Can MRI Be Used as a Sole Diagnostic Modality in Determining Clinical Stage in Cervical Cancer?

OBJECTIVE: The objective of this study was to compare staging by MRI to clinical staging in patients with cervical cancer and to determine the histological accuracy of staging by MRI and examination under anesthesia (EUA) in early stage disease. METHODS: This was a retrospective cohort study of patients diagnosed with cervical cancer between 2010 and 2020 at the Radboud University Medical Centre, the Netherlands. Pretreatment stage (FIGO 2009) by MRI was compared with staging by EUA. Diagnostic accuracy in terms of sensitivity, specificity, positive, and negative predictive value was calculated for MRI and EUA in patients undergoing surgery (early stage disease) with histological results as a reference standard. RESULTS: A total of 358 patients were included in the study and MRI-based stage differed from EUA stage in 30.7%. In 12.3% this meant a discrepancy in treatment assignment between MRI and EUA. Diagnostic accuracy of MRI in terms of sensitivity and specificity for detecting early stage disease was comparable to EUA in surgical patients. Further analyses showed that premenopausal status, early stage disease and a tumor diameter of <2 cm were associated with improved comparability of MRI and EUA (98%). CONCLUSION: There is still a large discrepancy between MRI and EUA. In patients with suspected early stage disease, diagnostic accuracy of MRI is similar to EUA, especially for premenopausal women with early stage disease and a tumor diameter of <2 cm.

Conservative surgical approaches for small volume FIGO stage IB1 cervical cancer. Updated survival and obstetric outcomes of an expanded cohort.

OBJECTIVE: Standard surgical treatment of FIGO stage 1B1 cervical cancer is open radical surgery. However, there is increasing evidence that for small tumours a more conservative approach can minimise fertility consequences without impacting on long term oncologic outcomes. The objective of our study is to present survival and obstetric outcomes following extended follow-up for patients who underwent conservative management of small-volume stage 1B1 disease. METHODS: All patients with FIGO stage 1B1 cancer and estimated tumour volume of <500 mm3 in a loop biopsy specimen treated in Northern Gynaecological Oncology Centre between December 2000 and December 2021, were included in the study. Clinico-pathological and demographic data were collated alongside detailed follow-up and obstetric outcomes in conjunction with primary care and death register. RESULTS: 117 patients underwent conservative surgery for small volume stage 1B1 disease. 58 (49.5%) underwent fertility sparing conservative management with LLETZ while 59 (50.5%) underwent simple hysterectomy. Overall, 95% (111/117) of the patients underwent bilateral pelvic lymphadenectomy and 1 positive node was identified. There was no death related to cervical cancer and 1 recurrence identified during a median follow up of 8.5 years (1-20). 17 pregnancies have been recorded in patients underwent LLETZ and 17 live babies were born. No second trimester miscarriages were noted and there was one preterm delivery (36 weeks). CONCLUSION: Non-radical surgery with negative pelvic lymphadenectomy for smallvolume stage 1B1 cervical cancer ensures excellent survival without compromising obstetric outcomes. Should these results be verified by the ongoing prospective studies, radical surgery for these patients may be avoided.

Finding the sentinel lymph node in early cervical cancer: When is unusual not uncommon?

OBJECTIVE: To report our institutional experience with sentinel lymph node (SLN) detection using indocyanine green for cervical cancer, in terms of detection rates, detection of SLN at unusual locations, and factors associated with unusual SLN locations. In addition, we performed a systematic review of the literature to identify factors associated with unusual SLN localizations. METHODS: This is a retrospective cohort study of women with early-stage cervical cancer undergoing sentinel lymph node mapping between 2015 and 2019. Outcome measures were SLN detection rates, detection rates of unusual locations for SLN and risk factors for aberrant lymphatic drainage pathways. In addition, studies evaluating factors associated with unusual SLN locations in cervical cancer were assessed in a systematic review. RESULTS: A total of 100 patients were included. The unilateral SLN detection rate was 88%, whereas the bilateral detection rate was 75%. In 37% of all patients, SLN were found in unusual locations, and in 10% of patients SLN were solely found in unusual locations. Body mass index (BMI) was associated with finding SLN in unusual locations, with unusual nodes detected in 52% of patients with BMI <25 kg/m2 and in 28% of patients with BMI ≥25 kg/m2. The systematic review identified three studies, identifying lower BMI, nulliparity and tumor size of >20 mm as factors associated with finding SLN at unusual locations. CONCLUSION: Aberrant drainage sites represent a significant proportion of SLN detected in cervical cancer. Factors associated with increased rates of unusual nodal locations are a lower BMI, with a possible association with nulliparity and tumor size of >20 mm.

