Treatment Of Squamous Cell Cancer Research Articles

The role of radiotherapy in the management of squamous cell cancer of the penis.

To review the evidence for radiotherapy in the management of primary penile cancer, either as brachytherapy or external beam radiation, and the role of external beam radiotherapy in node positive penile cancer. English language literature was reviewed for the past 3 decades. As penile cancer is uncommon in developed nations, high quality evidence to guide management is limited. Single institution reports often span decades during which time staging systems and treatments have evolved, reducing their relevance to current practice. Successful clinical trials require collaboration not only among disciplines but also among multiple institutions and nations. Radiotherapy is a definitive organ-preserving option for T1-T2 penile cancers. Interstitial brachytherapy is associated with penile preservation in 85% of men at 5years, maintained in 70% by 10years. Results of external radiotherapy are not quite as promising but nonetheless 60% of men will have an intact penis at 5years. Inguino-pelvic external radiotherapy has been reported to increase overall survival when delivered as adjuvant treatment for men with pN3 groin but pN0 pelvic nodes, and improve disease specific survival for those with involved pelvic nodes. InPACT (ECOG-ACRIN_8134) is investigating the role of inguino-pelvic chemo-radiotherapy for men with pN3 inguinal nodes but imaging negative pelvic nodes. Radiotherapy has a well-defined role to play in treatment of squamous cell cancers of other sites, such as vulva, anal canal, uterine cervix and head and neck malignancies. Emerging data support the incorporation of radiotherapy into treatment paradigms for penile cancer.

Indications for Adjuvant (Chemo) Radiotherapy in Vulvar Cancer with Groin Lymph Node Metastases

Guidelines recommend adjuvant treatment when positive lymph nodes are found after surgical treatment for squamous cell cancer of the vulva except for cases with a single occult intranodal metastasis. Recent studies questioned these recommendations and showed benefit of adjuvant radiotherapy for all patients with positive nodes irrespective of number of nodes. However, these studies did not take into account important nodal characteristics, such as clinical node status, extranodal spread or size of the metastasis. When these variables are taken into account, adjuvant radiotherapy does not seem to result in a better survival for patients with a single occult intranodal metastasis. Whether the addition of chemotherapy to the radiotherapy for patients with more than one positive node or extracapsular spread results in a better survival remains uncertain. Only a few studies have been published on this subject and come to the conclusion that adding chemotherapy results in a better survival. The conclusion is that adjuvant radiotherapy improves survival of patients with positive groin nodes, with the exception of patients with a single intranodal metastasis. The beneficial effect of chemo radiotherapy for subgroups of patients with positive nodes seems likely, although more data are needed before a definite conclusion can be made

SOD2 in platelets: with age comes responsibility

SOD2 in platelets: with age comes responsibility

Trends in Laryngeal Squamous Cell Cancer Treatment of the Elderly in Our Hospital from 2007 to 2018

Trends in Laryngeal Squamous Cell Cancer Treatment of the Elderly in Our Hospital from 2007 to 2018

Current Problems in the Diagnosis of Head and Neck Tumors

The article presents the literature review of modern approaches in the diagnosis and treatment of squamous cell cancer of the oropharyngeal region and larynx. Various views on the treatment of patients with oropharyngeal tumors are presented. Special attention is paid to the ultrasound examination of patients with laryngeal tumors and to the possibilities of ultrasound in assessing the integrity of the laryngeal cartilage. Various ultrasound techniques for assessing the thickness and depth of invasion of oral tumors are highlighted. The features of regional anatomy that affect the informative value of visualization techniques are discussed. In the article presents criteria for assessing the prevalence of the tumor process in the adjacent organs and tissues, metastasis in regional lymph nodes.

