TRImodal DEfinitive invasive vagiNal carcinoma Treatment (TRIDENT protocol): how a standardized approach may change prognostic outcomes.

OBJECTIVE: Vaginal carcinoma is a rare malignancy accounting for 1-2% of all gynecological cancers. Surgery has a limited role, while definitive radiotherapy-chemotherapy followed by interventional radiotherapy is considered a valid alternative. The aim of the TRIDENT (TRImodal DEfinitive invasive vagiNal carcinoma Treatment) pilot study was to report the results of a modern standardized trimodal protocol treatment consisting of image guided definitive radiotherapy-chemotherapy followed by image guided interventional radiotherapy in terms of safety and efficacy. METHODS: Between January 2019 and December 2021, we analyzed 21 consecutive patients with primary vaginal cancer who had received radiotherapy-chemotherapy followed by interventional radiotherapy. The primary study endpoint was local control, and secondary endpoints were metastasis free survival, overall survival, and rate and severity of acute and late toxicities. RESULTS: 14 patients had FIGO (International Federation of Gynecology and Obstetrics) stage II, five patients had stage III, and two had stage IVB disease. Median total external beam radiotherapy dose for the tumor was 45 Gy. Median total dose on positive nodes was 60 Gy. Median total dose for interventional radiotherapy was 28 Gy over four high dose rate fractions to achieve between 85 and 95 Gy equivalent dose, in 2 Gy fractions (EQD2)α/ß10, to the high risk clinical target volume, and 60 Gy EQD2α/ß10 to the intermediate risk clinical target volume. All patients received weekly platinum based chemotherapy. Median follow-up was 20 months (range 10-56 months). Two year actuarial local control, metastasis free survival, and overall survival rate were 79.4%, 90.5%, and 79.4%, respectively. In terms of acute toxicity, there were no grade 4 events and only one acute grade (G) 3 toxicity (skin). Only vaginal stenosis (G3) was documented 12 months after therapy due to late toxicity. CONCLUSIONS: In this study, definitive radiotherapy-chemotherapy followed by interventional radiotherapy was a safe and effective treatment modality for primary vaginal cancer.

Definitive chemoradiation in vulvar squamous cell carcinoma: outcome and toxicity from an observational multicenter Italian study on vulvar cancer (OLDLADY 1.1).

BACKGROUND: Vulvar carcinoma is a rather uncommon gynecological malignancy affecting elderly women and the treatment of loco-regional advanced carcinoma of the vulva (LAVC) is a challenge for both gynecologic and radiation oncologists. Definitive chemoradiation (CRT) is the treatment of choice, but with disappointing results. In this multicenter study (OLDLADY-1.1), several institutions have combined their retrospective data on LAVC patients to produce a real-world dataset aimed at collecting data on efficacy and safety of CRT. METHODS: The primary study end-point was 2-year-local control (LC), secondary end-points were 2-year-metastasis free-survival (MFS), 2-year-overall survival (OS) and the rate and severity of acute and late toxicities. Participating centers were required to fill data sets including age, stage, histology, grading as well as technical/dosimetric details of CRT. Data about response, local and regional recurrence, acute and late toxicities, follow-up and outcome measures were also collected. The toxicity was a posteriori documented through the Common Terminology Criteria for Adverse Events version 5 scale. RESULTS: Retrospective analysis was performed on 65 patients with primary or recurrent LAVC treated at five different radiation oncology institutions covering 11-year time interval (February 2010-November 2021). Median age at diagnosis was 72 years (range 32-89). With a median follow-up of 19 months (range 1-114 months), 2-year actuarial LC, MFS and OS rate were 43.2%, 84.9% and 59.7%, respectively. In 29 patients (44%), CRT was temporarily stopped (median 5 days, range 1-53 days) due to toxicity. The treatment interruption was statistically significant at univariate analysis of factors predicting LC (p: 0.05) and OS rate (p: 0.011), and it was confirmed at the multivariate analysis for LC rate (p: 0.032). In terms of toxicity profile, no G4 event was recorded. Most adverse events were reported as grade 1 or 2. Only 14 acute G3 toxicities, all cutaneous, and 7 late G3 events (3 genitourinary, 3 cutaneous, and 1 vaginal stenosis) were recorded. CONCLUSION: In the context of CRT for LAVC, the present study reports encouraging results even if there is clearly room for further improvements, in terms of both treatment outcomes, toxicity and treatment interruption management.

Electrochemotherapy with intravenous bleomycin for heavily pre-treated vulvar cancer patients.

