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Guidelines recommend adjuvant treatment when positive lymph nodes are found after surgical treatment for squamous cell cancer of the vulva except for cases with a single occult intranodal metastasis. Recent studies questioned these recommendations and showed benefit of adjuvant radiotherapy for all patients with positive nodes irrespective of number of nodes. However, these studies did not take into account important nodal characteristics, such as clinical node status, extranodal spread or size of the metastasis. When these variables are taken into account, adjuvant radiotherapy does not seem to result in a better survival for patients with a single occult intranodal metastasis. Whether the addition of chemotherapy to the radiotherapy for patients with more than one positive node or extracapsular spread results in a better survival remains uncertain. Only a few studies have been published on this subject and come to the conclusion that adding chemotherapy results in a better survival. The conclusion is that adjuvant radiotherapy improves survival of patients with positive groin nodes, with the exception of patients with a single intranodal metastasis. The beneficial effect of chemo radiotherapy for subgroups of patients with positive nodes seems likely, although more data are needed before a definite conclusion can be made

Introduction: To establish the impact of the number of lymph node metastases (nLNM) and the lymph node ratio (LNR) on survival in patients with early-stage cervical cancer after surgery. Material and methods: In this nationwide historical cohort study, all women diagnosed between 1995 and 2020 with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA2–IIA1 cervical cancer and nodal metastases after radical hysterectomy and pelvic lymphadenectomy from the Netherlands Cancer Registry were selected. Optimal cut-offs for prognostic stratification by nLNM and LNR were calculated to categorize patients into low-risk or high-risk groups. Kaplan–Meier overall survival analysis and flexible parametric relative survival analysis were used to determine the impact of nLNM and LNR on survival. Missing data were imputed. Results: The optimal cut-off point was ≥4 for nLNM and ≥0.177 for LNR. Of the 593 women included, 500 and 501 (both 84%) were categorized into the low-risk and 93 and 92 (both 16%) into the high-risk groups for nLNM and LNR, respectively. Both high-risk groups had a worse 5-year overall survival (p

PURPOSE The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL ( P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.

Objective: Since 2018 imaging and histopathology are incorporated in the International Federation of Gynecology and Obstetrics (FIGO) staging system of cervical cancer. The aim of this study was to assess the positive predictive value (PPV) and negative predictive value (NPV) of 2-[18F] fluoro-2-deoxy-D-glucose [18F] FDG-PET/CT ([18F] FDG-PET/CT) for lymph node involvement in patients with cervical cancer and to review the literature. Methods: First, PPV and NPV were calculated in a retrospective study including 98 patients with stage ≥IB1 cervical cancer that underwent a [18F] FDG-PET/CT before surgery. Second, the literature was reviewed on PPV and NPV of PET/CT in cervical cancer. Twenty-one studies were included and analyzed using the Spearman's rank correlation coefficient. Results: In the retrospective study 63 patients (64%) were treated with a radical hysterectomy and complete pelvic lymph node dissection, and 35 patients (36%) underwent a lymph node debulking followed by chemoradiation. The PPV was 79% (inconclusive PET/CT interpreted as suspicious) or 89% (inconclusive PET/CT interpreted as non-suspicious) and the NPV was 81% or 80% respectively. The PPV in the subgroup of 63 patients treated with pelvic node dissection was 56% or 70% respectively. The NPV was 81% for both strategies. Literature results showed a positive correlation (R = 0.354) between the percentage of patients with positive nodes and the PPV of PET/CT. Conclusion: [18F] FDG-PET/CT overestimates the incidence of lymph node metastases, especially in early stage cervical cancer. This may cause a shift of the treatment regime from surgery to radiotherapy. Therefore, histopathological confirmation of [18F] FDG-PET/CT-positive nodes is essential to guide therapy decisions.

Objective. To evaluate feasibility of chemoradiation as alternative for extensive surgery in patients with locally advanced vulvar cancer and to report on locoregional control, toxicity and survival. Methods. In a multicenter, prospective phase II trial patients with locally advanced vulvar cancer were treated with locoregional radiotherapy combined with sensitizing chemotherapy (capecitabine). Treatment feasibility, percentage locoregional control, survival and toxicity were evaluated. Results. 52 patients with mainly T2/T3 disease were treated according to the study protocol in 10 centers in the Netherlands from 2007 to 2019. Full dose radiotherapy (tumor dose of 64.8Gy) was delivered in 92% and full dose capecitabine in 69% of patients. Most prevalent acute >_ grade 3 toxicities were regarding skin/ mucosa and pain (54% and 37%). Late >_grade 3 toxicity was reported for skin/mucosa (10%), fibrosis (4%), GI incontinence (4%) and stress fracture or osteoradionecrosis (4%). Twelve weeks after treatment, local clinical complete response (cCR) and regional control (RC) rates were 62% and 75%, respectively. After 2 years, local cCR persisted in 22 patients (42%) and RC was 58%. Thirty patients (58%) had no evidence of disease at end of follow-up (median 35 months). In 9 patients (17%) extensive surgery with stoma formation was needed. Progression free survival was 58%, 51% and 45% and overall survival was 76%, 66%, 52% at 1,2, and 5 years. Conclusions. Definitive capecitabine-based chemoradiation as alternative for extensive surgery is feasible in locally advanced vulvar cancer and results in considerable locoregional control with acceptable survival rates with manageable acute and late toxicity. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

The current review provides a literature overview of studies assessing the oncological and fertility outcomes of treatment with neo-adjuvant chemotherapy followed by fertility-sparing surgery in patients with cervical cancer >2 cm. Six cohort studies were included showing severe heterogeneity regarding patient selection, chemotherapy regimen, and surgical approach. In total, 111 patients were studied, with overall favorable characteristics. Patients were on average 29 years old, had a tumor of 36 mm, no lymph node metastasis, and response to chemotherapy. In approximately 5-year follow-up, the recurrence rate was 13% (0%-21%) and overall death rate 2.7% (0%-10%). Three patients were alive with recurrent disease (2.7% and 0%-11%). Of the 111 patients, 90 underwent successful fertility-sparing treatment (83%). Roughly one-third conceived and one-fourth had a healthy live-born child. More research is essential to determine proper selection criteria for fertility-sparing treatment of cervical cancer >2 cm and the optimal treatment management.

Correct identification of patients with lymph node metastasis from cervical cancer prior to treatment is of great importance, because it allows more tailored therapy. Patients may be spared unnecessary surgery or extended field radiotherapy if the nodal status can be predicted correctly. This review captures the existing knowledge on the identification of lymph node metastases in cervical cancer. The risk of nodal metastases increases per 2009 FIGO stage, with incidences in the pelvic region ranging from 2% (stage IA2) to 14-36% (IB), 38-51% (IIA) and 47% (IIB); and in the para-aortic region ranging from 2 to 5% (stage IB), 10-20% (IIA), 9% (IIB), 13-30% (III) and 50% (IV). In addition, age, tumor size, lymph vascular space invasion, parametrial invasion, depth of stromal invasion, histological type, and histological grade are reported to be independent prognostic factors for the risk of nodal metastases. Furthermore, biomarkers can contribute to predict a patient's nodal status, of which the squamous cell carcinoma antigen (SCC-Ag) is currently the most widely used in squamous cell cervical cancer. Still, pre-treatment lymph node assessment is primarily performed by imaging, of which diffusion-weighted magnetic resonance imaging has the highest sensitivity and 2-deoxy-2-[18F]fluoro-D-glucose positron emission computed tomography the highest specificity. Imaging results can be combined with clinical parameters in nomograms to increase the accuracy of predicting positives nodes. Despite all the progress regarding pre-treatment prediction of lymph node metastases in cervical cancer in recent years, prediction rates are not robust enough to safely abandon surgical staging of the pelvic or para-aortic region yet.

