Audrey Tieko Tsunoda

Global cancer surgery: delivering safe, affordable, and timely cancer surgery

Surgery is essential for global cancer care in all resource settings. Of the 15.2 million new cases of cancer in 2015, over 80% of cases will need surgery, some several times. By 2030, we estimate that annually 45 million surgical procedures will be needed worldwide. Yet, less than 25% of patients with cancer worldwide actually get safe, affordable, or timely surgery. This Commission on global cancer surgery, building on Global Surgery 2030, has examined the state of global cancer surgery through an analysis of the burden of surgical disease and breadth of cancer surgery, economics and financing, factors for strengthening surgical systems for cancer with multiple-country studies, the research agenda, and the political factors that frame policy making in this area. We found wide equity and economic gaps in global cancer surgery. Many patients throughout the world do not have access to cancer surgery, and the failure to train more cancer surgeons and strengthen systems could result in as much as US

Perioperative morbidity and rate of upstaging after laparoscopic staging for patients with locally advanced cervical cancer: results of a prospective randomized trial

6.2 trillion in lost cumulative gross domestic product by 2030. Many of the key adjunct treatment modalities for cancer surgery--e.g., pathology and imaging--are also inadequate. Our analysis identified substantial issues, but also highlights solutions and innovations. Issues of access, a paucity of investment in public surgical systems, low investment in research, and training and education gaps are remarkably widespread. Solutions include better regulated public systems, international partnerships, super-centralisation of surgical services, novel surgical clinical trials, and new approaches to improve quality and scale up cancer surgical systems through education and training. Our key messages are directed at many global stakeholders, but the central message is that to deliver safe, affordable, and timely cancer surgery to all, surgery must be at the heart of global and national cancer control planning.

Lymphovascular space invasion portends poor prognosis in low-risk endometrial cancer

OBJECTIVEnThe International Federation of Gynecology and Obstetrics (FIGO) staging for cervical cancer is based on clinical examination. Previous studies have demonstrated significant upstaging with surgical staging. However, no randomized trial has ever shown a survival benefit when radiation combined with chemoradiation (RCTX) is modified according to surgical staging. The objective of the study was to evaluate the feasibility and outcomes of surgical staging prior to radical RCTX treatment among patients with locally advanced cervical cancer in the setting of a larger, prospective, randomized study (the Uterus-11 study of the German Gynecologic Oncology Group).nnnSTUDY DESIGNnBetween 2009 and 2013, 255 patients with advanced cervical cancer (FIGO IIB-IVA) were randomized to surgical staging and RCTX (arm A) or RCTX (arm B). RCTX in both arms included pelvic external beam radiotherapy with weekly cisplatin at 40 mg/m(2) and brachytherapy. Extended-field radiation was performed in cases of confirmed paraaortic metastases.nnnRESULTSnOne hundred thirty patients were randomized to surgical staging; 121 were eligible for this analysis. The mean patient age was 47.2 years, and the mean body mass index was 26.2 kg/m(2); the FIGO stages were IIB, IIIA, IIIB, and IVA in 85 (70.2%), 4 (3.3%), 29 (24%), and 3 (2.5%) patients, respectively. Arm A and arm B were similar with respect to Karnofsky performance status, histology, comorbidities, and lymphovascular space involvement. The surgical approach was transperitoneal laparoscopy in nearly all patients (93.4%), with no operative mortality. One patient (0.8%) had a conversion to laparotomy; 2 patients had more than 500 mL blood loss; the early postoperative complication rate was 7.3%. A mean of 19 pelvic and 17 paraaortic nodes were removed, with means of 2.4 and 1.3 positive nodes, respectively. RCTX began between 7 and 21 days after surgery. Operative staging led to upstaging in 40 of 121 (33%).nnnCONCLUSIONnSurgical staging in patients with locally advanced cervical cancer is safe and does not delay primary RCTX in a randomized study.