OBJECTIVE: The management of vulvar cancer recurrences is complicated by patients' advanced age and comorbidities. Bleomycin-based electrochemotherapy is a potential treatment option in this setting. However, no data on long-term outcomes are available. Therefore, a multicenter observational study was designed to evaluate the 5-year results in these patients. METHODS: Data about patients and tumor characteristics, electrochemotherapy cycles, clinical response, and follow-up were recorded. Treatment procedures were performed according to the European Standard Operating Procedures of Electrochemotherapy (ESOPE) guidelines. Response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULTS: Fifty-one patients (mean age 82.31±7.28 years) with squamous cell vulvar cancer underwent electrochemotherapy (median number of sessions 1; range 1-4). 20 patients had complete response and 32% of these were disease-free after 2 years (median progression-free survival 16.8 months). In 13 patients with partial response the median progression-free survival was 15.36 months, while patients with stable or progressive disease showed tumor relapse after 6.95 and 3.26 months, respectively (p<0.001). Median overall survival was 18.77, 13.07, 6.73, and 11.13 months in patients with complete response, partial response, stable disease, and progressive disease, respectively (p=0.001). CONCLUSION: Long-term follow-up of vulvar cancer patients showed reasonable tumor control after electrochemotherapy and improved progression-free survival and overall survival in responder subjects compared with non-responders. Further studies aimed at improving local response after electrochemotherapy are warranted. Thus, this approach represents a potential alternative for these patients.

Trans-inguinal pelvic lymphadenectomy in vulvar cancer patients: TRIPLE pilot study.

OBJECTIVE: The goal of this study was to assess the feasibility and safety of a retrograde extraperitoneal trans-inguinal novel approach to pelvic lymphadenectomy in vulvar cancer patients. The secondary objectives were to assess complications (early and late) and oncological outcomes. METHODS: In this pilot study, all patients referred to our institution from November 2019 to May 2021 were evaluated. The inclusion criteria were patients diagnosed with primary/recurrent vulvar cancer and who were candidates for concomitant groin and pelvic lymph node dissection. A consecutive sampling was planned during the study period. After conventional inguino-femoral lymph nodal dissection, ipsilateral extraperitoneal trans-inguinal pelvic lymphadenectomy (TRIPLE) was performed through a groin incision. Clinical data, type of treatment, perioperative complications, and follow-up were evaluated. RESULTS: 13 patients (8 primary, 5 recurrent vulvar cancer) underwent 16 TRIPLE procedures (10 unilateral, 3 bilateral). The median age was 69 years (range 58-93 years); 8 patients had comorbidities (61.5%). Up front locoregional radiotherapy was previously performed in two cases (15.4%). The pathology report showed metastatic lymph nodes in 20 (87%) groins and 11 (68.8%) pelvic sites; the mean number of removed and metastatic pelvic lymph nodes was 12.1 (range 5-33) and 2.9 (range 0-18), respectively. No intra-operative site-specific complications occurred. One (5.9%) post-operative site-specific complication was reported (pelvic abscess, grade 2), which was treated with antibiotics. One patient died due to concomitant pneumonia. No unilateral pelvic lymph node recurrence occurred during follow-up (median 13 months, range 2-43 months); 3 patients (23.1%) had distant site recurrence (median disease-free survival 9 months). CONCLUSIONS: TRIPLE seems to be a feasible and safe technique, providing adequate lymph node dissection. Despite being a high-risk and fragile population, morbidity was similar to previously reported data for conventional mini-invasive approaches. Prospective larger comparative series are necessary.

Clinical impact of SARS-CoV-2 infection among patients with vulvar cancer: the Gemelli Vul.Can multidisciplinary team.

BACKGROUND: 'Severe acute respiratory syndrome coronavirus-2' (SARS-CoV-2) infection has dramatically affected the management of patients with cancer, who are most vulnerable to the consequences of the infection. Patients with vulvar cancer are frequently elderly and affected by multiple co-morbidities, thus representing a particularly frail population. OBJECTIVE: To assess the clinical impact of the SARS-CoV-2 infection among patients scheduled for treatment for active vulvar cancer. METHODS: Data on patients with vulvar tumors referred to Fondazione Policlinico Universitario Agostino Gemelli IRCCS between February 2020 and July 2021 were retrospectively analyzed. Patients with a positive reverse transcription polymerase chain reaction in nasopharyngeal swab were considered as positive for SARS-Cov-2. RESULTS: One hundred and ninety-one patients with vulvar cancer were evaluated and scheduled for treatment. The median age was 72 years (range 35-94). Seven (3.7%) patients were diagnosed with SARS-Cov-2 infection: three (42.9%) had their treatment delayed, with no apparent consequences, two (28.6%) had their treatment delayed and later abandoned because of clinical worsening due to oncologic disease progression, and two (28.6%) contracted the infection in the post-operative period and died due to respiratory complications. CONCLUSIONS: In most cases the infection had major clinical implications, being associated with significant delays in oncologic treatments and extremely high mortality when contracted in the post-operative period.

