AJCC Classification Research Articles

OSSN in South India: Clinical presentation, treatment outcomes, and histopathologic correlations.

This study aimed to analyze the clinical presentation, treatment outcomes, and histopathology features of ocular surface squamous neoplasia (OSSN) in a South Indian population and correlate the area of lesions to the histopathological grade/severity of carcinoma in situ (CIN) and squamous cell carcinoma (SqCC) invasive and noninvasive tumors. The study was a retrospective cross-sectional study. The study reviewed electronic medical records (EMRs) of 99 eyes of 99 South Indian patients who underwent en bloc excision and biopsy for tumors in the corneal and conjunctival epithelium with suspicion of OSSN over 1 year from January 2019 to December 2019. Postoperatively, patients were treated with three cycles of topical 0.04% mitomycin C eye drops. Sixty-three had requisite EMR data with a follow-up period of 1 year. Patients had equal gender distribution with an age range of 28-83 years. The most common clinical variant was leukoplakic lesion, and the area of the lesion was the only predicting factor for SqCC and CIN. Bigger (T2) lesions should be strongly suspected for OSSN and promptly excised. Histopathologic analysis should be performed, and post-op topical mitomycin C or interferon alpha 2b is administered to avoid recurrence. In this study, by correlating the area of the lesion, we introduce a new variable that may aid in clinical prognostication alongside the AJCC classification.

Analysis of Expression and Regulation of AKR1C2 in HPV-Positive and -Negative Oropharyngeal Squamous Cell Carcinoma.

Head and Neck Squamous Cell Carcinoma (HNSCC), particularly Oropharyngeal Squamous Cell Carcinoma (OPSCC), is a major global health challenge due to its increasing incidence and high mortality rate. This study investigates the role of aldo-keto reductase 1C2 (AKR1C2) in OPSCC, focusing on its expression, correlation with Human Papillomavirus (HPV) status, oxidative stress status, and clinical outcomes, with an emphasis on sex-specific differences. We analyzed AKR1C2 expression using immunohistochemistry in formalin-fixed, paraffin-embedded tissue samples from 51 OPSCC patients. Additionally, we performed RT-qPCR in cultured HPV16-E6*I and HPV16-E6 overexpressing HEK293 cell lines (p53WT). Statistical analyses were performed to assess the correlation between AKR1C2 expression and patient data. Our results indicate a significant association between increased AKR1C2 expression and higher AJCC classification (p = 0.009) as well as positive HPV status (p = 0.008). Prognostic implications of AKR1C2 varied by sex, whereby female patients with high AKR1C2 expression had better overall survival, whereas male patients exhibited poorer outcomes. Additionally, AKR1C2 expression was linked to HPV status, suggesting a potential HPV-specific regulatory mechanism. These findings underscore the complex interplay among AKR1C2, HPV, and patient sex, highlighting the need for personalized treatment strategies for OPSCC. Targeted inhibition of AKR1C2, considering sex-specific differences, may enhance therapeutic outcomes. Future research should investigate these mechanisms to enhance treatment efficacy.

Neoadjuvant chemotherapy for advanced eyelid and periocular sebaceous gland carcinoma: a study of 25 cases.

To report the outcomes of platinum-based neoadjuvant chemotherapy (NACT) for eyelid and periocular sebaceous gland carcinoma (eSGC). Retrospective study of 25 patients. The mean age at presentation of eSGC was 59years. The mean tumor basal diameter was 46mm. By the 8th edition of AJCC classification, tumors belonged T2 (n = 2, 8%), T3 (n = 6, 24%), and T4 (n = 17, 68%); N1 (n = 12,48%); and M1 (n = 1, 4%). NACT with 5-fluorouracil (5-FU) and cisplatin/carboplatin was administered in 21 (84%)/4 (16%) patients, respectively. The mean number of cycles of neoadjuvant systemic chemotherapy per patient was 2 (median, 3). The mean percentage reduction of tumor basal volume after neoadjuvant chemotherapy was 65% (median, 60%). After NACT, 12 (48%) patients underwent surgical treatment, 6 (12%) patients underwent EBRT, and 4 (8%) underwent adjuvant chemotherapy. A total of 11 (44%) patients were lost to follow-up during the course of treatment, of whom 3 died from metastatic disease. In 16 patients followed up for ≥ 3months, complete tumor control was achieved in 11 (69%) patients, local tumor control in 14 (88%), and globe salvage in 7 (44%) at a mean follow-up of 25months (median, 7months; range, 3 to 110months). No tumor recurrence was seen in any case. One (4%) serious adverse event of cardiotoxicity was noted. Platinum-based NACT is a suitable option for eSGC with advanced tumors and locoregional metastasis. Adverse events are rare and in patients compliant with treatment, NACT-based combination therapy offers globe salvage and systemic tumor control.

