Editorial

Uziel Beller
2014 International Journal of Gynecological Cancer  
Aims Nerve sparing radical hysterectomy (NSRH) has proven physiological advantages over conventional radical hysterectomy (RH) with regard to bladder, bowel and sexual function. However, there is much debate about the long-term oncological outcome since large and robust studies are lacking. The aim of this study is to compare longterm oncological outcome of NSRH with RH. Methods This is a prospective cohort study comparing a RH-cohort (1994RH-cohort ( -1999 and a NSRHcohort (2001NSRHcohort (
more » ... 05. All patients presenting with cervical cancer FIGO stage IA2-IIA who did not want to preserve fertility were included prospectively and consecutively. Results 245 women (124-RH cohort and 121 NSRH-cohort) were included. Age, FIGO-stage and histological subtype did not differ (p=0.79, p=0.24 and p=0.17 respectively), but the percentage of women with deep infiltration and those receiving adjuvant therapy was significantly higher in the NSRH-cohort (p=0.03, p =0.03 respectively). There was a trend towards more lymph node metastasis in the NSRH-cohort (16.7% vs 26.3%, p=0.07). The 5 year local recurrence free survival (5yrsLRFS) (93.8% vs 89.1%, p = 0.12) and the 5 year disease specific survival (5yrsDSS) (82.3% vs 79.5%, p = 0.39) did not differ between both cohorts. Conclusion Despite significant worse prognostic factors in the NSRH-cohort, the 5yrsLRFS and 5yrsDSS did not differ significantly when compared to a cohort of women who underwent RH. More and especially larger studies are needed to strengthen our results but there is no reason to believe that NSRH is in any way inferior to RH with regard to long-term oncological outcome. Aims To survey gynecologic oncologists and fellows-in-training regarding the role of radical trachelectomy (RT) and conservative surgery in patients with early-stage cervical cancer. Methods From June 2012 to September 2012, Society for Gynecologic Oncology (SGO) member practitioners (n=1,353) and gynecologic oncology fellows (n=156) were sent group-specific surveys investigating current practice, training, and the future of radical trachelectomy (RT) for early-stage cervical cancer management. Results Twenty-two percent of practitioners (n=303) and 24.4% of fellows (n=38) completed the surveys. Of the practitioners, 50% (n=148) report performing RT, 98% (n=269) support RT as treatment for squamous carcinoma, and 71% (n=195) confirm use of RT for adenocarcinoma. The majority of practitioners offer RT treatment for stages IA2-IB1 <2cm (n=209, 76.8%) regardless of grade (77.7%) or lymphovascular space invasion (n=211, 79.3%). Only 8% (n=23) of practitioners feel RT is appropriate for stage IBI >2cm. Respectively, both practioners and fellows most frequently perform robotic-assisted (47.0%, n=101 and 59.1% n=13) and abdominal (40.5%, n=87 and 68.2%, n=15) RT approaches. Post training, fellows project use of robotic-assisted (71% n=22) or abdominal methods (58.1% n=18). Overall, 75% (n=227) of practitioners and 60% (n=23) of fellows speculate that over the next five years less radical procedures will be used to manage early-stage cervical cancer. Conclusion Our findings suggest that practitioners and fellows believe RT remains an option for early-stage cervical cancer patients. However, a significant proportion of all respondents believe less radical surgery may be a future consideration for patients with low-risk early-stage cervical cancer. Aims Primary HPV screening for cervical cancer will start in the Netherlands in 2016. In this new screening program non-responders of the regular screening can opt for HPV self-sampling. We determined whether the participation rate for a brush-based cervicovaginal self-sampling device is non-inferior to a lavage-based device. Additionally, hrHPV-positivity rates, detection rates for CIN2+/3+, and user comfort were compared. Methods A total of 35,477 non-responders of the regular cervical screening program aged 33-63 years were invited to participate. Eligible women (n=30,130) were randomly assigned (1:1) to receive either a brush-based or a lavage-based self-sampling device, and a questionnaire for reporting user-convenience. Women who submitted a self-collected sample and tested hrHPV-positive were invited for a physician-taken sample for cytological assessment. Triage-positive women were referred for colposcopy. Results A total of 5218 women responded in the brush-based sampling group (34.6%) and 4809 women in the lavage-based group (31.9%), i.e. an absolute difference of 2.7% (95%CI 1.8-4.2). The hrHPV-positivity rates in both groups were identical (8.3%). The detection rate of CIN2+ and CIN3+ in the brush-based group (2.0% and 1.3%) was similar to that in the lavage-based group (1.9% and 1.0%); cumulative RR of 1.01, 95%CI 0.83-1.24 for CIN2+ and 1.25, 95%CI 0.92-1.70 for CIN3+. The selfsampling devices performed similarly in user comfort. Conclusion Offering a brush-based device to non-responders is non-inferior to offering a lavagebased device in terms of participation