"Clock mapping" prior to excisional surgery in vulvar Paget's disease: tailoring the surgical plan.

INTRODUCTION: Paget disease is a rare neoplasm of the skin that mainly involves the vulvar region. Vulvar Paget's disease (VPD) can spread beyond the apparent edges of the lesion resulting in a high risk of involved surgical margins. Our aim is to verify the efficacy of a preoperative vulvo-vaginal intensive clock mapping in the prediction of the invasiveness and the extension of VPD. MATERIALS AND METHODS: All consecutive patients with primary VPD referred to our institution from July 2005 to December 2018 were subjected to a preoperative intensive biopsy mapping (clock mapping) of the vulvo-vaginal area: inside and outside the vulvar skin visible lesion, according to o'clock positions, and in the vagina. Patients with positive biopsies "only inside" or "also beyond" the visible lesion were included, respectively, in Group A and B. Surgical excision was drawn passing by the points with negative histology. Pathological findings of mapping biopsies were compared with those from radical surgery. RESULTS: A total of 28 women were enrolled. After clock mapping definitive histology: 17 (60.7%) and 11 (39.3%) patients were included in Group A and B. Definitive histology showed non-invasive, micro-invasive and invasive VPD, respectively, in 13 (46.4%), 11 (39.3%) and 4 (14.3%) patients, with 4 patients further upstaged. Overall, negative margins were found in 14 (50%) patients: 9 (32.1%) from Group A and 5 (17.9%) from Group B. In 23 cases (82.1%), clock mapping identified free surgical margins along the vulvo-perineal skin excision front. CONCLUSIONS: Preoperative clock mapping emerged as potentially useful workup tool to predict invasiveness and extension of VPD, to tailor surgical excision.

Treatment of Early-Stage Gynecological Cancer-Related Lower Limb Lymphedema by Lymphaticovenular Anastomosis-The Triple Incision Approach.

Background and Objectives: Lower extremity lymphedema (LEL) is one of the most relevant chronic and disabling sequelae after gynecological cancer therapy involving pelvic lymphadenectomy (PL). Supermicrosurgical lymphaticovenular anastomosis (LVA) is a safe and effective procedure to treat LEL, particularly indicated in early-stage cases when conservative therapies are insufficient to control the swelling. Usually, preoperative assessment of these patients shows patent and peristaltic lymphatic vessels that can be mapped throughout the limb to plan the sites of skin incision to perform LVA. The aim of this study is to report the efficacy of our approach based on planning LVA in three areas of the lower limb in improving early-stage gynecological cancer-related lymphedema (GCRL) secondary to PL. Materials and Methods: We retrospectively reviewed the data of patients who underwent LVA for the treatment of early-stage GCRL following PL. Patients who had undergone groin dissection were excluded. Our preoperative study based on indocyanine green lymphography (ICG-L) and color doppler ultrasound (CDU) planned three incision sites located in the groin, in the medial surface of the distal third of the thigh, and in the upper half of the leg, to perform LVA. The primary outcome measure was the variation of the mean circumference of the limb after surgery. The changes between preoperative and postoperative limbs' measures were analyzed by Student's t-test. p values < 0.05 were considered significant. Results: Thirty-three patients were included. In every patient, three incision sites were employed to perform LVA. A total of 119 LVA were established, with an average of 3.6 for each patient. The mean circumference of the operated limb showed a significant reduction after surgery, decreasing from 37 cm ± 4.1 cm to 36.1 cm ± 4.4 (p < 0.01). Conclusions: Our results suggest that in patients affected by early-stage GCRL secondary to PL, the placement of incision sites in all the anatomical subunits of the lower limb is one of the key factors in achieving good results after LVA.

Palliative electrochemotherapy in primary or recurrent vulvar cancer.