Surgical treatment of squamous cell cancer with anal margin localization developed on the background of condyloma acuminata: A case report

Surgical treatment of squamous cell cancer with anal margin localization developed on the background of condyloma acuminata: A case report

Long noncoding RNA EGFR-AS1 mediates epidermal growth factor receptor addiction and modulates treatment response in squamous cell carcinoma

Targeting EGFR is a validated approach in the treatment of squamous-cell cancers (SCCs), although there are no established biomarkers for predicting response. We have identified a synonymous mutation in EGFR, c.2361G>A (encoding p.Gln787Gln), in two patients with head and neck SCC (HNSCC) who were exceptional responders to gefitinib, and we showed in patient-derived cultures that the A/A genotype was associated with greater sensitivity to tyrosine kinase inhibitors (TKIs) as compared to the G/A and G/G genotypes. Remarkably, single-copy G>A nucleotide editing in isogenic models conferred a 70-fold increase in sensitivity due to decreased stability of the EGFR-AS1 long noncoding RNA (lncRNA). In the appropriate context, sensitivity could be recapitulated through EGFR-AS1 knockdown in vitro and in vivo, whereas overexpression was sufficient to induce resistance to TKIs. Reduced EGFR-AS1 levels shifted splicing toward EGFR isoform D, leading to ligand-mediated pathway activation. In co-clinical trials involving patients and patient-derived xenograft (PDX) models, tumor shrinkage was most pronounced in the context of the A/A genotype for EGFR-Q787Q, low expression of EGFR-AS1 and high expression of EGFR isoform D. Our study reveals how a 'silent' mutation influences the levels of a lncRNA, resulting in noncanonical EGFR addiction, and delineates a new predictive biomarker suite for response to EGFR TKIs.

Hybrid Benzoxazole-Coumarin Compounds Induce Death Receptor-Mediated Switchable Apoptotic and Necroptotic Cell Death on HN-5 Head and Neck Cancer Cell Line.

Efficacy of multimodality approaches for the treatment of squamous cell cancer of the head and neck has remained unsatisfactory and further advances are critically required. Targeted cell death induction is a novel therapeutic approach that may help to improve clinical management of Head and Neck cancer patients. The potency of novel hybrid benzoxazole-coumarins on the induction of apoptotic and/or necroptotic cell death were evaluated in a Head and Neck carcinoma cell line, HN-5, and a human skin cell line, AGO1522. Quantitative toxicity of the synthesized compounds were elucidated by MTT assay, the specific activity of caspase-3 and -9 were measured by the colorimetric method and zVAD was used to block apoptosis. Expression of cell death related genes were studied using quantitative PCR. All three compounds were revealed IC50 value around 51.96±7.15 microM in HN-5 cells which were significantly lower than observed IC50 for AGO1522, 121.93±3.66 microM (p=0.001). Significant increase expression of FAS, FASL and TRIAL were observed in the treated cells with or without pretreatment with zVAD. In the absence of pretreatment, treatment lead to the induction of apoptosis with a significant increase in caspase-3 gene expression and caspase-3 activity without a significant increase in expression or activity of caspase-9 and other components of the intrinsic apoptotic pathway. However, in the zVAD pretreated cells, necroptotic cell death with a significant increase in expression of RIP1, RIP3, and MLKL genes was observed Conclusion: The novel hybrid benzoxazole-coumarins effectively induce Caspase-3 dependent apoptosis in HN-5 cancer cells, but also could circumvent the blockage of apoptotic cell death by induction of necroptosis.

Treatment for Basal Cell and Squamous Cell Cancers in Older Patients

Treatment for patients with cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) — both so common in older patients — can vary in

