scholarly journals Developments in the Treatment of Locally Advanced and Metastatic Squamous Cell Carcinoma of the Skin: A Rising Unmet Need

2014 ◽  
pp. e397-e404 ◽  
Author(s):  
Paul Palyca ◽  
Vadim P. Koshenkov ◽  
Janice M. Mehnert
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Uv Radiation ◽  
Squamous Cell ◽  
Advanced Disease ◽  
Clinical Investigation ◽  
Locally Advanced ◽  
Unmet Need ◽  
Lymph Node Biopsy ◽  
Disease Biology

Squamous cell carcinoma of the skin (SCCS) is a common malignancy with potentially devastating consequences in patients with locally advanced or metastatic disease. Its rising incidence, primarily a result of an aging population and increased ultraviolet (UV) radiation exposure, characterize an emerging unmet need. A firm understanding of the biology of this disease, likely distinct from that of other squamous malignancies because of the influence of UV radiation, is necessary in the evaluation of treatment paradigms. Careful recognition of high-risk features pertaining to tumor and host characteristics is paramount to proper management. However, a lack of standardization in guidelines in this regard creates a challenge for physicians. Questions persist regarding additional evaluation and treatment for advanced disease such as the roles for sentinel lymph node biopsy and the adjuvant use of radiation and chemotherapy. With respect to advanced disease, multiple combinations of chemotherapy have been tested with variable success, but no rigorous randomized studies have been conducted. In addition, EGFR inhibitors such as cetuximab and erlotinib have displayed antitumor activity and as such, warrant further investigation. In sum, the treatment of locally advanced and metastatic SCCS is a ripe area for clinical investigation. This article summarizes the current understanding of disease biology and emerging questions in the management of this disease.

scholarly journals Study of epidemiology, clinicopathological correlation, prognostic factors and management in squamous cell carcinoma of vulva

2018 ◽  
Vol 8 (1) ◽  
pp. 223
Author(s):  
Chetana D. Parekh ◽  
Ruchi S. Arora ◽  
Shilpa M. Patel ◽  
Pabashi Poddar ◽  
Ava D. Desai ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Prognostic Factors ◽  
Hiv Infection ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Advanced Disease ◽  
Locally Advanced ◽  
Hpv 16 ◽  
Locally Advanced Disease

Background: Carcinoma of the vulva is rare cancer, pruritus is the most common and long-lasting reported symptom. It is found to be associated with HPV and HIV infection. Currently, a more individualized and less radical treatment is suggested. In this study we evaluated epidemiology, clinicopathological prognostic factors, HPV distribution and risk factors for metastases to lymph nodes. We also reviewed multidisciplinary clinical management carried out at our institute.Methods: It is a prospective study of 25 biopsy proven cases of Squamous Cell Carcinoma of Vulva, treated at our center from September 2014 to September 2016. We collected the data regarding the clinical presentation, histological details, treatment given, survival and complications. HPV 16 and 18 testing were done using PCR method. Median follow up of the patients are for 24 months.Results: The mean age of patients was 54.6 years. Commonest presentation was perineal itching (36%). HPV 16/18 were positive in 25% of the patients. Radical vulvectomy with bilateral groin dissection was done in 14/25 (56%) patients. Among these 14 patients, 35.7 % (5/14) has lymph node metastases, disease free survival was 63.6% and overall survival was 81.1% for median follow up of 24 months. About one third of the patient presented with locally advanced disease.  Six (24%) patients received only chemo radiation as a treatment.Conclusions: HPV and HIV infection increase the risk of vulvar cancer. Individualization of treatment is necessary. The use of preoperative chemoradiation in locally advanced disease might have promising results in future.