Prevention of Lymphoceles Using FloSeal and CoSeal After Laparoscopic Lymphadenectomy in Patients With Gynecologic Malignancies

Objective The prognostic significance of lymphovascular space invasion (LVSI) in patients with early-stage endometrial cancer is not established. We sought to determine if LVSI status in patients with early-stage low-risk endometrial cancer correlates with recurrence and survival. Methods The records of all women who underwent hysterectomy for primary treatment of endometrial cancer from January 2006 through January 2011 at 1 academic institution were reviewed. Patients with grade 1 or 2 endometrioid histology, myometrial invasion less than 50%, and disease confined to the uterus (clinical International Federation of Obstetrics and Gynecology stage IA) were analyzed. Fisher exact test and the Wilcoxon rank-sum test were applied to compare patients with and without LVSI. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results Two hundred forty patients met the inclusion criteria. Forty (16.7%) had LVSI. Ninety-one patients (37.9%) underwent lymphadenectomy. Median tumor size was 30 mm in patients with and 26 mm in patients without LVSI (P = 0.150). Thirty patients (12.5%) received adjuvant therapy. Site of recurrence did not differ between patients with and without LVSI. Patients with LVSI were more likely to have myometrial invasion (P < 0.001), postoperative pathologic grade 2 disease (P < 0.001), to undergo lymphadenectomy (P = 0.049) and receive adjuvant therapy (P < 0.001). The 5-year cumulative incidence of recurrence was 3.8% in the no-LVSI group and 14.2% in the LVSI group (P = 0.053). The presence of LVSI was significantly associated with worse RFS (P = 0.002) and OS (P = 0.013). Conclusions Patients with low-risk endometrial cancer and LVSI have worse RFS and OS despite being more likely to undergo lymphadenectomy and adjuvant therapy.

Pre-treatment MRI minimum apparent diffusion coefficient value is a potential prognostic imaging biomarker in cervical cancer patients treated with definitive chemoradiation

INTRODUCTIONnPelvic ± para-aortic lymphadenectomy (LAE) is an essential element of staging and treatment of different gynecologic malignancies. However, LAE can induce asymptomatic and symptomatic pelvic lymphoceles (LCs) in a considerable percentage of patients. Therapy of symptomatic LCs may cause additional morbidity. The best strategy to reduce the rate of LCs has not established yet.nnnMATERIALS AND METHODSnBetween January 2011 and May 2012, transperitoneal laparoscopic pelvic ± para-aortic LAE was performed at the Department of Gynecology at Charité University Hospital Berlin in 238 patients with cervical, endometrial, ovarian, or groin-positive vulvar cancer. The application of FloSeal (Baxter, Deerfield, IL) and CoSeal (Baxter) was used in 25 patients (group A) as an alternative to routine pelvic drainage after LAE. A case-control comparison was performed on 25 patients (group B) with bilateral drainage after complete LAE. The primary objective of this pilot study was to evaluate the feasibility and safety of the method. As a secondary objective, we evaluated the incidence of LCs and symptomatic LCs in both groups. The detection of LCs was performed during oncologic follow-up by sonography, computed tomographic imaging, or magnetic resonance imaging.nnnMEASUREMENTS AND MAIN RESULTSnPelvic (n = 50) or pelvic + para-aortic (n = 42) LAE was performed in 44 patients with cervical, 2 with endometrial, 1 with ovarian, and 2 with groin-positive vulvar cancer, respectively. In group B (n = 25), systematic bilateral pelvic drainage was placed after finishing LAE, whereas in group A (n = 25) LAE areas were sealed with 5 mL FloSeal on each side and sprayed with CoSeal afterward without placing drains. In 14 of 50 patients (28%), LCs were detected. In a subgroup of patients with cervical cancer (88% of the cohort), symptomatic LCs occurred in 11% in group A and 18% in group B. Operative revision of symptomatic LCs was necessary in 5% and 18% in groups A and B, respectively (p = .66). Mean Hospital stay was significant shorter in group A (6 days) versus B (8 days) (p = .027).nnnCONCLUSIONnThe results of this case-controlled pilot study indicate that the application of FloSeal and CoSeal after transperitoneal LAE is feasible and safe, may reduce hospital stay, and may potentially decrease the rate of symptomatic LCs in patients with gynecologic malignancies.