STABILITY INDICATING OPTIMIZED RP-HPLC METHOD APPLYING QBD PRINCIPLES FOR QUANTITATIVE ESTIMATION OF NIMORAZOLE

ICH Q8(R2) guidelines concerning the development of pharmaceutical process following a Quality by Design (QbD) approach can be implemented for analytical method developments. Nimorazole is a hypoxic radiosensitizer used in radiotherapy treatment for squamous cell cancer of the head and neck. The aim of the present work was to develop a simple, robust, optimized and stability indicating reverse phase high performance liquid chromatographic method underlying QbD principles for the estimation of nimorazole in pharmaceutical samples. The objectives were achieved at optimized chromatographic conditions using a column of dimensions, 250 x 4.6 mm, C18 (5 μm) (such as Sunfire C18), using mobile phase comprising a mixture of 51 volumes of 0.01 M KH2PO4 solution and 49 volumes of methanol using flow rate of 1.0 mL per minute, injection volume of 10 μl, column oven temperature at 27°C and 302 nm as detection wavelength. The developed method was found linear over the concentration range of 10-150 ppm with detection and quantitation limit of 2.73 ppm and 8.28 ppm respectively. The retention time of nimorazole is found about 4.9 minutes and the assay observed were 101.60 % and 99.52 % in bulk drug and tablet dosage form respectively. Whilst performing the forced degradation studies to demonstrate the specificity of analytical method, nimorazole suffers much degradation in oxidative, less in basic and least in acidic conditions, while no degradation was observed in thermal and photolytic conditions. The respective degradation products were well resolved from the pure drug. Hence, the method can be successfully employed for quantitative analysis of nimorazole in pharmaceutical samples.

Comprehensive Treatment of Squamous Cell Cancer of Head and Neck: Chinese Expert Consensus 2013

Head and neck cancer is the sixth most common malignant tumor worldwide, and squamous cell cancer of the head and neck accounts for more than 90% of head and neck cancers. In China, the incidence of oral cavity and pharyngolaryngeal cancer is 3.28 per 100,000 with a mortality of 1.37 per 100,000, and the incidence of nasopharyngeal cancer is 3.61 per 100,000 with a mortality was 1.99 per 100,000. In 2013, an expert consensus conference was held in China with the aim of establishing the optimum multimodality treatments that are applied in Chinese patients with squamous cell cancer of the head and neck. The experts, who met to review the literature and discuss and modify treatment strategies used in clinical practice in China, reached a consensus on the optimum therapy approaches, which, in general, combine surgery, radiotherapy, chemotherapy and targeted therapy. The experts strongly recommended that healthcare providers should integrate proper medical resources into a collaborative group involving specialists in several disciplines to agree upon and provide the most effective therapy for individual patients.

Results of transoral laser microsurgery in 102 patients with squamous cell carcinoma of the tonsil

The objective of this study is to assess the feasibility of transoral laser microsurgery (TLM) in the treatment of squamous cell cancer of the tonsil and to report the oncological and functional outcomes, using retrospective chart review in the setting of single-institute, academic tertiary referral center. Between October 1987 and December 2006, 102 patients were eligible for this study, mostly suffering from advanced disease: 13 % presented with stage I and II (UICC/AJCC 2002) tumors and 87 % with stages III and IVa. The median follow-up was 63 months. All patients were treated by TLM with (or without) neck dissection (95 %) and with (66 %) postoperative radiotherapy. Overall survival, recurrence-free survival, disease-free survival, local control and loco-regional control were analyzed as end points. Rate of tracheotomies, postoperative complications and swallowing function were also analyzed. 5-year Kaplan–Meier local and loco-regional control was 78 % for pT1 and pT2 and 75 % for pT3 and pT4a tumors. 5-year Kaplan–Meier disease-free survival, recurrence-free survival, and overall survival and was 74, 64 and 59 % for stage I and II, 68, 60 and 56 % for stage III and IVa, respectively. Our data supports the conclusion, that TLM should be considered as a therapeutic option for the treatment of cancer of the tonsil. The oncological and functional results are comparable to any other treatment regimen, while the morbidity and complications tend to be lower.

Oncological results after surgical treatment of squamous cell cancer of the lateral wall of the oropharynx

