Immunotherapy in HPV negative, PD-L1 negative advanced vulvar squamous cell carcinoma after failure of systematic treatment: a case report and literature review

Induction chemotherapy with cemiplimab in a patient with coexistent vulvar cancer and autoimmune disease: A case report

Pembrolizumab for vulvar squamous cell carcinoma: results from the phase 2 KEYNOTE-158 study

Efficacy and safety of pembrolizumab for patients with previously treated advanced vulvar squamous cell carcinoma: Results from the phase 2 KEYNOTE-158 study

Introduction: Chemotherapy plus immunotherapy is the standard treatment worldwide for advanced lung squamous cell carcinoma with high programmed cell death protein-1 (PD-1) expression. The use of immunotherapy alone against advanced lung squamous cell carcinoma is rarely reported, and data on PD-1 inhibitor camrelizumab are missing. We report the first case of camrelizumab monotherapy, which can be a reference for the clinical applications of camrelizumab in a wider context. Case Presentation: We herein present a 69-year-old male case of advanced squamous cell carcinoma with low PD-1 expression, in which camrelizumab monotherapy was administered every 3 weeks. Camrelizumab monotherapy reversed advanced lung squamous cell carcinoma without recurrence or obvious side effects during 26 months of follow-up. The patient is alive and in good conditions to date; thus, progression-free survival and overall survival are not determined. Conclusion: This case report provides evidence of the efficacy of camrelizumab monotherapy and highlights the feasibility of camrelizumab alone against advanced lung squamous cell carcinoma when chemotherapy is not applicable.

There are few randomized controlled studies to guide the treatment of advanced cutaneous squamous cell carcinoma. The existing treatments are mostly based on case reports and small case series. Here we review recently available insights concerning the treatment of locally advanced and metastatic squamous cell carcinoma, with a special emphasis on novel targeted therapy and immunotherapy. Surgery and combination of chemotherapy and radiation therapy have been long considered the gold standard options for advanced squamous cell carcinoma. The detection of clinically relevant driver mutations has opened the door to the use of novel targeted therapies. Recent studies have shown that aggressive cutaneous squamous cell carcinoma is characterized by a very high mutational background. Furthermore, the importance of the defective immunosurveillance in the growth of cutaneous squamous cell carcinoma and the critical role of programed cell death protein 1 and programmed death-ligand 1 interaction in skin tumor development provides a rationale for the use of immune checkpoint inhibitors. Epidermal growth factor receptor inhibitors have shown to have satisfactory antitumor activity with acceptable side-effect profile. However, their place in management of advanced cutaneous squamous cell carcinoma alone or in combination with either radiation therapy and/or chemotherapy needs to be better characterized. The available preliminary findings suggest that immune checkpoint inhibitors represent a potentially valuable alternative in cutaneous aggressive squamous cell carcinoma, promising a further expansion of their indication spectrum. Randomized controlled studies will allow us to better characterize their practical value.

Evaluating the efficacy of 8Spheres microsphere combined with Iodine-125 seeds in the treatment of advanced lung squamous cell carcinoma presenting with hemoptysis: A retrospective study.

Objective: To identify the determinants of secondary limb amputation in advanced squamous cell carcinoma. Material and Methods: This was a retrospective study carried out in the Orthopedic Traumatology Department of the Bouake University Hospital in Cote d’Ivoire from January 2013 to December 2016. It involved ten patients with locally advanced skin squamous cell carcinoma, confirmed by histology and having amputated limbs. The parameters studied were: demographic data (gender, age), socio-economic conditions (occupation, place of residence), the risk factors involved, the use of topical self-medication and the use of traditional medicine, antecedents and comorbidities factors, lifestyle, clinical aspects (seat, size), extension assessment (X-ray), anatomo-pathological examination data, duration of evolution of squamous cell carcinoma, the function of the affected limb, the treatment performed, the evolutionary modalities and the equipment. Results: Between 2013 and 2016, ten patients underwent either upper or lower limb amputations following locally advanced squamous cell carcinoma. The average age was 34.1 years (19 - 64 years). There were 7 men (70%) and 3 women (30%) and all our patients were black (sub-Saharan Africa). The majority of our patients were farmers (70%). The risk factors for squamous cell carcinoma were neglected chronic wounds. All our patients recognized during the interrogation a large use of the topicals of traditional medicine for the treatment of the initial cutaneous lesions. In terms of lifestyle, five (50%) were smokers and alcoholics. The mean time to progression of squamous cell carcinoma was 5.9 years. Lesions were localized preferentially to the pelvic limbs six (60%) cases and four (40%) to the limbs chest. The lesion was diagnosed late in all our patients. The size of the tumor in all our patients was greater than 5 cm and had a deep invasion (nerves, vessels and bone). The proximal ipsilateral ganglionic invasion was constant. The extension assessment (chest X-ray) showed two cases of pulmonary metastases. Seven patients (70%) had well-differentiated tumors. All patients underwent amputation of the affected limb, sometimes coupled with an accessible lymph node dissection. The evolution was favorable (no recurrence and infection of the amputation stump). The function of the affected limb was limited in all our patients. Seven patients (70%) survive, three of whom have been fitted to the lower limb and are regularly followed on an outpatient basis. We noted three (30%) deaths after the surgical treatment. Conclusion: Limb amputation in patients with locally advanced skin squamous cell carcinoma may be associated with cancer aggressiveness, the socio-economic conditions of patients, the quality of care, and the patient’s relationship to the disease.