ObjectiveTreatment strategies for bulky lymph nodes in patients with locally advanced cervical cancer scheduled for definitive chemoradiation include nodal boosting with radiotherapy, surgical debulking, or both. The aim of this retrospective cohort study was to compare survival and toxicity in patients receiving these treatments and to compare them with a group that received neither form of treatment.MethodsWomen diagnosed between January 2009 and January 2017 with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2, IIA2–IVA cervical cancer with lymph nodes ≥1.5 cm without upper limit on pretreatment imaging and treated with definitive chemoradiation were selected from the Netherlands Cancer Registry. Patients were categorized by intention-to-treat strategy: boosting, debulking, or neither treatment, with subgroup analysis for patients receiving both treatments, that is, debulking with boosting. Overall and relapse-free survival outcomes were compared by Kaplan-Meier and Cox regression analyses and toxicity by logistic regression analysis.ResultsOf 190 patients, 101 (53%) received only nodal boosting, 31 (16%) debulking alone, 29 (15%) debulking combined with boosting, and 29 (15%) received neither treatment. The 5 year overall and relapse-free survival for the treatment groups were 58%, 45% and 45% (p=0.19), and 47%, 44% and 46% (p=0.87), respectively. Multivariable Cox regression analyses demonstrated no differences in overall and relapse-free survival. Combination of debulking with boosting was associated with decreased overall and relapse-free survival compared with debulking alone (HR 2.47, 95% CI 1.22 to 5.00; and HR 2.37, 95% CI 1.14 to 4.93). Nodal boosting was independently associated with a decreased toxicity risk compared with debulking strategy (OR 0.37, 95% CI 0.16 to 0.83).ConclusionsThis study showed no survival benefit from either nodal boosting or debulking strategy in patients with suspicious bulky nodes. Nodal boosting might, however, be associated with less toxicity. Dual treatment with debulking and boosting showed a worse survival outcome because this group probably represents patients with poor prognostic factors.

Upon discovery of lymph node metastasis during radical hysterectomy with pelvic lymphadenectomy in early-stage cervical cancer, the gynaecologist may pursue one of two treatment strategies: abandonment of surgery followed by primary (chemo)radiotherapy (PRT) or completion of radical hysterectomy, followed by adjuvant (chemo)radiotherapy (RHRT). Current guidelines recommend PRT over RHRT, as combined treatment is presumably associated with increased morbidity. However, this review of literature suggests there are no significant differences in survival and recurrence and total proportions of adverse events between treatment strategies. Additionally, both strategies are associated with varying types of adverse events, and affect quality of life and sexual functioning differently, both in the short and long term. Although total proportions of adverse events were comparable between treatment strategies, lower extremity lymphoedema was reported more often after RHRT and symptom experience (e.g. distress from bladder or bowel problems) and sexual dysfunction more often after PRT. As reporting of adverse events, quality of life and sexual functioning were not standardised across the articles included, and covariate adjustment was not conducted in most of the analyses, comparability of studies is hampered. Accumulating retrospective evidence suggests no major differences on oncological outcome and morbidity after PRT and RHRT for intraoperatively discovered lymph node metastasis in cervical cancer. However, conclusions should be considered cautiously, as all studies were of retrospective design with small sample sizes. Still, treatment strategies seem to affect adverse events, quality of life and sexual functioning in different ways, allowing room for shared decision-making and personalised treatment.

Objectives: In pregnant patients with early stage cervical cancer, the preferred mode of delivery is a caesarean section (CS), which can be combined with a radical hysterectomy and pelvic lymphadenectomy (RHLD). The aim of this study was to compare this group of patients with non-pregnant cervical cancer patients treated by RHLD alone with regard to perioperative morbidity, oncological outcomes, and perinatal outcomes. Methods: We retrospectively reviewed all consecutive patients diagnosed with early stage cervical cancer during pregnancy who were treated by CS and RHLD at our institution. Nonpregnant counterparts served as controls and were matched on a 1 : 2 ratio. Key outcomes were perioperative complications, cancer outcome and perinatal outcome. Results: Nineteen pregnant women treated with a CS and RHLD were matched with 38 non-pregnant control patients with cervical cancer who underwent a RHLD. The only difference in morbidity was a higher estimated perioperative blood loss in the pregnant group (1600 mL) compared to the control group (800 mL; P = 0.001), resulting in seven (36.8%) and eight (21.1%) blood transfusions (P = 0.22; OR 2.19; 95% CI 0.65 to 7.38), respectively. Conclusion: Oncological outcomes were similar with 5- year overall survival rates of 94% in the pregnant group and 95% in the non-pregnant group. The neonatal survival rate was 100%. Complication rates and oncological outcomes after treatment with RHLD were comparable for pregnant and non-pregnant patients with early stage cervical cancer. Therefore we feel that it is safe to combine a CS with a RHLD in pregnant patients with early stage cervical cancer.

Correct identification of patients with lymph node metastasis from cervical cancer prior to treatment is of great importance, because it allows more tailored therapy. Patients may be spared unnecessary surgery or extended field radiotherapy if the nodal status can be predicted correctly. This review captures the existing knowledge on the identification of lymph node metastases in cervical cancer. The risk of nodal metastases increases per 2009 FIGO stage, with incidences in the pelvic region ranging from 2% (stage IA2) to 14-36% (IB), 38-51% (IIA) and 47% (IIB); and in the para-aortic region ranging from 2 to 5% (stage IB), 10-20% (IIA), 9% (IIB), 13-30% (III) and 50% (IV). In addition, age, tumor size, lymph vascular space invasion, parametrial invasion, depth of stromal invasion, histological type, and histological grade are reported to be independent prognostic factors for the risk of nodal metastases. Furthermore, biomarkers can contribute to predict a patient's nodal status, of which the squamous cell carcinoma antigen (SCC-Ag) is currently the most widely used in squamous cell cervical cancer. Still, pre-treatment lymph node assessment is primarily performed by imaging, of which diffusion-weighted magnetic resonance imaging has the highest sensitivity and 2-deoxy-2-[

Dear Editor, We would like to comment on the paper 'Prognostic factors in patients with vulvar cancer: the VULCAN study' by Zapardiel et al.[1][1] We have many concerns. For example, reference 3 refers to patients with vulvar intra-epithelial neoplasia, not invasive vulvar cancer. The latter is not

Background: Combined administration of intravenous (iv) and intraperitoneal (ip) (iv/ip) chemotherapy is an effective adjuvant treatment option after primary debulking surgery (PDS) for advanced ovarian cancer (OC). Increased toxicity and patient burden limit its use in daily practice. Objective: To assess toxicity and survival outcomes of iv/ip chemotherapy in daily practice in the Netherlands. Methods: This retrospective cohort study included 81 women who underwent at least an optimal PDS for FIGO stage III OC followed by iv/ip chemotherapy according to the Armstrong regimen, in four hospitals in the Netherlands between January 2007 and May 2016. We collected information on surgical procedure, abdominal port implantation, toxicity, and recurrence-free and overall survival. Results: All participants underwent PDS, of whom 60 (74%) had their ip catheter implanted during PDS. Most frequently reported all grade toxicity was haematological n = 44 (54%). Forty-four patients (54%) completed all six cycles of iv/ip chemotherapy. The most frequent causes of discontinuation of iv/ip administration were renal dysfunction (12/37 = 32%) and catheter problems (7/37 = 19%). Median recurrence-free survival and overall survival were 24 months (range 0 – 108) and 80 months (range 4-115), respectively. Surgical outcome, completion of more than three courses of treatment and intra-abdominal localisation of recurrent disease were associated with better survival outcomes. Conclusion: In daily practice, 54% of patients with advanced OC could complete all scheduled cycles of iv/ ip chemotherapy with acceptable morbidity and toxicity, leading to outcomes comparable with the results of published trials on iv/ip chemotherapy.

