Cancers

Research

10 pages, 966 KiB

Open AccessArticle

Penile-Sparing Surgery for Tumour Recurrence after Previous Glansectomy/Partial Penectomy: Treatment Feasibility and Oncological Outcomes

by Gennaro Musi, Filippo Molinari, Francesco A. Mistretta, Mattia Luca Piccinelli, Sonia Guzzo, Marco Tozzi, Elena Lievore, Oskar Blezien, Matteo Fontana, Antonio Cioffi, Daniela Cullurà, Elena Verri, Maria Cossu Rocca, Franco Nolè, Matteo Ferro, Ottavio de Cobelli and Stefano Luzzago

Cancers 2023, 15(19), 4807; https://doi.org/10.3390/cancers15194807 - 29 Sep 2023

Viewed by 821

Abstract

We tested the feasibility and oncological outcomes after penile-sparing surgery (PSS) for local recurrent penile cancer after a previous glansectomy/partial penectomy. We retrospectively analysed 13 patients (1997–2022) with local recurrence of penile cancer after a previous glansectomy or partial penectomy. All patients underwent [...] Read more.

We tested the feasibility and oncological outcomes after penile-sparing surgery (PSS) for local recurrent penile cancer after a previous glansectomy/partial penectomy. We retrospectively analysed 13 patients (1997–2022) with local recurrence of penile cancer after a previous glansectomy or partial penectomy. All patients underwent PSS: circumcision, excision, or laser ablation. First, technical feasibility, treatment setting, and complications (Clavien–Dindo) were recorded. Second, Kaplan–Meier plots depicted overall and local recurrences over time. Overall, 11 (84.5%) vs. 2 (15.5%) patients were previously treated with glansectomy vs. partial penectomy. The median (IQR) time to disease recurrence was 56 (13–88) months. Six (46%) vs. two (15.5%) vs. five (38.5%) patients were treated with, respectively, local excision vs. local excision + circumcision vs. laser ablation. All procedures, except one, were performed in an outpatient setting. Only one Clavien–Dindo 2 complication was recorded. The median follow-up time was 41 months. Overall, three (23%) vs. four (30.5%) patients experienced local vs. overall recurrence, respectively. All local recurrences were safely treated with salvage surgery. In conclusion, we reported the results of a preliminary analysis testing safety, feasibility, and early oncological outcomes of PSS procedures for patients with local recurrence after previous glansectomy or partial penectomy. Stronger oncological outcomes should be tested in other series to optimise patient selection. Full article

(This article belongs to the Special Issue Advanced Squamous Cell Carcinoma)

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13 pages, 1467 KiB

Open AccessArticle

Transcriptomic and Proteomic Profiles for Elucidating Cisplatin Resistance in Head-and-Neck Squamous Cell Carcinoma

by Yoelsis Garcia-Mayea, Lisandra Benítez-Álvarez, Almudena Sánchez-García, Marina Bataller, Osmel Companioni, Cristina Mir, Sergi Benavente, Juan Lorente, Nuria Canela, Ceres Fernández-Rozadilla, Angel Carracedo and Matilde E. LLeonart

Cancers 2022, 14(22), 5511; https://doi.org/10.3390/cancers14225511 - 09 Nov 2022

Cited by 1 | Viewed by 2399

Abstract

To identify the novel genes involved in chemoresistance in head and neck squamous cell carcinoma (HNSCC), we explored the expression profiles of the following cisplatin (CDDP) resistant (R) versus parental (sensitive) cell lines by RNA-sequencing (RNA-seq): JHU029, HTB-43 and CCL-138. Using the parental [...] Read more.

