Development and clinical application of a tool to identify frailty in elderly patients with gynecological cancers.

OBJECTIVE: Frailty is more reliable than chronological age in predicting the effectiveness and tolerability of treatments in cancer patients. An increasing number of screening tools have been proposed, however none have received unanimous consent or been specifically designed for women with gynecological malignancies.This study's aim was to develop a clinical application of a screening tool to identify frail patients >70 years old diagnosed with either ovarian or endometrial cancers. METHODS: A 20 item questionnaire was developed and administered to the cohort before surgery or neoadjuvant chemotherapy. A cut-off for frailty definition was determined by analyzing the correlation of questionnaire scores with the completion of treatments. The association between frailty and treatment related complications was assessed using a Chi-squared test for categorical variables and a t-test for continuous variables. RESULTS: Our study included 100 patients, 50% diagnosed with endometrial cancer and 50% with ovarian cancer. A questionnaire score of 4 was the best cut-off for frailty definition (sensitivity 77%, specificity 100%). Surgical grade III and grade IV complications were observed only in frail patients (p=0.01) and hospitalization was significantly longer in frail women affected by ovarian cancer (p=0.01). Frail patients were more exposed to chemotherapy administration delay (p=0.0005), treatment discontinuation (p=0.001) and hematological toxicities, especially anemia ≥grade 2 (p=0.009) and thrombocytopenia any grade (p=0.0001). CONCLUSION: With a cut-off score of 4, our tool can identify frail patients with significantly higher incidence of grade III-IV postoperative complications, length of stay, medical treatment discontinuation rates and hematological toxicities.

How challenging could be preoperative and intraoperative diagnosis of endometrial cancer?

BACKGROUND: Aim of this study was to rate the misdiagnosis of histological type between preoperative endometrial biopsy and final postoperative pathology focusing on non-endometrioid endometrial cancer (NEEC). Secondary objective is to assess the concordance between intraoperative assessment and final pathology in a subgroup of patients. METHODS: A multicenter retrospective study was conducted in patients with histological diagnosis of endometrial cancer who underwent surgical staging between 2011 and 2016. The concordance rate and the Kappa Cohen coefficient were calculated to assess the correlation concerning the histological type between endometrial biopsy and final pathology, and between intraoperative assessment and final pathology in a subgroup of patients. RESULTS: Two hundred ninety-five patients were enrolled, 226 were endometrioid carcinomas and 61 NEEC at final pathology. The concordance rate between pre-operative and final pathology for NEEC and the Kappa Cohen coefficient were 81.4% and 0.41 (CI 95% 0.3059-0.5122), respectively. 26 out of 61 (42.6%) NEEC were preoperatively misdiagnosed. The frozen section was performed in a subgroup of 86 patients (29.15%): the concordance rate between frozen section and final pathology for NEEC was 80% and the Kappa Cohen coefficient was 0.28 (CI 95% 0.212-0.347). CONCLUSIONS: Preoperative pathological histotype assessment predicts final pathology with a moderate grade of accuracy and the identification of NEEC could be challenging. Efforts should be directed toward molecular characterization of diagnostic samples in order to improve diagnostic accuracy and guide therapeutic decisions.

Immunonutrition in ovarian cancer: clinical and immunological impact?

OBJECTIVE: Malnutrition is frequent in ovarian cancer (OC) patients and may compromise post-operative outcomes. The aim of this study is to evaluate the impact of pre-operative immunonutrition on the surgical outcome of OC patients, and on their nutritional, inflammatory and peripheral blood immune status. METHODS: A prospective study was performed between September 2016 and April 2020. Immune-enhancing enteral nutrition was administered to 42 patients before surgery according to their nutritional status assessed by the Malnutritional Universal Screening Tool. Biochemical and hematological monitoring was performed before and after immunonutrition. Post-operative outcomes were assessed and compared with those of a similar group of patients treated without nutritional support. RESULTS: Of the 42 immune-nourished patients, 23 (54.8%) had a low, 11 (26.2%) an intermediate and 8 (19%) a high risk of malnutrition. After the immunonutritional intake, significant variations of prealbumin, creatinine and white blood cells were detected. All T cell populations had an increasing trend, in particular CD3+ T lymphocytes (p=0.020), CD3+CD8+ cytotoxic T lymphocytes (p=0.046) and lymphocyte with HLA-DR expression (p=0.012). The rate of grade II-III post-operative complications was lower (21.4% vs. 42.9%, p=0.035) and the time of hospitalization was shorter (7.5 vs. 9.2, p=0.009) in the immune-nourished group. CONCLUSION: Pre-operative immunonutrition improves the surgical outcome of OC patients. After immunonutrition, an increase of CD3+CD8+ cytotoxic T lymphocytes was observed.

Current Evidence of the Oncological Benefit-Risk Profile of Hormone Replacement Therapy.