The gold standard of treatment of cancer of the lateral wall of the oropharynx continues to be unclear, especially in advanced stages. In this study, we report our experience with surgical treatment of these cancers and describe the functional and oncological results of the procedures. Retrospective review. A total of 155 previously untreated patients with squamous cell carcinoma of the lateral wall of the oropharynx who underwent a surgical resection of the lesion at our department from January 1990 to January 2008 were included. Sixty-seven percent of these patients received postoperative radiotherapy. The records of these patients were reviewed to obtain measures such as local and regional control, disease-specific survival, and speech and swallowing function. Six patients had a stage I disease, 15 had a stage II disease, 31 had a stage III disease, 86 had a stage IVA, and 17 had stage IVB disease. The overall recurrence rate was 60%, and the local recurrence rate was 40%. The 5-year overall survival and disease-specific survival rates were 33% and 43%, respectively. Five-year disease-specific survival rates by stage were as follows: 100%, 59%, 57%, 31%, and 33% for stages I to IVB, respectively. Multivariate analysis showed two parameters that were independent predictors of a reduced disease-specific survival: cervical lymph node metastases pN2-3 (P = .027) and primary tumor classified as pT3-4 (P = .029). In 122 patients, a tracheotomy was performed, and it couldn't be sealed in 23% of them. Oral alimentation was successfully recovered in 93% of the patients. Surgical treatment of cancer of the lateral wall of the oropharynx provides acceptable oncological and functional results, especially in early and moderately advanced stages (stages I-III). In advanced stages (stage IV), we obtained good functional preservation rates but poor oncological outcomes. Consequently, these groups of patients could be considered for another treatment modality, such as radiochemotherapy.

Impact of HPV status on treatment of squamous cell cancer of the oropharynx: What we know and what we need to know

Studies report an increasing incidence of oropharyngeal cancers linked to infection by human papillomavirus (HPV). We reviewed trials assessing outcomes by HPV DNA status in patients with locally advanced oropharyngeal cancer. Seven of the eight studies identified showed significantly better survival in patients with HPV DNA-positive tumors vs. HPV DNA-negative tumors. The review also describes what needs to be defined regarding optimal treatments. Future trials should incorporate HPV DNA status as a risk determinant and explore treatments for high-risk patients needing therapy intensification, and low- and intermediate-risk patients needing treatment de-intensification to improve tolerability, without compromising survival.

Diffusion Magnetic Resonance Imaging: An Imaging Treatment Response Biomarker to Chemoradiotherapy in a Mouse Model of Squamous Cell Cancer of the Head and Neck

For the treatment of squamous cell cancer of the head and neck (SCCHN), the assessment of treatment response is traditionally accomplished by volumetric measurements and has been suggested to be prognostic for an eventual response to treatment. An early evaluation response during the course of radiation therapy could provide an opportunity to tailor treatment to individual patients. Diffusion magnetic resonance imaging (MRI) allows for the quantification of tissue water diffusion values, thus treatment-induced loss of tumor cells will result in the increase in water mobility at the microscopic level, which can be detected as an increase in tumor diffusion values before any volumetric changes occur. We evaluated the use of diffusion MRI as an imaging biomarker of treatment response in an orthotopic mouse model of SCCHN. Mice with murine squamous cells expressing the yeast transgene cytosine deaminase were treated with 5-fluorocytosine (5FC), ionizing radiation, and combined therapy and were compared with control animals both during and after treatment for changes in tumor volumes, diffusion values, and survival. Radiation therapy had minimal effect on volumetric growth rate, diffusion, or survival. Although 5FC and combination treatment resulted in similar reductions in tumor volumes, the combination treatment elicited a much greater increase in tumor diffusion values, which correlated with improved survival. Thus, diffusion MRI as an imaging biomarker has a potential for early evaluation of the response to chemoradiation treatment in SCCHN.

Accuracy of endoanal ultrasound in the follow-up assessment for squamous cell carcinoma of the anal canal treated with radiochemotherapy

Radiochemotherapy has largely replaced surgery in the treatment for squamous cell cancer of the anal canal. Transanal ultrasonography is well documented as an important investigation method in the management of anal carcinoma. This study aimed to evaluate the accuracy of endoanal ultrasound in the study of the postradiation findings and to distinguish between postradiation fibrosis, residual tumor, and local recurrence. The study enrolled 16 consecutive patients with biopsy-proven squamous carcinoma of the anal canal between 2003 and 2006. All the patients underwent a pretreatment and at least four posttreatment endosonographies, according to the follow-up period. All the patients were treated with the same radiochemotherapy protocol. Nine patients had stage uT2 disease; none had uT3 disease; and seven had uT4 disease. There was no evidence of residual tumor in the T2 group after treatment. In the T4 patients after treatment, ultrasound demonstrated tumor regression or abnormalities considered to be radiation-induced changes rather than residual diseases. Only for three patients was a posttreatment biopsy performed to evaluate recurrence (two uT2 and one uT4). Surgical treatment of recurrence was performed for two uT4 patients. Endoanal ultrasound is a safe and effective method for evaluating and following anal cancer before and after treatment. Experience and evaluation during the period of the ultrasonographic abnormalities could give a clear idea concerning the evolution of the anal tumors treated with radiochemotherapy.