To identify the novel genes involved in chemoresistance in head and neck squamous cell carcinoma (HNSCC), we explored the expression profiles of the following cisplatin (CDDP) resistant (R) versus parental (sensitive) cell lines by RNA-sequencing (RNA-seq): JHU029, HTB-43 and CCL-138. Using the parental condition as a control, 30 upregulated and 85 downregulated genes were identified for JHU029-R cells; 263 upregulated and 392 downregulated genes for HTB-43-R cells, and 154 upregulated and 68 downregulated genes for CCL-138-R cells. Moreover, we crossed-checked the RNA-seq results with the proteomic profiles of HTB-43-R (versus HTB-43) and CCL-138-R (versus CCL-138) cell lines. For the HTB-43-R cells, 21 upregulated and 72 downregulated targets overlapped between the proteomic and transcriptomic data; whereas in CCL-138-R cells, four upregulated and three downregulated targets matched. Following an extensive literature search, six genes from the RNA-seq (CLDN1, MAGEB2, CD24, CEACAM6, IL1B and ISG15) and six genes from the RNA-seq and proteomics crossover (AKR1C3, TNFAIP2, RAB7A, LGALS3BP, PSCA and SSRP1) were selected to be studied by qRT-PCR in 11 HNSCC patients: six resistant and five sensitive to conventional therapy. Interestingly, the high MAGEB2 expression was associated with resistant tumours and is revealed as a novel target to sensitise resistant cells to therapy in HNSCC patients. Full article

(This article belongs to the Special Issue Advanced Squamous Cell Carcinoma)

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18 pages, 4568 KiB

Open AccessArticle

The Vitamin D Receptor–BIM Axis Overcomes Cisplatin Resistance in Head and Neck Cancer

by Aya Khamis, Désirée Gül, Madita Wandrey, Qiang Lu, Shirley K. Knauer, Christoph Reinhardt, Sebastian Strieth, Jan Hagemann and Roland H. Stauber

Cancers 2022, 14(20), 5131; https://doi.org/10.3390/cancers14205131 - 19 Oct 2022

Cited by 4 | Viewed by 2346

Abstract

Treatment success of head and neck squamous cell carcinoma (HNSCC) is often hindered by cisplatin resistance. As inherent and acquired therapy resistance counteracts improvement in long-term survival, novel multi-targeting strategies triggering cancer cell apoptosis are urgently required. Here, we identify the vitamin D [...] Read more.

Treatment success of head and neck squamous cell carcinoma (HNSCC) is often hindered by cisplatin resistance. As inherent and acquired therapy resistance counteracts improvement in long-term survival, novel multi-targeting strategies triggering cancer cell apoptosis are urgently required. Here, we identify the vitamin D receptor (VDR) as being significantly overexpressed in tumors of HNSCC patients (n = 604; p = 0.0059), correlating with tumor differentiation (p = 0.0002), HPV status (p = 0.00026), and perineural invasion (p = 0.0087). The VDR, a member of the nuclear receptor superfamily, is activated by its ligand vitamin D (VitD) and analogs, triggering multiple cellular responses. As we found that the VDR was also upregulated in our cisplatin-resistant HNSCC models, we investigated its effect on overcoming cisplatin resistance. We discovered that VitD/cisplatin combinations synergistically killed even cisplatin-resistant cells at clinically achievable levels. Similar results were obtained for the clinically used VitD analog Maxacalcitol. Moreover, VitD/cisplatin combinations inhibited tumor cell migration by E-cadherin upregulation. Signaling pathway analyses revealed that VitD co-treatments triggered cancer cell death by increasing the expression of the pro-apoptotic BCL-2 family protein BIM. BIM’s pro-apoptotic activity in HNSCC cells was confirmed by ectopic overexpression studies. Importantly, BIM expression is positively associated with HNSCC patients’ (n = 539) prognosis, as high expression correlated with improved survival (p = 0.0111), improved therapy response (p = 0.0026), and remission (p = 0.004). Collectively, by identifying, for the first time, the VDR/BIM axis, we here provide a molecular rationale for the reported anti-cancer activity of VitD/analogs in combination therapies. Our data also suggest its exploitation as a potential strategy to overcome cisplatin resistance in HNSCC and other malignancies by inducing additional pro-apoptotic pathways. Full article

(This article belongs to the Special Issue Advanced Squamous Cell Carcinoma)