Open vs minimally invasive radical trachelectomy in early-stage cervical cancer: International Radical Trachelectomy Assessment Study.

BACKGROUND: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. OBJECTIVE: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. STUDY DESIGN: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005-2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. RESULTS: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20-42) years for open surgery vs 31 (18-45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0-31) mm for open surgery and 12 (0.8-40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20-16.70) years for open surgery and 3.1 years (0.02-11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6-97.0) for open surgery and 91.5% (95% confidence interval, 87.6-95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6-99.7) for open surgery and 99.0% (95% confidence interval, 79.0-99.8) for minimally invasive surgery. CONCLUSION: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management.

British Gynaecological Cancer Society recommendations for women with gynecological cancer who received non-standard care during the COVID-19 pandemic.

During the COVID-19 pandemic, pressures on clinical services required adaptation to how care was prioritised and delivered for women with gynecological cancer. This document discusses potential 'salvage' measures when treatment has deviated from the usual standard of care. The British Gynaecological Cancer Society convened a multidisciplinary working group to develop recommendations for the onward management and follow-up of women with gynecological cancer who have been impacted by a change in treatment during the pandemic. These recommendations are presented for each tumor type and for healthcare systems, and the impact on gynecological services are discussed. It will be important that patient concerns about the impact of COVID-19 on their cancer pathway are acknowledged and addressed for their ongoing care.

Post-operative pancreatic fistula following splenectomy with or without distal pancreatectomy at cytoreductive surgery in advanced ovarian cancer.

OBJECTIVE: Splenectomy with or without distal pancreatectomy may be necessary at time of cytoreductive surgery to achieve complete cytoreduction in advanced ovarian cancer. However, these procedures have been associated with peri-operative morbidity. The aims of this study were to determine the incidence of distal pancreatectomy among patients undergoing splenectomy during cytoreductive surgery for advanced ovarian cancer and to determine the incidence, management, treatment, and prognosis of patients with post-operative pancreatic fistula. METHODS: Retrospective cohort study of all consecutive patients with FIGO stage IIIC-IVB ovarian, fallopian tube, or primary peritoneal cancer who underwent splenectomy with or without distal pancreatectomy, during primary, interval, or secondary cytoreductive surgery between January 2007 and December 2017. All histologic subtypes were included; patients with borderline ovarian tumor and those undergoing emergency surgery were excluded from analysis. Univariate analyses for survival were generated by Kaplan-Meier survival curves and log-rank (Mantel-Cox) tests for statistical significance. Patients who underwent surgery for recurrence were excluded from survival analysis. Inter-group statistics were performed using Student's t-test for continuous variables, and chi-square test and Fisher's exact test for categorical variables. RESULTS: A total of 156/804 (19.4%) women underwent splenectomy, and of these 22 (14.1%) patients had distal pancreatectomy. Of patients who underwent splenectomy only, 2/134 (1.5%) developed grade B post-operative pancreatic fistula and 6/22 (27.3%) patients who underwent distal pancreatectomy developed grade B and C post-operative pancreatic fistula. Five (83.3%) of six of these patients were symptomatic. Distal pancreatectomy patients had a higher risk of developing post-operative pancreatic fistula when compared with patients who underwent splenectomy only (63.7% vs 9.7%, p=0.0001). Median length of hospital stay was longer in patients with post-operative pancreatic fistula: 16.5 (range 7-38) days compared with 10 (range 7-15) days (p=0.019). There was no progression-free survival (p=0.42) and disease-specific survival (p=0.33) difference between patients undergoing splenectomy with or without distal pancreatectomy. CONCLUSION: Clinically relevant post-operative pancreatic fistula is a relatively frequent complication (27.3%) following distal pancreatectomy and it is a possible complication after splenectomy only (1.5%).

International radical trachelectomy assessment: IRTA study.