ObjectiveThis study aimed to describe the pattern of recurrence and survival related to prognostic variables, including type of surgery as a clinical variable, in patients surgically treated for early cervix cancer.MethodsRecords of 2124 patients who underwent a radical hysterectomy for International Federation of Gynaecology and Obstetrics stage I/IIA cervical cancer between 1982 and 2011 were reviewed. Clinical-pathologic prognostic variables, also including extent of parametrectomy, were identified and used in a multivariable Cox proportional hazard model to explore associations between disease-free survival (DFS) and prognostic variables.ResultsThe 5-year DFS for the total group was 86%. Large tumor diameter, nonsquamous histology, lymph node metastases, parametrial involvement, lymph vascular space invasion, deep stromal invasion, and less radical surgery were independent poor prognostic variables for survival. Disease-free survival was independently associated with the type of radical hysterectomy with pelvic lymphadenectomy in favor of more radical parametrectomy (hazard ratio, 2.0; 95% confidence interval, 1.6–2.5). This difference was not found in tumors with a diameter of at least 20 mm.ConclusionsThis study confirms that variables such as large tumor diameter, nonsquamous histology, lymph vascular space invasion, deep stromal invasion, positive lymph nodes, and parametrial infiltration are poor prognostic variables in early cervix cancer treated by surgery. The extent of parametrectomy had no influence on survival in tumors of 20 mm or less. For larger tumors, a more radical hysterectomy might be associated with better DFS. Taking into account the possible bias in this study as a result of its retrospective design, ideally a prospective cohort study with clear definition of radicality is necessary to answer this important clinical question.

Introduction Management regarding completing hysterectomy in case of intraoperative finding of positive lymph nodes in early-stage cervical cancer differs between institutions. The aim of this study was to compare survival and toxicity after completed hysterectomy followed by adjuvant (chemo-)radiotherapy versus abandoned hysterectomy and primary treatment with chemoradiotherapy (CRT). Methods A retrospective multicenter cohort study was performed. All patients were scheduled for radical hysterectomy with pelvic lymphadenectomy (RHL). In the RHL group, hysterectomy was completed followed by adjuvant (chemo-)radiotherapy. In the second group, hysterectomy was abandoned, and CRT was conducted. Primary outcomes were disease-free survival (DFS) and overall survival. A multivariable analysis on DFS was performed. Toxicity was scored according to the National Cancer Institute CTCAE (Common Terminology Criteria for Adverse Events) v4.03. Results A total of 121 patients were included (RHL, n = 89; CRT, n = 32). There was no difference in overall survival (84% vs 77%). Five-year DFS was in favor of completing RHL (81% vs 67%). Multivariable analysis showed that, corrected for lymph node variables, treatment regimen was not associated with DFS. After RHL, pelvic recurrence rate was significantly lower compared with CRT (2% vs 16%). CTCAE grade 3–4 toxicity rates were higher in the CRT compared with the RHL group (59% vs 30%), mainly because of differences in chemotherapy-related hematologic toxicity. Conclusions In patients with clinically N0 early-stage cervical cancer with intraoperative detection of positive nodes, completing RHL followed by adjuvant (chemo-)radiotherapy may result in a better pelvic control compared with abandoning hysterectomy and treatment with chemoradiotherapy. However, if corrected for lymph node variables, treatment (RHL or CRT) was not associated with DFS.

IntroductionHyperthermic intraperitoneal chemotherapy (HIPEC) improved investigator-assessed recurrence-free survival and overall survival in patients with stage III ovarian cancer in the phase III OVHIPEC-1 trial. We analyzed whether an open-label design affected the results of the trial by central blinded assessment of recurrence-free survival, and tested whether HIPEC specifically targets the peritoneal surface by analyzing the site of disease recurrence.MethodsOVHIPEC-1 was an open-label, multicenter, phase III trial that randomized 245 patients after three cycles of neoadjuvant chemotherapy to interval cytoreduction with or without HIPEC using cisplatin (100 mg/m2). Patients received three additional cycles of chemotherapy after surgery. Computed tomography (CT) scans and serum cancer antigen 125 (CA125) measurements were performed during chemotherapy, and during follow-up. Two expert radiologists reviewed all available CT scans. They were blinded for treatment allocation and clinical outcome. Central revision included Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 measurements and peritoneal cancer index scorings at baseline, during treatment, and during follow-up. Time to centrally-revised recurrence was compared between study arms using Cox proportional hazard models. Subdistribution models compared time to peritoneal recurrence between arms, accounting for competing risks.ResultsCT scans for central revision were available for 231 patients (94%) during neoadjuvant treatment and 212 patients (87%) during follow-up. Centrally-assessed median recurrence-free survival was 9.9 months in the surgery group and 13.2 months in the surgery+HIPEC group (HR for disease recurrence or death 0.72, 95% CI 0.55 to 0.94; p=0.015). The improved recurrence-free survival and overall survival associated with HIPEC were irrespective of response to neoadjuvant chemotherapy and baseline peritoneal cancer index. Cumulative incidence of peritoneal recurrence was lower after surgery+HIPEC, but there was no difference in extraperitoneal recurrences.ConclusionCentrally-assessed recurrence-free survival analysis confirms the benefit of adding HIPEC to interval cytoreductive surgery in patients with stage III ovarian cancer, with fewer peritoneal recurrences. These results rule out radiological bias caused by the open-label nature of the study.

