Aureli Torné

Multimodal prehabilitation improves functional capacity in patients with advanced ovarian cancer undergoing cytoreductive surgery

Prehabilitation, defined as the preparatory intervention to increase patient preparedness in the lead-up to surgery, has shown a decrease in post-operative complications in various types of surgery. However, there is limited evidence in advanced ovarian cancer surgery. This study aimed to evaluate the benefits of multimodal prehabilitation in advanced ovarian cancer patients in terms of improving physical functioning, body composition, and psychological well-being during the pre-operative period. This single-center, ambispective study included patients with advanced ovarian cancer eligible for primary or interval cytoreductive surgery. Participants attended a multimodal prehabilitation program comprising medical optimization, supervised exercise training, nutritional counseling and supplementation, and psychological support. Functional capacity, nutritional status, and psychological well-being were assessed before the start of the program and before surgery. 62 patients were referred for the multimodal prehabilitation program from July 2019 to May 2023. Median adherence to the training program reached 75% (IQR 58-87%). 35 patients (59%) were evaluated pre-operatively. Patients attended a median of 8 (IQR 6-12) supervised exercise training sessions with no differences between those who underwent primary or interval cytoreductive surgery (p=0.80). A significant improvement was observed in functional capacity according to the 6 min walk test (mean 33.1 m, 95% CI 10.5 to 55.5) as well as in the 30 s sit-to-stand test (+3.3 repetitions, 95% CI 1.8 to 4.8), with both being above the minimal clinically important difference of 14 m and two repetitions, respectively. Patients also reported a significant decrease in depression, anxiety, and total scores of the Hospital Anxiety and Depression Scale. Multimodal prehabilitation in patients with advanced ovarian cancer undergoing cytoreductive surgery improves pre-operative physical functioning and decreases emotional distress. Further controlled studies with a larger sample size are warranted to corroborate improvement in functional capacity, body composition, and psychological well-being through prehabilitation programs.

Preliminary results of a vaginal constraint for reducing G2 late vaginal complications after postoperative brachytherapy in endometrial cancer: a prospective analysis

Abstract Purpose To evaluate the preliminary results of the use of 68 Gy EQD2(α/β=3 Gy) as a dose limit to the lowest dose in the most exposed 2 cm3 of the vagina in order to reduce G2 late vaginal problems in postoperative endometrial carcinoma (EC). Methods From November 2016 to October 2019, 69 postoperative EC patients receiving vaginal brachytherapy (VBT) ± external beam radiotherapy (EBRT) were prospectively analyzed. The median EBRT dose was 45 Gy (range: 44–50.4 Gy), 1.8−2 Gy/day, 5 fractions(Fr)/week. VBT was administered with the following schedule: 1Fr of 7 Gy after EBRT and 2 daily Fr × 7.5 Gy in exclusive VBT. The dose was prescribed at 0.5 cm from the applicator surface with an active length of 2.5 cm; 56 patients were treated with vaginal cylinders (49–3.5 cm, 6–3 cm, and 1–2.5 cm) and 13 with the colpostat technique. The overall VBT dose was adjusted to meet the vaginal restriction of < 68 Gy EQD2(α/β=3 Gy) at 2 cm3. Late toxicity was prospectively assessed using RTOG scores for bladder and rectum, and the objective LENT-SOMA criteria for vagina. Results With a median follow-up of 31.0 months, no vaginal-cuff recurrences were found. Late toxicity: only 1G1(1.4%) rectal toxicity; 21G1(30.4%) and 3G2(4.3%) vaginal complications. Only one (1.4%) of 3 G2 manifested as vaginal shortening. Conclusions In postoperative EC patients treated with VBT, only one developed G2 vaginal stenosis with the use of 68 Gy EQD2(α/β=3 Gy) as a dose constraint. These preliminary results seem to indicate the value of this dose limit for reducing G2 vaginal stenosis. Nonetheless, these findings should be confirmed in a larger number of patients with longer follow-up.