Hormone replacement therapy (HRT) remains the most effective treatment for menopausal symptoms and has been shown to prevent bone loss and fracture. The progestogen is added to provide endometrial protection in women with an intact uterus. After the publication of the initial WHI (Women's Health Initiative) results in 2002 reporting an overall increased risk of breast cancer, many women discontinued HRT. Despite the re-analysis of the results by subgroups of patients and updates with extended follow-up, much controversy remains, which we will analyze later in the text. Different types of estrogen or progestogen, as well as different formulations, doses, and durations, may play a role in HRT's effects on breast tissue. Evidence states that conjugated equine estrogen (CEE), compared to estro-progestin therapy, shows a better profile risk (HR 0.79, CI 0.65-0.97) and that, among different type of progestins, those structurally related to testosterone show a higher risk (RR 3.35, CI 1.07-10.4). Chronic unopposed endometrial exposure to estrogen increases the risk of endometrial hyperplasia and cancer, whereas the association with progestins, especially in continuous combined regimen, seems to reduce the risk (RR 0.71, CI 0.56-0.90). HRT was also associated with a protective effect on colon cancer risk (HR 0.61, CI 0.42-0.87). Data about ovarian and cervical cancer are still controversial.

Oral metronomic cyclophosphamide in advanced ovarian cancer: long-lasting clinical response in an elderly frailty patient.

Elderly patients with ovarian cancer are an increasing population and many of them are frailty with an increased risk of postoperative complications, chemotherapy intolerance and mortality. Metronomic chemotherapy is the chronic administration of low, equally spaced, doses of antineoplastic drugs with therapeutic efficacy and low toxicity. Oral metronomic cyclophosphamide has gained increasing interest in recent years in the treatment of patients with recurrent ovarian cancer. We report the case of a 87-year-old and -frailty woman with advanced ovarian cancer, not eligible for surgery or standard first-line intravenous chemotherapy. The patient has received oral metronomic cyclophosphamide with a long-lasting clinical response and improved performance status. Oral metronomic cyclophosphamide is a promising treatment for elderly and frailty advanced ovarian cancer patients and should be further investigated.

Development of a preoperative computed tomography score for the management of advanced epithelial ovarian cancer.

OBJECTIVE: The main objective is to develop a model based on computed tomographic features to predict surgical outcome and establish cut-offs to rationalize clinical management in advanced epithelial ovarian carcinoma. The secondary purpose is to identify parameters that should be reported by radiologists to allow a correct pre-operative evaluation. METHODS: This study evaluated the association between 17 radiologic parameters and surgical outcome through the review of 61 computed tomographic scans. Each parameter received a score according to the strength of statistical association and points were added to obtain a predictive index value. The absence of residual tumor was considered an optimal result. Receiver operating characteristic curves were applied to assess the ability to predict surgical outcome. The score was applied to the study population to verify if the therapeutic approach had been congruent with the predicted results and to define adequate cut-offs. RESULTS: Analysis with a receiver operating characteristic curve demonstrated a statistical association with surgical outcome (area under curve=0.949). The clinical approach agreed with the predicted outcome. Patients with lower scores received primary debulking surgery (mean predictive index value 2.4) whereas those with higher scores (mean 14.1) were given neoadjuvant chemotherapy. Further surgical investigation (laparoscopy) was performed in patients with higher predictive index value variability (0-17.5). Different cut-offs were analysed to define the model applicability. The results show that surgery is appropriate for patients with a predictive index value <6 (failure rate 11.5%) while a predictive index value >8 should address to neoadjuvant chemotherapy (0% of inappropriately unexplored patients). In addition, patients with a predictive index value between 6 and 8 could benefit from diagnostic exploration with a good success rate (71.4%). CONCLUSIONS: The model correctly discerns patients who can benefit from surgery (predictive index value <6) from those who should undergo neoadjuvant chemotherapy (>8) and establishes a range (6-8) where surgical investigations may be helpful. This score is a flexible tool where cut-offs can be changed according to the desire to be surgically more aggressive or more conservative.

Can Vulnerable Elders Survey-13 predict the impact of frailty on chemotherapy in elderly patients with gynaecological malignancies?

The management of gynaecological cancers in elderly women and high-risk patients is an even more relevant issue, because the increase in longevity and comorbidities. The assumption of frailty based on age alone may lead to inadequate and inappropriate treatment and frailty assessment is recommended. The aim of this study was to assess if Vulnerable Elders Survey-13 (VES-13), as indicator of frailty, can predict the toxicity of chemotherapy in gynaecological cancers.VES-13 was administered to patients aged ≥ 70 years with ovarian, endometrial and cervical cancers who underwent chemotherapy from 2010 to 2016.Eighty-four patients aged ≥ 70 years (mean age 74.6) were included, 36 patients (42.9%) resulted vulnerable (score ≥ 3). Thrombocytopenia and anaemia were more prevalent in the vulnerable subjects (81.3% versus 18.7%, P = .0005, and 81.8% versus 18.2%, P = .005, respectively), while neutropenia was similar between the 2 groups. Vulnerable women had higher risk of non-haematological toxicities. Most of the patients (77.4%) completed chemotherapy, but dose reductions and discontinuations were more common in the vulnerable group (66.7% versus 33.3%, P = .07 and 68.4% versus 31.6%, P = .01, respectively).To our knowledge, this is the first study to evaluate VES-13 exclusively in elderly women with gynaecological cancers. VES-13 may be useful to stratify this category of patients according to vulnerability in order to identify women at risk of toxicity and to prevent complications induced by chemotherapy.