) classification models. The predictive values of these classifiers were compared. The statistical regression algorithm presented a sensitivity of 95% to detect the SSA and a specificity of 80% to detect the HP. The NNET analysis was superior to the statistical analysis displaying a classification accuracy of 100%. The results of this study have confirmed the hypothesis that Fourier based texture image analysis is helpful in differentiating between HP and SSA. RESEARCH HIGHLIGHTS: Colorectal polyps can be divided in benign, like hyperplastic polyps (HP) and premalignant, like the sessile serrated adenomas (SSA). There is a high morphologic similarity between these two types of polyp that not-infrequently raises diagnostic difficulties. The results of our morphometric analysis that were used to build a neural network based model of prediction of the polyp types, have a great clinical importance of identifying SSA polyps which have significant potential of malignant progression as compared to HP.
(1) Purpose: Current study aimed at evaluating the relationship between quantitative metabolic and volumetric FDG PET/CT parameters and the response to definitive chemoradiation therapy in locally ...advanced cervical cancer patients; (2) Methods: Ninety newly diagnosed locally advanced cervical cancer patients (FIGO IB2-IVA) were investigated. All patients underwent PET/CT at staging and after treatment. Metabolic and volumetric parameters, including SUVmax, SUVmean, Total Lesion Glycolysis (TLG), and Metabolic Tumor Volume (MTV) of the primary tumor and metastatic lymph nodes were measured and compared between patients with and without complete metabolic response (CMR). A similar analysis was performed in a subgroup of FIGO IB2-IIB patients; (3) Results: SUVmax and SUVmean of the primary tumor as well as those of metastatic lymph nodes, MTV, and TLG were found to be significantly different between CMR and non-CMR patients. In a subgroup of patients with FIGO IB2-IIB disease, MTV and TLG identified women who will achieve CMR with a threshold of 31.1 cm3 for MTV and 217.8 for TLG; (4) Conclusions: PET/CT-derived quantitative metabolic and volumetric parameters are higher in locally advanced cervical cancer patients who will not respond to definitive chemoradiation therapy. Specifically, in patients who are not metastatic at staging, MTV and TLG values can serve as a predictor for treatment response and thus may alter treatment strategy.
Uterine serous papillary carcinoma (UPSC) is an aggressive tumor, often diagnosed as a metastatic disease and characterized by a high recurrence rate and poor prognosis. UPSC represents a distinct ...subtype of endometrial cancer which is different in clinical and pathological behaviors from endometrioid endometrial carcinoma (EEC) and resembles more to serous ovarian carcinoma. Since tumors of serous papillary of the ovary are hypothesized to stem from cells of the fallopian tube's fimbria, we hypothesized that UPSC may also origin in the fallopian tubes. In our previous study, using a novel method of computerized morphometry of the fimbrial epithelium we have found significant differences between fimbriae of healthy women and serous ovarian cancer patients. In this study we showed the presence of morphologic differences between twenty-four fimbriae from healthy women, and twenty six fimbriae from uterus cancer (13 from UPSC patients and 13 from EEC patients). All fimbriae reported by the pathologist as "normal" were subjected to a computerized histomorphometric analysis. Two-step method of computerized histomorphometry, i.e. Fast Fourier transformation (FFT) followed by a co-occurrence matrix analysis and an additional analysis of the nuclear symmetry of the tubal fimbrial epithelium were applied. Using these novel methods, we were able to show differences in the morphometric characteristics of the fimbriae in UPSC patients compared to EEC and healthy patients. It is yet to be determined the clinical significance of this observation.
Background:
The PRIMA phase 3 trial showed niraparib significantly prolongs median progression-free survival (PFS) versus placebo in patients with advanced ovarian cancer (OC) responsive to ...first-line platinum-based chemotherapy, including those who had tumors with homologous recombination deficiency (HRd). This analysis of PRIMA examined the quality-adjusted PFS (QA-PFS) and quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) of patients on maintenance niraparib versus placebo.
Methods:
Patients were randomized 2:1 to receive once-daily maintenance niraparib (n = 487) or placebo (n = 246). QA-PFS was defined as the PFS of patients adjusted for their health-related quality of life (HRQoL) prior to disease progression, measured using European Quality of Life Five-Dimension (EQ-5D) questionnaire index scores from the PRIMA trial. Q-TWiST was calculated by combining data on PFS, duration of symptomatic grade ⩾2 adverse events (fatigue or asthenia, nausea, vomiting, abdominal pain, and abdominal bloating) prior to disease progression, and EQ-5D index scores. Analyses used data collected up to the last date of PFS assessment (May 17, 2019).