BACKGROUND: Radical trachelectomy is considered a viable option for fertility preservation in patients with low-risk, early-stage cervical cancer. Standard approaches include laparotomy or minimally invasive surgery when performing radical trachelectomy. PRIMARY OBJECTIVE: To compare disease-free survival between patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive (laparoscopic or robotic) radical trachelectomy. STUDY HYPOTHESIS: We hypothesize that minimally invasive radical trachelectomy has similar oncologic outcomes to those of the open approach. STUDY DESIGN: This is a collaborative, multi-institutional, international, retrospective study. Patients who underwent a radical trachelectomy and lymphadenectomy between January 1, 2005 and December 31, 2017 will be included. Institutional review board approval will be required. Each institution will be provided access to a study-specific REDCap (Research Electronic Data Capture) database maintained by MD Anderson Cancer Center and will be responsible for entering patient data. INCLUSION CRITERIA: Patients with squamous, adenocarcinoma, or adenosquamous cervical cancer FIGO (2009) stages IA2 and IB1 (≤2 cm) will be included. Surgery performed by the open approach or minimally invasive approach (laparoscopy or robotics). Tumor size ≤2 cm, by physical examination, ultrasound, MRI, CT, or positron emission tomography (at least one should confirm a tumor size ≤2 cm). Centers must contribute at least 15 cases of radical trachelectomy (open, minimally invasive, or both). EXCLUSION CRITERIA: Prior neoadjuvant chemotherapy or radiotherapy to the pelvis for cervical cancer at any time, prior lymphadenectomy, or pelvic retroperitoneal surgery, pregnant patients, aborted trachelectomy (intra-operative conversion to radical hysterectomy), or vaginal approach. PRIMARY ENDPOINT: The primary endpoint is disease-free survival measured as the time from surgery until recurrence or death due to disease. To evaluate the primary objective, we will compare disease-free survival among patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive radical trachelectomy. SAMPLE SIZE: An estimated 535 patients will be included; 256 open and 279 minimally invasive radical trachelectomy. Previous studies have shown that recurrence rates in the open group range from 3.8% to 7.6%. Assuming that the 4.5-year disease-free survival rate for patients who underwent open surgery is 95.0%, we have 80% power to detect a 0.44 HR using α level 0.10. This corresponds to an 89.0% disease-free survival rate at 4.5 years in the minimally invasive group.

Hormone replacement therapy for women previously treated for endometrial cancer.

BACKGROUND: Endometrial cancer is the sixth most common cancer in women worldwide and most commonly occurs after the menopause (75%) (globocan.iarc.fr). About 319,000 new cases were diagnosed worldwide in 2012. Endometrial cancer is commonly considered as a potentially 'curable cancer,' as approximately 75% of cases are diagnosed before disease has spread outside the uterus (FIGO (International Federation of Gynecology and Obstetrics) stage I). The overall five-year survival for all stages is about 86%, and, if the cancer is confined to the uterus, the five-year survival rate may increase to 97%. The majority of women diagnosed with endometrial cancer have early-stage disease, leading to a good prognosis after hysterectomy and removal of the ovaries (oophorectomy), with or without radiotherapy. However, women may have early physiological and psychological postmenopausal changes, either pre-existing or as a result of oophorectomy, depending on age and menopausal status at the time of diagnosis. Lack of oestrogen can cause hot flushes, night sweats, genital tract atrophy and longer-term adverse effects, such as osteoporosis and cardiovascular disease. These changes may be temporarily managed by using oestrogens, in the form of hormone replacement therapy (HRT). However, there is a theoretical risk of promoting residual tumour cell growth and increasing cancer recurrence. Therefore, this is a potential survival disadvantage in a woman who has a potentially curable cancer. In premenopausal women with endometrial cancer, treatment induces early menopause and this may adversely affect overall survival. Additionally, most women with early-stage disease will be cured of their cancer, making longer-term quality of life (QoL) issues more pertinent. Following bilateral oophorectomy, premenopausal women may develop significant and debilitating menopausal symptoms, so there is a need for information about the risk and benefits of taking HRT, enabling women to make an informed decision, weighing the advantages and disadvantages of using HRT for their individual circumstances. OBJECTIVES: To assess the risks and benefits of HRT (oestrogen alone or oestrogen with progestogen) for women previously treated for endometrial cancer. SEARCH METHODS: We searched the Cochrane Register of Controlled Trials (CENTRAL 2017, Issue 5), MEDLINE (1946 to April, week 4, 2017) and Embase (1980 to 2017, week 18). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of review articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs), in all languages, that examined the efficacy of symptom relief and the safety of using HRT in women treated for endometrial cancer, where safety in this situation was considered as not increasing the risk of recurrence of endometrial cancer above that of women not taking HRT. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified 2190 unique records, evaluated the full text of seven studies and included one study with 1236 participants. This study reported tumour recurrence in 2.3% of women in the oestrogen arm versus 1.9% of women receiving placebo (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.54 to 2.50; very low-certainty evidence). The study reported one woman in the HRT arm (0.16%) and three women in the placebo arm (0.49%) who developed breast cancer (new malignancy) during follow-up (RR 0.80, 95% CI 0.32 to 2.01; 1236 participants, 1 study; very low-certainty evidence). The study did not report on symptom relief, overall survival or progression-free survival for HRT versus placebo. However, they did report the percentage of women alive with no evidence of disease (94.3% in the HRT group and 95.6% in the placebo group) and the percentage of women alive irrespective of disease progression (95.8% in the HRT group and 96.9% in the placebo group) at the end of the 36 months' follow-up. The study did not report time to recurrence and it was underpowered due to closing early. The authors closed it as a result of the publication of the Women's Health Initiative (WHI) study, which, at that time, suggested that risks of exogenous hormone therapy outweighed benefits and had an impact on study recruitment. No assessment of efficacy was reported. AUTHORS' CONCLUSIONS: Currently, there is insufficient high-quality evidence to inform women considering HRT after treatment for endometrial cancer. The available evidence (both the single RCT and non-randomised evidence) does not suggest significant harm, if HRT is used after surgical treatment for early-stage endometrial cancer. There is no information available regarding use of HRT in higher-stage endometrial cancer (FIGO stage II and above). The use of HRT after endometrial cancer treatment should be individualised, taking account of the woman's symptoms and preferences, and the uncertainty of evidence for and against HRT use.