Paraaortic sentinel lymph node detection in intermediate and high-risk endometrial cancer by transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR)

We aimed to evaluate the accuracy of sentinel lymph node (SLN) mapping with transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR) to detect lymph node (LN) metastases, in patients with intermediate and high-risk endometrial cancer (EC), focusing on its performance to detect paraaortic involvement. Prospective study including women with preoperative intermediate or high-risk EC, according to ESMO-ESGO-ESTRO consensus, who underwent SLN mapping using the TUMIR approach. SLNs were preoperatively localized by planar and single photon emission computed tomography/computed tomography images, and intraoperatively by gamma-probe. Immediately after SLN excision, all women underwent systematic pelvic and paraaortic lymphadenectomy by laparoscopy. The study included 102 patients. The intraoperative SLN detection rate was 79.4% (81/102). Pelvic and paraaortic drainage was observed in 92.6% (75/81) and 45.7% (37/81) women, respectively, being exclusively paraaortic in 7.4% (6/81). After systematic lymphadenectomy, LN metastases were identified in 19.6% (20/102) patients, with 45.0% (9/20) showing paraaortic involvement, which was exclusive in 15.0% (3/20). The overall sensitivity and negative predictive value (NPV) of SLNs by the TUMIR approach to detect lymphatic involvement were 87.5% and 97.0%, respectively; and 83.3% and 96.9%, for paraaortic metastases. After applying the MSKCC SLN mapping algorithm, the sensitivity and NPV were 93.8% and 98.5%, respectively. The TUMIR method provides valuable information of endometrial drainage in patients at higher risk of paraaortic LN involvement. The TUMIR approach showed a detection rate of paraaortic SLNs greater than 45% and a high sensitivity and NPV for paraaortic metastases in women with intermediate and high-risk EC.

Sentinel lymph node biopsy versus pelvic lymphadenectomy for early-stage cervical cancer: a retrospective institutional review

Abstract Objective To evaluate the oncologic and survival outcomes in patients diagnosed with early-stage cervical cancer who underwent both sentinel lymph node (SLN) and pelvic lymphadenectomy (PLD) compared with those who underwent SLN alone at primary surgery. Methods From 2001 to 2022, women who underwent SLN biopsy for nodal staging were recruited. The group of women who underwent SLN biopsy and PLD (SLN + PLD group) was compared with the group who underwent SLN mapping alone (SLN group). Results 210 patients were evaluated (98 and 112 in each group). The overall SLN detection rate was 97.6%. Lymph node involvement was detected in 23 patients (11%), and the rate of positive SLN increased from 6.2 to 11% after final pathological examination. At a median follow-up of 80 months, the recurrence and mortality rates were 6.2 and 2.4%, respectively. The 3-year progression-free survival (PFS) rate was 93.7 and 97.2%, and the overall survival (OS) rate was 98.9 and 99.0% in the SLN + PLD and SLN group, respectively. There were no significant differences in the Kaplan–Meier PFS (p = 0.471; HR 0.66; 95% CI 0.22–2.04) and OS (p = 0.228; HR 0.28; 95% CI 0.03–2.53) curves between the groups. Conclusion Pending further confirmation from prospective trials, SLN biopsy appears to be an effective method of nodal assessment in early-stage cervical cancer. This technique does not appear to increase the risk of recurrence compared with complete PLD in selected patients and may offer a viable, less invasive alternative for accurate nodal staging.

A multimodal intervention program to improve sexual health and self-perceived quality of life in patients treated for cervical cancer: a randomized prospective study (PROVIDENCE trial)

