Purpose of review Studies on treatment options for patients with locally advanced vulvar cancer (LAVC) are scarce, and high-level evidence for a primary treatment choice is lacking. Furthermore,... Show morePurpose of review Studies on treatment options for patients with locally advanced vulvar cancer (LAVC) are scarce, and high-level evidence for a primary treatment choice is lacking. Furthermore, current treatment options are associated with extensive morbidity and high complication rates. More effective treatment options are urgently needed. This review describes current treatment possibilities, focusing on literature regarding neoadjuvant chemotherapy (NACT) followed by surgery. Recent findings Although data are heterogeneous and limited, NACT followed by surgery might be an effective and well tolerated treatment alternative associated with lower morbidity compared with current treatment options, such as excenterative surgery or definitive chemoradiation. Up until now, several studies describe an overall response rate of 40-86%. Surgery turned out to be possible in 40-90% of the LAVC patients who received NACT. Prospective studies on the efficacy and safety of NACT followed by surgery with a homogeneous chemotherapy regimen are urgently awaited. NACT should, at this point, still be considered investigational. Show less
Zanden, V. van der; Soolingen, N.J. van; Viddeleer, A.R.; Trum, J.W.; Amant, F.; Mourits, M.J.E.; ... ; Munster, B.C. van 2022
Objective: To assess the association between loss of lumbar skeletal muscle mass and density during neoadjuvant chemotherapy (NACT) and postoperative complications after interval cytoreductive... Show moreObjective: To assess the association between loss of lumbar skeletal muscle mass and density during neoadjuvant chemotherapy (NACT) and postoperative complications after interval cytoreductive surgery (CRS) in older patients with ovarian cancer. Materials and methods: This multicenter, retrospective cohort study included patients aged 70 years and older with primary advanced stage ovarian cancer (International Federation of Gynecology and Ob-stetrics stage III-IV), treated with NACT and interval CRS. Skeletal muscle mass and density were retrospectively assessed using Skeletal Muscle Index (SMI) and Muscle Attenuation (MA) on routinely made Computed Tomography scans before and after NACT. Loss of skeletal muscle mass or density was defined as >2% decrease per 100 days in SMI or MA during NACT. Results: In total, 111 patients were included. Loss of skeletal muscle density during NACT was associated with developing any postoperative complication <30 days after interval CRS both in univariable (Odds Ratio (OR) 3.69; 95% Confidence Interval (CI) 1.57-8.68) and in multivariable analysis adjusted for functional impairment and WHO performance status (OR 3.62; 95%CI 1.27-10.25). Loss of skeletal muscle density was also associated with infectious complications (OR 3.67; 95%CI 1.42-9.52) and unintended discontinuation of adjuvant chemotherapy (OR 5.07; 95%CI 1.41-18.19). Unlike loss of skeletal muscle density, loss of skeletal muscle mass showed no association with postoperative outcomes. Conclusion: In older patients with ovarian cancer, loss of skeletal muscle density during NACT is asso-ciated with worse postoperative outcomes. These results could add to perioperative risk assessment, guiding the decision to undergo surgery or the need for perioperative interventions. Show less
Koskas, M.; Amant, F.; Mirza, M.R.; Creutzberg, C.L. 2021
Endometrial cancer is the most common gynecological malignancy in high- and middle-income countries. Although the overall prognosis is relatively good, high-grade endometrial cancers have a... Show moreEndometrial cancer is the most common gynecological malignancy in high- and middle-income countries. Although the overall prognosis is relatively good, high-grade endometrial cancers have a tendency to recur. Recurrence needs to be prevented since the prognosis for recurrent endometrial cancer is dismal. Treatment tailored to tumor biology is the optimal strategy to balance treatment efficacy against toxicity. Since The Cancer Genome Atlas defined four molecular subgroups of endometrial cancers, the molecular factors are increasingly used to define prognosis and treatment. Standard treatment consists of hysterectomy and bilateral salpingo-oophorectomy. Lymphadenectomy (and increasingly sentinel node biopsy) enables identification of lymph node-positive patients who need adjuvant treatment, including radiotherapy and chemotherapy. Adjuvant therapy is used for Stage I-II patients with high-risk factors and Stage III patients; chemotherapy is especially used in non-endometrioid cancers and those in the copy-number high molecular group characterized by TP53 mutation. In advanced disease, a combination of surgery to no residual disease and chemotherapy with or without radiotherapy results in the best outcome. Surgery for recurrent disease is only advocated in patients with a good performance status with a relatively long disease-free interval. Show less
Partridge, A.H.; Niman, S.M.; Ruggeri, M.; Peccatori, F.A.; Azim, H.A.; Colleoni, M.; ... ; Pagani, O. 2021
