Real-world data on niraparib maintenance treatment in patients with non-gBRCA mutated platinum-sensitive recurrent ovarian cancer.

OBJECTIVES: The aim of this study was to provide real-world efficacy and safety data on niraparib maintenance treatment in patients with non-germline (gBRCA)1/2 mutated platinum-sensitive recurrent ovarian cancer. METHODS: This retrospective multi-center cohort study included 94 platinum-sensitive recurrent ovarian cancer patients without known gBRCA1/2 mutation treated in an individual patient access program in Norway. The primary outcome was time from start of niraparib treatment to first subsequent treatment. Secondary endpoints included progression-free survival, safety, and tolerability. RESULTS: After median follow-up of 13.4 months (95% confidence interval (CI) 10.0 to 16.8), 68.1% had progressed and 22.3% had died. Of the entire cohort, 61.7% had commenced a new line of treatment, and 24.5% were still receiving niraparib. The median duration of niraparib treatment was 5.0 months (range 0.4 to 27.3), and the median time to first subsequent treatment was 10.7 months (95% CI 8.4 to 13.0). Patients with elevated CA125 prior to start of niraparib had shorter time to first subsequent treatment (7.3 months, 95% CI 4.2 to 10.3) than patients with normalized CA125 (12.2 months, 95% CI 10.9 to 13.7 (p=0.002). Patients who started on individual dose based on weight and platelet counts had fewer dose reductions (p<0.001) and interruptions (p=0.02). CONCLUSION: In a real-world setting, niraparib maintenance treatment in patients with non-gBRCA1/2 mutated recurrent platinum-sensitive ovarian cancer showed effectiveness comparable with published phase III studies and acceptable safety. Individualized dosing is essential to minimize adverse events. CA125 levels at start of niraparib treatment may help to estimate the individual prognosis.

Self-reported lower extremity lymphedema and quality of life after surgical staging of endometrial carcinoma: A population based cross-sectional study.

OBJECTIVES: Sentinel lymph node biopsy (SLN) has replaced lymphadenectomy in staging of endometrial carcinoma. The aims of the study were to explore the prevalence of self-reported lymphedema (LEL), identify factors associated with LEL, compare quality of life (QoL) scores using thresholds of clinical importance, and assess correlation between different questionnaires. METHODS: Women who underwent staging for endometrial carcinoma from 2006 to 2021 were invited to complete the Lower Extremity Lymphedema Screening Questionnaire (LELSQ), EORTC QLQ-C30, QLQ-EN24 and EQ-5D-5L. RESULTS: Of 2156 invited survivors, 61% participated in the study, whereof 1127 were evaluable by LELSQ. The LEL prevalence was 51%, 36% and 40% after lymphadenectomy, SLN and hysterectomy, respectively (p < 0.001). Higher BMI, undergoing lymphadenectomy and receiving adjuvant chemotherapy were associated with LEL; odds ratios 1.07 (95% CI 1.05-1.09), 1.42 (95% CI 1.03-1.97) and 1.43 (95% CI 1.08-1.89) respectively. QoL was lower for women with LEL compared to those without. In women with musculoskeletal complaints the prevalence of LEL was 59%, 50% and 53% after lymphadenectomy, SLN and hysterectomy (p = 0.115), respectively, compared to 39%, 17% and 18% (p < 0.001) in women without musculoskeletal complaints. Spearman's correlation was moderate to strong between the questionnaires. CONCLUSION: SLN implementation is not associated with increased LEL prevalence compared to hysterectomy alone, but is associated with a significantly lower prevalence compared to lymphadenectomy. LEL is associated with lower QoL. Our study demonstrates moderate to strong correlation between self-reported LEL and QoL scores. Available questionnaires may not distinguish between symptoms caused by LEL and musculoskeletal disease.

"Long-term outcome in endometrial cancer patients after robot-assisted laparoscopic surgery with sentinel lymph node mapping".