Patients with cervical cancer treatment experience an impairment of sexual function and quality of life. This issue is usually underreported and undertreated, and evidence-based interventions are lacking. Prevention of sexual dysfunction is a crucial pillar in improving the quality of life of these patients. The primary objective of this trial is to evaluate the impact of a multimodal intervention, encompassing prevention of vaginal dysfunction and patient education, on sexual function and quality of life in cervical cancer survivors utilizing patient-reported outcome measurements. Multi-institutional, randomized clinical trial where patients will be randomized 1:2 at diagnosis of initial or locally advanced cervical cancer to control arm or intervention arm. After treatment, control arm patients will undergo standard follow-up by their referring physician. The multimodal intervention for patients in the intervention group includes application of vaginal estrogens plus hyaluronic-acid cream along with use of vaginal vibrator, systematic evaluation of the need of systemic hormone replacement therapy and treatment if needed, and access to online content about sexuality, nutrition, sports and lifestyle habits. Through 4 appointments (at diagnosis, 1, 6, and 12 months after treatment), sexual health, vaginal trophism and self-perceived quality of life of patients in both arms will be assessed with validated questionnaires as female sexual function index (FSFI), European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30, and Cx-24, Cervantes Scale, vaginal health index and vaginal thickness assessed by ultrasound. The major inclusion criteria will be patients aged ≥18 years with the International Federation of Gynecology and Obstetrics stage I-III cervical cancer treated with surgery and/or radiotherapy. The primary endpoint will be FSFI score 12 months after treatment, which will be compared between groups. Uni- and multivariate analysis will be performed to identify factors influencing sexual function recovery after treatment. The sample size will be of 120 eligible patients, who will be randomized to detect an improvement of 5.2 points in FSFI score. Complete accrual is estimated in March 2026. To date, the present study has no external funding. ClinicalTrials.gov Identifier: NCT06031493.

Sentinel lymph node detection in early-stage ovarian cancer: a systematic review and meta-analysis

A systematic pelvic and para-aortic lymphadenectomy remains the surgical standard management of early-stage epithelial ovarian cancer. Sentinel lymph node mapping is being investigated as an alternative procedure; however, data reporting sentinel lymph node performance are heterogeneous and limited. This study aimed to evaluate the detection rate and diagnostic accuracy of sentinel lymph node mapping in patients with early-stage ovarian cancer. A systematic search was conducted in Medline (through PubMed), Embase, Scopus, and the Cochrane Library. We included patients with clinical stage I-II ovarian cancer undergoing a sentinel lymph node biopsy and a pelvic and para-aortic lymphadenectomy as a reference standard. We conducted a meta-analysis for the detection rates and measures of diagnostic accuracy and assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with identifying number CRD42022351497. After duplicate removal, we identified 540 studies, 18 were assessed for eligibility, and nine studies including 113 patients were analyzed. The pooled detection rates were 93.3% per patient (95% CI 77.8% to 100%; I Sentinel lymph node biopsy in early-stage ovarian cancer showed a high detection rate and negative predictive value. The utero-ovarian and infundibulo-pelvic injection using the indocyanine green and technetium-99 combination could increase sentinel lymph node detection rates. However, given the limited quality of evidence and the small number of reports, results from ongoing trials are awaited before its implementation in routine clinical practice.

Sentinel lymph node mapping in early-stage ovarian cancer: surgical technique in 10 steps

Vulvar squamous cell carcinoma arising on human papillomavirus‐independent precursors mimicking high‐grade squamous intra‐epithelial lesion: a distinct and highly recurrent subtype of vulvar cancer