Despite advancements in treatment modalities, the 10-year survival rate of women diagnosed with advanced-stage ovarian cancer has remained between 10% and 15% for the past 20 years. This is in part due to the majority of cases being diagnosed when disease has reached International Federation of Gynecology and Obstetrics stages III to IV. Approximately 70% of patients treated with cytoreductive surgery (CRS) and platinum-based chemotherapy experience recurrence within 18 months. The OVHIPEC trial, a randomized phase III trial found improved recurrence-free survival and overall survival with the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval CRS. This study aimed to conduct a cost-effectiveness analysis (CEA) to determine the incremental cost-effectiveness ratio (ICER) of treatment with a combination of interval CRS and HIPEC compared with interval CRS alone in patients with stage III ovarian cancer. Data for the CEAwere extracted fromthe OVHIPEC trial (n = 245), which compared survival outcomes for patients with stage III ovarian cancer receiving either combination therapy (n = 122) or interval CRS alone (n = 123). Treatment costs from diagnosis to the time of disease recurrence were calculated using the treatment schedule in the OVHIPEC trial. Unit costs for disease-related procedures and events such as hospital admissions were calculated from multiple sources including national registries. All costs were initially retrieved in 2017 euros or converted to 2017 euros using the inflation rate established by the Consumer Price Index. Three different treatment protocols were analyzed: (1) standard chemotherapy, considered carboplatin and paclitaxel and/or gemcitabine and/or doxorubicin; (2) carboplatin-gemcitabine-bevacizumab and maintenance bevacizumab for platinum-sensitive disease; (3) maintenance poly (ADP-ribose) polymerase inhibitors for high-grade serous recurrent disease. The Makov model built to perform the analysis consisted of 3 mutually exclusive health states with corresponding utilities: Recurrence-free survival, disease recurrence, and death. The duration of each cycle in the model was 3 months, and a 10-year time duration was selected. The difference between the 2 groups in terms of qualityadjusted life-years (QALY) and incremental mean costs was calculated using 1000 replicas, made by extrapolating data from OVHIPEC survival outcomes, representing women at 60 years of age. The primary outcome for this trial was the ICER, calculated by dividing the mean incremental costs by the mean incremental QALY. Mean health care costs of interval CRS and HIPEC were €85,791 (95% credibility interval [CrI], €78,776-93,935) compared with €70,046 (95% CrI, €64,016-€76,661) for the interval CRS group. Treatment with interval CRS and HIPEC resulted in mean life-years of 5.07 (95% CrI, 4.80-5.34) compared with 4.07 (95% CrI, 3.83-4.33) for the interval CRS group. Adjusting for health-related quality-of-life data from the OVHIPEC trial, the mean QALY for the interval CRS and HIPEC group was 2.68 (95% CrI, 2.11-3.28) compared with 2.12 (95% CrI, 1.66-2.64) in the CRS group. The results showed an ICER of €28,299 per QALYover the first 5 years for patients treated with CRS and HIPEC. Probabilistic sensitivity analysis showed the likelihood of interval CRS combined with HIPEC being cost-effective was 83% using the Dutch WTP threshold of €80,000 per QALY. These results show that treatment with interval CRS and HIPEC shows a robust incremental QALY benefit compared with CRS alone. The probabilistic sensitivity analysis found that treatment with this combination therapy falls within the accepted values for cost-effective treatment costs in the Netherlands.

BackgroundThe efficacy of adjuvant radiotherapy in patients with intermediate risk early cervical cancer after radical hysterectomy is still under debate. Most guidelines recommend adjuvant radiotherapy, whereas others consider observation a viable option.ObjectiveTo investigate if patients with intermediate risk factors for cervical cancer who underwent radical hysterectomy may benefit from adjuvant radiotherapy.MethodsConsecutive patients with tumor confined to the cervix and intermediate risk factors (according to Sedlis), treated between January 1982 and December 2014 who were observed after a type C2 radical hysterectomy formed the basis for this study. The frequency of recurrences, specifically isolated loco-regional recurrences, and the risk of death from recurrences, were analyzed. Data were analyzed using SPSS, version 23.0 for WindowsResultsA total of 161 patients were included in the analysis. Median age was 40 (range 20–76). Stages IB1 and IB2 were seen in 87 (54%) and 74 patients (46%), respectively. Squamous cell and non-squamous histology was seen in 114 (70.8%) and 47 patients (29.2%), respectively. Of the 161 patients, 25 (15.5%) had recurrent disease, of whom nine had an isolated loco-regional recurrence (5.6%). Median time to recurrence for isolated loco-regional recurrences was 28 months (range 9–151). Treatment for an isolated loco-regional recurrence was radiotherapy (n = 4) and chemoradiotherapy (n = 5). Four patients (2.5%) died from disease as a result of an isolated loco-regional recurrence. Actuarial disease- specific survival was 93.0% for the total group. No variables were found that predicted an isolated loco-regional recurrence.DiscussionThe mortality from isolated loco-regional recurrence in patients with intermediate risk factors for cervical cancer who underwent only radical hysterectomy type C2 was 2.5%. Further studies should compare outcomes between patients who undergo a type C2 radical hysterectomy without adjuvant radiotherapy with those undergoing a less radical hysterectomy but with adjuvant radiotherapy.

Contains fulltext : 174767.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Inguinofemoral lymphadenectomy (IFL) is performed in the treatment for vulvar cancer. One or more complications after IFL is reported in up to 85% of the patients. This review presents an overview of surgical techniques and peri- and post-operative care that has been studied in order to reduce the morbidity associated with IFL in vulvar cancer patients. Areas covered: Current knowledge on post-operative complications after different surgical techniques and peri- and post-operative protocols were discussed. A systematic literature review was conducted using MEDLINE, EMBASE and the Cochrane library on 20 February 2017. In order to be eligible for inclusion, studies must report the associated post-operative morbidity per surgical technique, or peri- or post-operative care given after IFL in vulvar cancer patients. Expert commentary: After the implementation of several new surgical techniques, the morbidity after IFL decreased but remains high and clinically meaningful. More research is needed on surgical techniques and peri-or post-operative care to further reduce the complication rates after IFL in vulvar cancer patients.

Dear Editor, In response to Salvo G et al:[1][1] “Measurement of tumor size in early cervical cancer: an ever-evolving paradigm”, an interesting review of the available literature on incorporation of tumor size into the 2018 FIGO classification. In the original FIGO publication,[2][2] errors

Contains fulltext : 216154.pdf (Publisher’s version ) (Open Access) Today, the patient who is diagnosed with early cervical cancer is offered a variety of treatments apart from standard therapy. Patients can be treated with a less radical hysterectomy (RH) regarding parametrectomy, a trachelectomy either vaginal or abdominal, and this can be performed through a minimal invasive or open procedure. All this in combination with nerve sparing and/or sentinel node technique. Level 1 evidence for the oncological safety of all these modifications is only available from 3 randomized controlled trials (RCTs). Two RCTs on more or less radical parametrectomy both showed that oncological safety was not compromised by doing less radical surgery. Because of the heterogeneity of the patient population and the high frequency of adjuvant radiotherapy, the true impact of surgical radicality cannot be assessed. Regarding the issue of oncological safety of fertility sparing treatments, case-control and retrospective case series suggest that trachelectomy is safe as long as the tumor diameter does not exceed 2 cm. Recently, both a RCT and 2 case-control studies showed a survival benefit for open surgery compared to minimally invasive surgery, whereas many previous case-control and retrospective case series on this subject did not show impaired oncological safety. In a case-control study the survival benefit for open surgery was restricted to the group of patients with a tumor diameter more than 2 cm. Although modifications of the traditional open RH seem safe for tumors with a diameter less than 2 cm, ongoing prospective RCTs and observational studies should give the final answer.