OBJECTIVE: Since vulvar cancer is such a rare disease, the international experience with electrochemotherapy has been derived from only a few centers. The aim of this study was to evaluate clinical outcome and side effects profile with the use of electrochemotherapy in patients with primary or recurrent vulvar cancer. METHODS: Data were retrospectively collected from November 2017 to November 2019 in two major Italian oncologic institutes: Regina Elena Institute and Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Electrochemotherapy was offered in a palliative setting to patients with a primary or recurrent vulvar cancer who were not candidates for surgery or any other treatment, because of poor performance status or previous delivered treatments. All patients underwent general anesthesia. Electrical pulses were delivered using a pulse generator. Intravenous bleomycin was administered in conjunction with electrochemotherapy. Follow-up examinations were performed at 1, 3, and 6 months. Primary endpoint was to assess the response rate of electrochemotherapy as palliative treatment in patients with vulvar cancer. RESULTS: A total of 15 patients were included in the study. Fourteen patients (93.3%) had a squamous cell carcinoma and one patient had vulvar carcinosarcoma. Ten patients (66.7 %) had a single lesion and 5 patients (33.3%) had multiple lesions. Median number of electrical pulses was 22 (range 3-42) and median operative time was 13 (range 7-20) min. No intra-procedure complications occurred. One patient had pneumonia during their post-operative stay. Overall response rate after 1 month was 80%. At the 3-month follow-up, 3 patients (20%) had disease progression, 3 patients (20%) had died from ongoing disease, 1 patient (6.7%) died for other reasons, whereas the other patients maintained their 1-month clinical response. A total of 8/13 patients (61.5%) were alive at 6-month follow-up, whereas 6/12 patients (50%) were alive at 1-year follow-up. CONCLUSIONS: Electrochemotherapy is a feasible, easy to perform, and reproducible procedure in patients with primary or recurrent vulvar cancer who are unable to undergo surgery. Survival after 1 year in this population was 50%. Electrochemotherapy may have a role in the management of vulvar cancer, especially as palliative treatment when other therapies are no longer applicable.

Multidisciplinary personalized approach in the management of vulvar cancer - the Vul.Can Team experience.

INTRODUCTION: Multidisciplinary treatment strategy involving adjuvant radiotherapy for advanced vulvar cancer could be useful in offering the best personalized clinical approach. In 2013, the VULvar CANcer Multi-Disciplinary Team (Vul.Can MDT) was set up in our institution, in order to share knowledge and expertise, high-quality diagnosis, and evidence-based decision making in the context of personalized medicine. The aim of this observational study was to report on our series of vulvar cancer patients managed postoperatively with radiotherapy within the framework of a formal multidisciplinary tumor board. METHODS: Coupling surgical and oncological international guidelines with "case-by-case" discussions, a multi-specialist consensus was progressively reached and internal recommendations were developed and introduced in the daily routine. Data from vulvar cancer patients who underwent primary surgery and adjuvant radiotherapy throughout a 5-year period were retrospectively collected. Actuarial local control was the primary endpoint, while secondary end-points were acute and late toxicities, disease-free survival, and overall survival. Toxicity was evaluated according to the Common Toxicity Criteria Adverse Event v 4.0 scale. RESULTS: The analysis included 35 patients with squamous vulvar cancer treated with adjuvant radiotherapy±chemotherapy, from April 2013 to September 2017. Median age was 70 years (range 18-87), all patients underwent surgery followed by concomitant chemoradiation (45.7%) or radiotherapy alone (54.3%). The median prophylactic dose on lymphatic drainage was 45 Gy, while positive nodes and perineal area received 51.2 Gy and 52.6 Gy, respectively. Chemotherapy involved the cisplatin-based regimen (45.7%)±5-fluorouracil (37.1%). Median follow-up was 32 months (range 6-72): the 24-months local control, disease-free survival, and actuarial overall survival rates were 88.6%, 82.0%, and 91.0%, respectively. Low rates of severe acute (12%) and late (3%) toxicities occurred. DISCUSSION: The outcomes of this series support the benefit of a multidisciplinary personalized approach in the management of vulvar cancer.

Local Perineal Capillary Perforator Flaps: A Minimally Invasive Technique for the Correction of Vulvar Stenosis.

