Vulvar cancer is an uncommon gynecological malignancy primarily affecting postmenopausal women. There is no specific screening and the most effective strategy to reduce vulvar cancer incidence is the opportune treatment of predisposing and preneoplastic lesions associated with its development. While vulvar cancer may be asymptomatic, most women present with vulvar pruritus or pain, or have noticed a lump or ulcer. Therefore, any suspicious vulvar lesion should be biopsied to exclude invasion. Once established, the most common subtype is squamous cell carcinoma. Treatment of vulvar cancer depends primarily on histology and surgical staging. Treatment is predominantly surgical, particularly for squamous cell carcinoma, although concurrent chemoradiation is an effective alternative, particularly for advanced tumors. Management should be individualized and carried out by a multidisciplinary team in a cancer center experienced in the treatment of these tumors.

The aim of this study was to assess trends in the age‐specific incidence of vulvar cancer in 13 high‐income countries satisfying a priori conditions regarding the availability of cancer registry data over a 20‐year period; these were Canada, the United States, nine European countries, Australia and Japan. Five‐yearly incidence and population at risk were obtained from the International Agency for Research on Cancer's Cancer Incidence in Five Continents for the years 1988–1992 (Volume 7) to 2003–2007 (Volume 10). The 5‐yearly average percent change (AvPC) over the period and standardised rate ratios (SRRs) for 2003–2007 versus 1988–1992 were used to assess changes in the age‐standardised incidence rates of vulvar cancer for all ages, and for <60 years and 60+ years. During the study period, the 5‐yearly AvPC across the 13 countries increased by 4.6% (p = 0.005) in women of all ages, and 11.6% (p = 0.02) in those <60 years. No change was observed in women aged 60+ years (5‐yearly AvPC = 0.1%, p = 0.94). The SRR for 2003–2007 versus 1988–1992 was significantly elevated in women <60 years of age (SRR = 1.38, 95% CI: 1.30–1.46), but not in women of 60+ years (SRR = 1.01, 95% CI: 0.97–1.05). The increase in incidence in women <60 years of age drove a significant increase in the overall SRR in women of all ages (SRR = 1.14, 95% CI: 1.11–1.18). Some differences in the specific findings at the individual country level were observed. The findings are consistent with changing sexual behaviours and increasing levels of exposure to human papillomavirus (HPV) in cohorts born around/after about 1950, but younger cohorts offered HPV vaccination are likely to receive some protection against developing vulvar cancer in the future.

The objective of this study was to assess trends in vulvar cancer incidence and mortality in Australia.Case numbers for invasive carcinoma of the vulva (1982-2009) and vulvar cancer deaths (1982-2011) were obtained from the National Cancer Statistics database. Standardized rate ratios (SRRs) were used to assess changes in age-standardized incidence and mortality rates, for all ages and for younger than 60 years and 60+ years.Age-standardized incidence rates in women across all ages did not significantly change from 1982-1984 to 2007-2009 (from 2.1 to 2.5 per 100,000 women; SRR from the later to the earlier period, 1.13 [95% CI, 1.00-1.27]). However, there was a significant 84% increase in incidence in women younger than 60 years (SRR, 1.84 [95% CI, 1.49-2.26]), with no change for women 60+ years (SRR, 0.90 [95% CI, 0.79-1.04]). Age-standardized mortality in women across all ages significantly decreased by 22% from 1982-1986 to 2007-2011 (from 0.7 to 0.5 per 100,000 women; SRR, 0.78 [95% CI, 0.66-0.93]). However, this was driven by declines in older women, with stable rates in women younger than 60 years (SRR, 1.05 [95% CI, 0.62-1.79]); rates in 60+ years decreased by 24% (SRR, 0.76 [95% CI, 0.63-0.91]).Since the early 1980s, vulvar cancer incidence has increased by more than 80% in women younger than 60 years in Australia, but there has been no increased incidence in older women. These findings are consistent with the possibility of increased exposure to the human papillomavirus in cohorts born after 1950. By contrast, age-standardized vulvar cancer mortality rates have been stable in younger women, but have declined in older women.

Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget’s disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.