Background: The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery (CRS) improves recurrence-free and overall survival in patients with FIGO stage III ovarian cancer. We evaluated the effect of HIPEC on patient's health-related quality of life (HRQoL) in the OVHIPEC trial. Methods: OVHIPEC was a multicentre, open-label, randomized phase III trial for patients with stage III epithelial ovarian cancer. Patients were randomly assigned (1:1) to receive interval CRS with or without HIPEC with cisplatin. HRQoL was assessed using the EORTC QLQ-C30, and the ovarian cancer (QLQ-OV28) and colorectal cancer (QLQ-CR38) modules. HRQoL was assessed at baseline, after surgery, following the last cycle of chemotherapy, and every three months thereafter until a maximum of two years after randomization. HRQoL was a secondary endpoint of the OVHIPEC trial, with the prespecified focus on the QLQ-C30 summary score and symptom scales for fatigue, neuropathy and gastro-intestinal symptoms. HRQoL data were analysed using linear and non-linear mixed effect models, with time from randomization in weeks as temporal variable. Findings: From April 2007 through April 2016, 245 patients were randomized. One-hundred-ninety-seven patients (80%) completed at least one questionnaire. No significant difference in QLQ-C30 summary scores was observed between the study arms over time (p-values for linear and non-linear growth: p>0·133). The pattern over time for the symptom scales for fatigue, neuropathy and gastro-intestinal symptoms did not significantly differ between treatment arms. Interpretation: The addition of HIPEC to interval CRS does not negatively impact HRQoL in patients with stage III ovarian cancer who are treated with interval CRS. These HRQoL results, together with the improvement in recurrence-free and overall survival, support the viability of HIPEC as an important treatment option in this patient population. Clinical Trial Number: ClinicalTrials.gov number, NCT00426257; EudraCT number2006-003466-34 Funding Statement: This HRQoL study was performed without funding. The OVHIPEC trial was funded by the Dutch Cancer Society, NKI 2006-4176 Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The local ethical committees of all participating centres approved the study protocol. All participating patients provided written informed consent and agreed to complete questionnaires as part of their consent.

The majority of patients with ovarian cancer (OC) receive an initial diagnosis of advanced disease that has spread from the ovaries to the peritoneal surface. The most effective treatment for patients with advanced disease is cytoreductive surgery followed by systemic chemotherapy. As an alternative, interval cytoreductive surgery is performed after 3 cycles of chemotherapy. Following these treatments, the primary site of disease recurrence is the peritoneal surface. Delivery of chemotherapy by the intraperitoneal (IP) route enhances drug delivery at the peritoneal surface and eliminates residual microscopic peritoneal disease more efficiently than intravenous administration. Previous trials have shown that after primary cytoreductive surgery combined use of intravenous and IP chemotherapy results in longer overall survival among patients with stage III OC compared with intravenous administration alone. Combined intravenous/IP chemotherapy has several drawbacks that have hampered its adoption in many countries. These include catheter-related problems, increased demands on the patient, and gastrointestinal and renal adverse effects. Most of these drawbacks can be circumvented by delivery of the IP chemotherapy at the end of surgery. Delivery of IP chemotherapy during surgery under hyperthermic conditions—termed hyperthermic IP chemotherapy (HIPEC)—increases the penetration of chemotherapy at the peritoneal surface. Although addition of HIPEC to interval cytoreductive surgery is feasible in women with OC, efficacy data from randomized trials are lacking. This multicenter, randomized, open-label, phase 3 trial was designed to assess the efficacy and safety of interval cytoreductive surgery with HIPEC as compared with interval cytoreductive surgery without HIPEC in patients with stage III epithelial OC. Subjects were patients receiving neoadjuvant chemotherapy who had at least stable disease after 3 cycles of carboplatin (area under the curve of 5–6 mg/mL per minute) and paclitaxel (175 mg/m2 of body surface area). Of these patients, 245 were randomized: 122 to the surgery-plus-HIPEC group and 123 to the surgery-without-HIPEC group. Randomization was performed at the time of surgery in cases in which surgery that would result in complete cytoreduction (no visible disease) or optimal cytoreduction (≥1 residual tumors measuring ≤10 mm in diameter) was deemed to be feasible. Patients received an additional 3 cycles of carboplatin and paclitaxel postoperatively. Recurrence-free survival was the primary study end point. Key secondary end points were overall survival and the side effect profile. Data for recurrence-free and overall survival were analyzed according to intention to treat. Among patients who underwent cytoreductive surgery, disease recurrence or death occurred in 89% (110/123) of patients in the surgery-without-HIPEC group and 81% (99/122) of patients in the surgery-plus-HIPEC group; the hazard ratio for disease recurrence or death was 0.66, with a 95% confidence interval of 0.50 to 0.87, P = 0.003. The median recurrence-free survival was 3.5 months longer in the surgery-plus-HIPEC group than in the surgery-without-HIPEC group (14.2 vs 10.7 months). At a median follow-up of 4.7 years, 62% (76/123) of patients in the surgery-without-HIPEC group and 50% (61/122) in the surgery-plus-HIPEC group had died (hazard ratio, 0.67; 95% confidence interval, 0.48–0.94; P = 0.02). There were no significant differences in the incidence of adverse events of any grade between the 2 groups (25% in the surgery-withoutHIPEC group and 27% in the surgery-plus-HIPEC group, P = 0.76). These data indicate that among patients with stage III epithelial OC addition of HIPEC to interval cytoreductive surgery provides longer recurrence-free survival and overall survival compared with surgery alone and no higher rates of adverse effects.

Introduction The aim of this study was to retrospectively determine the objective response rate to hormone therapy (HT) for patients with a measurable adult granulosa cell tumor (GCT) of the ovary in a consecutive series of patients. Material and methods All patients with an adult GCT who were treated with HT [steroidal progestins, selective estrogen receptor modulators, aromatase inhibitors and gonadotropin-releasing hormone agonists] within three referral hospitals were identified and their records were screened for HT administration. The main outcome measure was the objective response rate to HT. Results We identified 127 patients with an adult GCT, of whom 81 (64%) had a recurrence. Twenty-five of these patients (20%) were treated with hormones, of whom 22 had measurable disease at the start of their treatment, i.e. a tumor of more than 1 cm in diameter as seen on imaging, either as a recurrence or as residual disease. The pooled objective response rate, defined as the proportion of patients whose best overall response to hormone therapy was either complete response or partial response to HT, was 18% (4/22) (95% confidence interval 6–41%). In one patient (4.5%) a complete response and in three (14%) a partial response was described. Fourteen patients (64%) had stable disease and in four patients (18%) disease was progressive. Conclusions Although several case reports described good responses to HT in patients with a GCT, we found a response in only four of 22 patients in this relatively large consecutive series of patients.

Objective Models to predict the probability of recurrence free survival exist for various types of malignancies, but a model for recurrence free survival in individuals with an adult granulosa cell tumor (GCT) of the ovary is lacking. We aimed to develop and internally validate such a prognostic model. Methods We performed a multicenter retrospective cohort study of patients with a GCT. Demographic, clinical and pathological information were considered as potential predictors. Univariable and multivariable analyses were performed using a Cox proportional hazards model. Using backward stepwise selection we identified the combination of predictors that best predicted recurrence free survival. Discrimination (c-statistic) and calibration were used to assess model performance. The model was internally validated using bootstrapping techniques to correct for overfitting. To increase clinical applicability of the model we developed a nomogram to allow individual prediction of recurrence free survival. Results We identified 127 patients with a GCT (median follow-up time was 131months (IQR 70-215)). Recurrence of GCT occurred in 81 out of 127 patients (64%). The following four variables jointly best predicted recurrence free survival; clinical stage, Body Mass Index (BMI), tumor diameter and mitotic index. The model had a c-statistic of 0.73 (95% CI 0.66–0.80) and showed accurate calibration. Conclusions Recurrence free survival in patients with an adult GCT of the ovary can be accurately predicted by a combination of BMI, clinical stage, tumor diameter and mitotic index. The introduced nomogram could facilitate in counseling patients and may help to guide patients and caregivers in joint decisions on post-treatment surveillance.