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11 pages, 1553 KiB

Open AccessArticle

Treatment Sequences in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Cetuximab Followed by Immunotherapy or Vice Versa

by Chuan-Chien Yang, Ching-Feng Lien, Tzer-Zen Hwang, Chih-Chun Wang, Chien-Chung Wang, Yu-Chen Shih, Shyh-An Yeh and Meng-Che Hsieh

Cancers 2022, 14(10), 2351; https://doi.org/10.3390/cancers14102351 - 10 May 2022

Cited by 2 | Viewed by 2404

Abstract

Background: The prognosis was poor when patients had recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Herein, we conducted an observational study of cetuximab followed by immunotherapy (Cet-IO) versus immunotherapy followed by cetuximab (IO-Cet) in patients with R/M HNSCC. Methods: [...] Read more.

Background: The prognosis was poor when patients had recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Herein, we conducted an observational study of cetuximab followed by immunotherapy (Cet-IO) versus immunotherapy followed by cetuximab (IO-Cet) in patients with R/M HNSCC. Methods: Patients who were diagnosed with R/M HNSCC and treated with a sequential cetuximab-containing regimen and immunotherapy-containing regimen were enrolled in our study. Kaplan-Meier curves were estimated for progression-free survival (PFS) and overall survival (OS). Results: A total of 75 patients were enrolled in our study for oncologic outcomes evaluation, with 40 patients in Cet-IO and 35 patients in IO-Cet. The median PFS1 was 5.1 months in Cet-IO and 4.5 months in IO-Cet (p = 0.777) and the median PFS2 was 16.5 months in Cet-IO and 11.4 months in IO-Cet (p = 0.566). The median OS was 23.7 months versus 22.8 months in Cet-IO and IO-Cet, respectively (p = 0.484). The overall response rate (ORR) were 73% in Cet-IO versus 37% in IO-Cet (p = 0.002). Multivariate analysis demonstrated that the treatment sequences, Cet-IO or IO-Cet, were insignificantly different with survival. Conclusion: Both Cet-IO and IO-Cet are effective in R/M HNSCC patients with insignificant survival differences. The higher ORR of Cet-IO might render it to be considered in patients with large tumor burdens and urgent needs for treatment responses. Further prospective studies are merited to validate our conclusions. Full article

(This article belongs to the Special Issue Advanced Squamous Cell Carcinoma)

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13 pages, 2809 KiB

Open AccessArticle

Comprehensive Evaluation of Vocal Outcomes and Quality of Life after Total Laryngectomy and Voice Restoration with J-Flap and Tracheoesophageal Puncture

by Chung-Kan Tsao, Filippo Marchi, Chung-Jan Kang, Claudio Sampieri, Yi-An Lu, Shiang-Fu Huang, Yu-Ting Chen, Giorgio Giordano, Giorgio Peretti, Giampiero Parrinello, Andrea Iandelli and Tuan-Jen Fang

Cancers 2022, 14(3), 544; https://doi.org/10.3390/cancers14030544 - 21 Jan 2022

Cited by 3 | Viewed by 2477

Abstract

Background: Tracheoesophageal puncture with a voice prosthesis is the gold standard for speech rehabilitation in patients that receive a laryngopharyngectomy. However, a novel surgical technique, using a tubularized anterolateral tight flap, named “J-flap,” has been demonstrated to produce adequate voice restoration. We aimed [...] Read more.