AimsEach category of vulvar squamous cell carcinoma (VSCC), human papillomavirus (HPV)‐associated and HPV‐independent, arises on a specific intra‐epithelial precursor: high‐grade squamous intra‐epithelial lesions (HSIL) and differentiated vulvar intra‐epithelial neoplasia (dVIN), respectively. However, a subset of HPV‐independent VSCC arises on an intra‐epithelial precursor closely mimicking HSIL. We aimed to explore the clinicopathological features of the HPV‐independent tumours with HSIL‐like lesions and compare them with HPV‐independent VSCC with dVIN and HPV‐associated tumours with HSIL.Methods and resultsWe retrospectively identified 105 cases of surgically treated VSCC with adjacent intra‐epithelial precursors. The cases were classified into three groups based on the HPV status and the adjacent precursor identified: (i) HPV‐associated VSCC with HSIL (n = 26), (ii) HPV‐independent VSCC with dVIN lesions (n = 54) and (iii) HPV‐independent VSCC with HSIL‐like lesions (n = 25). We analysed the histological and clinical features including the recurrence‐free survival and disease‐specific survival in the three groups. Patients with HPV‐independent VSCC with HSIL‐like lesions and with dVIN were older than patients with HPV‐associated VSCC (76 and 77 versus 66 years, respectively, P < 0.001). HPV‐independent VSCC with HSIL‐like lesions recurred more frequently [hazard ratio (HR) = 3.87; P < 0.001] than HPV‐independent VSCC with dVIN (HR = 2.27; P = 0.1) and HPV‐associated VSCC (HR = 1). In the multivariate analysis, HPV‐independent VSCC with HSIL‐like lesions remained significant for recurrence. No differences in disease‐specific survival were observed between the three groups.ConclusionsEven though VSCC with HSIL‐like lesions are not associated with higher mortality, they are more likely to recur and might benefit from more intensive treatment strategies and closer surveillance after treatment.

Molecular Landscape of Vulvar Squamous Cell Carcinoma

Vulvar squamous cell carcinoma (VSCC) is a rare malignancy with dual pathogenesis, Human papillomavirus (HPV)-associated and HPV-independent, with a poorly explored molecular landscape. We aimed to summarize the findings of the series analyzing molecular hallmarks of this neoplasm. In January 2021, we conducted a comprehensive literature search using Pubmed Medline and Scopus to identify publications focused on genomic profiling of VSCC. Observational studies, including both prospective and retrospective designs, evaluating molecular alterations in VSCC were deemed eligible. A total of 14 studies analyzing 749 VSCC were identified. The study series were heterogeneous in HPV testing and sequencing strategies, included small sets of tumors and cancer genes, and commonly lacked survival analysis. Only one extensive targeted next-generation sequencing-based study comprised a large cohort of 280 VSCC. The mutated genes, their number, and frequencies were highly variable between the series. Overall, TP53 and CDKN2A, followed by PIK3CA, HRAS, and PTEN, were the most frequently studied and mutated genes. Mutations involved in the PI3K/AKT/mTOR pathway, including TP53, HRAS, KRAS, and PIK3CA, have been consistently reported across the studies. However, the role of individual mutations or pathways in the development of VSCC remains unclear. In conclusion, heterogeneity and the small sample size of available molecular series contribute to a limited view of the molecular landscape of VSCC. Large-scale genome- or exome-wide studies with robust HPV testing are necessary to improve the molecular characterization of VSCC.

Steerable DROP-IN radioguidance during minimal-invasive non-robotic cervical and endometrial sentinel lymph node surgery

Abstract Purpose The recently introduced tethered DROP-IN gamma probe has revolutionized the way robotic radioguided surgery is performed, fully exploiting the nature of steerable robotic instruments. Given this success, the current first-in-human study investigates if the DROP-IN can also provide benefit in combination with steerable non-robotic instruments during conventional laparoscopic surgery, showing equivalence or even benefit over a traditional rigid gamma probe. Methods The evaluation was performed in ten patients during laparoscopic cervical (n = 4) and endometrial (n = 6) cancer sentinel lymph node (SLN) procedures. Surgical guidance was provided using the hybrid, or bi-modal, SLN tracer ICG-99mTc-nanocolloid. SLN detection was compared between the traditional rigid laparoscopic gamma probe, the combination of a DROP-IN gamma probe and a steerable laparoscopic instrument (LaproFlex), and fluorescence imaging. Results The gynecologists experienced an enlarged freedom of movement when using the DROP-IN + LaproFlex combination compared to the rigid laparoscopic probe, making it possible to better isolate the SLN signal from background signals. This did not translate into a change in the SLN find rate yet. In both cervical and endometrial cancer combined, the rigid probe and DROP-IN + LaproFlex combination provided an equivalent detection rate of 96%, while fluorescence provided 85%. Conclusion We have successfully demonstrated the in-human use of steerable DROP-IN radioguidance during laparoscopic cervical and endometrial cancer SLN procedures, expanding the utility beyond robotic procedures. Indicating an improved surgical experience, these findings encourage further investigation and consideration on a path towards routine clinical practice and improved patient outcome. Trial registration HCB/2021/0777 and NCT04492995; https://clinicaltrials.gov/study/NCT04492995