BACKGROUND: Vulvar stenosis is a debilitating condition that compromises sexual function, urination, and the ability to undergo gynecological examinations. The purpose of this study is to describe the technique of capillary perforator perineal flaps (CPPF) for the correction of vulvar stenosis. METHODS: We retrospectively examined patients with vulvar stenosis treated through surgical separation and reconstruction with CPPF. The procedure involved vulvar separation with the creation of a subsequent defect, repaired using a flap, harvested laterally to the labia majora including a capillary perforator and transferred through a subcutaneous tunnel to repair the vulvar defect. The functional outcome was evaluated with the Bradford scale, comparing the preoperative and postoperative scores using the Student's t-test. RESULTS: thirteen patients were included, three with stenosis following treatment for vulvar cancer and ten due to lichen sclerosus. In total, we analyzed 29 flaps, with an average size of 15.6 cm2. We always included just one perforator in the flap and no postoperative complications. Stenosis was resolved in all patients, with no recurrences one year after the surgery. The preoperative average severity of the stenosis was 2.3 + 0.6, reducing to 0.3 + 0.4 post-intervention, indicating a significant improvement (p < 0.01). CONCLUSIONS: CPPF has proven to be a quick and safe method for the reconstruction of vulvar stenosis.

Surgical Bedside Electrochemotherapy for Local Control of a Recurrent Phylloid Malignant Breast Tumor: A Case Report.

BACKGROUND: We present the case of a recurrent malignant phyllodes tumor of the breast, after mastectomy and radiotherapy, in which electrochemotherapy (ECT) was applied to the tumor bed, to achieve better local control. CASE REPORT: A 66-year-old woman with a large malignant phyllodes tumor of the right breast with a size of 40 cm underwent right radical mastectomy and right axillary lymph node sampling. One month after surgery, with histologically clear margins, the woman presented with multiple small oval masses in the upper portion of the chest wall, indicating rapid disease progression. A second radical excision with clear margins was performed, followed by adjuvant radiotherapy. Two months after the end of treatment, a new 3-cm mass was present in the right axillary extension. The patient underwent a third extensive debulking surgery. At the end of the resection, ECT was applied on the tumor bed along the extensive skin flaps and resection margins. After eight months of follow-up, breast magnetic resonance imaging and total body computed tomography showed disease recurrence in the anterior portion of the right serratus muscle and in the lungs bilaterally. The area undergoing previous ECT showed no disease recurrence. The patient received two lines of palliative chemotherapy. She died 28 months after diagnosis. At the time of death, the large area treated with ECT was geometrically spared from local disease progression. CONCLUSION: This case report suggests the potential efficacy of ECT at the operating bedside to increase local control in aggressive malignancies.

Evaluating the Risk of Inguinal Lymph Node Metastases before Surgery Using the Morphonode Predictive Model: A Prospective Diagnostic Study in Vulvar Cancer Patients.

Ultrasound examination is an accurate method in the preoperative evaluation of the inguinofemoral lymph nodes when performed by experienced operators. The purpose of the study was to build a robust, multi-modular model based on machine learning to discriminate between metastatic and non-metastatic inguinal lymph nodes in patients with vulvar cancer. One hundred and twenty-seven women were selected at our center from March 2017 to April 2020, and 237 inguinal regions were analyzed (75 were metastatic and 162 were non-metastatic at histology). Ultrasound was performed before surgery by experienced examiners. Ultrasound features were defined according to previous studies and collected prospectively. Fourteen informative features were used to train and test the machine to obtain a diagnostic model (Morphonode Predictive Model). The following data classifiers were integrated: (I) random forest classifiers (RCF), (II) regression binomial model (RBM), (III) decisional tree (DT), and (IV) similarity profiling (SP). RFC predicted metastatic/non-metastatic lymph nodes with an accuracy of 93.3% and a negative predictive value of 97.1%. DT identified four specific signatures correlated with the risk of metastases and the point risk of each signature was 100%, 81%, 16% and 4%, respectively. The Morphonode Predictive Model could be easily integrated into the clinical routine for preoperative stratification of vulvar cancer patients.

Secondary post-oncologic vulvar reconstruction - a simplified algorithm.