As part of its mission to improve the quality of care for women with gynecological cancers across Europe, the European Society of Gynaecological Oncology (ESGO) first published in 2017 evidence-based guidelines for the management of patients with vulvar cancer.To update the ESGO guidelines based on the new evidence addressing the management of vulvar cancer and to cover new topics in order to provide comprehensive guidelines on all relevant issues of diagnosis and treatment of vulvar cancer.The ESGO Council nominated an international development group comprised of practicing clinicians who provide care to vulvar cancer patients and have demonstrated leadership through their expertize in clinical care and research, national and international engagement and profile as well as dedication to the topics addressed to serve on the expert panel (18 experts across Europe). To ensure that the statements were evidence-based, new data identified from a systematic search were reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Prior to publication, the guidelines were reviewed by 206 international practitioners in cancer care delivery and patient representatives.The updated guidelines cover comprehensively diagnosis and referral, staging, pathology, pre-operative investigations, surgical management (local treatment, groin treatment, sentinel lymph node procedure, reconstructive surgery), (chemo)radiotherapy, systemic treatment, treatment of recurrent disease (vulvar, inguinal, pelvic, and distant recurrences), and follow-up. Management algorithms are also defined.© IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.

There is a definite trend toward vulvar conservation and individualized management of patients with early vulvar cancer. This approach initially was used only for patients with T1 disease, but with increasing experience with conservative surgery and the integration of postoperative adjuvant radiation when appropriate, some investigators have broadened the indications to include carefully selected patients with T2 lesions. A recent literature review suggests that the local invasive recurrence rate for T1 disease is 7.2% (12 of 165) after radical local excision compared with 6.3% (23 of 365) after radical vulvectomy (P = 0.85). Surgical margins must be at least 1 cm, and the rest of the vulva must be healthy if an increased local recurrence rate is to be avoided. Local recurrences usually can be treated successfully if diagnosed early, but recurrence in the groin is usually fatal. Inguinal-femoral lymphadenectomy should be done on all patients if the primary tumor is more than 2 cm in diameter and in patients with T1 disease in whom the depth of invasion is greater than 1 mm. Separate groin incisions may be used, but pelvic and groin irradiation should be given if there is at least one large node replaced with tumor or multiple nodes containing micrometastases. Careful patient selection is critical if modified operations are used, or an increased rate of recurrence will follow.

Vulvar reconstruction may be required after vulvectomy or any vulvar surgery. Providers should be familiar with techniques for reconstruction to improve clinical outcomes.This article reviews the different techniques for reconstruction after vulvectomy and describes the decision-making process for selection of appropriate techniques, postoperative care, and expected outcomes.A literature search was conducted, focusing on the plastic surgery and gynecologic oncology literature, using the following search terms: "vulvar reconstruction," "perineal reconstruction," "vulvectomy," and "vulvar cancer." The search was limited to English publications.Reconstruction after vulvectomy can be performed using a variety of techniques ranging from simple or complex closure to adjacent tissue rearrangement to skin grafting, locoregional, and free flaps. The appropriate technique is best chosen based on the characteristics of the patient and postablative defect, as well as the reconstructive goals. Postoperative complications are usually minor.Vulvar reconstruction techniques vary widely and offer patients improved outcomes.Knowledge of vulvar reconstruction techniques is necessary for gynecologists performing vulvar surgery to ensure optimal patient outcomes.

Reconstruction of total vulvectomy defect represents a challenge, and reconstructive methods include skin graft, local skin flap, musculocutanous flap, and pedicled perforator flap. We report a case of a 63‐year‐old patient affected by extramammary Paget's disease of vulva who underwent total vulvectomy receiving reconstruction with bilateral profunda artery perforator based V‐Y rotation advancement flap. The literature about vulva reconstruction was reviewed. This innovative flap design combined the classic rotation flap and V‐Y advancement flap with inclusion of the profunda artery perforators to augment the flap blood supply. Besides, the internal pudendal nerve was preserved to maintain the sensation of the neo‐uvula. The flap survived completely without major post‐operative complications with 9‐months follow‐up. Profunda artery perforator based V‐Y rotation advancement flap may represent a valuable option in total vulvectomy defect reconstruction. © 2015 Wiley Periodicals, Inc. Microsurgery 35:668–671, 2015.

