Evaluation of Depth of Invasion and Tumor Thickness as a Prognostic Factor for Early-Stage Oral Squamous Cell Carcinoma: A Retrospective Study

The aim of this study was to compare the effect of using depth of invasion (DOI) versus tumor thickness (TT) as a prognostic factor for early-stage oral squamous cell carcinoma (OSCC). A total of 57 patients with early-stage OSCC treated surgically from 2009 to 2014 at our institution were reviewed retrospectively. Histopathological measurement of DOI and TT was performed. The validation of DOI and TT as prognostic factors was conducted using a Kaplan–Meier survival analysis. TT had no association with disease-specific survival (DSS) or progression-free survival (PFS) in this cohort; however, increased DOI was significantly associated with decreased DSS but not correlated to decreased PFS. The T category of the 7th edition of AJCC was statistically associated with both DSS and PFS; however, the T category of the 8th edition of the AJCC was only associated with DSS. In this study group, TT could not be used as a prognostic factor, and DOI was not by itself sufficient to predict prognosis for early-stage OSCC. The T category in AJCC 8th Edition cannot be considered the sole prognostic factor for early OSCC, so additional prognostic factors may need to be considered.

Detailed patient-individual reporting of lymph node involvement in oropharyngeal squamous cell carcinoma with an online interface

Purpose/ObjectiveWhereas the prevalence of lymph node level (LNL) involvement in head & neck squamous cell carcinomas (HNSCC) has been reported, the details of lymphatic progression patterns are insufficiently quantified. In this study, we investigate how the risk of metastases in each LNL depends on the involvement of upstream LNLs, T-category, HPV status and other risk factors.Materials/MethodsWe retrospectively analyzed patients with newly diagnosed oropharyngeal HNSCC treated at a single institution, resulting in a dataset of 287 patients. For all patients, involvement of LNLs I-VII was recorded individually based on available diagnostic modalities (PET, MR, CT, FNA) together with clinicpathological factors. To analyze the dataset, a web-based graphical user interface (GUI) was developed, which allows querying the number of patients with a certain combination of co-involved LNLs and tumor characteristics.ResultsThe full dataset and GUI is part of the publication. Selected findings are: Ipsilateral level IV was involved in 27% of patients with level II and III involvement, but only in 2% of patients with level II but not III involvement. Prevalence of involvement of ipsilateral levels II, III, IV, V was 79%, 34%, 7%, 3% for early T-category patients (T1/T2) and 85%, 50%, 17%, 9% for late T-category (T3/T4), quantifying increasing involvement with T-category. Contralateral levels II, III, IV were involved in 41%, 19%, 4% and 12%, 3%, 2% for tumors for tumors with and without midline extension, respectively. T-stage dependence of LNL involvement was more pronounced in HPV negative than positive tumors, but overall involvement was similar. Ipsilateral level VII was involved in 14% and 6% of patients with primary tumors in the tonsil and the base of tongue, respectively.ConclusionsDetailed quantification of LNL involvement in HNSCC depending on involvement of upstream LNLs and clinicopathological factors may allow for further personalization of CTV-N definition in the future.

A hidden Markov model for lymphatic tumor progression in the head and neck

Currently, elective clinical target volume (CTV-N) definition for head and neck squamous cell carcinoma (HNSCC) is mostly based on the prevalence of nodal involvement for a given tumor location. In this work, we propose a probabilistic model for lymphatic metastatic spread that can quantify the risk of microscopic involvement in lymph node levels (LNL) given the location of macroscopic metastases and T-category. This may allow for further personalized CTV-N definition based on an individual patient’s state of disease. We model the patient's state of metastatic lymphatic progression as a collection of hidden binary random variables that indicate the involvement of LNLs. In addition, each LNL is associated with observed binary random variables that indicate whether macroscopic metastases are detected. A hidden Markov model (HMM) is used to compute the probabilities of transitions between states over time. The underlying graph of the HMM represents the anatomy of the lymphatic drainage system. Learning of the transition probabilities is done via Markov chain Monte Carlo sampling and is based on a dataset of HNSCC patients in whom involvement of individual LNLs was reported. The model is demonstrated for ipsilateral metastatic spread in oropharyngeal HNSCC patients. We demonstrate the model's capability to quantify the risk of microscopic involvement in levels III and IV, depending on whether macroscopic metastases are observed in the upstream levels II and III, and depending on T-category. In conclusion, the statistical model of lymphatic progression may inform future, more personalized, guidelines on which LNL to include in the elective CTV. However, larger multi-institutional datasets for model parameter learning are required for that.