Vulvar squamous cell carcinoma with sarcoma-like stroma represents an extremely rare histological entity showing the co-existence of both epithelial and mesenchymal features: these tumors, firstly described in the skin by Martin and Stewart in 1935 have been further described in other anatomic sites including oral cavity, larynx, breast, lung and oesophagus. The complexity of the histology, as well as its aggressive clinical behaviour makes the diagnosis and the exploitment of effective therapeutic approaches very difficult, so that no definitive guidelines for treatments are currently available. Here, we describe a case of advanced stage vulvar squamous cell carcinoma with sarcoma-like stroma showing an unfavourable prognosis despite the use of an aggressive multimodal approach. A revision of the currently published cases have been also provided.

BackgroundThis study aimed to investigate the correlation between miRNA-216b expression in patients with non-small cell lung cancer (NSCLC) and 18F-fluorodeoxyglucose (FDG) uptake by PET/CT and to explore the clinical application value of 18F-FDG PET/CT in miRNA-216b based on therapy for NSCLC.MethodsEighty patients with NSCLC and 40 healthy subjects were enrolled in our study. The SUVmax of the lesion area by PET/CT imaging was calculated. SUVmax represented the highest concentration of 18F-FDG in the lesion. The expression of miRNA-216b in the plasma and fiber bronchoscopic puncture of NSCLC patients was detected by RT qPCR. Then Pearson correlation analysis was used to analyze the correlation between miRNA-216b expression and 18F-FDG uptake in patients with different types of NSCLC.ResultsCompared with healthy subjects, SUVmax of early adenocarcinoma and advanced adenocarcinoma were increased. Compared with healthy subjects, SUVmax of early squamous and advanced squamous were increased. And the SUVmax content of advanced adenocarcinoma and squamous cell carcinoma was higher than that of early adenocarcinoma and squamous cell carcinoma. Compared with healthy subjects, the expression of miRNA-216b in the plasma of patients with early and advanced adenocarcinoma was reduced, and the expression of miRNA-216b in the plasma of patients with early and advanced squamous cell carcinoma was reduced. Compared with adjacent tissues, the expression of miRNA-216b in early adenocarcinoma tissues and advanced adenocarcinoma tissues was reduced, and the expression in early squamous cell carcinoma and advanced squamous cell carcinoma was reduced. Pearson correlation analysis showed a negative correlation between SUVmax and miRNA-216b (plasma and tissue) in patients with four types of NSCLC.ConclusionmiRNA-216b expression was negatively correlated with 18F-FDG uptake in NSCLC. miRNA-216b could be used for the classification and staging of non-small cell lung cancer. 18F-FDG PET/CT may be used to evaluate the therapeutic response in application of miRNA-216b-based cancer treatment.

Vulvar cancer is an uncommon tumor and represents 3%-5% of all female genital tract malignancies. Squamous cell carcinoma (SCC) is the most common carcinoma of the vulva. Distant metastasis of recurrent vulvar squamous cell carcinoma is rare and occurs late in the disease process. We report the first case of kidney metastasis from a vulvar squamous cell carcinoma in a 68-year-old Caucasian female. On initial presentation she was treated with radical vulvectomy, upper urethrectomy with bilateral inguinal and deep femoral lymph node dissection. She was staged as FIGO stage IVA and also received adjuvant chemo-radiation. She remained in remission for 24 months. Subsequently she was found to have a kidney tumor and underwent nephrectomy and was diagnosed with metastatic squamous cell carcinoma from the vulva to the kidney. In cases of recurrent vulvar carcinoma distant metastasis to the bones, breast, and brain is only rarely reported. Metastasis to kidneys from vulvar carcinoma is exceptionally rare with no reported cases in the literature. Renal metastasis should be considered in the differential diagnosis of kidney tumor in this group of women.