A comparison of ICG-NIR with blue dye and technetium for the detection of sentinel lymph nodes in vulvar cancer.

INTRODUCTION: The sentinel lymph node (SLN) procedure for vulva cancer is a safe alternative to a radical inguino-femoral lymphadenectomy (IFLN) for small unifocal tumours. SLN evaluation through biopsy and ultra-staging has helped gynaecological oncology surgeons improve operative morbidity with no cost to oncologic safety. Established techniques for groin SLN detection and excision in vulvar cancer use 99mTc-nanocolloid radiotracer and blue dye (BD) for identification of the SLN. Indocyanine green (ICG)-near infrared (ICG-NIR) techniques for SLN mapping have proven utility in other gynaecological cancer sites and is gaining interest as a technique for SLN mapping in vulvar cancer METHODS: Fifty consecutive patients with unifocal vulvar squamous cell cancers of <40 mm lateral diameter and with depth of invasion > 1 mm underwent SLN mapping and excision using a combination of 99mTc-nanocolloid, BD and ICG. SLN detection results were recorded on a per-patient and per-groin basis. The success rates SLN for detection by individual tracer substance or combinations of tracer were determined by presence of one or more tracer, detectable in the SLN specimen. RESULTS: 92% of patients had a successful SLN procedure. The per-groin detection rate was 84%. All successfully mapped SLN were identified with the combination of ICG-NIR and 99mTc-nanocolloid compared to 69% with BD 99mTc-nanocolloid. Success rates for the SLN procedure were not dependent on prior excision of the primary lesion or operator experience. CONCLUSIONS: Incorporation of ICG-NIR into standard SLN mapping protocols may allow for the abandonment of routine use of BD and its poor side effect profile.

Is Cardiopulmonary Exercise Testing Predictive of Surgical Complications in Patients Undergoing Surgery for Ovarian Cancer?

