Early-stage Squamous Cell Cancer Research Articles

Early-Stage Glottic Squamous Cell Carcinoma in the Era of Image-Guided Radiotherapy.

Early-stage squamous cell cancer (SCC) of the glottis has a good prognosis. Therefore, patients have long survival outcomes and may potentially suffer from late toxicities of radiotherapy. Radiotherapy with a conventional parallel-opposed-pair or anterior-oblique beam arrangements for stage 1 and 2 glottic SCC have field borders that traditionally cover the entire larynx, exposing organs-at-risk (e.g. carotid arteries, contralateral vocal cord, contralateral arytenoid and inferior pharyngeal constrictor muscles) to high radiation doses. The potential long-term risk of cerebrovascular events has attracted much attention to the dose that carotid arteries receive. Swallow and respiratory motion of laryngeal structures has been an important factor that previously limited reduction of the radiation treatment volume. Motion has been evaluated using multiple imaging modalities and this information has been used to calculate PTV margins for generation of more limited target volumes. This review discusses the current literature surrounding dose-effect relationships for various organs-at-risk and the late toxicities that are associated with them. This article also reviews the currently available data and effects of laryngeal motions on dosimetry to the primary target. We also review the current limitations and benefits of a more targeted approach of radiotherapy for early-stage glottic SCCs and the evolution of CT-based IGRT and MR-guided radiotherapy techniques that may facilitate a shift away from a conventional 3D-conformal radiotherapy approach.

Endoscopic Therapy for Esophageal Squamous High-Grade Dysplasia and Early Squamous Cell Carcinoma: A North American Experience

Introduction: Squamous cell cancer (SCC) represents the predominant histological subtype of esophageal cancer worldwide. Endoscopic mucosal resection (EMR) and ablative therapies, such as radiofrequency ablation (RFA) and photodynamic therapy (PDT), have become established treatments for early stage SCC in high-incidence regions. According to national guidelines, endoscopic therapy is the preferred treatment approach for high-grade dysplasia (HGD) and early stage SCC and adenocarcinoma; however, data supporting endoscopic therapy for SCC in low-incidence countries are limited. We report the experience with endoscopic treatment for this cancer subtype at a North American comprehensive cancer center. Methods: We performed a retrospective search of the institutional electronic medical record to identify cases of esophageal squamous HGD or early stage esophageal SCC between 1998 and 2017 that were managed endoscopically by EMR, RFA, PDT and/or argon plasma coagulation (APC). Demographic data, disease characteristics, and clinical outcomes were collected. Results: Twenty patients (11 Tis, 6 T1a, 3 T1b) were included in this study, with a median age of 73 years (IQR 65.5-77.9). There were 14 (70.0%) female patients in our series. Fifteen patients (75.0%) achieved an initial complete remission of dysplasia at a median of 95 days (IQR 78.5-265.0). The complete remission rates for Tis, T1a, and T1b lesions were 81.8%, 83.3% and 33.3%, respectively. Patients required a mean of 1.9 (range 1-4) endoscopic procedures to achieve remission. Five patients (25.0%) required further therapy, including esophagectomy (n=1), intraluminal brachytherapy (n=1), chemoradiation (n=1), or were lost to follow up (n=2). Eleven (73.3%) out of the fifteen patients, who achieved initial remission, remained disease-free at a median follow-up of 79.8 months (IQR 45.2-132.0). Four patients (26.6%) had disease recurrence requiring further endoscopic therapy (n=2) or chemoradiation (n=1), while one patient with low-grade dysplasia recurrence chose to undergo surveillance. Five of sixteen patients treated with EMR (31.3%) and two of eight patients treated with RFA (25.0%) developed minor complications. There were no severe complications.Table: Table. Demographic and Tumor CharacteristicsTable: Table. Treatment and OutcomesConclusion: This study describes a North American experience with squamous HGD and T1 SCC treated endoscopically. This study demonstrates that endoscopic therapy is highly effective and durable in eradicating squamous HGD and T1 SCC of the esophagus.