to HPV self-sampling. The two self-sampling methods are equally effective in detecting hrHPV, CIN2+/CIN3+ and are both well accepted. Aims Although a large part of patients with cervical adenocarcinoma are young, oophorectomy is commonly performed in those who receive hysterectomy. The purpose of this study is to examine the safety of ovarian preservation in young women with cervical adenocarcinoma. Methods Patients ≤ 45 years with stage I cervical adenocarcinoma and adenosquamous carcinoma were identified in the Surveillance, Epidemiology, and End Results (SEER) program (1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007). Characteristics of the patients with ovarian preservation were compared with that of women with oophorectomy. Univariate Kaplan-Meier analysis and multivariate Cox proportional hazard model were used to explore the effects of ovarian preservation on survival. Results The study sample consisted of 1639 women, including 1062 (64.8%) who underwent oophorectomy and 577 (35.2%) who had ovarian preservation at the time of hysterectomy. Younger age (P < 0.001), more recently diagnosed (P < 0.001), lowgrade (P < 0.001) and smaller tumor (P < 0.001), white population (P = 0.015) and less likely to undergo lymphadenectomy (P < 0.001) and adjuvant radiotherapy (P = 0.041) were associated with ovarian preservation. Ovarian preservation had no effect on either cancer-specific (HR 0.90; 95% CI, 0.50 -1.61) or overall (HR 0.81; 95% CI, 0.49 -1.33) survival in the Cox proportional hazard model. When patients without radiotherapy were separately analyzed, the effect on either cancer-specific (HR 1.24; 95% CI, 0.44 -3.54) or overall (HR 0.77; 95% CI, 0.35 -1.73) survival were not statistically significant. Conclusion Ovarian preservation may have oncological safety in young women with stage I cervical adenocarcinoma. Aims To determine whether the addition of concurrent chemotherapy (CCT) or sequential chemotherapy (SCT) to adjuvant pelvic radiotherapy (RT) will improve survival of patients with early-stage cervical carcinoma who had adverse pathological factors. Methods After radical surgery, patients with stage IB1 to IIA2 cervical cancer who had one or more following pathological factors were recruited: lymph node metastases (LNM), positive parametrium or margins (PPM), lymphatic vascular space involvement (LVSI), deep invasion of cervical stromal (DIS). Eligible patients were randomized to three groups. Group A underwent 50 GY RT alone. Group B received concurrent weekly cisplatin and RT. Group C received paclitaxel and bolus cisplatin every three weeks for two cycles before RT, followed by two cycles. Results The 564 cases were assessable. There was no statistically significant difference in disease-free survival (DFS) among three groups (P=0.96). The DFS was better in patients with DIS or/and LVSI than in those with LNM or PPM (65 vs 49 months, P<0.05). For the patients with LNM or PPM, no significant difference in DFS was Volume 24, Supplement 4,November 2014 8 found between three groups (38 vs 46 vs 54 months, P=0.27). However, there was a trend indicating that prognosis favored to Group C (SCT+RT). Grades 3 and 4 leukopenia was most common in Group B (P<0.05). More patients in Group B experienced gastrointestinal toxicity than other groups (P<0.05). Conclusion LNM and PPM should be considered as high-risk factors for recurrence in early-stage cervical cancer. Adjuvant SCT+RT might improve DFS in high-risk patients and was more tolerable than CCT+RT. Aim: To determine the impact of prior conization on the detection of sentinel lymph nodes in patients with early-stage cervical cancer undergoing radical or simple hysterectomy, radical trachelectomy or conization and bilateral pelvic lymphadenectomy. Methods: A retrospective chart review was performed of patients who underwent lymphatic mapping at the time of definitive surgery for early-stage cervical cancer between January 2000 through January 2014. Medical records were reviewed for demographic/clinical information, surgical details and pathologic results. Sentinel node identification were compared between patients who had undergone previous conization and those who had not. Results: A total of 142 patients met inclusion criteria for the study. Median age for all patients was 38.5 years (range, 21-68). 