Histopathological Analysis of Retinoblastoma: Insights into Prognostic Factors and Chemotherapeutic Response

Background: Retinoblastoma is a highly aggressive ocular malignancy that mainly impacts young children. It is essential to comprehend the histopathological characteristics of this tumour to determine the most effective treatment approaches. Furthermore, recognizing high-risk histopathological factors can help predict the prognosis and guide treatment decisions for patients with retinoblastoma. Objective: To analyse the histopathological features in eyes with retinoblastoma primarily treated by enucleation and those treated with chemoreduction. The goal is to identify high-risk factors and improve treatment modalities, prognosis, and reduce morbidity and mortality. Methods: 40 enucleated eyes registered from October 2021 to October 2023 had been studied. Histopathological findings were evaluated according to age, sexlaterality, choroid, sclera, optic nerve, subarachnoid space involvement, necrosis, and calcification, degree of differentiation, chemotherapeutic effect and tumor regression after chemotherapy and histoprognostic factors. Grading and staging were done according to 8th AJCC classification of eye tumor. Results: Rosettes, necrosis, calcification were common histological findings in this study. High risk factor assessment was very crucial in staging and prognosis. Chemotherapy treated eyes showed varying degrees of response. Conclusion: Histopathological evaluation guide further management to prevent metastasis.

The 8th AJCC classification is inferior to a new neck stage based on intraparotid lymph node in parotid gland cancer

BackgroundLymph node (LN) status is an important prognostic factor for parotid gland cancer (PGC). This study aimed to analyze the impact of extranodal extension (ENE) of intraparotid LN and LN metastasis burden on survival in PGC.MethodsPatients with surgically treated PGC and at least one metastatic cervical LN were retrospectively enrolled. Primary outcome variables were distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS). The impact of ENE and LN metastasis burden was assessed using the Cox model.ResultsA total of 292 patients were included. ENE in cervical or intraparotid LN was not associated with DMFS, DSS, or OS. Intraparotid LN metastasis had a significant impact on prognosis, and the presence of only one metastatic intraparotid LN offered an approximately 1.5-fold risk of distant metastasis. Prognostic models based on the number of positive LNs (1 vs. 2–3 vs. 4+) were superior to the AJCC N stage in terms of DMFS, DSS, and OS.ConclusionsENE of cervical or intraparotid LN has a limited effect on the prognosis of PGC, and the number of positive LNs is better than the AJCC N stage in LN status evaluation.

VMAT-IGRT Hypofractionated Radiotherapy for Locally Advanced Thyroid Cancer in Resource-Limited Settings: A Retrospective Report from Bolivia