Background: Tracheoesophageal puncture with a voice prosthesis is the gold standard for speech rehabilitation in patients that receive a laryngopharyngectomy. However, a novel surgical technique, using a tubularized anterolateral tight flap, named “J-flap,” has been demonstrated to produce adequate voice restoration. We aimed to compare the outcomes and the quality of life of patients who underwent voice rehabilitation with both techniques. Methods: We enrolled patients that underwent laryngopharyngectomy and voice restoration surgery. The control group received a tracheoesophageal puncture with a voice prosthesis, while the study group received J-flap reconstruction. A total of 20 patients received voice prosthesis rehabilitation, while 18 received J-flap reconstruction. Speech and vocal outcomes and quality of life metrics were collected. Results: The objective phonatory performances and the acoustic voice analysis did not outline a significant difference. Speech pathologists judged the consonant pronunciation in the J-flap group as less accurate (p < 0.001). The voice handicap index revealed a moderate impairment for the J-flap group (p < 0.001). Quality of life scores were higher for the voice prosthesis group. Conclusion: Voice prostheses and J-flaps share similar objective phonatory outcomes. Quality of life was more impaired in the J-flap group. In our view, these two techniques possess complementary characteristics in clinical practice, taking into account health care system regulations and patients’ social background. Full article

(This article belongs to the Special Issue Advanced Squamous Cell Carcinoma)

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12 pages, 1545 KiB

Open AccessArticle

Surveillance for Patients with Oral Squamous Cell Carcinoma after Complete Surgical Resection as Primary Treatment: A Single-Center Retrospective Cohort Study

by Chonji Fukumoto, Ryo Oshima, Yuta Sawatani, Ryo Shiraishi, Toshiki Hyodo, Ryouta Kamimura, Tomonori Hasegawa, Yuske Komiyama, Sayaka Izumi, Atsushi Fujita, Takahiro Wakui and Hitoshi Kawamata

Cancers 2021, 13(22), 5843; https://doi.org/10.3390/cancers13225843 - 21 Nov 2021

Cited by 8 | Viewed by 1883

Abstract

Background: The surveillance methods oral squamous cell carcinoma (OSCC) patients may be chosen by considering the risk for recurrence, and it is important to establish appropriate methods during the period in which latent/dormant cancer cells become more apparent. To investigate the appropriate surveillance [...] Read more.

Background: The surveillance methods oral squamous cell carcinoma (OSCC) patients may be chosen by considering the risk for recurrence, and it is important to establish appropriate methods during the period in which latent/dormant cancer cells become more apparent. To investigate the appropriate surveillance of patients with OSCC based on the individual risk for recurrence and/or metastasis, we performed a retrospective cohort study after the complete surgical resection of OSCC as the primary treatment. Methods: The study was performed in 324 patients with OSCC who had been primarily treated with surgery from 2007 to 2020 at our hospital. We investigated the period, timing, and methods (visual examination, palpation and imaging using FDG-PET/CT or CECT) for surveillance in each case that comprised postsurgical treatment. Results: Regarding the time to occurrence of postsurgical events, we found that half of cases of local recurrence, cervical lymph node metastasis, and distant metastasis occurred within 200 days, and 75% of all of these events occurred within 400 days. However, the mean time for second primary cancer was 1589 days. The postsurgical events were detected earlier by imaging examinations than they were by visual examination and palpation. Conclusions: For the surveillance of patients with OSCC after primary surgery, it is desirable to perform FDG-PET/CT within 3–6 months and at 1 year after surgery and to consider CECT as an option in between FDG-PET/CT, while continuing history and physical examinations for about 5 years based on individual risk assessment. Full article

(This article belongs to the Special Issue Advanced Squamous Cell Carcinoma)

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17 pages, 5153 KiB

Open AccessArticle

Variations of en Bloc Resection for Advanced External Auditory Canal Squamous Cell Carcinoma: Detailed Anatomical Considerations

by Noritaka Komune, Daisuke Kuga, Koichi Miki and Takashi Nakagawa

Cancers 2021, 13(18), 4556; https://doi.org/10.3390/cancers13184556 - 10 Sep 2021

Cited by 5 | Viewed by 2656

Abstract

Currently, only lateral temporal bone resection (LTBR) and subtotal temporal bone resection (STBR) are widely utilized for the surgical treatment of advanced squamous cell carcinoma of the external auditory canal (EAC-SCC). However, there are few descriptions of variations on these surgical approaches. This [...] Read more.