78.9% underwent radical hysterectomy, 14.1% had radical trachelectomy, 3.5% had simple hysterectomy, and 2.1% had conization. Eighty-four (59.2%) patients had prior conization. There were no differences in the rate of sentinel node detection between the patients who had undergone previous conization and those who had not (91.7% vs. 86.2%, p=0.123). There was also no difference in sentinel lymph node detection when comparing by type of surgery (p=0.854). Furthermore, there was no difference in sentinel node identification between the use of the combination blue dye/Tc-99 and indocyanine green (92.2% vs. 95.2%, p=0.99). Conclusions: Prior conization had no impact on rate of sentinel node detection in patients with early-stage cervical cancer. Aims Cervical cancer is a major public health problem worldwide. We have recently identified novel significantly recurrent somatic mutations in HLA-B, ERBB2 and MAPK1 in cervical carcinomas (Nature 2014). This study seeks to identify relationships between somatic genomic alterations and clinical phenotype in cervical carcinomas. Methods DNA from cervical carcinoma lesions from 100 patients with tumor stages I -IV were explored by whole exome sequencing. Somatic single nucleotide variants and small insertion/deletions were identified (MuTect and Indelocator algorithms). Mutations were classified as clonal or subclonal (ABSOLUTE algorithm). Somatic copy number (CN) data were derived from WES data using the CapSeg algorithm, and significantly recurrent CN alterations were identified (GISTIC2.0). HPV typing was done by the multiplex fluorescent f-HPV DNA and MassARRAY assays. The log-rank test was used to compare survival curves. Results Non-localized tumors (FIGO stages ≥ II) were associated with focal amplification of the FGFR2 gene on chromosomal cytoband 10q26 (GISTIC q = 0.18531). Six of eight (75%) tumors with FGFR2 amplification were non-localized, in contrast to 16 of 92 (17%) tumors without FGFR2 amplification (p = 0.001). In addition, patients with somatic ERBB2 mutations and/or amplifications (p = 0.04), somatic TP53 mutations Aims GOG 240 demonstrated that chemotherapy plus bevacizumab significantly improved overall survival (OS) in advanced cervical cancer. In subgroup analysis, the benefit conferred by bevacizumab was not sustained among the 27% with adenocarcinoma (AC)/adenosquamous (AS) histology, suggesting that AC/AS is a different disease than squamous cell carcinoma (SCCA). To increase sample size we pooled cases of AC/AS from other phase 3 GOG studies and developed a training set. Methods Three phase III GOG trials (179, 204, 240) of systemic therapy in advanced cervical cancer were studied. Binary exchange analysis was performed using Pearson's test to evaluate response rate (RR), Kaplan-Meier method to estimate progression-free survival (PFS) and OS, and Cox proportional hazards model to estimate the effect of histology on PFS and OS. Aims Twelve common variant genetic susceptibility loci that modestly increase invasive epithelial ovarian cancer (EOC) risk have been identified using genome wide association studies. Most of these variants also affect EOC risk in BRCA1 and BRCA2 mutation carriers. The aim of this study was to identify additional common low penetrance EOC risk loci. Methods EOC cases and controls from the Ovarian Cancer Association Consortium (OCAC) and the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) were genotyped for >200,000 single nucleotide polymorphisms. After imputation to the publically available 1000 Genomes Project data, associations of 11 million genetic variants with EOC risk were assessed in 15,397 EOC cases and 30,816 controls from OCAC, and in 15,252 BRCA1 carriers and 8,211 BRCA2 carriers from CIMBA (3,096 BRCA1/2 carriers had EOC). The results were then combined for meta-analysis. Results Six new genome wide significant (p<5x10 -8 ) EOC susceptibility loci were discovered. Variants at 1p36 (nearest gene WNT4), 1p34.3 (RSPO1), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 6p22.1 (GPX6) specifically with serous EOC risk. These SNPs increase ovarian cancer risk from 5-11% per copy of the risk allele in analyses of OCAC data and similar associations were found for BRCA1/2 carriers in CIMBA. Conclusion The six novel loci reported increase the number of genome wide significant common EOC risk loci to eighteen. Incorporating EOC susceptibility variants into risk assessment tools has the potential to improve risk prediction and may be particularly useful for predicting penetrance of EOC in BRCA1/2 mutation carriers. Aims Although innovative devices are increasingly used in cancer surgery, the benefit has unfrequently been adequately assessed. Groin dissection generates a high rate of local complications including lymph fluid leaks, wound disruption, and wound infection. Groin dissection is then a model for clinical trials of new devices that are theoretically able to ensure lymphostasis Methods Non-blinded randomized controlled surgery comparing the use of harmonic scalpel (Ultracision®) to standard methods (clips, electrosurgery, or ligatures) for lymphostasis in full groin dissection. Randomization was done for both sides in case of bilateral dissection. The estimated sample size was 125. Primary outcome : postoperative morbidity as defined by one of the following events : symptomatic lymphocele, wound disruption > 2 cm, infectious complications requiring surgery. Inclusion criteria : vulvar cancer or melanoma of the lower limb. Exclusion criteria : previous surgery of the groin, fixed diseased groin node, or removal of sentinel node only. Results The trial was interrupted for slow accrual after 61 patients were included. 