Régression de carcinomes basocellulaire et épidermoïde cutanés sous pembrolizumab

Rationale:Advanced squamous cell carcinoma (SCC) of the lung remains a major clinical challenge due to limited therapeutic options, particularly in the post-immunotherapy setting. Combining immune checkpoint inhibitors with small-molecule multi-targeted tyrosine kinase inhibitors that include anti-angiogenic effects offers a promising approach to overcome treatment resistance and improve survival outcomes.Patient concerns:A 44-year-old female with a 2-year history of recurrent cough and sputum production presented with worsening symptoms over the past month, including increased cough frequency and sputum volume. No significant systemic symptoms, such as hemoptysis or dyspnea, were reported.Diagnoses:Chest computed tomography revealed a 35 mm × 31 mm mass in the right middle lung with enlarged supraclavicular and mediastinal lymph nodes. A biopsy confirmed the diagnosis of SCC. Staging was determined as cT3N3M1a (stage IVA), and genetic testing revealed no actionable driver mutations, while PD-L1 expression was 30% (tumor proportion score).Interventions:The patient initially received first-line treatment with pembrolizumab combined with docetaxel and nedaplatin, achieving partial response. After progression, second-line therapy included gemcitabine and cisplatin chemotherapy with synchronous radiotherapy, followed by camrelizumab and anlotinib. Regular imaging follow-ups guided therapy adjustments, including extended dosing intervals for camrelizumab during disease stabilization.Outcomes:Over 4 years of treatment, the patient achieved durable partial response, with significant reduction in tumor burden and no new metastases. As of the most recent follow-up, the patient exhibited an overall survival of 59 months and progression-free survival of 51 months for second-line therapy, with manageable adverse effects including secondary hypothyroidism and grade 2 hypertension.Lessons:This case underscores the potential efficacy of combining immune checkpoint inhibitors with small-molecule multi-targeted tyrosine kinase inhibitors in treating advanced SCC of the lung after progression on first-line therapy. The complementary mechanisms of immune modulation and tumor microenvironment normalization may offer an effective strategy for addressing immune resistance in SCC.

Rapid response to cemiplimab for advanced cutaneous squamous cell carcinoma

There are limited treatment options for recurrent advanced esophageal squamous cell carcinoma. A good response with a possible abscopal effect was observed in a patient with programmed death-ligand 1 (PD-L1)-negative recurrent advanced esophageal squamous cell carcinoma treated with an anti-PD-1 monoclonal antibody plus stereotactic body radiotherapy (SBRT). A 66-year-old male patient was diagnosed with recurrent advanced esophageal squamous cell carcinoma with multiple lung metastases (13 metastatic nodules in total) four months after completing radical radiotherapy plus concurrent and consolidated chemotherapy, and PD-L1 expression in the primary esophageal tumor was negative. This patient received 25 cycles of camrelizumab (an anti-PD-1 monoclonal antibody) in total plus upfront SBRT for two metastatic nodules, which was administered after the first cycle of camrelizumab. After this combined treatment, for most nontarget nodules, an obvious volume decrease and fuzzy change were observed, including two nodules that completely vanished. At the end of follow-up, the progression-free survival and duration of response of this patient were 34 months and 32 months, respectively. This case report indicated that an anti-PD-1 monoclonal antibody combined with SBRT was a promising therapeutic strategy for recurrent esophageal squamous cell carcinoma even in patients with negative PD-L1 expression.

Recurrent vulvar squamous cell carcinoma with multiple site metastases is a rare entity – (up to 14.2% of the total number of recurrences), with a poor prognosis (only 15% of the patients alive at 5 years). Due to its “hard to find” character, there are no standardized guidelines available and the treatment is extrapolated from advanced cervical carcinoma, anal carcinoma and other squamous cell carcinomas. Immunotherapy has shown some positive results in vulvar carcinoma with PD-L1 positive, high TMB, high MSI or with MMR deficiency. An alternative for selected cases without therapeutic resources could be the HPV vaccine. We present the case of a 64-year-old woman diagnosed in 2014 with vulvar squamous cell carcinoma stage II for which she underwent radical vulvectomy with bilateral inguinal lymphadenectomy followed by external radiotherapy. In 2019 she developed local recurrence associated with lung, pleural, lymph nodes and subcutaneous metastasis, treated with three lines of chemotherapy: paclitaxel/carboplatin followed by cisplatin/5-fluorouracil and carboplatin/gemcitabine. The patient’s general health status altered progressively, and she died after the 4th cycle of carboplatin/gemcitabine. This case’s management could be a starting point for the vulvar carcinoma cases where the standard therapeutical options do not represent a choice anymore, providing the necessary example on how to approach it.