This study evaluated the efficacy and safety of hypofractionated external beam irradiation with VMAT-IGRT in patients with locally advanced thyroid cancer (LATC) who are ineligible for surgery or I-131 in a resource-limited setting such as Bolivia. Thirty-three patients were treated with H-VMAT-IGRT between August 2018 and November 2022. Axial CT images were acquired every 3 mm from the base of the skull to the middle of the chest. GTV was determined based on contrast-enhanced tumor on T1 MRI or CT scans. CTV 55 Gy at 2.75 Gy was defined based on visible residual tumor and included dissected nodal stations with pathologically positive nodes. CTV 44 at 2.2 Gy for non-dissected nodal stations with low risk of recurrence, we escalated the dose up to 60 Gy at 3 Gy for small tumors up to 20 cc. PTVs were created by adding a 0.3 cm margin around CTVs, with a reduced margin of minus 3-5 mm for critical organs such as esophagus, pharynx, and brachial plexus. Equivalent dose in 2Gy (EQD2 10-3) was reported for tumor control and OAR constraints. Acute toxicity was reported according to RTOG criteria, and response to treatment was assessed at baseline, end of treatment, and every third month thereafter. The mean time since last follow-up was 24 months (r: 8-40). Patients were 80% female and 20% male. The mean age was 50 years (r: 29-72). Local recurrence was treated in 52% (13) of patients and LATC in 48% (12). Papillary carcinomas accounted for 68% of patients, followed by anaplastic (24%) and follicular (8%) carcinomas. Tumors were classified according to the AJCC classification. Of the patients treated for LATC, 25% were at stage II, 25% at stage III, 16.67% at stage IVA, and 33.33% at stage IVB. Among patients treated for local recurrence, the initial stage before progression was stage I in 61.5%, stage II in 30.8%, and stage IVA in 7.7%. The median PTV was 383.8 cc (r: 51.7 - 627.3) and the median CTV55 was 189.2 cc (r: 39.6 - 519.8). Grade 1 (10%), Grade 2 (90%) dysphagia, Grade 1 (40%), Grade 2 (60%) acute pharyngeal mucositis, and no Grade 3 acute toxicity were observed. No reports of chronic upper damage GI, 30% xerostomia G2. Two-year local control was 70% and overall survival was also 70%. We suggest that reducing treatment duration while maintaining efficacy is particularly beneficial in resource-limited areas with a shortage of trained personnel and overburdened treatment centers. We report good local control rates with no detrimental effects on quality of life with hypofractionation. No evidence of delayed damage, such as spinal cord dysfunction, mandibular osteoradionecrosis, or brachial plexopathy, was noted. We emphasize the importance of using VMAT with IGRT for reliable and accurate daily treatment of the target area, while minimizing side effects. However, these results should be confirmed with a larger sample of patients.

Eosinophils in metastatic melanoma

The potential significance of tissue eosinophils melanomas is unknown. We strove to determine a potential association between the presence of tissue eosinophils and prognosis of patients with metastatic melanoma (MM). A retrospective electronic data base was queried to identify patients (age ≥18 years) evaluated January 1, 2011-October 1, 2022 (inclusive) at our multi-site medical center, who had metastatic melanoma and at least 1 biopsy of melanoma or a melanocytic nevus that was reported to show eosinophils. Patient demographics, histopathological tumor features, AJCC classification parameters, and peripheral blood eosinophilia (PBE) obtained during the patients' routine care were recorded. Seven patients met inclusion criteria had checkpoint inhibitor therapy for MM; 4/7 had prominent eosinophil infiltrates among their melanocytic nevi or/and melanomas, and all had absent or less than predicted tumor progression. In our small cohort of patients undergoing immunotherapy for metastatic melanoma, the presence of tissue eosinophils among nevi or melanomas was associated with a favorable response. While lymphocytes have been considered key in the host response to melanoma, the role of eosinophils may be underappreciated.

YTHDF2 exerts tumor-suppressor roles in gastric cancer via up-regulating PPP2CA independently of m6A modification

BackgroundYTHDF2 is one of important readers of N6-methyladenosine (m6A) modification on RNA. Growing evidence implicates that YTHDF2 takes an indispensable part in the regulation of tumorigenesis and metastasis in different cancers, but its biological functions and underlying mechanisms remain elusive in gastric cancer (GC).AimTo investigate the clinical relevance and biological function of YTHDF2 in GC.ResultsCompared with matched normal stomach tissues, YTHDF2 expression was markedly decreased in gastric cancer tissues. The expression level of YTHDF2 was inversely associated with gastric cancer patients’ tumor size, AJCC classification and prognosis. Functionally, YTHDF2 reduction facilitated gastric cancer cell growth and migration in vitro and in vivo, whereas YTHDF2 overexpression exhibited opposite phenotypes. Mechanistically, YTHDF2 enhanced expression of PPP2CA, the catalytic subunit of PP2A (Protein phosphatase 2A), in an m6A-independent manner, and silencing of PPP2CA antagonized the anti-tumor effects caused by overexpression of YTHDF2 in GC cells.ConclusionThese findings demonstrate that YTHDF2 is down-regulated in GC and its down-regulation promotes GC progression via a possible mechanism involving PPP2CA expression, suggesting that YTHDF2 may be a hopeful biomarker for diagnosis and an unrevealed treatment target for GC.

Validation of the TNM-8 AJCC classification for HPV-positive oropharyngeal cancers in patients undergoing trans-oral robotic surgery.