Currently, only lateral temporal bone resection (LTBR) and subtotal temporal bone resection (STBR) are widely utilized for the surgical treatment of advanced squamous cell carcinoma of the external auditory canal (EAC-SCC). However, there are few descriptions of variations on these surgical approaches. This study aimed to elucidate the variations of en bloc resection for advanced EAC-SCC. We dissected the four sides of cadaveric heads to reveal the anatomical structures related to temporal bone resection. From the viewpoint of surgical anatomy, surgical patterns of temporal bone cutting can be divided into four categories: conventional LTBR, extended LTBR, conventional STBR, and modified STBR. Extended LTBR is divided into four types: superior, inferior, anterior, and posterior extensions. Several extension procedures can be combined based on the extension of the tumor. Furthermore, en bloc resection with the temporomandibular joint or glenoid fossa increases the technical difficulty of a surgical procedure because the exposure and manipulation of the petrous segment of the internal carotid artery are limited from the middle cranial fossa. Surgical approaches for advanced SCC of the temporal bone are diverse. They require accurate preoperative evaluation of the tumor extension and preoperative consideration of the exact line of resection to achieve marginal negative resection. Full article

(This article belongs to the Special Issue Advanced Squamous Cell Carcinoma)

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18 pages, 4420 KiB

Open AccessArticle

Small Extracellular Vesicles from Head and Neck Squamous Cell Carcinoma Cells Carry a Proteomic Signature for Tumor Hypoxia

by Alicja Głuszko, Mirosław J. Szczepański, Theresa L. Whiteside, Torsten E. Reichert, Jacek Siewiera and Nils Ludwig

Cancers 2021, 13(16), 4176; https://doi.org/10.3390/cancers13164176 - 19 Aug 2021

Cited by 5 | Viewed by 3342

Abstract

Tissue hypoxia is commonly observed in head and neck squamous cell carcinomas (HNSCCs), resulting in molecular and functional alterations of the tumor cells. The aim of this study was to characterize tumor-derived small extracellular vesicles (sEVs) released under hypoxic vs. normoxic conditions and [...] Read more.

Tissue hypoxia is commonly observed in head and neck squamous cell carcinomas (HNSCCs), resulting in molecular and functional alterations of the tumor cells. The aim of this study was to characterize tumor-derived small extracellular vesicles (sEVs) released under hypoxic vs. normoxic conditions and analyze their proteomic content. HNSCC cells (FaDu, PCI-30, SCC-25) and HaCaT keratinocytes were cultured in 21, 10, 5, and 1% O₂. sEVs were isolated from supernatants using size exclusion chromatography (SEC) and characterized by nanoparticle tracking analysis, electron microscopy, immunoblotting, and high-resolution mass spectrometry. Isolated sEVs ranged in size from 125–135 nm and contained CD63 and CD9 but not Grp94. sEVs reflected the hypoxic profile of HNSCC parent cells: about 15% of the total detected proteins were unique for hypoxic cells. Hypoxic sEVs expressed a common signature of seven hypoxia-related proteins (KT33B, DYSF, STON2, MLX, LIPA3, NEK5, P12L1) and were enriched in pro-angiogenic proteins. Protein profiles of sEVs reflected the degree of tumor hypoxia and could serve as potential sEV-based biomarkers for hypoxic conditions. Adaptation of HNSCC cells to hypoxia is associated with increased release of sEVs, which are enriched in a unique protein profile. Thus, tumor-derived sEVs can potentially be useful for evaluating levels of hypoxia in HNSCC. Full article

(This article belongs to the Special Issue Advanced Squamous Cell Carcinoma)

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14 pages, 2542 KiB

Open AccessArticle

CD73 Promotes Tumor Progression in Patients with Esophageal Squamous Cell Carcinoma

by Yen-Hao Chen, Hung-I Lu, Chien-Ming Lo and Shau-Hsuan Li

Cancers 2021, 13(16), 3982; https://doi.org/10.3390/cancers13163982 - 09 Aug 2021

Cited by 12 | Viewed by 2226

Abstract

Cluster of differentiation (CD)-73 plays pivotal roles in the regulation of immune reactions via the production of extracellular adenosine, and the overexpression of CD73 is associated with worse outcomes in several types of cancers. Here, we identified 167 esophageal squamous cell carcinoma (ESCC) [...] Read more.