Anemia During Sequential Induction Chemotherapy and Chemoradiation for Head and Neck Cancer: The Impact of Blood Transfusion on Treatment Outcome

Sequential treatment (chemotherapy followed by concomitant chemoradiation; CCRT) is increasingly being used for radical treatment of squamous cell cancer of the head and neck (SCCHN), which results in increased myelosuppression. In this study, we review the incidence of anemia and the effect of a policy of hemoglobin (Hb) maintenance by blood transfusion on disease outcomes in these patients. Retrospective review of the records of patients with SCCHN treated with sequential CCRT formed the basis of this study. The incidence of anemia and statistics on blood transfusion were documented. For the purpose of outcome analyses, patients were divided into four categories by (1) transfusion status, (2) nadir Hb concentration, (3) number of transfusion episodes, and (4) number of units of blood transfused (NOUT). Data on 3-year locoregional control (LRC), relapse-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) were analyzed. One hundred and sixty-nine patients were identified. The median follow-up was 23.6 months. The RFS (52% vs. 41%, p = 0.03), DSS (71% vs. 66%, p = 0.02), and OS (58% vs. 42% p = 0.005) were significantly better for patients who did not have a transfusion vs. those who did. The LRC, RFS, DSS, and OS were also significantly better for patients with nadir Hb level >12 vs. <12 g/dL and NOUT 1-4 vs. >4. Our study seems to suggest that blood transfusion during radical treatment for SCCHN might be detrimental. Further research should be undertaken into the complex interactions among tumor hypoxia, anemia, and the treatment of anemia before making treatment recommendations.

Nigro regimen treatment of squamous cell cancer of the anus

14545 Background: To identify prognostic factors for patients with squamous cell cancer (SCC) of the anus treated with Nigro Regimen chemo/radiation therapy. Methods: Survival data of 61 patients with SCC of the anal canal were reviewed who were treated with definitive radiochemotherapy (RCT) between 9/83 and 3/06. All patients received RCT at the Cleveland Clinic Foundation. Results: Patient characteristics were typical of other studies. Median age was 57 years (34–82), women: men (42:19), PS 0–1 (95%), smokers 52%, and clinically lymph node positive tumors 27%. T3–4 tumors were 50%, high for most series. The median follow-up time was 52 mos (7–246 mos). The median disease free survival (DFS) and overall survival (OS) have not been reached. 5-year DFS was 76% (95% C.I. 62–88%) and 5-year OS was 76% (95% C.I. 60–86%). Colostomy free survival at 5-years was 41/61 (67%). Log rank analyses showed that female sex (5-yr DFS 82 vs 55%, p=0.03), and clinical stage (5-yr DFS, stage 1 100%, stage 2 80%, stage 3a 65%, stage 3b 0%) correlated with better disease free survival. Patient age (less than 60 or greater), time of diagnosis (before 1996 or later), and smoking status did not correlate with better disease free survival. There were 14 recurrences, 7 systemic, 7 local with APR salvaging 4 patients with local relapse. There were 2 cases of treatment related hemolytic uremic syndrome, with one death. Conclusions: The Nigro regimen is successful in curing anal cancer in a significant majority of patients. We appear to have reached a therapeutic plateau and have not had any significant improvement in cure rates over the last two decades. Identification of subsets more prone to relapse is crucial, to target with more intense treatment in future trials. In the current series, male sex and advanced clinical stage correlated with poor disease free survival, when anal cancer patients were treated with the Nigro regimen RCT. Future studies should investigate whether more intensive treatment is needed in males, and patients with more advanced disease. No significant financial relationships to disclose.