The Gut Microbiome as a Promising Biomarker of Cancer Progression Among Female Never-smokers With Lung Adenocarcinoma

Background: The gut microbiome plays an important role in the immune system and has attracted attention as a biomarker of various diseases, including cancer. As such, we examined the relationship between the gut microbiome and lung cancer progression. In addition, we assessed the correlation between the gut microbiome and epidermal growth factor receptor (EGFR) mutation status.Methods: Female never-smokers diagnosed with lung adenocarcinoma were consecutively and prospectively enrolled between May 2018 and August 2019. Fecal samples were collected within 1 month before or after diagnosis and before administration of any lung cancer treatment. Principal coordinate analyses were retrospectively performed using Bray-Curtis distance matrices to investigate the effects of clinical variables (age, body mass index, Tumor-Node-Metastasis stage, T category, N category, M category, primary tumor size, performance status, and EGFR mutation status) on the gut microbial community. A correlation analysis was also performed to determine the strength of association between the dominant taxonomy (comprising ≥1% of the relative abundance of bacterial DNA sequences) and clinical variables.Results: A total of 37 patients were enrolled. T category and primary tumor size were significantly correlated with the gut microbial community (p=0.018 and 0.041, respectively). At the genus level, a significant positive correlation was observed between the relative abundance of Faecalibacterium and both T category (correlation coefficient, R=0.51, p=0.0013) and primary tumor size (R=0.37, p=0.024), whereas a significant negative correlation was observed between the relative abundances of Fusicatenibacter and Bacteroides and T category (R=−0.35, p=0.034 and R=−0.32, p=0.05, respectively) and primary tumor size (R=−0.36, p=0.029 and R=−0.41, p=0.012, respectively). EGFR mutation status had no statistically significant effect on the gut microbial community (p=0.11). However, the relative abundances of Bifidobacterium and Faecalibacterium were significantly higher in EGFR mutation–negative patients than EGFR mutation–positive patients (p=0.012 and 0.041), whereas the relative abundance of Blautia was significantly lower in EGFR mutation–negative patients (p=0.036).Conclusions: This is the first study identifying the gut microbiome as a promising biomarker of lung cancer progression. Further elucidation of the role of the gut microbiome in lung cancer progression could facilitate development of new treatments for lung cancer.

Urinary bladder cancer as a late sequela of traumatic spinal cord injury

Background Traumatic spinal cord injury (SCI) is also a combat-related injury that is increasing in modern warfare. The aim of this work is to inform medical experts regarding the different course of bladder cancer in able-bodied patients compared with SCI patients based on the latest medical scientific knowledge, and to present decision-making aids for the assessment of bladder cancer as a late sequela of traumatic SCI. Methods A study conducted between January 1998 and December 2019 in the BG Trauma Hospital Hamburg formed the basis for the decision-making aids. Urinary bladder cancer was diagnosed in 40 out of 7396 treated outpatient and inpatient SCI patients. General patient information, latency period, age at initial diagnosis, type of bladder management and survival of SCI patients with bladder cancer were collected and analysed. T category, grading and tumour entity in these patients were compared with those in the general population. Relevant bladder cancer risk factors in SCI patients were analysed. Furthermore, relevant published literature was taken into consideration. Results Initial diagnosis of urinary bladder cancer in SCI patients occurs at a mean age of 56.4 years (SD ± 10.7 years), i.e., approximately 20 years earlier as compared with the general population. These bladder cancers are significantly more frequently muscle invasive (i.e., T category ≥ T2) and present a higher grade at initial diagnosis. Furthermore, SCI patients show a significantly higher proportion of the more aggressive squamous cell carcinoma than that of the general population in areas not endemic for the tropical disease schistosomiasis. Consequently, the survival time is extremely unfavourable. A very important finding, for practical reasons is that, in the Hamburg study as well as in the literature, urinary bladder cancer is more frequently observed after 10 years or more of SCI. Based on these findings, a matrix was compiled where the various influencing factors, either for or against the recognition of an association between SCI and urinary bladder cancer, were weighted according to their relevance. Conclusions The results showed that urinary bladder cancer in SCI patients differs considerably from that in able-bodied patients. The presented algorithm is an important aid in everyday clinical practice for assessing the correlation between SCI and bladder cancer.

Epidemiological characteristics and clinical course of eyelid squamous cell carcinoma patients from a large tertiary centre between 2009 and 2020

Background/aimsTo assess epidemiological tumour features, risk factors, clinical management and outcome of eyelid squamous cell carcinoma (SCC) and changes thereof. Furthermore, we searched for validating predictors of the American Joint Committee on Cancer (AJCC) 8 classification system.MethodsWe evaluated data of 117 patients with histologically proven eyelid SCC at a large tertiary German university centre between January 2009 and March 2020. This retrospective, monocentric analysis included descriptive statistics and non-parametric tests (p<0.05).ResultsHistologically controlled excision and follow-up was performed in 88 (75.2%) patients. In the remaining patients with higher T-category, individual adjuvant therapy combinations were initiated. We found higher numbers of nodal metastasis and recurrence for male patients and higher T-category (p=0.035, p=0.008 and p=0.001, p<0.001). Recurrence rates proved higher for patients with multiple lesions (p=0.008). Disease-specific survival (DSS) was 95.7% at 2 and 94.9% at 5 years of follow-up. Six patients (5.1%) died from eyelid SCC with nodal metastasis and higher T-category being negative prognostic factors (p<0.001 and p=0.009). Mortality was associated with tumour location in the medial upper eyelid, nodal metastasis being more frequent (p=0.001 and p=0.009) and tumour of the lower eyelid alone as positive predictor (p=0.012). T category differed in 34 (29.1%) patients when comparing AJCC 7 and 8 (p<0.001). Changes in T category as per the AJCC 8 classification resulted in better prediction of DSS (p=0.024).ConclusionSpecial attention should be paid to male patients, tumour location in the upper medial eyelid and lymph node diagnostics. Prediction of DSS proved superior as per the AJCC 8 staging system.