Esophageal squamous cell carcinoma in the VA population: What is the optimal treatment modality

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15042-15042
Author(s):  
M. M. Safa ◽  
M. S. Beg ◽  
M. Atiq ◽  
S. Ali ◽  
R. Komrokji
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Treatment Modality ◽  
Advanced Disease ◽  
Locally Advanced ◽  
Early Disease ◽  
Trimodality Therapy ◽  
Squamous Cell Esophageal Cancer

15042 Introduction: Surgery for esophageal squamous cell carcinoma (SCC) has been the mainstay of treatment despite dismal outcome and significant surgical complications. There is no standard treatment modality for esophageal SCC. Methods: The VA (veteran affairs) Central Cancer Registry (VACCR) is a function of the Chief, Program Office for Oncology at VA Headquarters in Washington DC. We queried the VACCR database for all diagnosed squamous cell esophageal cancer cases between 1995 and 2005 using ICD codes 150–159. The data was transformed, entered and analyzed using SPSS v.13.0. We analyzed, in a retrospective fashion, survival in VA patients with early disease (stages 1–2), and locally advanced (stage 3) SCC comparing the treatment modality: chemoradiation alone (CRT), surgical resection alone (SUR) or trimodality therapy (TMT) which includes all three treatment options. Results: Out of a total of 6874 patients diagnosed with esophageal carcinoma, 2894 patients had SCC. A total of 433 patients were included in this study that were staged as 1–3 and had complete treatment information available. Baseline characteristics were not different between the three groups and are summarized in table 1 . Out of those, 57 (13.2%) received SUR, 323 (74.6%) CRT, and 53 (12.2%) TMT. Kaplan Meier analysis for median survival in early disease was 14 mo for SUR, 17 mo in CR, and 79 mo in TMT (p = 0.0288). There was no difference in survival among patients with locally advanced disease between the treatment groups (p = 0.7079) Conclusion: In VA patients with early esophageal SCC, TMT confers better survival than SUR or CRT. However, in patients with advanced disease, SUR, CRT and TMT groups showed comparable outcome. [Table: see text] No significant financial relationships to disclose.

Squamous Cell Carcinoma of the Esophagus: Multimodal Therapy in Locally Advanced Disease

2001 ◽  
Vol 26 (1) ◽  
pp. 72-78 ◽  
Author(s):  
Issam El Nakadi, M.D. ◽  
Jean-Luc Van Laethem, M.D. ◽  
Jean-Jacques Houben, M.D. ◽  
France Gay, M.D. ◽  
Jean Closset, M.D. ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Multimodal Therapy ◽  
Advanced Disease ◽  
Locally Advanced ◽  
Carcinoma Of The Esophagus ◽  
Locally Advanced Disease

scholarly journals Risk Factors and Diagnosis of Advanced Cutaneous Squamous Cell Carcinoma

2021 ◽  
Vol 11 (S2) ◽  
pp. e2021166S
Author(s):  
Gabriella Brancaccio ◽  
Maria Concetta Fargnoli ◽  
Giulia Briatico ◽  
Cristina Pellegrini ◽  
Tea Rocco ◽  
...  
Keyword(s):  
Risk Factors ◽  
Squamous Cell Carcinoma ◽  
Prognostic Factors ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Advanced Disease ◽  
Locally Advanced ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Tumor Diameter ◽  
Locally Advanced Disease

Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer affecting humans. The combination of the increasing incidence and high mortality in advanced stages of the disease, defines cSCC as an emerging public health problem. Advanced disease includes metastatic and locally advanced cSCC. Metastatic disease refers to the presence of locoregional metastasis (in transit or to regional lymph nodes) or distant metastasis. Locally advanced disease has been defined as non-metastatic cSCC that is unlikely to be cured with surgery, radiotherapy, or combination treatment. While metastatic cSCC is easily diagnosed, locally advanced disease lacks consensus definition and diagnosis is made after multidisciplinary board consultation. Identifying patients with aggressive cSCC at highest risk for relapse may prevent the occurrence of advanced disease. Prognostic factors suggested by most guidelines include tumor diameter (>2 cm), localization on temple/ear/lip/area, thickness (>6 mm), or invasion beyond subcutaneous fat, poor grade of differentiation, desmoplasia, perineural invasion, bone erosion, immunosuppression, undefined borders, recurrence, growth rate, site of prior radiotherapy, and lymphatic or vascular involvement. Although risk factors associated with worse outcomes are well known, there is still a gap of knowledge on the precise risk of each factor taken individually. The aim of this review is to summarize cSCC prognostic factors and encompass the various staging systems to guide management and follow-up in cSCC patients at higher risk for local recurrence and metastasis. Finally, we describe the hallmarks of the advanced disease. Advanced cSCC diagnosis should be made by a multidisciplinary board considering patients’ performance status and disease characteristics