Concurrent radiotherapy with paclitaxel/carboplatin chemotherapy as a definitive treatment for squamous cell carcinoma of the uterine cervix

To evaluate the toxicity and the efficacy of paclitaxel/carboplatin chemoradiotherapy as a definitive treatment for squamous cell cancer of the uterine cervix. From March 2000 to January 2004, 33 patients with squamous cell cancer of the uterine cervix were treated with concurrent chemoradiotherapy including 2 cycles of paclitaxel (135 mg/m(2)) and carboplatin (area under the time-concentration curve 4.5 mg min/ml) at 4-week interval. Seven patients received adjuvant chemotherapy with the same chemotherapeutic regimen. All patients received external beam radiotherapy with 41.4-51.4 Gy (median 50.4 Gy) to the whole pelvis. Twenty-eight patients received boost irradiation to the cervix by brachytherapy with 25.6-43.3 Gy (median 34.6 Gy) and 5 patients by external beam radiotherapy with 10.8-14.4 Gy (median 14.4 Gy). A median follow-up period was 27 months (range: 6-53 months). Acute hematological toxicity of grade 3 or 4 developed in 20 patients (61%), and acute gastrointestinal toxicity of grade 3 developed in 1 patient (3%). Vesicovaginal fistula occurred in 2 patients (6%). All patients achieved objective response (CR 70%, PR 30%) in 2 months after termination of treatment. One patient had a local progression in cervix, and 4 patients developed distant metastases. The 3-year estimated disease-free survival rates for stages I-IIA, IIB, III and IV were 67%, 91%, 88% and 50%, respectively. The 3-year estimated survival rates for stages I-IIA, IIB, III and IV were 89%, 91%, 88% and 50%, respectively. Concurrent chemoradiotherapy with paclitaxel and carboplatin is effective to achieve an excellent pelvic control.

The role of cetuximab in the treatment of squamous cell cancer of the head and neck

The epidermal growth factor receptor (EGFR) is a member of the HER family of tyrosine kinase growth factor receptors. Binding to EGFR by its natural ligands, mainly epidermal growth factor (EGF) or transforming growth factor (TGF)-α, results in a conformational change in the receptor, which promotes homo- or heterodimerisation or oligomerisation with other EGFR molecules or other HER family members. Dimerisation results in the activation of intracellular tyrosine kinase, autophosphorylation and activation of signal transduction molecules, ultimately leading to cell cycle progression, reduced apoptotic capacity, angiogenesis and the metastatic phenotype. EGFR is expressed on normal human cells and also across a range of malignancies. Tumour EGFR expression correlates with poor prognosis and resistance to therapy. Cetuximab is a chimeric human:murine monoclonal antibody that binds competitively to the EGFR. Binding of the antibody to the EGFR prevents activation of the receptor by endogenous ligands; proliferation is reduced, apoptosis enhanced, and angiogenesis, invasiveness and metastasis reduced. Binding of cetuximab to the receptor also results in internalisation and degradation of the antibody–receptor complex, downregulating EGFR expression. EGFR has been recognised as an important therapeutic target in cancer. Other antibodies are also in development, and small molecular inhibitors of the tyrosine kinase domain are available. Cetuximab adds to the activity of radiotherapy in locoregional head and neck cancer, and when given with platinum-based chemotherapy is active in a proportion of patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck, as is cetuximab monotherapy. When cetuximab is added to cisplatin monotherapy in the first-line treatment of recurrent or metastatic squamous cell carcinoma of the head and neck, the objective response rate is significantly improved and the hazard ratio for progression is 0.78. The most commonly reported adverse event associated with cetuximab treatment is an acneiform rash that occurred in 70 – 80% of patients treated with cetuximab. Presence of the characteristic rash is significantly associated with response and/or survival. It is possible that development of acneiform rash may become an important clinical prognostic marker. Serious cetuximab-related toxicities include hypersensitivity reactions. Thus, cetuximab is biologically active across a range of clinical scenarios in squamous cell carcinoma of the head and neck. Ongoing studies will be important in establishing its role in the routine management of head and neck cancer.