Preoperative cardiopulmonary exercise testing (CPET) provides an objective assessment of functional capability. In other intra-abdominal surgical specialties, CPET outcomes are predictive of operative morbidity. However, in ovarian cancer surgery, its predictive value remains unknown. In this study, we evaluated the association between CPET performance and surgical morbidity in ovarian cancer patients. Secondly, we assessed the association between CPET performance and other surgical outcomes (i.e., hospital stay, readmission and residual disease). This was a retrospective cohort study of patients undergoing primary surgery for ovarian cancer between 2020 and 2023. CPET performance included peak oxygen uptake (VO2 max), ventilatory efficiency (VE/VO2) and anaerobic threshold. Outcomes were operative morbidity and included intra- and postoperative complications (Clavien-Dindo), hospital stay, readmission within 30 days and residual disease. A total of 142 patients were included. A lower VO2 peak and a higher VE/VCO2 were both associated with the occurrence of postoperative complications, and a poorer anaerobic threshold was associated with more transfusions. VE/VCO2 remained significantly associated after multivariate analysis (p = 0.035). None of the CPET outcomes were associated with length of stay, readmission or residual disease. In conclusion, VE/VCO2 was significantly associated with an increased risk of all-cause postoperative complications in ovarian cancer patients undergoing primary surgery.

Cytoreductive surgery in recurrent endometrial cancer: A new paradigm for surgical management?

The objective was to review the literature on the effect of surgical cytoreduction in recurrent endometrial cancer on survival, and identify baseline and clinical factors associated with improved survival. In addition, we sought to assess the effect of previous radiotherapy on surgical achievement. This review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. We performed a search of PubMed and Cochrane Library to identify studies comparing cytoreductive surgery to medical management and studies reporting on patients receiving cytoreductive surgery as part of multi-modal treatment. Primary outcomes included overall survival and progression free survival, secondary outcomes included factors associated with improved survival. A total of 11 studies fulfilled the inclusion criteria, comprising 1146 patients. All studies were retrospective studies. Cytoreduction as part of treatment for recurrent endometrial cancer was associated with prolonged overall survival and progression free survival. Complete cytoreduction was an independent factor associated with improved survival. Other factors associated with prolonged survival were tumor grade 1, endometrioid histology, ECOG performance status 0, and isolated pelvic recurrences. Factors associated with obtaining complete cytoreduction included solitary disease, tumor size <6 cm and ECOG performance status 0. Previous radiotherapy was not associated with achieving complete cytoreduction. Cytoreductive surgery may benefit patients meeting specific selection criteria based on a limited number of retrospective studies, with complete cytoreduction showing the largest survival gain. However, further prospective studies are needed to validate the survival benefit and aid in patient selection.

Prehabilitation to Improve Outcomes of Patients with Gynaecological Cancer: A New Window of Opportunity?

The literature evaluating the effect of prehabilitation programmes on postoperative outcomes and quality of life of patients with gynaecological cancer undergoing surgery was reviewed. Databases including Pubmed, Medline, EMBASE (Ovid) and PsycINFO were systematically searched to identify studies evaluating the effect of prehabilitation programmes on patients with gynaecological cancer. Both unimodal and multimodal prehabilitation programmes were included encompassing physical exercise and nutritional and psychological support. Primary outcomes were surgical complications and quality of life. Secondary outcomes were anthropometric changes and adherence to the prehabilitation programme. Seven studies fulfilled the inclusion criteria, comprising 580 patients. Included studies were nonrandomised prospective studies (n = 4), retrospective studies (n = 2) and one case report. Unimodal programmes and multimodal programmes were included. In patients with ovarian cancer, multimodal prehabilitation resulted in significantly reduced hospital stay and time to chemotherapy. In patients with endometrial and cervical cancer, prehabilitation was associated with significant weight loss, but had no significant effects on surgical complications or mortality. No adverse events of the programmes were reported. Evidence on the effect of prehabilitation for patients with gynaecological cancer is limited. Future studies are needed to determine the effects on postoperative complications and quality of life.

Determining the Potential of DNA Damage Response (DDR) Inhibitors in Cervical Cancer Therapy.

Cisplatin-based chemo-radiotherapy (CRT) is the standard treatment for advanced cervical cancer (CC) but the response rate is poor (46-72%) and cisplatin is nephrotoxic. Therefore, better treatment of CC is urgently needed. We have directly compared, for the first time, the cytotoxicity of four DDR inhibitors (rucaparib/PARPi, VE-821/ATRi, PF-477736/CHK1i and MK-1775/WEE1i) as single agents, and in combination with cisplatin and radiotherapy (RT) in a panel of CC cells. All inhibitors alone caused concentration-dependent cytotoxicity. Low ATM and DNA-PKcs levels were associated with greater VE-821 cytotoxicity. Cisplatin induced ATR, CHK1 and WEE1 activity in all of the cell lines. Cisplatin only activated PARP in S-phase cells, but RT activated PARP in the entire population. Rucaparib was the most potent radiosensitiser and VE-821 was the most potent chemosensitiser. VE-821, PF-47736 and MK-1775 attenuated cisplatin-induced S-phase arrest but tended to increase G2 phase accumulation. In mice, cisplatin-induced acute kidney injury was associated with oxidative stress and PARP activation and was prevented by rucaparib. Therefore, while all inhibitors investigated may increase the efficacy of CRT, the greatest clinical potential of rucaparib may be in limiting kidney damage, which is dose-limiting.