Introduction: Surgical treatment is the gold standard of care for vulvar cancer and is burdened by a high risk of wound complications due to the poor healing typical of the female genital area. Moreover, this malignancy has a high risk of local relapse even after wide excision. For these reasons, secondary reconstruction of the vulvoperineal area is a relevant and challenging scenario for gynecologists and plastic surgeons. The presence of tissue already operated on and undermined, scars, incisions, the possibility of previous radiation therapy, contamination of urinary and fecal pathogens in the dehiscent wound or ulcerated tumor, and the unavailability of some flaps employed during the primary procedure are typical complexities of this surgery. Due to the rarity of this tumor, a rational approach to secondary reconstruction has never been proposed in the literature. Methods: In this observational retrospective study, we reviewed the clinical data of patients affected by vulvar cancer who underwent secondary reconstruction of the vulvoperineal area in our hospital between 2013 and 2023. Oncological, reconstructive, demographic, and complication data were recorded. The primary outcome measure was the incidence of wound complications. The secondary outcome measure was the indication of the different flaps, according to the defect, to establish an algorithm for decision-making. Results: Sixty-six patients were included; mean age was 71.3 ± 9.4 years, and the mean BMI was 25.1 ± 4.9. The mean size of the defect repaired by secondary vulvar reconstruction was 178 cm2 ± 163 cm2. Vertical rectus abdominis myocutaneous (VRAM), anterolateral thigh (ALT), fasciocutaneous V-Y (VY), and deep inferior epigastric perforator (DIEP) were the flaps more frequently employed. We observed five cases of wound breakdown, one case of marginal necrosis of an ALT flap, and three cases of wound infection. The algorithm we developed considered the geometry and size of the defect and the flaps still available after previous surgery. Discussion: A systematic approach to secondary vulvar reconstruction can provide good surgical results with a low rate of complications. The geometry of the defect and the use of both traditional and perforator flaps should guide the choice of the reconstructive technique.

The Role of Ultrasound in the Evaluation of Inguinal Lymph Nodes in Patients with Vulvar Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVE: To determine the efficacy of ultrasound in assessing the inguinal lymph nodes in patients with vulvar cancer. METHODS: A systematic review of published research up to October 2020 that compares the results of ultrasound to determine groin node status with histology was conducted. All study types that reported primary data on the role of ultrasound in the evaluation of groin lymph nodes in vulvar cancer were included in the systematic review. Data retrieved from the included studies were pooled in random-effects meta-analyses. RESULTS: After the screening and selection process, eight articles were deemed pertinent for inclusion in the systematic review and meta-analysis. The random-effects model showed a pooled Se of 0.85 (95% CI: 0.81-0.89), Sp of 0.86 (95% CI: 0.81-0.91), PPV of 0.65 (95% CI: 0.54-0.79) and NPV of 0.92 (95% CI: 0.91-0.94). There was a pooled LR+ and LR- of 6.44 (95% CI: 3.72-11.4) and 0.20 (95% CI: 0.14-0.27), respectively. The pooled accuracy was 0.85 (95% CI: 0.80-0.91). CONCLUSIONS: Although the studies had small sample sizes, this review represents the best summary of the data so far. Ultrasound has revealed high sensitivity and high negative predictive value in the assessment of nodal status in vulvar cancer.

Lymphatic Function of the Lower Limb after Groin Dissection for Vulvar Cancer and Reconstruction with Lymphatic SCIP Flap.

Inguinofemoral lymphadenectomy, frequently performed for vulvar cancer, is burdened with substantial immediate and long-term morbidity. One of the most disabling treatment-related sequelae is lower limb lymphedema (LLL). The present study aims to describe the wound complications and the severity of LLL in patients who have undergone groin dissection for vulvar cancer and immediate inguinal reconstruction with the Lymphatic Superficial Circumflex Iliac Perforator flap (L-SCIP). We retrospectively reviewed the data of patients who underwent bilateral groin dissection and unilateral inguinal reconstruction with the L-SCIP. The presence and severity of postoperative LLL during the follow-up period were assessed by lymphoscintigraphy and limbs' volume measurement. In addition, immediate complications at the level of the inguinal area were registered. The changes between preoperative and postoperative limb volumes were analyzed by Student's t test. p values < 0.05 were considered significant. Thirty-one patients were included. The mean variation of volume was 479 ± 330 cc3 in the side where groin reconstruction had been performed, and 683 ± 425 cc3 in the contralateral side, showing smaller variation in the treated side (p = 0.022). Lymphoscintigraphy confirmed the clinical findings. Based on our results, inguinal reconstruction with L-SCIP performed at the same time of groin dissection in patients treated for vulvar cancer can provide a significant protective effect on LLL.

Feasibility, indications and complications of SCIP flap for reconstruction after extirpative surgery for vulvar cancer.