High-risk human papillomaviruses (HPV) are associated with some oropharyngeal squamous cell carcinomas (OPSCC). HPV-OPSCC have better survival outcomes compared to HPV negative tumours. The new TNM-8 AJCC staging (2018) is based on ICON-S data with 98% of patients treated with primary chemoradiation. To validate the TNM-8 AJCC classification in HPV-OPSCC treated primarily with surgery (trans-oral robotic surgery or open). There were 102 patients with HPV-OPSCC treated between July 2009 and December 2014 at the Royal Adelaide Hospital. The median age was 57years (range: 38-83) and mostly males (84.5%). 27.2% were active smokers and 50.5% reformed smokers. Early T-stage cancer in 72.8%. Primary treatment was surgery & adjuvant therapy (70%) while primary chemoradiation (30%). Survival analyses were performed for the 7th and 8th AJCC systems. The reclassification to the AJCC 8th edition staging system resulted in a change of 54 patients from stage 4 to stages 1 and 2. This was mainly an effect of changes with N2a and N2b nodal disease being reclassified to N1. Survival outcomes were comparable with the ICON-S data. The new TNM-8 classification is, therefore, validated in a cohort treated, predominantly, with primary surgery and adjuvant therapy.

Influence of different methods for classification of lymph node metastases on the survival of patients with oral squamous cell carcinoma

BackgroundDespite the advances in the classification of oral squamous cell carcinoma (OSCC) based on its extension by the TNM system, there is still a need for methods to better classify the patients to predict prognosis and indicate adjuvant therapy. ObjectivesTo analyze the influence of the number of positive lymph nodes (PN), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) in survival of patients with OSCC. MethodsClinicopathologic data from patients with OSCC who were treated with curative purposes by surgery and neck dissection (ND) with or without subsequent adjuvant therapies from 1991 to 2015 was retrospectively assessed. The impact of the PN, LNR, LODDS, and other variables on overall survival (OS) and disease-free survival (DFS) was analyzed in univariate and multivariate analyses. ResultsOne hundred nineteen patients were included in this study. In the univariate analysis the PN had a significant impact on OS (p = 0.001) and DFS (p = 0.020), and the LNR had a significant impact on the OS (p = 0.042). In the multivariate analysis with other relevant clinicopathologic variables, the PN was the only significantly independent factor influencing in the OS (p = 0.017) but not in DFS (p = 0.096). ConclusionsThe PN is an independent prognostic indicator for OS and DFS in patients with OSCC and has the potential to aggregate the current AJCC classification. The LNR has potential to be an important prognostic indicator, but the methods for this classification require lapidation. The LODDS did not demonstrate prognostic potential.

Low Prevalence of HPV Related Oropharyngeal Carcinogenesis in Northern Sardinia.

Simple SummaryOropharyngeal squamous cell carcinomas (OPSCCs) are the only head and neck malignancy with a clear increase in prevalence in Western countries, due to the HPV epidemics with an increasing proportion of HPV-related OPSCCs. Such figures, however, are extremely variable around the globe. The present report is the first to assess the prevalence of HPV-related OPSCC in Sardinia, a relatively isolated population in the West. The rate of HPV-driven OPSCC in such a population is close to that of less developed areas, with clear implications on epidemiology, prognosis, and reliability of methods for assessing HPV-related carcinogenesis. In fact, in the present setting, the specificity of p16 IHC alone in diagnosing HPV-related carcinogenesis is only 75% with a 25% false positive rate.HPV infection is a clear etiopathogenetic factor in oropharyngeal carcinogenesis and is associated with a markedly better prognosis than in smoking- and alcohol-associated cases, as specified by AJCC classification. The aim of the present work is to evaluate the prevalence of HPV-induced OPSCC in an insular area in the Mediterranean and to assess the reliability of p16 IHC (immunohistochemistry) alone, as accepted by AJCC, in the diagnosis of HPV-driven carcinogenesis in such a setting. All patients with OPSCC consecutively managed by the referral center in North Sardinia of head and neck tumor board of AOU Sassari, were recruited. Diagnosis of HPV-related OPCSS was carried out combining p16 IHC and DNA testing on FFPE samples and compared with the results of p16 IHC alone. Roughly 14% (9/62) of cases were positive for HPV-DNA and p16 IHC. Three more cases showed overexpression of p16, which has a 100% sensitivity, but only 75% specificity as standalone method for diagnosing HPV-driven carcinogenesis. The Cohen’s kappa coefficient of p16 IHC alone is 0.83 (excellent). However, if HPV-driven carcinogenesis diagnosed by p16 IHC alone was considered the criterion for treatment deintensification, 25% of p16 positive cases would have been wrongly submitted to deintensified treatment for tumors as aggressive as a p16 negative OPSCC. The currently accepted standard by AJCC (p16 IHC alone) harbors a high rate of false positive results, which appears risky for recommending treatment deintensification, and for this aim, in areas with a low prevalence of HPV-related OPSCC, it should be confirmed with HPV nucleic acid detection.