To assess clinical outcomes of inguinal lymph node surgical resection compared to primary groin radiotherapy for locally advanced, surgically unresectable vulvar cancer.All patients treated with radiation for vulvar cancer were identified between Jan 1, 2000 - Dec 31, 2020 at 2 academic centres. Inclusion criteria were those treated with curative intent primary radiotherapy +/- chemotherapy, tumors >4 cm, and surgically unresectable squamous cell vulvar carcinoma. Groin recurrence-free survival (RFS) was compared for groin surgery and primary groin radiotherapy using the Kaplan Meier method and log rank test. Groin failures are described by treatment modality, radiation dose and lymph node size.Of 476 patients treated with radiation for vulvar cancer, 112 patients (23.5%) met inclusion and exclusion criteria. The median (95% CI) follow up was 1.9 (1.4-2.5) years. Complete clinical response was significantly higher (80.0%) in patients with surgical groin resection compared to patients treated with primary groin radiotherapy (58.2%) (p = 0.04). On multivariable analysis, after adjusting for clinical and/or radiologically abnormal lymph nodes (p = 0.67), surgical groin resection was significantly associated with lower groin recurrence (HR 0.2 (95%CI 0.05-0.92), p = 0.04). The 3-year groin recurrence-free survival (RFS) was significantly higher at 94.4% (87.1-100) in patients with surgical groin resection compared to 79.2% (69.1-90.9) in patients treated with primary radiation (p = 0.02).In locally advanced squamous cell vulvar cancer, surgical groin management improves groin RFS compared to radiotherapy alone.Copyright © 2024. Published by Elsevier Inc.

Women with locally advanced vulvar carcinoma have an excellent chance of a cure by undergoing a radical vulvectomy with an "en bloc" inguinofemoral lymphadenectomy, but the morbidity associated this surgical approach is substantial. To achieve an outcome comparable with the traditional radical method in terms of oncologic safety, and an improved post-operative quality of life, we modified the classic triple-incision technique and suggested it as an alternative for these patients. The aim of this study was to report this new technique.Between January 2004 and November 2009, 24 patients with clinical stage T2 (≥ 4 cm) or T3 invasive vulvar cancer underwent surgical treatment with our modified triple incision technique. Their clinical and surgical complications and follow-up data were retrospectively reviewed.The post-surgical complications were as follows: lymphoedema in 45.8%, wound breakdown in 20.8% and cellulitis in 8.3%. After a median follow-up of 35.5 months, three (12.5%) patients developed a recurrence in the skin bridge (2/24, 8.3%) or lungs (1/24, 4.2%). All patients suffering from skin bridge recurrences were salvaged by local re-resection. Four (16.7%) cases of death were noted: three (12.5%) patients died of non-cancer-related diseases and one (4.2%) died from a multifocal pulmonary metastasis; no evidence of vulvar or groin disease was observed at these patients' last follow-up.The modified triple-incision technique described in this preliminary study appears to be safe, feasible and tolerable for patients with a locally advanced vulvar cancer, and offers an acceptable morbidity.Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Inguinal lymph nodes dissection (ILND) is recommended in patients presenting with high-risk penile (PC) or vulvar cancers (VC). Though, this surgical procedure is underused because of its anticipated morbidity. Minimally invasive approaches were proposed to minimize complications associated with open surgery. In this review, we analyze current available data exploring intra and perioperative outcomes of robot-assisted ILND (RAIL).On April 9, 2023, a literature search was conducted using the PubMed and Scopus databases. The search employed the combination of the following terms: ("robotic assisted" OR "robot-assisted" OR "robotic") AND ("inguinal lymph node dissection" OR "lymphadenectomy") AND ("penile cancer" OR "vulvar cancer"). Out of the 404 identified articles, 18 were used for the present scoping review and their results were reported according to the PRISMA statement.Data on 171 patients, ranging in age from 32 to 85 years, were obtained. Most of them (90.6%) harbored a penile squamous cell carcinoma and presented with no palpable nodes (85%). Operation time (OT) ranged between 45 and 300 min. Estimated blood loss varied from 10 to 300 mL. One single intra-operative complication was reported and one conversion to open was recorded. The lymph nodes (LNs) count spanned from 3 to 26 per groin, with 17 studies reporting a median yield >7 nodes. Hospital stay was 1-7 days, while the duration of drainage ranged from 4 to 72 days. Post-operative complications included lymphocele (22.2%; 0-100%), lymphedema (13.4%; 0-40%), cellulitis (11.1%; 0-25%), skin necrosis (8.7%; 0-15.4%). seroma (3.5%; 0-20%) and wound breakdown/wound infection (2.9%; 0-10%). Out of the included studies, 7 provided at least a 12-month follow-up, with recurrence-free rates ranging from 50% to 100% in patients affected by penile cancer and from 92% to 100% in vulvar cancer patients.The available evidence on RAIL for the treatment of PC and VC is limited. The approach appears to be safe and effective, as it provides an adequate lymph node yield while ensuring a minimally morbid postoperative course and a short hospital stay.