INTRODUCTION: Surgical therapy for vulvar cancer involves wide defects that often require flap-based reconstruction. The goal of the reconstruction is fast wound healing with low donor site morbidity. MATERIALS AND METHODS: This is a retrospective observational cohort study in which we reviewed all patients who underwent surgery for vulvar cancer followed by reconstruction using the Superficial Circumflex Iliac Artery Perforator (SCIP) flap between 2015 and 2020. The primary outcome measure of this investigation was the incidence of wound complications. The secondary outcomes were the surgical indications in terms of establishing the anatomical subunits involved in the resection that made us choose this flap for reconstruction. This study adheres to the STROBE guidelines. RESULTS: Thirty-two patients were included; in two cases, the flap was performed bilaterally for a total of 34 SCIP flaps. The mean age of patients was 70.6 ± 8.6 years, and the mean BMI was 26.8 ± 4.7. The SCIP flap was always feasible. The mean flap size was 128.8 ± 74.3cm2. Three patients showed wound complications. In every patient, the defect involved the vulva, perineum and inguinal area; in 18 patients, the mons pubis was also involved. The mean follow-up was 30 months. During the follow-up, six patients died, and four showed local or nodal cancer relapse. CONCLUSION: Our results suggest that the advantages of SCIP flap for the reconstruction of vulvoperineal defects secondary to vulvar cancer surgery include low complication rate, minimal donor site morbidity, quick dissection, proximity of donor and recipient sites, possibility to harvest large skin islands of variable thickness and chimeric flaps.

Gov➔Value: How to combine reported quality experiences and patient-reported outcome measures. First results on vulvar cancer patients in an Italian Research Hospital.

Introduction: Vulvar cancer (VC) accounts for <1% of cancers affecting the female gender. Clinical Pathways (CP) and Clinical Outcomes Monitoring are useful for providing high-quality care to these patients. However, it is essential to integrate them with the patient's perspective according to Value-Based Healthcare paradigms. Patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) are tools for assessing outcomes and experiences with health care from the patient's perspective. The aim of this paper is to collect and synthesize PROMs and main stakeholders' experience on the VC CP, according to a value-based approach. Materials and methods: To select the most appropriate instrument, a review was conducted on the main databases and official websites of specific institutions and organizations. In the second phase, a 2-round Delphi survey was conducted to assess the Reported Experience Measures (REMs) tool. Questions were evaluated according to four criteria (general relevance, evidence-based, measurability, actionability) and included if strong agreement was reached. A Principal Component Analysis (PCA) was executed. Cronbach's alpha and McDonald's omega were computed. Fisher's exact test and Wilcoxon rank sum test were used to compare ratings between groups. Descriptive statistics were performed for both PROMs and REMs instruments. Results: For PROMs assessment, EORTC QLQ-C30 questionnaire was selected and administered to 28 patients. Global Health Status/Quality of Life and Functional Scales Scores were high or very high, while symptoms scale reported low or medium scores. The final REMs consists of 22 questions for professionals and 16 for patients and caregivers. It was administered to 22 patients, 11 caregivers, 5 physicians, 2 nurses and 1 clinical senior manager. PCA identified 4 components. Scale reliability was acceptable (α = 0.75 95% CI: 0.61-0.85; ω = 0.69; 95% CI: 0.54, 0.82). A statistically significant difference between the patient/caregiver group and the professionals was found for items 8 (follow-up), 10 (perceived quality), 12 (safety), and 16 (climate) (p = 0.02; p = 0.03; p < 0.001; p < 0.001, respectively). Discussion: PROMs could provide new ways of intercepting patients' needs and feedback, thus acting on them. The proposed REMs tool would allow to detect information not available elsewhere, which, through Audit and feedback strategies, could lead to enhancement of healthcare experience, according to a value-based approach.

BRCA Mutation Status in Triple-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Pivotal Role for Treatment Decision-Making.

Triple-negative breast cancer (TNBC) is characterized by earlier recurrence and shorter survival compared with other types of breast cancer. Moreover, approximately 15 to 25% of all TNBC patients harbor germline BRCA (gBRCA) 1/2 mutations, which confer a more aggressive phenotype. However, TNBC seems to be particularly sensitive to chemotherapy, the so-called 'triple negative paradox'. Therefore, Neoadjuvant chemotherapy (NACT) is currently considered the preferred approach for early-stage TNBC. BRCA status has also been studied as a predictive biomarker of response to platinum compounds. Although several randomized trials investigated the addition of carboplatin to standard NACT in early-stage TNBC, the role of BRCA status remains unclear. In this retrospective analysis, we evaluated data from 136 consecutive patients with Stage I-III TNBC who received standard NACT with or without the addition of carboplatin, in order to define clinical features and outcomes in BRCA 1/2 mutation carriers and non-carrier controls. Between January 2013 and February 2021, 67 (51.3%) out of 136 patients received a standard anthracyclines/taxane regimen and 69 (50.7%) patients received a platinum-containing chemotherapy regimen. Deleterious germline BRCA1 or BRCA2 mutations were identified in 39 (28.7%) patients. Overall, patients with deleterious gBRCA1/2 mutation have significantly higher pCR rate than non-carrier patients (23 [59%] of 39 vs. 33 [34%] of 97; p = 0.008). The benefit of harboring a gBRCA mutation was confirmed only in the subset of patients who received a platinum-based NACT (17 [65.4%] of 26 vs. 13 [30.2%] of 43; p = 0.005) while no differences were found in the platinum-free subgroup. Patients who achieved pCR after NACT had significantly better EFS (OR 4.5; 95% CI 1.9-10.7; p = 0.001) and OS (OR 3.3; 95% CI 1.3-8.9; p = 0.01) than patients who did not, regardless of BRCA1/2 mutation status and type of NACT received. Our results based on real-world evidence show that TNBC patients with the gBRCA1/2 mutation who received platinum-based NACT have a higher pCR rate than non-carrier patients, supporting the use of this chemotherapy regimen in this patient population. Long-term follow-up analyses are needed to further define the role of gBRCA mutation status on clinical outcomes in patients with early-TNBC.