5503 Background: Conflicting evidence on the value of neoadjuvant chemotherapy followed by surgery compared to concomitant chemoradiation in Stage IB2-IIB cervical carcinoma led to this multinational multicenter trial. As the trial is approaching completion of its follow-up, preliminary results are presented. Methods: Between May 2002 and June 2014 a total of 620 patients with FIGO stage Ib2-IIb were randomized between neoadjuvant chemotherapy followed by surgery (NACTS, arm 1, N=311) with standard concomitant chemoradiotherapy (CCRT, arm 2, N=309) . In arm 1, radical hysterectomy was required within 6 weeks after completion of cisplatin-based chemotherapy with a cumulative minimum of 225mg/m2, in arm 2, radiation consisted of 45-50 Gy plus boost concurrent with weekly cisplatin chemotherapy (40 mg/m2 per week). Primary endpoint was 5-yrs overall survival (OS). Results: Median follow-up time was 8.2 years ( 95% CI = 7.8 yrs – 8.6 yrs)) and similar between both arms. A total of 191 deaths (31%) occurred. Age, stage and histological cell type were balanced in both arms. Protocol treatment was completed in 459 (74%) patients (71% for NACTS; 82% for CCRT). In arm 1 238 (76%) patients underwent surgery. Main reasons for not having surgery as per protocol, were toxicity (25/74, 34%), progressive disease (18/74, 24%) and insufficient response to NACT (12/74, 16%). Additional radiotherapy was given to 113 patients (36.3%) in arm 1; additional surgery performed in 9 patients (2.9%) in arm 2. Short term severe adverse events (≥G3) occurred more frequently in arm 1 than in arm 2 (35% vs 21%, p < 0.001). The 5 year OS was 72% in arm 1 and 76% in arm 2 (not statistically significant, difference = 4.0% (95%CI: -4% - 12%); HR 0.87, 95%CI: 0.65-0.15, p=0.332). Conclusions: These preliminary results revealed no difference in 5-year OS between NACTS and CCRT, indicating that quality of life and long term toxicity are important to decide optimal treatment. The final results will be available by April 2019, including long-term toxicity and treatment effect across prognostic factors. Clinical trial information: NCT00039338.

ObjectiveThe aim of this study was to develop clinically relevant and evidence-based guidelines as part of European Society of Gynaecological Oncology’s mission to improve the quality of care for women with gynecologic cancers across Europe.MethodsThe European Society of Gynaecological Oncology Council nominated an international development group made of practicing clinicians who provide care to patients with vulvar cancer and have demonstrated leadership and interest in the management of patients with vulvar cancer (18 experts across Europe). To ensure that the statements are evidence based, the current literature identified from a systematic search has been reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group (expert agreement). The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 181 international reviewers including patient representatives independent from the development group.ResultsThe guidelines cover diagnosis and referral, preoperative investigations, surgical management (local treatment, groin treatment including sentinel lymph node procedure, reconstructive surgery), radiation therapy, chemoradiation, systemic treatment, treatment of recurrent disease (vulvar recurrence, groin recurrence, distant metastases), and follow-up.

Programmed death-ligand 1 (PD-L1) is expressed in various immune cells and tumor cells, and is able to bind to PD-1 on T lymphocytes, thereby inhibiting their function. At present, the PD-1/PD-L1 axis is a major immunotherapeutic target for checkpoint inhibition in various cancer types, but information on the clinical significance of PD-L1 expression in cervical cancer is largely lacking. Here, we studied PD-L1 expression in paraffin-embedded samples from two cohorts of patients with cervical cancer: primary tumor samples from cohort I (squamous cell carcinoma, n=156 and adenocarcinoma, n=49) and primary and paired metastatic tumor samples from cohort II (squamous cell carcinoma, n=96 and adenocarcinoma, n=31). Squamous cell carcinomas were more frequently positive for PD-L1 and also contained more PD-L1-positive tumor-associated macrophages as compared with adenocarcinomas (both P

Introduction There is ongoing discussion about the primary treatment of women with bulky early-stage cervical cancer. Because of the high number of patients who need adjuvant (chemo)radiotherapy after initial surgical treatment, some state that primary (chemo)radiotherapy should be the treatment of choice to prevent morbidity. The aim of our study is to assess the results of radical surgery for women with bulky early-stage cervical cancer in terms of recurrence patterns and survival. Materials and methods We conducted a retrospective cohort study. We included 129 women who underwent a radical hysterectomy with pelvic lymphadenectomy for stage IB2/IIA2 cervical cancer between 1984 and June 2010. Disease-specific survival was measured using a Kaplan-Meier method and univariate and multivariate regression analyses were performed to determine prognostic factors associated with survival. A literature search was performed to analyze our data in the context of findings from the literature. Results Five-year disease-specific survival was 84%. Fifty percent of the women received adjuvant treatment. The pelvic recurrence rate was 8%. With our multivariate analysis we found that histology, tumor diameter, and parametrial involvement were independently associated with disease-specific survival. Our literature search showed wide diversity in rates of adjuvant treatment after initial surgery as well as for survival and recurrence rates. Conclusions In the context of current knowledge about survival and side effects of various treatments for bulky early-stage cervical cancer, radical surgery is a good treatment option in these patients. Depending on the type of surgery used, adjuvant radiotherapy can be minimized.

This study aims to explain bodily pain using the Sprangers and Schwartz theoretical model (1999) on quality of life (QL) and response shift in its entirety. Response shift refers to the phenomenon that the meaning of a person's self-evaluation changes over time. In this model, response shift mediates effects of changes in health status (catalysts), stable characteristics of the person (antecedents), and coping mechanisms (mechanisms) on QL. Methods: Cancer patients (202) were assessed prior to and 3 months following surgery. Measures were for catalysts: type of operation and possibility of tumor resection; for antecedents: age, duration of pain, optimism, and rigidity; for mechanisms: post-traumatic growth, social comparisons, social support, denial, and acceptance; and for QL: bodily pain; for response shift: the pretest-minus-thentest bodily pain score, further referred to as recalibration response shift. Structural equation modeling and sequential regression analyses were used. Results:The final model reached close fit (RMSEA = 0.03; 90% CI = 0.000-0.071; χ2 (18) = 21.13; p = 0.27). Significant effects were found for catalysts on mechanisms, antecedents on mechanisms, mechanisms on response shift, and response shift on bodily pain. Four extra model effects had to be permitted. Using sequential regression analysis, recalibration response shift added 4.4% to the total amount of 29.8% explained variance of bodily pain. Conclusion: Many effects as hypothesized by the model were found. Recalibration response shift had a unique albeit small contribution to the explanation of bodily pain

ObjectiveTo identify associations between demographic, disease-related, and psychological variables and severe distress from pelvic floor symptoms (PFSs) after cervical cancer treatment.MethodsThis study was cross-sectional and questionnaire based. We included patients with cervical cancer treated between 1997 and 2007 in the Academic Medical Center, Amsterdam. Pelvic floor symptoms were assessed with urogenital distress inventory and defecatory distress inventory. Scores were dichotomized into severe (>90th percentile) versus nonsevere distress. Disease-related variables were extracted from medical files. Psychological factors included mental and physical well-being, optimism, and body image, which were assessed with standardized questionnaires. Univariate and multivariate logistic regression analyses were performed.ResultsA total of 282 patients were included: 148 were treated with radical hysterectomy and pelvic lymph node dissection, 61 patients were treated with surgery and adjuvant radiotherapy, and 73 patients were treated with primary radiotherapy. Demographic: Multivariate analyses showed no significant relation between demographic variables and symptoms. Disease-related: None of these variables were significantly associated in multivariate analyses. Psychosocial: In all treatment groups, multivariate associations were found. In general, better mental and physical well-being was associated with nonsevere PFSs. Increased body image disturbance was associated with severe defecation symptoms.ConclusionsFew associations were found between demographic and disease-related variables and distress from PFS after cervical cancer treatment. However, better mental and physical well-being is associated with nonsevere distress from urogenital and defecation symptoms and more body image disturbance with severe PFSs. Improving these factors might reduce distress from PFSs and should be a focus of future research.