Clinical characteristics of women diagnosed with carcinoma who tested positive for cervical and anal high-risk human papillomavirus DNA and E6 RNA

BackgroundDiffusion Weighted (DW) Magnetic Resonance Imaging (MRI) has been studed in several cancers including cervical cancer. This study was designed to investigate the association of DW-MRI parameters with baseline clinical features and clinical outcomes (local regional control (LRC), disease free survival (DFS) and disease specific survival (DSS)) in cervical cancer patients treated with definitive chemoradiation.MethodsThis was a retrospective study approved by an institutional review board that included 66 women with cervical cancer treated with definitive chemoradiation who underwent pre-treatment MRI at our institution between 2012 and 2013. A region of interest (ROI) was manually drawn by one of three radiologists with experience in pelvic imaging on a single axial CT slice encompassing the widest diameter of the cervical tumor while excluding areas of necrosis. The following apparent diffusion coefficient (ADC) values (×10−3 mm2/s) were extracted for each ROI: Minimum - ADCmin, Maximum - ADCmax, Mean - ADCmean, and Standard Deviation of the ADC - ADCdev. Receiver operating characteristic (ROC) curves were built to choose the most accurate cut off value for each ADC value. Correlation between imaging metrics and baseline clinical features were evaluated using the Mann Whitney test. Confirmatory multi-variate Cox modeling was used to test associations with LRC (adjusted by gross tumor volume – GTV), DFS and DSS (both adjusted by FIGO stage). Kaplan Meyer curves were built for DFS and DSS. A p-valueu2009<u20090.05 was considered significant.Women median age was 52xa0years (range 23–90). 67xa0% had FIGO stage I-II disease while 33xa0% had FIGO stage III-IV disease. Eighty-two percent had squamous cell cancer. Eighty-eight percent received concurrent cisplatin chemotherapy with radiation. Median EQD2 of external beam and brachytherapy was 82.2xa0Gy (range 74–84).ResultsWomen with disease staged III-IV (FIGO) had significantly higher mean ADCmax values compared with those with stage I-II (1.806 (0.4) vs 1.485 (0.4), pu2009=u20090.01). Patients with imaging defined positive nodes also had significantly higher mean (±SD) ADCmax values compared with lymph node negative patients (1.995 (0.3) vs 1.551 (0.5), pu2009=u20090.03).With a median follow-up of 32xa0months (range 5–43) 11 patients (17xa0%) have developed recurrent disease and 8 (12xa0%) have died because of cervical cancer. ROC curves based on DSS showed optimal cutoffs for ADCmin (0.488 × 10−3), ADCmean (0.827 × 10−3), ADCmax (1.838 × 10−3) and ADCdev (0.148 × 10−3). ADCmin higher than the cutoff was significantly associated with worse DFS (HRu2009=u20093.632–95xa0% CI: 1.094–12.054; pu2009=u20090.035) and DSS (HRu2009=u20094.401–95xa0% CI: 1.048–18.483; pu2009=u20090.043).ConclusionPre-treatment ADCmax measured in the primary tumor may be associated with FIGO stage and lymph node status. Pre-treatment ADCmin may be a prognostic factor associated with disease-free survival and disease-specific survival in cervical cancer patients treated with definitive chemoradiation. Prospective validation of these findings is currently ongoing.

Is Routine Curettage a Useful Tool to Evaluate Persistent Tumor in Patients Who Underwent Primary Chemoradiation for Locally Advanced and/or Lymph Node Positive Cervical Cancer?