From 1977 to 1984, 114 eligible patients with invasive squamous cell carcinoma of the vulva and positive groin nodes after radical vulvectomy and bilateral groin lymphadenectomy were randomized to receive either radiation therapy or pelvic node resection. Fifty-three of the 59 patients randomized to radiation therapy received a 4500- to 5000-rad tumor dose in five to 6.5 weeks bilaterally to the groins and to the midplane of the pelvis even if only unilateral positive groin nodes had been detected; no radiation was given to the central vulvar area. Fifty-three of the 55 patients randomized to further surgery had pelvic node resection performed on the side containing positive groin nodes either unilaterally or bilaterally. Acute and chronic morbidity was similar for both regimens. The two major poor prognostic factors were clinically suspicious or fixed ulcerated groin nodes and two or more positive groin nodes. The difference in survival for the 114 evaluable patients was significant, favoring the adjunctive radiation therapy group (P =.03). The estimated two-year survival rates were 68% for the radiation therapy group and 54% for pelvic node resection group. The most dramatic survival advantage for radiation therapy was in patients who had either of the two major poor prognostic factors present; at this time, the benefit of radiation therapy for the remaining patients is uncertain. In this randomized prospective study, the addition of adjunctive groin and pelvic irradiation therapy after radical vulvectomy and inguinal lymphadenectomy proved superior to pelvic node resection.

To evaluate feasibility of chemoradiation as alternative for extensive surgery in patients with locally advanced vulvar cancer and to report on locoregional control, toxicity and survival.In a multicenter, prospective phase II trial patients with locally advanced vulvar cancer were treated with locoregional radiotherapy combined with sensitizing chemotherapy (capecitabine). Treatment feasibility, percentage locoregional control, survival and toxicity were evaluated.52 patients with mainly T2/T3 disease were treated according to the study protocol in 10 centers in the Netherlands from 2007 to 2019. Full dose radiotherapy (tumor dose of 64.8Gy) was delivered in 92% and full dose capecitabine in 69% of patients. Most prevalent acute ≥ grade 3 toxicities were regarding skin/mucosa and pain (54% and 37%). Late ≥grade 3 toxicity was reported for skin/mucosa (10%), fibrosis (4%), GI incontinence (4%) and stress fracture or osteoradionecrosis (4%). Twelve weeks after treatment, local clinical complete response (cCR) and regional control (RC) rates were 62% and 75%, respectively. After 2 years, local cCR persisted in 22 patients (42%) and RC was 58%. Thirty patients (58%) had no evidence of disease at end of follow-up (median 35 months). In 9 patients (17%) extensive surgery with stoma formation was needed. Progression free survival was 58%, 51% and 45% and overall survival was 76%, 66%, 52% at 1,2, and 5 years.Definitive capecitabine-based chemoradiation as alternative for extensive surgery is feasible in locally advanced vulvar cancer and results in considerable locoregional control with acceptable survival rates with manageable acute and late toxicity.Copyright © 2021. Published by Elsevier Inc.

The therapeutic outcomes of patients with advanced vulvar cancer are poor. Multi-modality treatments including concurrent chemoradiation or different regimens of neoadjuvant chemotherapy (NACT), and surgery have been explored to reduce the extent of surgery and morbidity. The present single-institution trial aimed to evaluate the efficacy and toxicity of paclitaxel and cisplatin in locally advanced vulvar cancer.From 2002 to 2009, 10 patients with stage III-IV locally advanced squamous cell carcinoma of the vulva were prospectively treated with 3 courses of paclitaxel-ifosfamide-cisplatin or paclitaxel-cisplatin. Nine of them subsequently underwent radical local excision or radical partial vulvectomy and bilateral inguino-femoral lymphadenectomy.The clinical response rate of all enrolled patients was 80%, whereas the pathological responses included 1 case with complete remission, 2 with persistent carcinoma in situ, and 6 invasive cancer cases with tumor shrinkage of more than 50%. Four patients had positive nodes. Forty percent of patients experienced grade 3-4 bone marrow toxicity, which was successfully managed with granulocyte-colony stimulating factor, even in cases of elderly patients. Median progression-free survival after surgery was 14 months (range, 5 to 44 months). Six of the 7 recurrent cases were local, and 3 of them were treated with salvage surgery while the other 3 received radiation with or without chemotherapy. After a median follow-up period of 40 months (range, 5 to 112 months), 55.5% of patients remained alive with no evidence of disease, including 2 long-term survivors after recurrence at 5 and 9 years.Based on the high response rate and manageable toxicity, NACT with paclitaxel and cisplatin with or without ifosfamide followed by surgery could be considered as a therapeutic option for locally advanced vulvar cancer.