OBJECTIVE: Sentinel Lymph Node (SLN) mapping is increasingly used as an alternative to lymphadenectomy in endometrial cancer. There is, however, limited data regarding the clinical outcome and survival after SLN mapping. The aim of the study was to determine long-term outcome data in endometrial cancer patients undergoing robot-assisted laparoscopic surgery and SLN mapping. STUDY DESIGN: Retrospective cohort study of 108 patients with primary endometrial cancer who underwent robot-assisted laparoscopic surgery and sentinel lymph node mapping using the Memorial Sloan Kettering Cancer Center (MSKCC) algorithm with near-infrared fluorescence detection of indocyanine green for endometrial cancer, from November 20th 2012 to January 1st 2016 at St. Olav's Hospital in Norway. The primary endpoint was recurrence-free survival. Secondary endpoints were overall survival and treatment complications. RESULTS: Among 108 patients operated in accordance with the SLN algorithm, 17 (16%) had lymph node metastases. Adjuvant chemotherapy was administered on indication endometrial cancer to 36 (33%) of the patients. After a median follow up of 75 months (range 61-98), five (4.6%) patients had recurrence, and three patients had died from the disease. Four of the patients who had recurrence had lymph node metastasis at diagnosis. The 5-year recurrence-free survival was 95.4% (95% CI, 91.5 - 99.3). The 5-year disease-specific survival was 97.2% (95% CI, 94.1 - 100.3). The 5-year overall survival was 92.6% (95% CI, 87.7 - 97.5). Peripheral neuropathy after chemotherapy was the most common complication (9.3%), followed by lower limb lymphedema (2%) and postoperative hernia (2%). CONCLUSION: The present study demonstrated excellent oncologic outcome and low long-term treatment complication rate in patients treated according to the SLN algorithm more than five years after diagnosis.

Initial experience with positron emission tomography/computed tomography in addition to computed tomography and magnetic resonance imaging in preoperative risk assessment of endometrial cancer patients.

OBJECTIVE: Improved preoperative evaluation of lymph node status could potentially replace lymphadenectomy in women with endometrial cancer. PET/CT was routinely implemented in the preoperative workup of endometrial cancer at St Olav's University Hospital in 2016. Experience with PET/CT is limited, and there is no consensus about the use of PET/CT in the diagnostic workup of endometrial cancer. The aim of the study was to evaluate the diagnostic accuracy of PET/CT compared to standard CT/MRI in identifying lymph node metastases in endometrial cancer with histologically confirmed lymph node metastases as the standard of reference. We especially wanted to look at PET/CT as a supplement to the sentinel lymph node algorithm in the detection of paraaortic lymph nodes. STUDY DESIGN: A retrospective study included all women undergoing surgery for endometrial cancer from January 2016 through July 2019 at St Olav's University Hospital. Clinical data, results of CT, MRI, and PET/CT, and histopathological results were analyzed. RESULTS: Among 185 patients included, 27 patients (15 %) had lymph node metastases. 17 (63 %) had pelvic lymph node metastases, one (4 %) had isolated paraaortic lymph node metastases, and 9 (33 %) had lymph node metastases in both the pelvis and the paraaortic region. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of PET/CT for the detection of lymph node metastases were 63 %, 98 %, 85 %, 94 %, and 93 %, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CT/MRI were 41 %, 98 %, 73 %, 91 %, and 90 %, respectively (p = 0.07). For the 26 pelvic lymph node metastases, PET/CT had a sensitivity of 58 %, compared to 42 % for CT/MRI (p = 0.22). PET/CT detected all 10 paraaortic lymph node metastases, for a sensitivity of 100 %, compared to 50 % for CT/MRI (p = 0.06). CONCLUSIONS: PET is superior to CT/MRI for detection of lymph node metastases in endometrial cancer, particularly in detecting paraaortic lymph node metastases. The ability of preoperative PET to exclude paraaortic lymph node metastases may strengthen the credibility of the sentinel lymph node algorithm.

Prevalence of human papillomavirus infection among women in rural Nepal.