Background: Premenopausal women with early hormone-receptor positive (HR+) breast cancer receive 5-10 years of adjuvant endocrine therapy (ET) during which pregnancy is contraindicated and... Show moreBackground: Premenopausal women with early hormone-receptor positive (HR+) breast cancer receive 5-10 years of adjuvant endocrine therapy (ET) during which pregnancy is contraindicated and fertility may wane. The POSITIVE study investigates the impact of temporary ET interruption to allow pregnancy. Methods: POSITIVE enrolled women with stage I-III HR + early breast cancer, <42 years, who had received 18-30 months of adjuvant ET and wished to interrupt ET for pregnancy. Treatment interruption for up to 2 years was permitted to allow pregnancy, delivery and breastfeeding, followed by ET resumption to complete the planned duration. Findings: From 12/2014 to 12/2019, 518 women were enrolled at 116 institutions/20 countries/4 continents. At enrolment, the median age was 37 years and 74.9 % were nulliparous. Fertility preservation was used by 51.5 % of women. 93.2 % of patients had stage I/II disease, 66.0 % were node-negative, 54.7 % had breast conserving surgery, 61.9 % had received neo/adjuvant chemotherapy. Tamoxifen alone was the most prescribed ET (41.8 %), followed by tamoxifen + ovarian function suppression (OFS) (35.4 %). A greater proportion of North American women were <35 years at enrolment (42.7 %), had mastectomy (59.0 %) and received tamoxifen alone (59.8 %). More Asian women were nulliparous (81.0 %), had node negative disease (76.2%) and received tamoxifen + OFS (56.0 %). More European women had received chemotherapy (69.3 %). Interpretation: The characteristics of participants in the POSITIVE study provide insights to which patients and doctors considered it acceptable to interrupt ET to pursue pregnancy. Similarities and variations from a regional, sociodemographic, disease and treatment standpoint suggest specific sociocultural attitudes across the world. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Show less
Zanden, V. van der; Soolingen, N.J. van; Viddeleer, A.R.; Trum, J.W.; Amant, F.; Mourits, M.J.E.; ... ; Souwer, E.T.D. 2021
Objective. To determine the predictive value of lumbar skeletal muscle mass and density for postoperative outcomes in older women with advanced stage ovarian cancer.Methods. A multicenter,... Show moreObjective. To determine the predictive value of lumbar skeletal muscle mass and density for postoperative outcomes in older women with advanced stage ovarian cancer.Methods. A multicenter, retrospective cohort study was performed in women >= 70 years old receiving surgery for primary, advanced stage ovarian cancer. Skeletal muscle mass and density were assessed in axial CT slices on level L3. Low skeletal muscle mass was defined as skeletal muscle index < 38.50 cm(2)/m(2). Low skeletal muscle density was defined as one standard deviation below the mean (muscle attenuation < 22.55 Hounsfield Units). The primary outcome was any postoperative complication <-30 days after surgery. Secondary outcomes included severe complications, infections, delirium, prolonged hospital stay, discharge destination, discontinua-tion of adjuvant chemotherapy and mortality.Results. In analysis of 213 patients, preoperative low skeletal muscle density was associated with postopera-tive complications <-30 days after surgery (Odds Ratio (OR) 2.83; 95% Confidence Interval (CI) 1.41-5.67), severe complications (OR 3.01; 95%CI 1.09-8.33), infectious complications (OR 2.79; 95%CI 1.30-5.99) and discharge to a care facility (OR 3.04; 95%CI 1.16-7.93). Preoperative low skeletal muscle mass was only associated with infec-tious complications (OR 2.32; 95%CI 1.09-4.92). In a multivariable model, low skeletal muscle density was of added predictive value for postoperative complications (OR 2.57; 95%CI 1.21-5.45) to the strongest existing pre-dictor functional impairment (KATZ-ADL >= 2).Conclusion. Low skeletal muscle density, as a proxy of muscle quality, is associated with poor postoperative outcomes in older patients with advanced stage ovarian cancer. These findings can contribute to postoperative risk assessment and clinical decision making. (C) 2021 The Author(s). Published by Elsevier Inc. Show less
Gerwen, M. van; Maggen, C.; Cardonick, E.; Verwaaijen, E.J.; Heuvel-eibrink, M. van den; Shmakov, R.G.; ... ; International Network Cancer Infer 2021
IMPORTANCE Chemotherapy during the first trimester of pregnancy should be avoided owing to the risk of congenital malformations. However, the precise gestational age at which chemotherapy can be... Show moreIMPORTANCE Chemotherapy during the first trimester of pregnancy should be avoided owing to the risk of congenital malformations. However, the precise gestational age at which chemotherapy can be initiated safely remains unclear.OBJECTIVE To assess congenital malformation rates associated with gestational age at initiation of chemotherapy among pregnant women with cancer.DESIGN, SETTING, AND PARTICIPANTS This multicenter cohort study evaluated all pregnant women who received chemotherapy between 1977 and 2019 registered in the International Network on Cancer, Infertility and Pregnancy (INCIP) database. Data were analyzed from February 15 