Patent Blue SLN in Early Ovarian Cancer Prospective Study (FIGO I-II) Evaluating Patent Blue SLN Mapping. Injection Into IP/UO Ligaments in Situ. Goals: Assess Feasibility and Accuracy vs Standard Lymphadenectomy to Minimize Surgical Morbidity

the standard of care in case of early ovarian cancer (stage I or II) is a complete surgery. This surgery includes : hysterectomy (remove of the uterus), bilateral salpingo-oophorectomy (remove of the adnexa), omentectomy (remove of the epiploon), bilateral pelvic lymphadenectomy (remove of pelvic lymph nodes) and para-aortic lymphadenectomy (remove of para-aortic lymph nodes). This procedure is diagnostic, curative and prognostic surgery. In fact, it allows us provider care giver to stratify the stage of the cancer, hence we give the appropriate adjuvant therapy. However, this surgery, especially the extended lymphadenectomy, is associated with some risks: lymphocele, vessel injury, blood loss, morbidity, long recovery period ... In order to reduce these risks, we propose a sentinel lymph node biopsy. This intervention allows us to detect first lymph node relay whether pelvic or para-aortic. In our study, we chose the patent blue dye as a tracer. This tracer is widely used in oncologic surgery (for example in breast cancer) and approved but not in ovarian cancer yet. During surgery for early stage ovarian cancer, we will inject the patent blue dye on both side of the ovarian tumor. Then, we will check for first colorful lymph node, in both pelvic and para-aortic regions. We will send these dissected lymph node to pathology for analysis. Finally, we will continue the procedure as the standard of care. Our objective is to compare the results between the sentinel lymph node and the complete lymphadenectomy and to study the technique of sentinel lymph node biopsy using the blue patent dye as tracer.

Extended Versus Short Prehabilitation Programme for Patients With Advanced Ovarian Cancer Undergoing Major Surgery

Standard treatment for advanced ovarian cancer includes a combination of cytotoxic chemotherapy and citorreductive surgery. During neo-adjuvant administration of chemotherapy, many patients experience a decline in their functional capacity, leading to an increased risk of postoperative complication as a combination of potential malnutrition, decreased physical activity levels and increased anxiety. Prehabilitation programs conducted within Enhanced Rescovery After Surgery (ERAS) pathways have shown to reduce postoperative complications and length of hospital stay in a diverse group of cancer surgeries and, according to some preliminary evidence, can also increase tumour response in patients receiving neoadjuvant chemotherapy. The aim of this study is to compare two modalities of prehabilitation (extended versus estandard) on postoperative complications and response to neoadjuvant chemotherapy. A total of 225 patients will be randomized in a 2:1 ratio to extended prehabilitation (initiated at the onset of neoadjuvant therapy) or standard prehabilitation (initiated after the course of neoadjuvant therapy is completed). In both groups the prehabilitation program will be delivered in the same manner, including supervised (virtual or facility-based) exercise training, nutritional optimization and psychological support and will be supported by a digital platform.

A Multimodal Intervention Program to Improve Sexual Health and Self-perceived Quality of Life in Patients Treated for Cervical Cancer (PROVIDENCE)

The PROVIDENCE Trial aims to explore the improvement of sexual health and self-perceived health related quality of life (measured by Patient Reported Outcome Measures) through a multimodal intervention that includes patient education on healthy habits and the prevention of vaginal dysfunction using vaginal moisturizers and topical estrogens. To achieve this, a randomized design is proposed to assess sexual health and quality of life in patients treated for cervical cancer who undergo this intervention compared to those who receive standard care.