Measurement of Residual Breast Cancer Burden after Neoadjuvant Chemotherapy

Aim: To determine the frequency of residual cancer burden after neoadjuvant chemotherapy for breast cancer patients undergoing surgery. Study Design: Descriptive study. Place and Duration of Study: Department of Surgery, Dr. Ruth K.M. Pfau Civil Hospital Karachi from 8th May 2019 to 7th November 2019. Methodology: One hundred and twenty six females aged 25 to 75 years with stage IIA, IIB and IIIA were enrolled. Patients who had received standard protocol of neoadjuvant chemotherapy from outside i.e. six cycles of fluorouracil, anthracycline and cyclophosphomide (FAC) every 3 weeks and for HER2+ tumors, FAC was followed by 12 cycles of Trastuzumab every 3 weeks were included. Data regarding tumor characteristic, age, HER 2 status, PR status, KI 67status and nodal involvement was noted. Results: The mean age was 47.32±13 years and mean cancer cellularity was 14.88±10.4%. Nuclear grade III was present in 39.7% patients and 48.4% patients belonged to T1 stage. Majority of patients were menopausal. FAC regime was used in 58.7% patients. RCB I (minimal residual disease) was present in 12.7% patients, RCB II (moderate residual disease) was present in 51.6% patients and RCB III (extensive residual disease) was found in 35.7% patients. Cross tabulation for age, T stage, pathological AJCC classification, histological classification and nuclear grading was not significant (p>0.05). Conclusion: Neoadjunctive therapy is associated with decrease rate of residual cancer burden. Keywords: Breast carcinoma. Neo adjunctive therapy, Decreases residual cancer burden

Prognostic significance of the CP-GEP assay combining clinicopathologic factors and gene expression profiling in patients (pts) with AJCC v8 stage I/II cutaneous melanoma (CM).

9564 Background: AJCC v8 includes Breslow thickness and ulceration to subdivide stage I and II CM pts into risk groups. In light of the results from adjuvant therapy in stage II CM, it has been discussed that pts’ follow-up and eventually treatment should consider additional markers, namely CP-GEP, to further refine the risk classification provided by the AJCC v8. The aim of this single center study was to clinically validate a prognostic CP-GEP-based risk score for stage I/II CMs combining Breslow, age and the expression of 8 genes SERPINE2, GDF15, ITGB3, CXCL8, LOXL4, TGFBR1, PLAT and MLANA. Methods: All obtainable formalin-fixed paraffin-embedded primaries of stage I/II CMs with negative sentinel lymph node (SLN) from the Central Malignant Melanoma Registry of Germany diagnosed between 2000-2017 and archived in Tuebingen were included. Study hypothesis and protocol were prospectively formulated. Tumors were analyzed blinded to clinical outcome. Quantitative reverse transcription polymerase chain reaction of the 8 genes was performed and combined with age and tumor thickness to define CP-GEP low- vs. high-score groups. Relapse-free survival (RFS), distant metastasis free survival (DMFS) and overall survival (OS) were evaluated using Kaplan-Meier curves. CP-GEP score performance was tested using multivariate Cox regression adjusted for tumor thickness, ulceration and age. Results: We included 543 pts with Stage IA (n=78); IB (n=223); IIA (n= 123); IIB (n=73); IIC (n=46). 43% were females, median Breslow was 1.7mm and 25% of tumors had ulceration. The median follow-up was 78 months (IQR 47-116). 311 (57%) patients had a high-risk CP-GEP score. The 5-y RFS rate was 71% and 92% (HR 4.2; p<0.001), the 5-y DMFS rate was 86% and 96% (HR 4.35; p<0.001) and the 5-y OS was 85% and 95% (HR 3.2; p=0.001), respectively for high and low-risk CP-GEP score. In multivariate Cox regression analysis for RFS including Breslow thickness, ulceration and age, contribution of CP-GEP score remained independently significant (HR 2.75; p=0.0008) compared to age (HR 1.03; p<0.0007), Breslow (HR 1.21; p<0.0001) and ulceration (HR 1.37; p=0.1694). Conclusions: CP-GEP risk score is a non-invasive and independent prognostic model for risk of relapse in stage I/II melanoma validated in this study. It identifies SLN negative pts at high risk of relapse and should be considered for complementing AJCC classification and for inclusion in future clinical trials.[Table: see text]