222 Increased PD-L1 tumor expression correlates with high rate of response to PD-1 inhibitors in patients with unresectable, recurrent, and metastatic cutaneous squamous cell carcinoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A241-A241
Author(s):  
Nate Bowers ◽  
Kimberly Burcher ◽  
Jess Savas ◽  
Phillip Williford ◽  
Laura Doerfler ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumor Tissue ◽  
Advanced Disease ◽  
Locally Advanced ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Maximum Response ◽  
Locally Advanced Disease ◽  
Rate Of Response

BackgroundPD-1 inhibitors were approved for locally advanced and metastatic cutaneous squamous cell carcinoma (CSCC) in 2019.1 The identification of tumor characteristics that predict potential responders to immune checkpoint inhibitors (ICI) is an area of ongoing research. Here we present a series of consecutive patients with locally advanced, recurrent, or metastatic CSCC treated with PD-1 inhibitors and analyze tumor and blood genomics as well as PD-L1 expression with the aim of correlating with treatment response.MethodsWe analyzed cases of CSCC treated with single agent PD-1 inhibitors in the last 2 years at Wake Forest. Demographic and outcome data were collected. Tumor tissue, whenever available, was tested for PD-L1, TMB, MSI, and genetic mutations. Blood was tested for circulating tumor at the beginning of treatment and at the time of maximum response.ResultsFourteen patients with CSCC treated with PD-1 ICI were included in this study. Six had locally advanced disease, seven had recurrent locally advanced disease, and one had metastatic disease. Four patients received treatment for >12 months and all had complete response (CR). Five patients had 6–12 months of treatment and all had near CR (pending imaging studies and ctDNA to confirm). Three patients had <6 months of treatment and had partial response (PR). Two of the patients had progressive disease, although one with possible pseudoprogression based on review of post-treatment surgical pathology specimen. Treatment was well tolerated with no immune related side-effects except one case of grade I hypothyroidism. Eleven patients had sufficient tumor tissue for genomic and PD-L1 testing. Initial blood genomic testing was performed in 12 of 13 patients and in follow up in patients who achieved maximum response. Patients with CR had PD-L1 of at least 30%. The additional tested patients had PD-L1 above 10%. The most frequently mutated gene was TP53 present in tumor in all tested patients and in blood in 6 patients, followed by NOTCH1/2 detected in the tumor of 10 of 11 patients tested. TMB was intermediate/high in tested patients except in the only patient who presented clear tumor progression.ConclusionsTreatment of locally advanced, recurrent, and metastatic CSCC with ICI led to a dramatic change in the management and prognosis of CSCC. Our series of patients with CSCC had a higher than reported rate of response. This corresponded with high TP53 alterations, NOTCH 1/2 alterations, high/intermediate TMB, and high level of expression of PD-L1. PD-L1 rates were higher than previously published.1 2Ethics ApprovalThe study was approved by Wake Forest University Institution’s Ethics Board, approval number IRB00056249.ReferencesMigden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med. 2018;379:341–51.Garcia-Pedrero JM, Martinez-Camblor P, Diaz-Coto S, et al. Tumor programmed cell death ligand 1 expression correlates with nodal metastasis in patients with cutaneous squamous cell carcinoma of the head and neck. J Am Acad Dermatol 2017;77(3):527–533.

scholarly journals Increased PD-L1 Tumor Expression Correlates with High Rate of Response to PD-1 Inhibitors in Patients with Unresectable, Recurrent, and Metastatic Cutaneous Squamous Cell Carcinoma

2021 ◽  
Vol 5 (1) ◽  
pp. 22-24
Author(s):  
Nathan Bowers ◽  
Mercedes Porosnicu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Advanced Disease ◽  
Locally Advanced ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Imaging Studies ◽  
Tumor Expression ◽  
Rate Of Response