INTRODUCTION: In this study we aimed to determine the overall and type-specific prevalence of cervical human papillomavirus (HPV) infection and risk factors for such infection among women in rural Nepal, and to investigate the distribution of HPV infection by cervical cytology. MATERIAL AND METHODS: The study was conducted among women aged ≥15 years in five rural villages within Kavre District in Nepal. Sociodemographic data and information on risk factors for cervical cancer were obtained through an interview, and a cervical specimen was collected for HPV DNA detection and typing using the Anyplex™ ll HPV28 Detection system, and for Papanicolaou test. RESULTS: Among the 1289 women in whom a valid HPV result was obtained the median age was 40 years (range 17-86 years). Overall, the HPV prevalence was 14.4%, 7.9% for high-risk and 6.5% for low-risk HPV types, and was similar between age groups. The five most common HR types were HPV-18 (2.3%), HPV-51 (1.2%), HPV-59 (1.1%), HPV-31 (0.9%), and HPV-16 (0.8%). The prevalence of high-risk types in women with and without abnormal cytology was 8.3 and 7.7%, respectively. HPV infection was associated with current smoking, formal education, and being married to a husband with at least one previous marriage. CONCLUSIONS: This is the first population-based study to report the prevalence of a broad range of HPV types among women from rural Nepal. These data are crucial for development of preventive strategies to reduce cervical cancer burden in the country.

Indocyanine green fluorescence imaging of lymph nodes during robotic-assisted laparoscopic operation for endometrial cancer. A prospective validation study using a sentinel lymph node surgical algorithm.

OBJECTIVE: A sentinel lymph node (SLN) strategy may have particular value in endometrial cancer (EC) because a therapeutic effect of lymphadenectomy per se is unproven. The aim was to evaluate indocyanine green (ICG) and near-infrared (NIR) fluorescence mapping using a surgical algorithm. METHODS: From November 2012 through December 2015, women with apparently early stage EC underwent robot-assisted laparoscopic hysterectomy including ICG fluorescence SLN mapping following the Memorial Sloane Kettering Cancer Center (MSKCC) surgical algorithm. RESULTS: Among 108 patients included, ≥1 SLNs was identified in 104 (96%), bilaterally in 84 (78%) and unilaterally in 20 patients (18%). Four patients failed SLN mapping. All SLN-positive patients had pelvic SLNs. Median number of nodes were 4.0 and 6.0 (p<0.001), when SLNs only and SLNs plus non-SLNs were removed, respectively. Lymph node metastases were detected in 17 patients (16%). One patient who failed SLN mapping had a non-SLN metastasis. The remaining 16 patients had metastases in SLNs, 12 in SLNs only and four in both SLNs and non-SLNs. Routine pathology detected 75% of patients with cancer positive SLNs while 25% were based on extended pathology. Lymph node metastases were found among 9% with low-, 11% with intermediate- and 32% with high-risk profiles, respectively. CONCLUSIONS: We have reproduced the high total and bilateral SLN mapping using cervical ICG injection and NIR fluorescence. Practical application of the MSKCC algorithm allowed high lymph node metastasis detection in combination with a low extent of lymph node removal.

Ten years' experience with centralized surgery of ovarian cancer in one health region in Norway.

BACKGROUND: Better outcome of advanced ovarian cancer after centralized surgery has led to the recommendation for centralized surgery in a Norwegian health region. Whether the practice pattern has changed according to this recommendation has not been examined. OBJECTIVE: The objective of this study was to evaluate the referral practice and treatment of ovarian cancer in a Norwegian health region after the introduction of centralized surgery. METHODS: This was a retrospective, population-based study, including all women undergoing surgery for primary ovarian, tubal, and peritoneal cancer between 2000 and 2005, in Health Region IV of Norway. Clinical data and data regarding treatment and 5-year follow-up were analyzed. RESULTS: In total, 279 cases of ovarian, peritoneal, and tubal cancer were included. Eighty-four percent underwent primary surgery at the teaching hospital and 16% at the nonteaching hospitals. After an immediate rise in the number of cases undergoing primary surgery at the teaching hospital after the introduction of centralization in 1995, the percentage distribution between the teaching and nonteaching hospitals was stable during the study period. The women who underwent surgery at the nonteaching hospitals had a higher percentage of early-stage disease and were at higher risk of reoperation for comprehensive staging. CONCLUSIONS: Centralization of ovarian cancer surgery has been successfully accomplished in a health region in Norway. The referral practice of assumed advanced ovarian cancer cases shows satisfactory compliance with centralization at 10 years after the implementation of centralized surgery.

Circulating interleukin-8 and plasminogen activator inhibitor-1 are increased in women with ovarian carcinoma.