The Radiotherapy Role in the Multidisciplinary Management of Locally Advanced Vulvar Cancer: A Multidisciplinary VulCan Team Review.

Locally advanced vulvar cancer (LAVC) is a challenging disease, requiring multidisciplinary management. The aim of this review is to propose an integrated clinical approach including radiotherapy (RT) in the multidisciplinary management of LAVC to customize the treatment. A review of the literature was conducted on PubMed, Scopus, and Cochrane library to acquire all relevant studies on RT in LAVC. Based on the available evidence, RT, with or without concurrent chemotherapy, has a relevant role as adjuvant and exclusive treatment or in the neoadjuvant setting. However, multicentric prospective trials are needed to define the best treatment options based on tumor and patient characteristics. A multidisciplinary and multidimensional assessment can also be useful to identify the most suitable approach, considering patients' age and comorbidities, in view of a better treatment personalization.

The Vulvar Immunohistochemical Panel (VIP) Project: Molecular Profiles of Vulvar Squamous Cell Carcinoma.

INTRODUCTION: The study's aim was to investigate the immunohistochemical (IHC) expression of biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma (VSCC). METHODOLOGY: A series of 101 patients surgically treated at our center from 2016 to 2020 were retrospectively enrolled: 53 node-negative (Group A) and 48 node-positive (Group B). A total of 146 samples, 101 from primary tumor (T) and 45 from nodal metastases (N), were investigated. The IHC panel included: p16, p53, MLH1, MSH2, MSH6, PMS2, PD-L1, CD3, HER2/neu, ER, PR, EGFR, VEGF, and CD31. The reactions were evaluated on qualitative and semi-quantitative scales. Generalized Linear Model (GLM) and cluster analysis were performed in R statistical environment. A distance plot compared the IHC panel of T with the correspondent N. RESULTS: In Group A: p16-positive expression (surrogate of HPV-dependent pathway) was significantly higher (20.8% vs. 6.2%, p = 0.04). In Group B: PD-L1 positivity and high EGFR expression were found, respectively, in 77.1% and 97.9% patients (T and/or N). Overall, p16-negative tumors showed a higher PD-L1 expression (60.9% vs. 50.0%). In both groups: tumoral immune infiltration (CD3 expression) was mainly moderate/intense (80% vs. 95%); VEGF showed strong/moderate-diffuse expression in 13.9% of T samples; CD31, related to tumoral microvessel density (MVD), showed no difference between groups; a mutated p53 and over-expressed PD-L1 showed significant association with nodal metastasis, with Odds Ratios (OR) of 4.26 (CI 95% = 1.14-15.87, p = 0.03) and 2.68 (CI 95% = 1.0-7.19, p < 0.05), respectively; since all mismatch repair proteins (MMR) showed a retained expression and ER, PR, and HER2/neu were negative, they were excluded from further analysis. The cluster analysis identified three and four sub-groups of molecular profiles, respectively, in Group A and B, with no difference in prognosis. The molecular signature of each N and corresponding T diverged significantly in 18/41 (43.9%) cases. CONCLUSIONS: Our results support a potential role of immune checkpoint inhibitors and anti-VEGF and anti-EGFR drugs especially in patients with worse prognosis (metastatic, HPV-independent). A panel including EGFR, VEGF, PDL1, p16, and p53 might be performed routinely in primary tumor and repeated in case of lymph node metastases to identify changes in marker expression.