Investigating the possible impact of peritoneal tumor exposure amongst women with early stage cervical cancer treated with minimally invasive approach.

INTRODUCTION: Recent findings show a detrimental impact of the minimally invasive approach on patients with early stage cervical cancer (ECC). Reasons beyond these results are unclear. The aim of the present article is to investigate the possible role of peritoneal contamination during intracorporeal colpotomy. METHODS: patients with early stage cervical cancer were divided into 2 groups: no intraperitoneal exposure (N-IPE) intraperitoneal exposure (IPE) during minimally invasive surgery. Patients of the 2 groups were propensity-matched according to the major risk factors. RESULTS: 226 cases of the IPE group had a significant worst prognosis than the 142 cases of the N-IPE group (4.5-years disease free survival: 86.6% vs 95.9% respectively, p = 0.005), while N-IPE had similar survival to open surgery (4.5-years disease free survival: 95.0% vs 90.5% respectively, p = 0.164). Distant recurrence was more frequent among IPE patients with a borderline significance (3.5% vs 0.4% among IPE and N-IPE respectively, p = 0.083). On multivariate analysis, intraperitoneal tumor exposure was an independent prognostic factors for worse survival; patients belonging to the N-IPE group had a risk of recurrence of about 3-fold lower compared to patients of the IPE group (hazard ratio: 0.37, 95% confidence interval: 0.15-0.88, p = 0.025). CONCLUSION: it would be advisable that further prospective studies investigating the efficacy of different surgical approach in ECC take into consideration of this issue. Moreover, all other measures that could potentially prevent peritoneal exposure of tumor should be adopted during minimally invasive surgery for early stage cervical cancer to provide higher survival outcomes.

Targeting the ATR-CHK1 Axis in Cancer Therapy.

Targeting the DNA damage response (DDR) is a new therapeutic approach in cancer that shows great promise for tumour selectivity. Key components of the DDR are the ataxia telangiectasia mutated and Rad3 related (ATR) and checkpoint kinase 1 (CHK1) kinases. This review article describes the role of ATR and its major downstream target, CHK1, in the DDR and why cancer cells are particularly reliant on the ATR-CHK1 pathway, providing the rationale for targeting these kinases, and validation of this hypothesis by genetic manipulation. The recent development of specific inhibitors and preclinical data using these inhibitors not only as chemosensitisers and radiosensitisers but also as single agents to exploit specific pathologies of tumour cells is described. These potent and specific inhibitors have now entered clinical trial and early results are presented.

Bevacizumab for the treatment of cervical cancer.

INTRODUCTION: Cervical cancer is still a major cause of morbidity and mortality in women. Early stages and locally advanced cervical cancer are currently treated respectively with surgery and chemoradiation with good prognosis. Persistent, recurrent and metastatic cervical cancers have a poor prognosis. Angiogenesis has been identified as a crucial factor for cervical cancer growth. Recently, research has increasingly focused on the development of targeted therapies, such as anti-angiogenic drugs. Amongst such drugs, bevacizumab, a recombinant humanized monoclonal antibody has been the subject of extensive investigation, including its use in cervical cancer. This was recently approved for the treatment of patients with metastatic, recurrent, or persistent cervical cancer. AREAS COVERED: The aim of this review is to discuss the role of bevacizumab in both locally advanced and metastatic or recurrent cervical cancer and to analyze the studies that have led to the approval of bevacizumab in cervical cancer. EXPERT OPINION: The use of bevacizumab in combination with other chemotherapies in cervical cancer has been proven safe and effective, with a significant improvement in overall survival of patients with advanced cervical cancer. Combination therapy using bevacizumab has been demonstrated to increase toxicity rates but it does not impair patient's quality of life.