to June 2, 2020.EXPOSURES Cancer treatment with chemotherapy during pregnancy.MAIN OUTCOMES AND MEASURES Analysis was focused on major and minor structural malformations in offspring, defined by EUROCAT, detected during pregnancy or at birth.RESULTS A total of 755 women in the INCIP database who underwent cancer treatment with chemotherapy during pregnancy were included in analysis. The median (range) age at cancer diagnosis was 33 (14-48) years. Among offspring, the major congenital malformation rate was 3.6% (95% CI, 2.4%-5.2%), and the minor congenital malformation rate was 1.9%(95% CI, 1.0%-3.1%). Chemotherapy exposure prior to 12 weeks gestational age was associated with a high rate of major congenital malformations, at 21.7%(95% CI, 7.5%-43.7%; odds ratio, 9.24 [95% CI, 3.13-27.30]). When chemotherapy was initiated after gestational age 12 weeks, the frequency of major congenital malformationswas 3.0%(95% CI, 1.9%-4.6%), whichwas similar to the expected rates in the general population. Minor malformations were comparable when exposure occurred before or after gestational age 12 weeks (4.3%[95% CI, 0.1%-21.9%] vs 1.8%[95% CI, 1.0-3.0]; odds ratio, 3.13 [95% CI, 0.39-25.28]). Of 29 women who received chemotherapy prior to 12 weeks gestation, 17 (58.6%) were not aware of pregnancy, and 6 (20.7%) experienced a miscarriage (3 women [10.3%]) or decided to terminate their pregnancy (3 women [10.3%]).CONCLUSIONS AND RELEVANCE This cohort study found that chemotherapy was associated with an increased risk of major congenital malformations only in the first 12 weeks of pregnancy. The risk of congenital malformations when chemotherapy was administered during the first trimester and the high number of incidental pregnancies during cancer treatment in the INCIP registry underscore the importance of contraceptive advice and pregnancy testing at the start of chemotherapeutic treatment in young women with cancer. Show less
Zanden, V. van der; Soolingen, N.J. van; Viddeleer, A.R.; Trum, J.W.; Amant, F.; Mourits, M.J.E.; ... ; Munster, B.C. van 2021
Endometrial cancer is the most common gynecological malignancy in high-income countries. Although the overall prognosis is relatively good, high-grade endometrial cancers have a tendency to recur.... Show moreEndometrial cancer is the most common gynecological malignancy in high-income countries. Although the overall prognosis is relatively good, high-grade endometrial cancers have a tendency to recur. Recurrence needs to be prevented since the prognosis for recurrent endometrial cancer is dismal. Treatment tailored to tumor biology is the optimal strategy to balance treatment efficacy against toxicity. Standard treatment consists of hysterectomy and bilateral salpingo-oophorectomy. Lymphadenectomy (with ongoing studies of sentinel node biopsy) enables identification of lymph node positive patients who need adjuvant treatment, including radiotherapy and chemotherapy. Adjuvant radiotherapy is used for Stage I-II patients with high-risk factors and Stage III lymph node negative patients. In advanced disease, a combination of surgery to no residual disease and chemotherapy results in the best outcome. Surgery for recurrent disease is only advocated in patients with a good performance status with a relatively long disease-free interval. Show less
Temko, D.; Gool, I.C. van; Rayner, E.; Glaire, M.; Makino, S.; Brown, M.; ... ; Tomlinson, I. 2018
Objective A cancer diagnosis during pregnancy may be considered as an emotional challengefor pregnant women and their partners. We aimed to identify women and partners at risk for highlevels of... Show moreObjective A cancer diagnosis during pregnancy may be considered as an emotional challengefor pregnant women and their partners. We aimed to identify women and partners at risk for highlevels of distress based on their coping profile.Methods Sixty‐one pregnant women diagnosed with cancer and their partners filled out theCognitive Emotion Regulation Questionnaire (CERQ) and the newly constructed Cancer andPregnancy Questionnaire (CPQ). K‐means cluster analysis was performed on the CERQ scales.Scores on the CPQ were compared between the women and their partners and between theCERQ‐clusters.Results Comparison of women and partners on the CPQ did not reveal significant differenceson distress about the child’s health, the cancer disease, and the pregnancy or on information sat-isfaction (P = .16, P = .44, P = .50, and P = .47, respectively). However, women were more inclinedto maintain the pregnancy than their partners (P = .011). Three clusters were retrieved based onthe CERQ scales, characterized by positive coping, internalizing coping, and blaming. Women andpartners using internalizing strategies had significantly higher scores on concerns about thechild’s health (P = .039), the disease and treatment (P < .001), and the pregnancy and delivery(P = .009) compared with positive and blaming strategies. No cluster differences were foundfor information satisfaction (P = .71) and tendency to maintain the pregnancy (P = .35).Conclusion Women and partners using internalizing coping strategies deal with the highestlevels of distress and may benefit from additional psychosocial support. Show less