Vulvar cancer (VC) is a rare neoplasm, usually arising in postmenopausal women, although human papilloma virus (HPV)-associated VC usually develop in younger women. Incidences of VCs are rising in many countries. Surgery is the cornerstone of early-stage VC management, whereas therapies for advanced VC are multimodal and not standardized, combining chemotherapy and radiotherapy to avoid exenterative surgery. Randomized controlled trials (RCTs) are scarce due to the rarity of the disease and prognosis has not improved. Hence, new therapies are needed to improve the outcomes of these patients. In recent years, improved knowledge regarding the crosstalk between neoplastic and tumor cells has allowed researchers to develop a novel therapeutic approach exploiting these molecular interactions. Both the innate and adaptive immune systems play a key role in anti-tumor immunesurveillance. Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in multiple tumor types, improving survival rates and disease outcomes. In some gynecologic cancers (e.g., cervical cancer), many studies are showing promising results and a growing interest is emerging about the potential use of ICIs in VC. The aim of this manuscript is to summarize the latest developments in the field of VC immunoncology, to present the role of state-of-the-art ICIs in VC management and to discuss new potential immunotherapeutic approaches.

Nivolumab was assessed in patients with virus-associated tumors in the phase I/II CheckMate 358 trial (ClinicalTrials.gov identifier: NCT02488759). We report on patients with recurrent/metastatic cervical, vaginal, or vulvar cancers.Patients received nivolumab 240 mg every 2 weeks. Although patients with unknown human papillomavirus status were enrolled, patients known to have human papillomavirus-negative tumors were ineligible. The primary end point was objective response rate. Duration of response (DOR), progression-free survival, and overall survival were secondary end points. Safety and patient-reported outcomes were exploratory end points.Twenty-four patients (cervical, n = 19; vaginal/vulvar, n = 5) were enrolled. Most patients had received prior systemic therapy for metastatic disease (cervical, 78.9%; vaginal/vulvar, 80.0%). Objective response rates were 26.3% (95% CI, 9.1 to 51.2) for cervical cancer and 20.0% (95% CI, 0.5 to 71.6) for vaginal/vulvar cancers. At a median follow-up of 19.2 months, median DOR was not reached (range, 23.3 to 29.5+ months; + indicates a censored observation) in the five responding patients in the cervical cohort; the DOR was 5.0 months in the single responding patient in the vaginal/vulvar cohort. Median overall survival was 21.9 months (95% CI, 15.1 months to not reached) among patients with cervical cancer. Any-grade treatment-related adverse events were reported in 12 of 19 patients (63.2%) in the cervical cohort and all five patients in the vaginal/vulvar cohort; there were no treatment-related deaths. In the cervical cohort, nivolumab treatment generally resulted in stabilization of patient-reported outcomes associated with health status and health-related quality of life.The efficacy of nivolumab in patients with recurrent/metastatic cervical and vaginal or vulvar cancers is promising and warrants additional investigation. No new safety signals were identified with nivolumab treatment in this population.