Results:
The restricted mean QA-PFS was significantly longer with niraparib versus placebo in the HRd (n = 373) and overall intention-to-treat (ITT; n = 733) populations (mean gains of 6.5 95% confidence interval; CI, 3.9–8.9 and 4.1 95% CI, 2.2–5.8 months, respectively). There were also significant improvements in restricted mean Q-TWiST for niraparib versus placebo (mean gains of 5.9 95% CI, 3.5–8.6 and 3.5 95% CI, 1.7–5.6 months, respectively) in the HRd and ITT populations.
Conclusions:
In patients with advanced OC, first-line niraparib maintenance was associated with significant gains in QA-PFS and Q-TWiST versus placebo. These findings demonstrate that niraparib maintenance treatment is associated with a PFS improvement and that treatment benefit is maintained even when HRQoL and/or toxicity data are combined with PFS in a single measure.
Trial registration:
ClinicalTrials.gov: NCT02655016; trial registration date: January 13, 2016
Plain language summary
Background: In a large clinical trial called PRIMA, patients with advanced cancer of the ovary (ovarian cancer) were given either niraparib (a type of cancer medicine) or placebo (a pill containing no medicine/active substances) after having chemotherapy (another type of cancer medicine). Taking niraparib after chemotherapy is called maintenance therapy and aims to give patients more time before their cancer returns or gets worse than if they were not given any further treatment. In the PRIMA trial, patients who took niraparib did have more time before their cancer progressed than if they took placebo. However, it is important to consider patients’ quality of life, which can be made worse by cancer symptoms and/or side effects of treatment. Here, we assessed the overall benefit of niraparib for patients in PRIMA.
Methods: Both the length of time before disease progression (or survival time) and quality of life were considered using two different analyses:
● The first analysis was called quality-adjusted PFS (QA-PFS) and looked at how long patients survived with good quality of life.
● The second analysis was called quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) and looked at how long patients survived without cancer symptoms or treatment side effects.
Results: The PRIMA trial included 733 patients; 487 took niraparib and 246 took placebo. Around half of the patients in both groups had a type of ovarian cancer that responds particularly well to drugs like niraparib – they are known as homologous recombination deficiency (HRd) patients.
● When information on quality of life (collected from patient questionnaires) and survival was combined in the QA-PFS analysis, HRd patients who took niraparib had approximately 6.5 months longer with a good quality of life before disease progression than those who took placebo. In the overall group of patients (including HRd patients and non-HRd patients), those who took niraparib had approximately 4 months longer than with placebo.
● Using the second analysis (Q-TWiST) to combine information on survival with cancer symptoms and treatment side effects, the HRd patients taking niraparib had approximately 6 months longer without cancer symptoms or treatment side effects (such as nausea or vomiting) than patients taking placebo. In the overall group of patients, those taking niraparib had approximately 3.5 months longer without these cancer symptoms/side effects than patients receiving placebo.
Conclusions: These results show that the survival benefits of niraparib treatment remain when accounting for patients’ quality of life. These benefits were seen not only in HRd patients who are known to respond better to niraparib, but in the overall group of patients who took niraparib.
To compare survival measures of women with early-stage endometrial cancer who underwent either hysteroscopy or a non-hysteroscopic procedure as a diagnostic procedure.
An Israel Gynecologic Oncology ...Group multicenter study of 1324 patients with stage I endometrial cancer who underwent surgery between 2002 and 2014. Patients were divided into two groups: hysteroscopy and non-hysteroscopy (curettage or office endometrial biopsy). Clinical, pathological, and survival measures were compared between the groups.
There were 355 patients in the hysteroscopy group and 969 patients in the non-hysteroscopy group. The median follow-up was 52 months (range 12–120 months). There were no differences between the groups in the 5-year recurrence-free survival (90.2% vs. 88.2%; p = 0.53), disease-specific survival (93.4% vs. 91.7%; p = 0.5), and overall survival (86.2% vs. 80.6%; p = 0.22).
Our findings affirm that hysteroscopy does not compromise the survival of patients with early-stage endometrial cancer.
Purpose
The purpose of this study was to compare the implementation process and the learning curves of laparoscopic and robotic-assisted laparoscopic sacrocolpopexy (LSC and RSC, respectively) for ...vaginal apex prolapse.