The Gut Microbiome as a Promising Biomarker of Cancer Progression Among Female Never-smokers With Lung Adenocarcinoma

Background: The gut microbiome plays an important role in the immune system and has attracted attention as a new biomarker of various diseases, including cancer. As such, in this study, we examined the relationship between the gut microbiome and lung cancer progression. In addition, we assessed the correlation between the gut microbiome and epidermal growth factor receptor (EGFR) mutation status.Methods: Female never-smokers diagnosed with lung adenocarcinoma were consecutively enrolled between May 2018 and August 2019. Fecal samples were collected within 1 month before or after diagnosis and before administration of any lung cancer treatment. Principal coordinate analyses were performed using Bray-Curtis distance matrices to investigate the effects of clinical variables (age, body mass index, Tumor-Node-Metastasis stage, T category, N category, M category, primary tumor size, performance status, and EGFR mutation status) on the gut microbial community. A correlation analysis was also performed to determine the strength of association between the dominant taxonomy (comprising ≥1% of the relative abundance of bacterial DNA sequences) and clinical variables.Results: A total of 37 patients were enrolled. T category and primary tumor size were significantly correlated with the gut microbial community (p=0.018 and 0.041, respectively). At the genus level, a significant positive correlation was observed between the relative abundance of Faecalibacterium and both T category (correlation coefficient, R=0.51, p=0.0013) and primary tumor size (R=0.37, p=0.024), whereas a significant negative correlation was observed between the relative abundances of Fusicatenibacter and Bacteroides and T category (R=−0.35, p=0.034 and R=−0.32, p=0.05, respectively) and primary tumor size (R=−0.36, p=0.029 and R=−0.41, p=0.012, respectively). EGFR mutation status had no statistically significant effect on the gut microbial community (p=0.11). However, the relative abundances of Bifidobacterium and Faecalibacterium were significantly higher in EGFR mutation–negative patients than EGFR mutation–positive patients (p=0.012 and 0.041), whereas the relative abundance of Blautia was significantly lower in EGFR mutation–negative patients (p=0.036).Conclusions: This is the first study identifying the gut microbiome as a promising biomarker of lung cancer progression. Further elucidation of the role of the gut microbiome in lung cancer progression could facilitate development of new treatments for lung cancer.

Prognostic relevance of the TNM classification 8th edition and new criteria of staging for retroperitoneal liposarcoma

For the first time a section appeared for staging of non-organ retroperitoneal tumors in the UICC TNM classification 8th edition. Aim.To assess the prognostic significance of the TNM classification eighth edition for the most common retroperitoneal tumors-liposarcoma. Materials and methods.The distribution of patients by stages and survival in accordance with the TNM-8 classification were studied in192 patients with retroperitoneal non-organ liposarcoma (RLPS). Results.In the TNM-8 classification, only the degree of malignancy of the tumor has a prognostic value, and the T-category does not reflect the actual size of the RLPS and is considered T4 in 93%, which leads to inadequate staging. During the 15-year period, there were no cases with stages II and IIIA, and the survival rate was estimated only in patients with stages I and IIIB. A TNM classification with new values of the T-category was proposed, which demonstrated a more adequate distribution of patients by stages and the reliability ofintergroup differences in the survival rate. Conclusion.It is advisable to create a special TNM classification for RLPS, which makes up more than half of all retroperitoneal sarcomas.

The Gut Microbiome as a Promising Biomarker of Cancer Progression Among Female Never-smokers With Lung Adenocarcinoma

The gut microbiome plays an important role in the immune system and has attracted attention as a biomarker of diseases, including cancer. As such, in this study, we examined the relationship between the gut microbiome and lung cancer progression. Female never-smokers diagnosed with lung adenocarcinoma were consecutively enrolled between May 2018 and August 2019, and fecal samples were collected. Principal coordinate analyses were retrospectively performed using Bray-Curtis distance matrices to investigate the effects of clinical variables (age, body mass index, Tumor-Node-Metastasis stage, T category, N category, M category, primary tumor size, performance status, and EGFR mutation status) on the gut microbial community. A total of 37 patients were enrolled. T category and primary tumor size were significantly correlated with the gut microbial community (p=0.018 and 0.041, respectively). At the genus level, the relative abundance of Faecalibacterium was positively correlated with both T category and primary tumor size, whereas the relative abundances of Fusicatenibacter and Bacteroides were negatively correlated with these variables. This is the first study identifying the gut microbiome as a promising biomarker of lung cancer progression. Further elucidation of the role of the gut microbiome in lung cancer progression could facilitate development of new treatments for lung cancer.