Effects of neoadjuvant chemotherapy on patients with primary vaginal squamous cell carcinoma.

Vaginal cancer is a rare gynecological malignancy, mainly treated by radiotherapy and surgery. However, the effect of neoadjuvant chemotherapy on patients with vaginal cancer has not been extensively evaluated. The aim of the present study was to assess the feasibility and efficacy of irinotecan and cisplatin in the management of patients with vaginal squamous cell cancer (SCC). Two patients with International Federation of Obstetrics and Gynecology (FIGO) stage I and one patient with FIGO stage II vaginal SCC were treated with irinotecan (240 mg) and cisplatin (100 mg) every 3-4 weeks. The effect of chemotherapy after 2-4 courses was assessed and the next step of treatment was determined according to the outcome. In the present study, all 3 patients had complete remission after 2-4 courses of chemotherapy. In case 1, the patient received a total of 6 courses of chemotherapy and had no recurrence after 45 months of follow-up. In case 2, the patient received 4 courses of chemotherapy and partial vaginal resection, and had no recurrence after 48 months of follow-up. In case 3, the patient underwent laparoscopic radical surgery and peritoneal vaginoplasty after 2 courses of chemotherapy, and no residual tumors were identified in the resected tissues on postoperative pathological examination. Effective neoadjuvant chemotherapy may decrease the size of the tumor, induce tumor regression, or even achieve pathologically-confirmed complete tumor eradication. Thus, neoadjuvant chemotherapy with irinotecan combined with cisplatin is a feasible treatment for patients with early-stage vaginal SCC. In the present study, all the patients achieved good therapeutic results following chemotherapy.

Identification of haptoglobin peptide as a novel serum biomarker for lung squamous cell carcinoma by serum proteome and peptidome profiling.

To date, a number of potential biomarkers for lung squamous cell cancer (SCC) have been identified; however, sensitive biomarkers are currently lacking to detect early stage SCC due to low sensitivity and specificity. In the present study, we compared the 7 serum proteomic profiles of 11 SCC patients, 7 chronic obstructive pulmonary disease (COPD) patients and 7 healthy smokers as controls to identify potential serum biomarkers associated with SCC and COPD. Two-dimensional difference gel electrophoresis (2D-DIGE) and mass-spectrometric analysis (MS) using an affinity column revealed two candidate proteins, haptoglobin (HP) and apolipoprotein 4, as biomarkers of SCC, and α-1-antichymotrypsin as a marker of COPD. The iTRAQ technique was also used to identify SCC-specific peptides. HP protein expression was significantly higher in SCC patients than in COPD patients. Furthermore, two HP protein peptides showed significantly higher serum levels in SCC patients than in COPD patients. We established novel polyclonal antibodies for the two HP peptides and subsequently a sandwich enzyme-linked immunosorbent assay (ELISA) for the quantification of these specific peptides in patient and control sera. The sensitivity of detection by ELISA of one HP peptide (HP216) was 70% of SCC patients, 40% of COPDs patients and 13% of healthy controls. We also measured CYFRA, a cytokeratin fragment clinically used as an SCC tumor marker, in all the 28 cases and found CYFRA was detected in only seven SCC cases. However, when the measurement of HP216 was combined with that of CYFRA, 100% (10 of 10 patients) of SCC cases were detected. Our proteomic profiling demonstrates that the SCC-specific HP peptide HP216 may potentially be used as a diagnostic biomarker for SCC.

Early stage squamous cell cancer of the oral tongue—clinicopathologic features affecting outcome