Methods
A retrospective study of the first 40 LSC and first 40 RSC procedures performed at one medical center. The primary outcomes were intraoperative bleeding, operative time, and hospitalization. Secondary outcomes were surgical complications. The independent
t
test, paired
t
test, χ
2
test, Fisher’s exact test and Pearson’s correlation were used to analyze the data. We assumed that 34 participants were needed in each group to detect a 50 ml or more difference in estimated blood loss between laparoscopic and robotic surgeries,
Main results
Age, preoperative pelvic organ prolapse quantification (POPQ) staging, and concomitant medical disorders did not differ significantly by procedure type. For LSC and RSC, the mean estimated intraoperative blood loss was 206 ± 107 and 48 ± 55 ml,
P
< 0.0001; mean operative times were 176 (110–380 min) and 186 (105–345 min),
P
= 0.34; and mean length of hospital stay, 3.8 ± 1 and 2.4 ± 1 days,
P
< 0.0001, respectively. Adverse events were rare, not severe, and did not differ significantly by procedure type.
Conclusions
RSC and LSC are feasible procedures with acceptable complication rates. RSC enables operating more anatomically with less bleeding.
•Sentinel lymph nodes biopsy method for surgical staging of endometrial cancer is safe and reliable.•Sentinel lymph nodes biopsy is associated with lower rate of external beam pelvic radiation.•The ...survival of patients operated by sentinel lymph nodes method is comparable to patients undergoing full lymphadenectomy.
To compare the rates of post-operative radiotherapy between two methods of lymph nodes assessment during surgical staging for endometrial cancer (EC).
We conducted a comparative study of all consecutive women with endometrial cancer who underwent sentinel lymph node detection and biopsy using blue dye and isotope scan (SLNB) at Kaplan Medical Center and patients from the IGOG database, who underwent staging lymphadenectomy (PLND). The primary outcome was the rate of adjuvant and therapeutic radiation. The secondary outcome was a comparison of disease-free survival (DFS) and overall survival (OS).
There were 138 patients in the SLNB group and 1022 women in the PLND group. The detection rate of SLN was 74% for unilateral detection and 54% for bilateral detection. In the PLND group 57% were high risk patients vs. 47% in SLNB group (p = 0.03). 43% of high-risk patients in the PLND group received adjuvant or therapeutic pelvic radiation vs. 28% of high-risk women in the SLNB arm (p = 0.017). No statistically significant difference in recurrence rates nor in death rates had been observed in the high-risk group patients. The 5-years survival in the high-risk PLND group was 80% and the recurrence rate was 19% vs. 75% 5-year survival and 14% recurrence in high-risk SLNB cohort, log-rank p = 0.82 for survival and long-rank p = 0.25 for recurrence.
Endometrial cancer patients undergoing lymph node assessment by sentinel lymph node biopsy, receive less pelvic radiotherapy.
This article briefly reviews the epidemiology, diagnosis, and treatment of the common gynecologic malignancies, with an emphasis on the shortcomings of current clinical practice. The persistent need ...to achieve early diagnosis, adjust proper treatment, enhance surveillance, and improve the outcome of these patients has led to the development of new diagnostic modalities. Novel tools such as 18F-fluorodeoxyglucose PET/CT should aim at enhancing the clinician's ability to make critical decisions in treating difficult scenarios.
Robotic laparoendoscopic single-site (R-LESS) seems to be the next route in advancing minimal invasive surgery, with the potential for better cosmetic results and reduced patient morbidity compared ...with multi-port surgery. This review describes the history and development of (R-LESS) gynecologic surgery and outlines the latest advancements in the realm of gynecology. The review was conducted according to the PRISMA guidelines. Pubmed and ClinicalTrials.gov (www.clinicaltrials.gov) were the main search engines utilized for retrieval of study data (1990 – present). The following subject headings and keywords were searched: “robotic laparoscopic single incision”, “robotic laparoendoscopic single site”, “single incision robotic surgery” and “single-port robotic surgery”. All original research articles including randomized, non-randomized controlled trials, cohort studies, patient series, and case reports were included. The search produced a total of 1127 results. After duplicate removal, 452 remained, and each title and abstract was reviewed by 2 reviewers. Subsequently, 56 full texts were selected for full review and an additional 20 excluded, leaving 36 studies that were included in the final review. Based on the data gathered we reached the conclusion that R-LESS surgery is feasible, safe and has equivalent surgical outcomes as conventional LESS surgery; in addition to shorter recovery times, less postoperative pain and better cosmetic outcomes than robotic multi-port surgery. To conclude, R-LESS is a feasible approach with low complication rates, minimal blood loss and postsurgical pain, fast recovery, and virtually scar-free results. However, the lack of large comparative prospective randomized controlled studies prevents drawing absolute conclusions.
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