12 of them had bilateral groin dissection. Taking into account one protocol deviation, per protocol analysis was performed. Morbidity was 38% in the Ultracision group versus 60.5% in the control group (p=0.059). The proportion of patients with drain and the length of drainage were significantly reduced in the Ultracision group Conclusion In spite of the lack of power of this study, it is likely that Ultracision ensures better lymphostasis, thus reducing the related morbidity, in groin node dissection Background: Cervical cancer screening has failed dramatically in developing areas of the world. Self-sampling seems effective and acceptable to most women, usually offered outside health facilities. Due to differences in culture, knowledge and education these data cannot necessarily be extrapolated to other communities. Objective: Questionnaire study, conducted to determine acceptability and uptake of self-sampling with Evalyn® brush offered to women at a rural primary health care clinic in the Eastern Cape, South Africa. Methods: Consecutive female clinic attendees >20 years were informed, invited to participate in screening and to complete an administered questionnaire. Results: All 186 women recruited elected to participate; 183 questionnaires were available for analysis. Participants had reasonable educational levels (87% reported secondary education), low levels of employment (39% employed in any sector) and high parity (27% had four or more children). Although 89% have heard of cervical cancer, only 35% reported previous screening. All invited women elected to screen with the Evalyn® brush and 99.5% found it comfortable. 100% said they would choose it again; 35% were 'positive', 65% 'very positive' about the method. All participants said that the instructions were understandable, the test met their expectations and that they found it easy and private. Conclusion: Self-collection of cervical screening tests using the Evalyn® brush was highly acceptable and satisfactory to rural women accessing the primary health facilities. This method can facilitate screening of high risk women using the heath care infrastructure in under resourced rural areas. Aims: Pazopanib(P) is an oral, multi-target kinase inhibitor of VEGFR-1, -2, -3, PDGFR-α, -β, and c-KIT. We evaluated the efficacy and tolerability of combining P with weekly paclitaxel (T) in women with ovarian cancer.Methods: Eligible patients included persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with 1-3 prior regimens and performance status (PS) of 0-2. All patients received T 80mg/m 2 D1, 8, 15, every 28 days and were randomized 1:1 to P 800mg PO daily or placebo. Primary endpoint was progression-free survival (PFS). Study was designed to detect a 37.5% reduction in the hazard with 80% power (alpha=10%). Secondary endpoints were toxicity, response (RR) and overall survival (OS).Results:106 enrolled; 100 evaluable for toxicity. Arms were well balanced for age (median 61: range 35-87), PS (0: 75%, 1-2: 25%), measurable disease, and prior bevacizumab. RR was 31.8% vs 22.7% for PT vs T, p=0.47. Median PFS was 7.5 versus 6.2mos for PT vs T, HR 0.84 (90% CI 0.57-1.22), p=0.2. Median OS was 20.7 vs 23.3 mos for PT vs T, HR 1.04 (90% CI 0.6-1.79), p=0.9. Severe hypertension was more common on the PT arm, relative risk 12 (95% CI 1.62-88.84). One patient died of sudden death, NOS, on the PT arm, p=NS. More patients discontinued treatment on T arm for disease progression (65.4% vs 31.5%), and more on PT arm for adverse events (37% vs 9.6%). Conclusion: The combination of PT is not superior to T in women with recurrent ovarian cancer. Aims: In 2011 NICE recommended CA125 as the primary test to investigate symptoms potentially signifying ovarian cancer. We aimed to evaluate whether the addition of HE4 testing in primary care improves the accuracy of detecting ovarian cancer. Methods: Between November 2013 and June 2014 all women who presented in primary care, in a geographical area with a population of 200 000, meeting NICE indications to undergo Ca125 also received an HE4 test. If either or both were elevated, patients were referred for urgent gynecological review. Radiological and histological outcomes were recorded. Results: During the study period, 306 women met the inclusion criteria and their results were analysed. Of those, 290 had a normal CA125; of which HE4 was normal in 269 (92.7%) and raised in 21 (7.2%). A total of 16 had an abnormal CA125; of which 9 (56.3%) had a normal and 5 (31.3%) an abnormal HE4 score. One womea had ovarian cancer in which both tests were abnormal. One woman had colorectal cancer in which CA125 was raised but HE4 normal. 19 The sensitivity, specificity, PPV and NPV of CA125 were 100%, 95%, 6.25% and 100%; of HE4 100%, 92%, 3.85% and 100%; and of the 2 combined 100%, 98.6%, 20% and 100% respectively. Of note, 204 (67.3%) women had imaging irrespective of the tumour marker results. Conclusions: This pilot study shows the addition of HE4 testing to CA125 in primary care may improve the diagnostic test accuracy statistics for ovarian malignancy and assist management protocols.
doi:10.1097/igc.0000000000000061 pmid:24356409 fatcat:l2gj6y7ddzdqvhqp3gbredy3w4