Background: PD-1 inhibitors were approved for locally advanced and metastatic cutaneous squamous cell carcinoma (CSCC) in 2019 with ORR of 47% and CR of 4%. The identification of tumor characteristics that predict potential responders to immune checkpoint inhibitors (ICI) is an area of ongoing research. Here we present a series of consecutive patients with locally advanced unresectable, recurrent, or metastatic CSCC treated with PD-1 inhibitors and analyze tumor and blood genomics as well as PD-L1 expression with the aim to correlate with treatment response. Methods:  We analyzed all cases of CSCC treated with single agent PD-1 inhibitors in the last 2 years at Wake Forest Comprehensive Cancer Center. Demographic and outcome data was collected. Tumors tested for genomics and PD-L1 expression in all cases with available tissue. PD-L1 tumor expression was tested by IHC utilizing DAKO 22C3 pharmDx antibodies.  Tumor genomic studies including TMB and MSI were performed by Foundation Medicine platform. Blood was tested for circulating tumor DNA by Guardant 360 platform, at the beginning of treatment and in follow up at the time of maximum response.  Response was assessed by RECIST 1.1 Criteria. Results (Table 1): Eleven patients with CSCC treated with PD-1 ICI were included in this study. Five patients had locally advanced disease, five patients had recurrent locally advanced disease, and three patients had metastatic disease. Three patients received treatment for at least 12 months and all have CR to date. Two patients have been on treatment for 6 months, and they have excellent PR with possible CR per imaging studies. Of the six patients who have been on treatment for less than 6 months, one patient has excellent PR with negative PET, three patients have very good clinical response with imaging studies pending, one patient has questionable response, and one patient only recently started treatment. Treatment is well tolerated with no treatment discontinuation. Immune-related complications are rare consisting of only one patient developing hypothyroidism during treatment. Eight patients had sufficient tumor tissue for genomic and PD-L1 testing. Initial blood genomic testing was performed in 10 of 11 patients and in follow up in all three patients who achieved maximum response. Patients with CR had PD-L1 of at least 30%. The additional tested patients have PD-L1 above 10%.  The most frequently mutated tDNA gene was TP53 and the second most frequently mutated gene was the NOTCH1/2. TMB was intermediate or high in all tested patients. Discussion:  Treatment of locally advanced unresectable, recurrent, and metastatic CSCC with ICI has led to a dramatic change in the management and prognosis of CSCC. Our series of patients with CSCC has a higher than reported rate of response and especially complete response. This corresponds with high TP53 alterations (100% of patients), NOTCH 1/2 alterations (90 % of patients) and high level of expression of PD-L1 (90% patients). Interestingly, PD-L1 rates were higher than previously published.

scholarly journals Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: A Big and Intriguing Challenge Which May Be Resolved by Integrated Treatments Combining Locoregional and Systemic Therapies

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2371
Author(s):  
Franco Ionna ◽  
Paolo Bossi ◽  
Agostino Guida ◽  
Andrea Alberti ◽  
Paolo Muto ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Poor Prognosis ◽  
Multidisciplinary Approach ◽  
Advanced Disease ◽  
Locally Advanced ◽  
Abscopal Effect ◽  
Systemic Therapies

Squamous cell carcinoma of the head and neck (SCCHN) is a complex group of malignancies, posing several challenges to treating physicians. Most patients are diagnosed with a locally advanced disease and treated with strategies integrating surgery, chemotherapy, and radiotherapy. About 50% of these patients will experience a recurrence of disease. Recurrent/metastatic SCCHN have poor prognosis with a median survival of about 12 months despite treatments. In the last years, the strategy to manage recurrent/metastatic SCCHN has profoundly evolved. Salvage treatments (surgery or re-irradiation) are commonly employed in patients suffering from locoregional recurrences and their role has gained more and more importance in the last years. Re-irradiation, using some particularly fractionating schedules, has the dual task of reducing the tumor mass and eliciting an immune response against cancer (abscopal effect). In this review, we will analyze the main systemic and/or locoregional strategies aimed at facing the recurrent/metastatic disease, underlining the enormous importance of the multidisciplinary approach in these types of patients.

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