Purpose To study the interobserver variability of MRI for visualization of the internal os and measuring the distance between tumor and the internal os in patients with early cervical carcinoma and to compare the distance between tumor and the internal os measured on MRI with invasion of the internal os determined by histopathology. Materials and methods All T2-weighed MRI examinations between January 2003 and December 2007 of patients who underwent hysterectomy, of ≤40 years, with clinical stage IB1 cervix carcinoma and tumor size ≤2 cm were retrieved. 27 patients fulfilled these criteria. Two radiologists retrospectively reviewed the images for visualization of the internal os and the distance between tumor and the internal os; agreement and intraclass correlation coefficients (ICCs) were calculated to determine interobserver variability. The distance between tumor and the internal os measured on MRI was compared with invasion of the internal os determined by histopathology. Results In 26 patients, visualization of the internal was rated as good or moderate by both radiologists (agreement 96%). In 15 patients, both radiologists observed a tumor and the ICC for the distance between tumor and the internal os was 0.752 (95%CI: 0.406–0.909). Assuming 5 mm distance between tumor and the internal os on MRI as criterion for invasion of the internal os, 1 true-positive, 2 false-positives and none false-negatives were observed. Assuming 1 cm as criterion increases the number of false-positives, respectively 3 and 5 by radiologist 1 and radiologist 2. Conclusion MRI has high interobserver values for visualization of the internal os and no false-negatives for involvement of the internal os.

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OBJECTIVE: To assess the quality of surgical pathology reports of advanced stage ovarian, fallopian tube and primary peritoneal cancer. This quality assurance project was performed within the EORTC-GCG 55971/NCIC-CTG OV13 study comparing primary debulking surgery followed by chemotherapy with neoadjuvant chemotherapy and interval debulking surgery. METHODS: Four hundred and seventy nine pathology reports from 40 institutions in 11 different countries were checked for the following quality indicators: macroscopic description of all specimens, measuring and weighing of major specimens, description of tumour origin and differentiation. RESULTS: All specimens were macroscopically described in 92.3% of the reports. All major samples were measured and weighed in 59.9% of the reports. A description of the origin of the tumour was missing in 20.5% of reports of the primary debulking group and in 23.4% of the interval debulking group. Assessment of tumour differentiation was missing in 10% of the reports after primary debulking and in 20.8% of the reports after interval debulking. Completeness of reports is positively correlated with accrual volume and adversely with hospital volume or type of hospital (academic versus non-academic). Quality of reports differs significantly by country. CONCLUSION: This audit of ovarian cancer pathology reports reveals that in a substantial number of reports basic pathologic data are missing, with possible adverse consequences for the quality of cancer care. Specialisation by pathologists and the use of standardised synoptic reports can lead to improved quality of reporting. Further research is needed to better define pre- and post-operative diagnostic criteria for ovarian cancer treated with neoadjuvant chemotherapy.

BACKGROUND: In the management of early stage cervical cancer, knowledge about the prognosis is critical. Although many factors have an impact on survival, their relative importance remains controversial. This study aims to develop a prognostic model for survival in early stage cervical cancer patients and to reconsider grounds for adjuvant treatment. METHODS: A multivariate Cox regression model was used to identify the prognostic weight of clinical and histological factors for disease-specific survival (DSS) in 710 consecutive patients who had surgery for early stage cervical cancer (FIGO [International Federation of Gynecology and Obstetrics] stage IA2-IIA). Prognostic scores were derived by converting the regression coefficients for each prognostic marker and used in a score chart. The discriminative capacity was expressed as the area under the curve (AUC) of the receiver operating characteristic. RESULTS: The 5-year DSS was 92%. Tumor diameter, histological type, lymph node metastasis, depth of stromal invasion, lymph vascular space invasion, and parametrial extension were independently associated with DSS and were included in a Cox regression model. This prognostic model, corrected for the 9% overfit shown by internal validation, showed a fair discriminative capacity (AUC, 0.73). The derived score chart predicting 5-year DSS showed a good discriminative capacity (AUC, 0.85). CONCLUSIONS: In patients with early stage cervical cancer, DSS can be predicted with a statistical model. Models, such as that presented here, should be used in clinical trials on the effects of adjuvant treatments in high-risk early cervical cancer patients, both to stratify and to include patients. Cancer 2011. © 2010 American Cancer Society.

Contains fulltext : 89256.pdf (Publisher’s version ) (Closed access) BACKGROUND: Currently, all patients with vulvar cancer with a positive sentinel node undergo inguinofemoral lymphadenectomy, irrespective of the size of sentinel-node metastases. Our study aimed to assess the association between size of sentinel-node metastasis and risk of metastases in non-sentinel nodes, and risk of disease-specific survival in early stage vulvar cancer. METHODS: In the GROningen INternational Study on Sentinel nodes in Vulvar cancer (GROINSS-V), sentinel-node detection was done in patients with T1-T2 (

Objective: Low-grade endometrial stromal sarcoma (EES) is a rare tumour with a high recurrence rate but a very good prognosis. Responses to hormonal treatment of these recurrences have been published in case reports. The aim of this study was to determine the objective response rate and response duration of hormonal treatment for recurrent or residual low-grade ESS in a consecutive series of patients. Study design: Thirteen consecutive patients with residual or recurrent disease were retrieved from the files. Eleven patients with measurable disease were treated with hormones and form the basis of this study. The following data were collected: age, date of primary diagnosis, type of primary treatment, the presence and localization of residual or recurrent disease, type of treatment, response, duration of response and survival. Results: After hormonal treatment 9 (82%) patients showed an objective response (4 complete response; 5 partial response), one showed stable disease (26+ months) and one progressive disease. Response duration was from 4+ to 252+ months (median 48+ months). Conclusion: Hormonal treatment for measurable residual or recurrent low-grade ESS has a high response rate and should be considered as the treatment of choice for patients in which recurrent disease cannot easily be resected. (C) 2009 Elsevier Ireland Ltd. All rights reserved

Background and purpose: Tumor recurrence after surgery for cervical carcinoma is associated with high fatality and morbidity, forming a major therapeutic challenge. This paper presents our experience with treatment of this patient group by salvage radiotherapy with curative intent. Materials and methods: Thirty-five patients with a pelvic recurrence after hysterectomy received high-dose radiotherapy. A retrospective analysis of long-term outcome and prognostic factors was performed. Results: After a median follow-up period of 12.1 years, actuarial 2-,5- and 10-year overall survival rates were 66%, 43% and 33%; disease-free survival rates were 62%, 45% and 41%, respectively. Pelvic control rates at 2-,5- and 10-years were 77%, 69% and 62%. Unfavorable prognostic factors on univariate analysis for survival were: recurrence extending to the pelvic wall versus central recurrence, early recurrence after surgery, external boost versus brachytherapy boost, low total dose and high age. Only a brachytherapy boost and a long interval between surgery and recurrence were significant on multivariate analysis. Severe complications (>= grade 3) were seen in 6 patients (17%; actuarial after 5 years, 21%). Conclusions: Salvage radiotherapy for recurrent cervical carcinoma following surgery may result in 40-50% long-term disease-free survival and an acceptable risk of severe treatment complications, even in patient with recurrences extending to the pelvic wall. (c) 2008 Elsevier Ireland Ltd. ALL rights reserved. Radiotherapy and Oncology 89 (2008) 197-204