The objective of this study was to report the authors' experience in the management of patients with early stage squamous cell cancer (SCC) of the oral tongue and determine clinicopathologic factors predictive of outcome. Two hundred sixteen patients with early stage (cT1T2N0) SCC of the oral tongue were identified from a pre-existing database of patients with oral cancer who were treated at Memorial Sloan-Kettering Cancer Center from 1985 to 2005. Patient, tumor, and treatment characteristics were recorded. Overall survival (OS), disease-specific survival (DSS), and recurrence free survival (RFS) were calculated using the Kaplan-Meier method. Predictors of outcome were identified using multivariate analysis. With a median follow-up of 80 months (range, 1-186 months), the 5-year DSS, OS, and RFS rates were 86%, 79%,and 70%, respectively. Local, neck, and distant recurrences occurred in 24 patients (11%), 40 patients (18%), and 5 patients (2%), respectively. Multivariate analysis identified occult neck metastases as the main independent predictor of OS, DSS, and RFS; patients who had occult metastases had a 5-fold increased risk of dying of disease compared with patients who did not have occult metastases (5-year DSS, 85.5% vs 48.5%; P = .001). A positive surgical margin was the main independent predictor for local RFS (91% vs 66% for a negative surgical margin; P = .0004), and depth of invasion was the main predictor for neck RFS (91% vs 73% for depth of invasion <2 mm and >2 mm, respectively; P = .02). In the authors' experience, patients with early stage oral tongue cancer have excellent outcomes. In the current study, the presence of occult metastases was the main predictor of survival outcome.

Management of vulvar cancers

Aim The radical surgical approach in the treatment of vulvar cancer patients has led to a favorable prognosis for the majority of the patients with early stage squamous cell cancer. However, the morbidity is impressive, leading to more individualized treatment. The aim of this review is to give an overview of the management of vulvar cancer. Methods We have reviewed the literature on the modifications in treatment of vulvar cancer with the emphasis on surgery and radiotherapy for primary disease. Results While surgery is the cornerstone of treatment for early stage squamous cell vulvar cancer (with wide local excision and uni- or bilateral inguinofemoral lymphadenectomy via separate incisions as standard treatment), until now there has been a limited role for primary radiotherapy although this may be an attractive alternative for the inguinofemoral lymphadenectomy in the future. The sentinel lymph node procedure with the combined technique (preoperative lymphoscintigraphy with 99mtechnetium-labeled nanocolloid and Patente Blue) is a promising staging technique for patients with vulvar cancer. The clinical implementation of the sentinel lymph node procedure and the role of additional histopathological techniques of the sentinel lymph nodes have to be investigated. In advanced vulvar cancer, chemoradiation followed by surgery should be regarded as the treatment of first choice for these patients. Conclusions Due to the rarity of vulvar cancer it is quite clear that further studies will have to be performed by international collaborative groups. The sentinel lymph node procedure and primary radiotherapy are promising methods to reduce morbidity of treatment, but their safety needs to be studied in clinical trials.

Noninvasive detection of inguinofemoral lymph node metastases in squamous cell cancer of the vulva by L-

In the majority of patients with early stage squamous cell cancer (SCC) of the vulva, an inguinofemoral lymphadenectomy is performed (in retrospect) for diagnostic reasons: exclusion of inguinofemoral lymph node metastases. The morbidity of this procedure, however, is significant. The aim of the present study was to evaluate noninvasive detection of inguinofemoral lymph node metastases by positron emission tomography (PET) using L-[1-11C]-tyrosine (TYR) as tracer. In patients with SCC of the vulva, scheduled for resection of the primary tumor and uni- or bilateral inguinofemoral lymphadenectomy, results of preoperative palpation of the groins and TYR-PET imaging were compared with histopathology. PET imaging was performed using two different methods. In a first group (n = 16), nonattenuation corrected 'whole body' scans were performed, and in a second group (n = 9), attenuation corrected static emission scans. Sensitivity, specificity, accuracy, and positive and negative predictive value for palpation were 62%, 89%, 82%, 67%, and 87% per groin. Sensitivity, specificity, accuracy, and positive and negative predictive value for TYR-PET were calculated for the two methodologies separately and overall. There were no significant differences. Overall values were 53%, 95%, 94%, 33%, and 98% per lymph node and 75%, 62%, 65%, 41% and 88% per groin. Detection of inguinofemoral lymph node metastases by TYR-PET is not superior to palpation. Neither palpation nor TYR-PET is able to adequately predict or exclude presence of inguinofemoral lymph node metastases in patients with SCC of the vulva.