Tumour mutational burden (TMB) has been retrospectively correlated with response to immune checkpoint blockade. We prospectively explored the association of high tissue TMB (tTMB-high) with outcomes in ten tumour-type-specific cohorts from the phase 2 KEYNOTE-158 study, which assessed the anti-PD-1 monoclonal antibody pembrolizumab in patients with selected, previously treated, advanced solid tumours.In the multi-cohort, open-label, non-randomised, phase 2 KEYNOTE-158 study, patients were enrolled from 81 academic facilities and community-based institutions across 21 countries in Africa, the Americas, Asia, and Europe. Eligible patients were aged 18 years or older, had a histologically or cytologically confirmed advanced (ie, unresectable or metastatic, or both) incurable solid tumour (eligible tumour types were anal, biliary, cervical, endometrial, mesothelioma, neuroendocrine, salivary, small-cell lung, thyroid, and vulvar), progression on or intolerance to one or more lines of standard therapy, had measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) assessed by independent central radiological review, Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 3 months, adequate organ function, and a tumour sample for biomarker analysis. Participants were given pembrolizumab 200 mg intravenously every 3 weeks for up to 35 cycles. Tissue TMB (tTMB) was assessed in formalin-fixed paraffin-embedded tumour samples using the FoundationOne CDx assay (Foundation Medicine, Cambridge, MA, USA). The prespecified definition of tTMB-high status was at least 10 mutations per megabase. The primary endpoint was the proportion of patients with an objective response (complete or partial response) as per Response Evaluation Criteria in Solid Tumours (version 1.1) by independent central review. This prespecified analysis assessed the association between antitumour activity and tTMB in treated patients with evaluable tTMB data. Efficacy was assessed in all participants who received at least one dose of pembrolizumab, had evaluable tTMB data, and were enrolled at least 26 weeks before data cutoff (June 27, 2019), and safety was assessed in all participants who received at least one dose of pembrolizumab and had tTMB-high status. KEYNOTE-158 is registered at ClinicalTrials.gov, NCT02628067, and is ongoing.Between Jan 15, 2016, and June 25, 2019, 1073 patients were enrolled. 1066 participants were treated as of data cutoff (June 27, 2019), of whom 805 (76%) were evaluable for TMB, and 105 (13%) of 805 had tTMB-high status and were assessed for safety. 1050 (98%) of 1066 patients enrolled by at least 26 weeks before data cutoff, of whom 790 (75%) were evaluable for TMB and included in efficacy analyses. 102 (13%) of these 790 patients had tTMB-high status (≥10 mutations per megabase), and 688 (87%) patients had non-tTMB-high status (<10 mutations per megabase). Median study follow-up was 37·1 months (IQR 35·0-38·3). Objective responses were observed in 30 (29%; 95% CI 21-39) of 102 patients in the tTMB-high group and 43 (6%; 5-8) of 688 in the non-tTMB-high group. 11 (10%) of 105 patients had treatment-related serious adverse events. 16 (15%) participants had a grade 3-5 treatment-related adverse event, of which colitis was the only such adverse event that occurred in more than one patient (n=2). One patient had fatal pneumonia that was assessed by the investigator to be treatment related.tTMB-high status identifies a subgroup of patients who could have a robust tumour response to pembrolizumab monotherapy. tTMB could be a novel and useful predictive biomarker for response to pembrolizumab monotherapy in patients with previously treated recurrent or metastatic advanced solid tumours.Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc.Copyright © 2020 Elsevier Ltd. All rights reserved.

To evaluate the efficacy and toxicity of erlotinib in the management of squamous cell carcinoma (SCC) of the vulva.Patients with vulvar lesions amenable to surgery or chemoradiation (cohort 1) or those with metastatic measurable disease (cohort 2) received erlotinib 150 mg daily. Patients were monitored for toxicity. Responses were determined by digital photography or RECIST 1.1. Cohort 1 underwent pre and post treatment biopsies. EGFR immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH), and mutational analysis were performed.41 patients were enrolled: 17 in cohort 1 and 24 in cohort 2. Notable grade 3 or 4 toxicities included allergic reaction (1), diarrhea/electrolyte abnormalities (3), ischemic colitis (1), and renal failure (3) and electrolyte abnormalities (n=2). Mean number of cycles for cohort 2 was 3.3. Overall clinical benefit rate was 67.5% with 11 (27.5%) partial responses (PR), 16 (40.0%) stable disease (SD), and 7 (17.5%) progressive disease. Responses were of short duration. All pre and post treatment biopsies exhibited 2-3+ EGFR staining. 5 of 14 patients (35%) were found to have EGFR amplification (n=3) or high polysomy/trisomy (n=2). These five patients had either a PR (n=3) or SD (n=2). Gain of function mutations were not been identified.This is the first reported controlled trial evaluating erlotinib for the management of vulvar carcinoma. Toxicities were acceptable given the lack of treatment options for these patients. Given the observed clinical benefits erlotinib may represent one of the most active agents available to treat vulvar SCC.Copyright © 2012 Elsevier Inc. All rights reserved.