Purpose To investigate the safety and clinical utility of the sentinel node procedure in early-stage vulvar cancer patients. Patients and Methods A multicenter observational study on sentinel node detection using radioactive tracer and blue dye was performed in patients with T1/2 (< 4 cm) squamous cell cancer of the vulva. When the sentinel node was found to be negative at pathologic ultrastaging, inguinofemoral lymphadenectomy was omitted, and the patient was observed with follow-up for 2 years at intervals of every 2 months. Stopping rules were defined for the occurrence of groin recurrences. Results From March 2000 until June 2006, a sentinel node procedure was performed in 623 groins of 403 assessable patients. In 259 patients with unifocal vulvar disease and a negative sentinel node (median follow-up time, 35 months), six groin recurrences were diagnosed (2.3%; 95% CI, 0.6% to 5%), and 3-year survival rate was 97% (95% CI, 91% to 99%). Short-term morbidity was decreased in patients after sentinel node dissection only when compared with patients with a positive sentinel node who underwent inguinofemoral lymphadenectomy (wound breakdown in groin: 11.7% v 34.0%, respectively; P < .0001; and cellulitis: 4.5% v 21.3%, respectively; P < .0001). Long-term morbidity also was less frequently observed after removal of only the sentinel node compared with sentinel node removal and inguinofemoral lymphadenectomy (recurrent erysipelas: 0.4% v 16.2%, respectively; P < .0001; and lymphedema of the legs: 1.9% v 25.2%, respectively; P < .0001). Conclusion In early-stage vulvar cancer patients with a negative sentinel node, the groin recurrence rate is low, survival is excellent, and treatment-related morbidity is minimal. We suggest that sentinel node dissection, performed by a quality-controlled multidisciplinary team, should be part of the standard treatment in selected patients with early-stage vulvar cancer.

Objective. Standard treatment of primary T1 squamous cell carcinoma (SCC) of the vulva

Drainage, following radical hysterectomy and pelvic lymph node dissection to prevent postoperative lymphocyst formation and surgical morbidity, is controversial. To study the clinical significance of drainage, 253 patients were registered and 234 patients were randomised into two arms. In one arm (n=117) postoperative drainage was performed, in the other arm (n=117) no drains were inserted. In both arms closure of the peritoneum of the operating field was omitted. The main exclusion criteria were blood loss of more than 3000 ml during surgery or persistent oozing at the end of the operation. Clinical and ultrasound or CT-scan evaluation was done at one and 12 months postoperatively. The median follow-up amounted to 13.3 months. No difference in the incidence of postoperative lymphocyst formation or postoperative complications was found between the two study arms. The late (12 months) incidence of symptomatic lymphocysts was 3.4% (drains: 5.9%; no drains: 0.9%). The difference showed a p-value of 0.06 in Fisher's Exact test. The operating time was related to the occurrence of postoperative lymphocyst formation. It was concluded that drains can be safely omitted following radical hysterectomy and pelvic node dissection without pelvic reperitonisation in patients without excessive bleeding during or oozing at the end of surgery.

AIM: To validate tissue microarray (TMA) for endometrial cancer by comparing immunohistochemical staining results of triplicate core biopsies on TMA with the results of full-section analysis. METHODS: The study material consisted of slides and selected tissue blocks of 41 patients with endometrioid cancer of the endometrium. A TMA was constructed. Both the TMA and the slides were stained with the same antibodies against progesterone receptor (PR), oestrogen receptor, p53 and epithelial membrane antigen (EMA). Concordance between results was expressed as the kappa statistic. RESULTS: Concordance between the staining results of TMA and whole slides was good for PR (kappa = 0.69), oestrogen receptor (kappa = 0.78), p53 (kappa = 0.81) and EMA (kappa = 0.72). Concordance between the results on TMA and slides depends on the number of assessable cores per tumour. Three assessable cores per case result in outcomes that are at least 94% similar to those achieved using conventional tissue sections with a two-class scoring system. This is independent of focal or diffuse staining patterns. CONCLUSION: TMA is a useful tool for further analysis of the molecular pathways in endometrial cancer. The effect of selection has to be taken into account when the prognostic value of protein expression on TMA is determined

Introduction. Antecedent term pregnancy is an adverse prognostic factor in Gestational Trophoblastic Disease (GTD). In The Netherlands, patients with post term choriocarcinoma are considered high-risk independent of WHO score. In the present study, we assessed whether post term choriocarcinoma always has to be considered high-risk, requiring first line treatment with combination chemotherapy, or whether a subgroup of patients is distinguishable in which single-agent Methotrexate is a safe alternative. Patients and methods. The study is a retrospective multicenter cohort study. Patients registered by the Dutch Working Party on Trophoblastic Disease between 1986 and 2004 with choriocarcinoma after a non-molar pregnancy were eligible. Hospital and outpatient records of the patients were reviewed. Results. In total, 68 patients with non-molar choriocarcinoma were registered of whom 44 had an antecedent term pregnancy. Most post term patients (77%) were high-risk according to the WHO staging system. The majority of patients presented with metrorraghia and high hCG levels. Lung and liver metastases were common (respectively 64% and 28%), probably caused by a delay in diagnosis (median interval 16 weeks). Patients were often Methotrexate-resistant (75%). Overall survival was 86% in patients with a post term choriocarcinoma. Conclusions. Although term pregnancy is an adverse prognostic factor in GTD, current survival is comparable to the general survival in high-risk patients. A subgroup of patients in which monotherapy would be sufficient could not be identified. Immediate administration of combination chemotherapy seems justified, even in those few cases when scoring systems would suggest low- or medium-risk disease.

BACKGROUND. Patients with advanced cervical carcinoma are treated routinely with radiotherapy and cisplatin-containing chemotherapy. It has been shown that hyperthermia can improve the results of both radiotherapy and cisplatin. In the current study, the feasibility and efficacy of the combination of all three modalities was studied in previously untreated patients with cervical carcinoma. METHODS. Patients with advanced cervical carcinoma were registered prospectively in the U.S., Norway, and the Netherlands. External-beam radiotherapy and brachytherapy were administered for a biologically effective dose ! 86.7 gray. At least 4 courses of weekly cisplatin (40 mg/m 2 ) and 4 sessions of weekly locoregional hyperthermia were added to radiotherapy. RESULTS. Sixty-eight patients with a median age of 45 years were enrolled. Fulldose radiotherapy was delivered to all patients according to plan. At least 4 courses of chemotherapy were received by 97% of patients, and at least 4 courses of hyperthermia treatment were received by 93% of patients. Toxicity was fully comparable to that described for chemoradiotherapy alone, and the median total treatment time was 45 days. Complete remission was achieved by 61 patients (90%). After a median follow-up of 538 days, 74% of patients remained alive without signs of recurrence, and the overall survival rate was 84%. CONCLUSIONS. The combination of full-dose radiotherapy, chemotherapy, and hyperthermia was feasible and effective in a multicenter international setting among patients with advanced cervical carcinoma. A Phase III study comparing this novel triplet with standard chemoradiation, designed to show at least a 15% improvement in overall survival, has been launched. Cancer 2005;104:763‐70. © 2005 American Cancer Society.