Cluster of differentiation (CD)-73 plays pivotal roles in the regulation of immune reactions via the production of extracellular adenosine, and the overexpression of CD73 is associated with worse outcomes in several types of cancers. Here, we identified 167 esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy, including 64 and 103 patients with high and low expression levels of CD73, respectively. Univariate and multivariate analyses showed high expression of CD73 was an independent prognostic factor for worse disease-free survival and overall survival. In addition, we selected another cohort consisting of 38 ESCC patients receiving nivolumab or pembrolizumab and found that treatment response and survival benefit to immunotherapy were strongly correlated with the expression levels of CD73/programmed death ligand 1. Moreover, the transwell assay revealed knockdown of CD73 in two ESCC cell lines, TE1 and KYSE30, exhibited significantly reduced abilities of cell invasion and migration. CD73 silencing also showed that the protein expression levels of CD73, vimentin, and snail were downregulated, while those of E-cadherin were upregulated in Western blotting. The findings of our study indicate CD73 may be an independent prognostic factor for ESCC patients who underwent esophagectomy. Furthermore, it may be associated with the patient responses to immunotherapy. Full article

(This article belongs to the Special Issue Advanced Squamous Cell Carcinoma)

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16 pages, 1994 KiB

Open AccessArticle

Immune Cell Infiltrates and Neutrophil-to-Lymphocyte Ratio in Relation to Response to Chemotherapy and Prognosis in Laryngeal and Hypopharyngeal Squamous Cell Carcinomas

by Mario Sánchez-Canteli, Luis Juesas, Esther Redin, Alfonso Calvo, Fernando López, Aurora Astudillo, Luis M. Montuenga, Juana M. García-Pedrero and Juan P. Rodrigo

Cancers 2021, 13(9), 2079; https://doi.org/10.3390/cancers13092079 - 25 Apr 2021

Cited by 4 | Viewed by 2369

Abstract

Our goal was to assess the correlation of immune parameters with the response to induction chemotherapy (ICT) in head and neck squamous cell carcinoma (HNSCC) patients. Pretreatment biopsies from 64 patients with HNSCC that received ICT were assessed for PD-L1 protein expression and [...] Read more.

Our goal was to assess the correlation of immune parameters with the response to induction chemotherapy (ICT) in head and neck squamous cell carcinoma (HNSCC) patients. Pretreatment biopsies from 64 patients with HNSCC that received ICT were assessed for PD-L1 protein expression and density of CD8+ and FOXP3+ tumor infiltrating lymphocytes (TIL). In addition, the neutrophil-to-lymphocyte ratio (NLR) was calculated from pretreatment whole blood counts. In total, 55% of cases exhibited PD-L1 combined proportion score (CPS) positivity (≥1% stained cells). PD-L1 CPS positivity correlated with a high density of both CD8+ (p = 0.01) and FOXP3+ (p < 0.001) TILs. There was no correlation between PD-L1 expression or TIL density and NLR values. In univariate analyses, the absence of PD-L1 CPS expression (p = 0.042) and a high NLR (p = 0.034) were significantly correlated with response to ICT. Neither CD8+ TIL (p = 0.99) nor FOXP3+ TIL densities (p = 0.71) were associated with response to ICT. In multivariate analysis, only a high NLR was associated with response to ICT (HR = 4.06, 95% CI = 1.06–15.5, p = 0.04). In addition, a high NLR was also independently associated with lower disease-specific (p = 0.03) and overall survival rates (p = 0.04), particularly in the subset of patients who received definitive surgical treatment. These results suggest that NLR could emerge as a predictive biomarker of response to ICT. Full article

(This article belongs to the Special Issue Advanced Squamous Cell Carcinoma)