High-risk human papillomavirus (hrHPV) is an essential cause of cervical carcinoma and is also strongly related to anal cancer development. The hrHPV E6 oncoprotein plays a major role in carcinogenesis. We aimed to evaluate the frequency of hrHPV DNA and E6 oncoprotein in the anuses of women with cervical carcinoma. We analyzed 117 women with cervical cancer and 103 controls for hrHPV and the E6 oncogene. Positive test results for a cervical carcinoma included 66.7xa0% with hrHPV-16 and 7.7xa0% with hrHPV-18. One case tested positive for both HPV variants (0.9xa0%). The samples from the anal canal were positive for HPV-16 in 59.8xa0% of the cases. Simultaneous presence of HPV in the cervix and anal canal was found in 53.8xa0% of the cases. Regarding expression of E6 RNA, positivity for HPV-16 in the anal canal was found in 21.2xa0% of the cases, positivity for HPV-16 in the cervix was found in 75.0xa0%, and positivity for HPV-18 in the cervix was found in 1.9xa0%. E6 expression in both the cervix and anal canal was found in 19.2xa0% of the cases. In the controls, 1xa0% tested positive for HPV-16 and 0xa0% for HPV-18. Anal samples from the controls showed a hrHPV frequency of 4.9xa0% (only HPV16). The presence of hrHPV in the anal canal of women with cervical cancer was detected at a high frequency. We also detected E6 RNA expression in the anal canal of women with cervical cancer, suggesting that these women are at risk for anal hrHPV infection.

Prognostic scores after surgical treatment for cervical intraepithelial neoplasia: A proposed model and possible implications for post-operative follow-up

Objective Response evaluation after primary chemoradiation (RCTX) in patients with cervical cancer remains difficult. Routine hysterectomy after primary RCTX is associated with considerable surgical morbidity without impact on survival. The purpose of the present study was to evaluate value of routine curettage after RCTX to detect persistent tumor. Methods Between 2006 and 2012, patients (n = 217) with cervical cancer in International Federation of Gynecology and Obstetrics stages IB1 N1 (14%), IB2 (9%), IIA (5%), IIB (46%), IIIA (4%), IIIB (15%), IVA (6%), and IVB (1%), respectively, underwent primary RCTX. After RCTX, curettage was recommended to all patients to evaluate response. Results In 136 (63%) of patients with cervical cancer, 1 or 2 consecutive curettages were performed at least 6 weeks after primary RCTX without any complications. In 21 (15%) patients, at least 1 curettage was positive for cervical cancer. In 7 patients, secondary hysterectomy was performed after 1 positive finding and persistent tumor was found in all of them. In the remaining 14 patients, there were 2 positive curettages in 5, 1 undetermined result followed by 1 positive in 3, and 1 positive followed by 1 negative in 6 patients, respectively. In the latter group, no tumor was detected in the uterus, whereas in all other patients with 2 curettages except one, residual carcinoma was detected. Five (24%) of 21 patients with positive histology are free of disease during follow-up. Decision for or against secondary hysterectomy was correct due to histological finding of curettage in 99%. Conclusions Routine curettage is a useful tool to guide decision for secondary hysterectomy with high accuracy after primary RCTX and avoids overtreatment.

Developing institutions for cancer care in low-income and middle-income countries: from cancer units to comprehensive cancer centres

To develop a prognostic model for women who underwent surgical treatment for cervical intraepithelial neoplasia.

Incidence of Histologically Proven Pelvic and Para-Aortic Lymph Node Metastases and Rate of Upstaging in Patients with Locally Advanced Cervical Cancer: Results of a Prospective Randomized Trial

Global cancer centres operate across different sizes, scales, and ecosystems. Understanding the essential aspects of the creation, organisation, accreditation, and activities within these settings is crucial for developing an affordable, equitable, and quality cancer care, research, and education system. Robust guidelines are scarce for cancer units, cancer centres, and comprehensive cancer centres in low-income and middle-income countries. However, some robust examples of the delivery of complex cancer care in centres in emerging economies are available. Although it is impossible to create an optimal system to fit the unique needs of all countries for the delivery of cancer care, we summarise what has been published about the development and management of cancer centres in low-income and middle-income countries so far and highlight the need for clinical and political leadership.