NTRK1, NTRK2 and NTRK3 gene fusions (NTRK gene fusions) occur in a range of adult cancers. Larotrectinib is a potent and highly selective ATP-competitive inhibitor of TRK kinases and has demonstrated activity in patients with tumours harbouring NTRK gene fusions.This multi-centre, phase I dose escalation study enrolled adults with metastatic solid tumours, regardless of NTRK gene fusion status. Key inclusion criteria included evaluable and/or measurable disease, Eastern Cooperative Oncology Group performance status 0-2, and adequate organ function. Larotrectinib was administered orally once or twice daily, on a continuous 28-day schedule, in increasing dose levels according to a standard 3 + 3 dose escalation scheme. The primary end point was the safety of larotrectinib, including dose-limiting toxicity.Seventy patients (8 with tumours with NTRK gene fusions; 62 with tumours without a documented NTRK gene fusion) were enrolled to 6 dose cohorts. There were four dose-limiting toxicities; none led to study drug discontinuation. The maximum tolerated dose was not reached. Larotrectinib-related adverse events were predominantly grade 1; none were grade 4 or 5. The most common grade 3 larotrectinib-related adverse event was anaemia [4 (6%) of 70 patients]. A dose of 100 mg twice daily was recommended for phase II studies based on tolerability and antitumour activity. In patients with evaluable TRK fusion cancer, the objective response rate by independent review was 100% (eight of the eight patients). Eight (12%) of the 67 assessable patients overall had an objective response by investigator assessment. Median duration of response was not reached. Larotrectinib had limited activity in tumours with NTRK mutations or amplifications. Pharmacokinetic analysis showed exposure was generally proportional to administered dose.Larotrectinib was well tolerated, demonstrated activity in all patients with tumours harbouring NTRK gene fusions, and represents a new treatment option for such patients. CLINCALTRIALS.NCT02122913.© 2019 THE AUTHORS. Published by Elsevier Ltd on behalf of the European Society for Medical Oncology. This is an open access article under the CC-BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).

Some gynaecological cancers are uncommon, such as sex cord-stromal tumours, malignant germ-cell tumours, vulvar carcinoma, melanoma of the female genital tract, clear-cell carcinoma of the ovary and endometrium, neuroendocrine tumours of the cervix, and gestational trophoblastic neoplasia. All these cancers have different clinicopathological characteristics, suggesting different molecular biological pathogeneses. Despite aggressive treatment, some cancers recur or respond poorly to therapy. Comprehensive knowledge of the molecular biology of each cancer might help with development of novel treatments that maximise efficacy and minimise toxic effects. Targeted therapy is a new treatment strategy that has been investigated in various tumours in clinical and laboratory settings. Since these cancers are rare and large clinical trials are difficult to do, molecular biological techniques might allow rapid proof-of-principle experiments in few patients. Novel targeted agents either alone or in combination with other treatments offer promising therapeutic options.2010 Elsevier Ltd. All rights reserved.

Despite the less frequent use of surgery in patients with vulvar cancer, the high rates of postoperative complications are still a matter of concern. The aim of the present study was to identify risk factors that influence postoperative complications rates in vulvar cancer and identify specific clinical parameters that may influence their incidence.Patients who underwent curative-intent surgery for squamous cell carcinoma of the vulva from 2003 to 2018 were selected. All patient characteristics were analyzed as risk factors for the development of postoperative lymphocele, lymphedema, and wound dehiscence. The patients were followed up for 2 years postoperatively.The investigation comprised 121 patients, of whom 18.1% developed wound dehiscence, 17.7% a lymphocele, and 20.4% lymphedema. We found no significant evidence of an association between patient's characteristics and postoperative complications. The depth of tumor invasion and the appearance of lymph-node metastasis were significantly associated with postoperative complications. Free resection margins of 5 mm or more were associated with a reduced risk of postoperative complications compared to resection margins less than 5 mm. No complications were encountered after sentinel node biopsy (SNB). Complication rates were associated with inguinofemoral lymphadenectomy, but not with the extent of lymphadenectomy. The development of a lymphocele or wound dehiscence may be correlated with the development of long-term lymphedema.FIGO stage at diagnosis influences the risk of postoperative complications. The use of SNB minimized postoperative complications. Correlations between the free microscopic resection margin distance and the risk of postoperative wound dehiscence must be investigated further.© 2021. The Author(s).