Elevated serum levels of several cytokines have been reported in ovarian cancer. We have previously found a diagnostic and prognostic value of hepatocyte growth factor (HGF). The aims of this study were to evaluate the diagnostic and prognostic value of multiple serum cytokines in women with ovarian tumors, and to examine possible associations between serum levels of cytokines and the previously analyzed HGF. Preoperative levels of multiple cytokines were quantified by serum-based immunoassays in 113 women with a pelvic mass: 57 carcinomas, 23 borderline tumors, and 33 benign ovarian tumors. The results were related to clinicopathological parameters. Univariate and multivariate analyses of five-year overall survival were performed. The women with ovarian carcinoma had significantly higher preoperative serum levels of cancer antigen 125 (CA 125), interleukin 8 (IL-8), and plasminogen activator inhibitor-1 (PAI-1) than women with benign ovarian tumors. Serum IL-8 and PAI-1 levels were positively correlated to serum levels of HGF. In a multivariate analysis of five-year overall survival, IL-8 had a prognostic impact. Serum levels of IL-8 and PAI-1 were elevated in women with ovarian carcinoma compared to women with benign ovarian tumors, and positively correlated to serum HGF levels in women with ovarian tumors. IL-8 also seemed to have a prognostic impact.

The proliferation markers Ki-67/MIB-1, phosphohistone H3, and survivin may contribute in the identification of aggressive ovarian carcinomas.

The identification of new proliferation markers could have clinical implications in ovarian carcinoma by stratifying patients for treatment and follow-up. The aim of this study was to evaluate the diagnostic and prognostic value of the proliferation markers Ki-67/MIB-1, phosphorylated histone H3 (PHH3), and survivin in epithelial ovarian tumors. Ninety women with a pelvic mass who underwent surgery at the Department of Gynecological Oncology were included: 68 ovarian carcinomas, 11 borderline tumors, and 11 ovarian cystadenomas. We performed mitotic count and immunohistochemical analyses of Ki-67/MIB-1, PHH3, and survivin, related to clinicopathological parameters. Uni- and multivariate analyses of five-year overall survival were performed. We found statistically significant correlations between mitotic count, Ki-67/MIB-1, PHH3, and survivin. The expression of all proliferation markers was significantly higher in the carcinomas than in the borderline and benign tumors (p<0.05). There was, however an overlap of indices between the different malignancy groups. Women with advanced stage cancers (FIGO stage III and IV) had significantly higher tumor expression of all markers compared to patients with early stage cancers (FIGO stage I and II). Women with advanced disease and complete chemotherapy response had higher Ki67/MIB-1 expression than women without complete chemotherapy response. All markers had an impact on survival in the univariate analyses. In the multivariate analysis, however, only age and stage of disease reached statistical significance as prognostic factors. In conclusion, the proliferation markers Ki-67/MIB-1, PHH3, and survivin are positively correlated with each other and with tumor grade, and may contribute in the identification of aggressive ovarian carcinomas.

Increased circulating hepatocyte growth factor (HGF): a marker of epithelial ovarian cancer and an indicator of poor prognosis.

OBJECTIVE: Hepatocyte growth factor (HGF) has been described to be increased in different cancers. In the present study we wanted to investigate whether HGF in serum can distinguish between benign and malignant ovarian tumors, and whether serum HGF levels can predict the outcome in patients with ovarian carcinomas. METHODS: We included 123 consecutive patients appointed for laparotomy due to a pelvic mass. Preoperative levels of serum cancer antigen 125 (CA 125), HGF and HGF activator (HGFA) were quantified with immunological methods. We performed immunohistochemical analyses of HGFα, HGFß and the receptor c-Met. Five-year survival of patients with advanced disease (stage III and stage IV) was analyzed with the Kaplan-Meier method. RESULTS: Sixty patients had ovarian carcinomas, 23 borderline tumors, and 40 benign ovarian tumors. Patients with ovarian carcinomas had significantly higher preoperative HGF and CA 125 serum levels than patients with benign ovarian tumors, and borderline tumors. Patients with borderline tumors had significantly higher CA 125 values than benign cases. A combination of CA 125 and HGF increased the specificity in predicting carcinoma. We observed abundant HGFα, HGFß and c-Met expressions in all ovarian tumors. Patients with advanced disease and preoperative serum HGF values ≥2SD above reference value had a shorter disease-free survival than patients with advanced disease and serum HGF <2SD above reference value. CONCLUSIONS: HGF in serum is an indicator of ovarian carcinoma in women with a pelvic mass, and of a poor prognosis in advanced ovarian cancer.