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12 pages, 1003 KiB

Open AccessArticle

Cutaneous Squamous Cell Carcinoma in Patients with Hidradenitis Suppurativa

by Elysia Racanelli, Abdulhadi Jfri, Amnah Gefri, Elizabeth O’Brien, Ivan V. Litvinov, Andrey Zubarev, Evgeny Savin and Elena Netchiporouk

Cancers 2021, 13(5), 1153; https://doi.org/10.3390/cancers13051153 - 08 Mar 2021

Cited by 10 | Viewed by 3044

Abstract

Background: Cutaneous squamous cell carcinoma (cSCC) is a rare complication of hidradenitis suppurativa (HS). Objectives: To conduct a systematic review and an individual patient data (IPD) meta-analysis to describe the clinical characteristics of HS patients developing cSCC and determine predictors of [...] Read more.

Background: Cutaneous squamous cell carcinoma (cSCC) is a rare complication of hidradenitis suppurativa (HS). Objectives: To conduct a systematic review and an individual patient data (IPD) meta-analysis to describe the clinical characteristics of HS patients developing cSCC and determine predictors of poor outcome. Methods: Medline/PubMed, Embase, and Web of Science were searched for studies reporting cSCC arising in patients with HS from inception to December 2019. A routine descriptive analysis, statistical hypothesis testing, and Kaplan–Meier survival curves/Cox proportional hazards regression models were performed. Results: A total of 34 case reports and series including 138 patients were included in the study. The majority of patients were males (81.6%), White (83.3%), and smokers (n = 22/27 reported) with a mean age of 53.5 years. Most patients had gluteal (87.8%), Hurley stage 3 HS (88.6%). The mean time from the diagnosis of HS to the development of cSCC was 24.7 years. Human papillomavirus was identified in 12/38 patients tested. Almost 50% of individuals had nodal metastasis and 31.3% had distant metastases. Half of the patients succumbed to their disease. Conclusions: cSCC is a rare but life-threatening complication seen in HS patients, mainly occurring in White males who are smokers with severe, long-standing gluteal HS. Regular clinical examination and biopsy of any suspicious lesions in high-risk patients should be considered. The use of HPV vaccination as a preventive and possibly curative method needs to be explored. Full article

(This article belongs to the Special Issue Advanced Squamous Cell Carcinoma)

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Review

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12 pages, 261 KiB

Open AccessReview

Multimodal Treatment Strategies to Improve the Prognosis of Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma: A Narrative Review

by Tadashi Higuchi, Yoshiaki Shoji, Kazuo Koyanagi, Kohei Tajima, Kohei Kanamori, Mika Ogimi, Kentaro Yatabe, Yamato Ninomiya, Miho Yamamoto, Akihito Kazuno, Kazuhito Nabeshima and Kenji Nakamura

Cancers 2023, 15(1), 10; https://doi.org/10.3390/cancers15010010 - 20 Dec 2022

Cited by 3 | Viewed by 1799

Abstract

Esophageal cancer is the seventh most common malignancy and sixth most common cause of cancer-related death globally. Esophageal squamous cell carcinoma (ESCC) with aortic or tracheal invasion is considered unresectable, and has an extremely poor prognosis; its standard treatment is definitive chemoradiotherapy (dCRT). [...] Read more.

Esophageal cancer is the seventh most common malignancy and sixth most common cause of cancer-related death globally. Esophageal squamous cell carcinoma (ESCC) with aortic or tracheal invasion is considered unresectable, and has an extremely poor prognosis; its standard treatment is definitive chemoradiotherapy (dCRT). In recent years, induction chemotherapy (ICT) has been reported to yield high response rates for locally advanced ESCC, and the efficacy and safety of ICT followed by conversion surgery (CS) have been investigated. Multimodal treatment, combining surgery with induction chemoradiotherapy (ICRT) or ICT, is necessary to improve ESCC prognosis. CS is generally performed for locally advanced ECC after ICRT or ICT when tumor downstaging is achieved, although its prognostic benefit remains controversial. The Japan Clinical Oncology Group (JCOG) has conducted a three-arm phase III randomized controlled trial (JCOG1510) to confirm the superiority of DCF (docetaxel, cisplatin, and 5-fluorouracil) ICT, over conventional dCRT, among patients with initially unresectable ESCC. In recent years, researchers have reported favorable outcomes of induction therapy followed by CS and salvage surgery, after dCRT or systemic immunochemotherapy. In this review, we will describe the latest developments in the multimodal treatment including chemotherapy, CRT, surgery, and immunotherapy, which may improve oncological and survival outcomes for patients with cT4 ESCC. Full article

(This article belongs to the Special Issue Advanced Squamous Cell Carcinoma)

11 pages, 244 KiB

Open AccessReview

Recent Advances in Combination of Immunotherapy and Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma

by Ruixi Wang, Shiliang Liu, Baoqing Chen and Mian Xi

Cancers 2022, 14(20), 5168; https://doi.org/10.3390/cancers14205168 - 21 Oct 2022

Cited by 12 | Viewed by 2965

Abstract

Esophageal cancer has a high mortality rate and a poor prognosis, with more than one-third of patients receiving a diagnosis of locally advanced cancer. Esophageal squamous cell carcinoma (ESCC) is the dominant histological subtype of esophageal cancer in Asia and Eastern Europe. Although [...] Read more.

Esophageal cancer has a high mortality rate and a poor prognosis, with more than one-third of patients receiving a diagnosis of locally advanced cancer. Esophageal squamous cell carcinoma (ESCC) is the dominant histological subtype of esophageal cancer in Asia and Eastern Europe. Although neoadjuvant or definitive chemoradiotherapy (CRT) has been the standard treatment for locally advanced ESCC, patient outcomes remain unsatisfactory, with recurrence rates as high as 30–50%. The combination of immune checkpoint inhibitors (ICIs) and CRT has emerged as a novel strategy to treat esophageal cancer, and it may have a synergistic action and provide greater efficacy. In the phase III CheckMate-577 trial, one year of adjuvant nivolumab after neoadjuvant CRT improved disease-free survival in patients with residual disease on pathology. Moreover, several phase I and II studies have shown that ICIs combined with concurrent CRT may increase the rate of pathologic complete response for resectable ESCC, but they lack long-term follow-up results. In unresectable cases, the combination of camrelizumab and definitive CRT showed promising results against ESCC in a phase Ib trial. Phase III randomized trials are currently ongoing to investigate the survival benefits of ICIs combined with neoadjuvant or definitive CRT, and they will clarify the role of immunotherapy in locally advanced ESCC. Additionally, valid biomarkers to predict tumor response and survival outcomes need to be further explored. Full article

(This article belongs to the Special Issue Advanced Squamous Cell Carcinoma)

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Jump to: Research, Review

8 pages, 245 KiB

Open AccessCommentary

Recent Advanced in the Treatment of Advanced SCC Tumors

by Nicole Basset-Seguin and Eve Maubec

Cancers 2022, 14(3), 550; https://doi.org/10.3390/cancers14030550 - 22 Jan 2022

Cited by 2 | Viewed by 1538

Abstract

Squamous cell carcinoma (SCC) is the second most frequent form of skin cancer after basal cell carcinoma. While most SCC can be treated by surgery or radiotherapy, some progress into an advanced form and are no longer suitable for these treatments. Guidelines and [...] Read more.

Squamous cell carcinoma (SCC) is the second most frequent form of skin cancer after basal cell carcinoma. While most SCC can be treated by surgery or radiotherapy, some progress into an advanced form and are no longer suitable for these treatments. Guidelines and staging systems have help to define these advanced SCC (aSCC), for which prognosis was very poor until recently. Platin-based chemotherapy was traditionally used, but few prospective trials and no treatment regimen was recommended. Furthermore, toxicity in elderly patients limited its use. The development of immunotherapy has improved the prognosis of these difficult-to-treat aSCC. In this review, we define high risk and aSCC and explored current treatment strategies for these tumors. Full article

(This article belongs to the Special Issue Advanced Squamous Cell Carcinoma)

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