Postoperative lymphatic recurrence distribution and delineation of the radiation field in lower thoracic squamous cell esophageal carcinomas: a real-world study

BackgroundTo study lymphatic recurrence distribution after radical surgery in the real world and guide clinical tumor volume delineation for regional lymph nodes during postoperative radiotherapy for lower thoracic squamous cell esophageal carcinomas.MethodsWe enrolled patients who underwent radical esophagectomy, without radiation before or after surgery, at 3 cancer hospitals. Patients were classified into groups according to tumor locations. We included patients with tumors in the lower thoracic segment and analyzed the postoperative lymph node recurrence mode. A cutoff value of 10% was used to differentiate high-risk lymph node drainage areas from others.ResultsWe enrolled 1905 patients in the whole study series, including 652 thoracic esophageal carcinomas that met our inclusion criteria; there were 241 cases of lower thoracic esophageal carcinomas. 1st, 2nd, 4th, 7th, 8th groups of lymph nodes, according to the 8th edition of the AJCC classification, displayed as high-risk recurrence areas, representing 17.8%, 23.9%, 11.7%, 10.9% and 12.2% of lymph node recurrence. Stage III-IV tumors located in the lower segment of the thoracic esophagus showed a tendency to recur in the left gastric nodes (7.9%) and celiac nodes (10.6%).ConclusionsAccording to our results, we recommended including the 4th, 7th and 8th groups of lymph nodes in the radiation field, and for patients with stage III-IV disease, the 17th and 20th groups of nodes should be irradiated during postoperative treatment. Whether including 1st/2nd groups in preventive irradiation needed more proofs.

Depth of Invasion as an Independent Predictor of Survival in Patients of Stage III Squamous Cell Carcinoma of the Oral Tongue.

Depth of invasion (DOI) has been incorporated in the new AJCC 8th classification. However, even with this new AJCC classification stage III oral tongue squamous cell carcinoma (OTSCC) remains a heterogenous group. The study aims at finding a discreet group within stage III using DOI as a cut-off of 10 mm. The institutional database was reviewed from 2012 to 2018 for postoperative stage III OTSCC patients who subsequently received postoperative radiotherapy. Ninety-six patients matched the inclusion criteria. Two groups were created using a DOI cut-off of 10 mm (superficial and deep groups). The groups were analyzed for overall survival (OS) and relapse-free survival (RFS). The baseline and treatment characteristics were comparable between the groups except for the higher number of extensive surgeries, endophytic configuration, pT3 and, DOI in the deep group. For a median follow-up of 40.5 (range: 4-139) months, the median OS and RFS for the superficial group were not reached. The median OS and RFS for the deep group were 101 (range: 73.7-128.3) and 60 (range: 46.6-73.4) months, respectively. The difference was statistically significant for median RFS (P=.008) and trended toward significance for median OS (P=.066) for the superficial group. Multivariate Cox regression analysis showed DOI cut-off as a significant predictor for RFS but not for OS. DOI significantly predicts poor RFS. However, showed a trend toward poor OS. This study hints toward a possibility of sub-dividing stage III OTSCC based on DOI cut-off. 3 (Retrospective cohort study) Laryngoscope, 132:1594-1599, 2022.

AACE2021-A-1098: Clinical and Pathological Characteristics of Thyroid Cancer in Adolescents and Young Adults (AYA): An Algerian Observation

We aim to describe clinical and pathological characteristics of thyroid cancer in an Algerian cohort of adolescents and adults patients. Medical records of patients followed in the endocrinology department of Constantine University Hospital during the period between July 2014 and December 2018 were retrospectively reviewed. Patients were subdivided into two age groups: < 30 (Group 1) and ≥ 40 years old (Group 2). Thyroid function, type of initial surgery, lymph node dissection, and histological findings were collected. 101 patients were included, the mean age was 31 (17- 40 years), 30.17% were aged <30 years and 85.1% were females. Diagnosis circumstances were multinodular goiter and unique thyroid nodule in 57.4% ,27.7% respectively and 12% had abnormal TSH at the moment of diagnosis. As the initial surgery, total thyroidectomy was done in 88.1% and lymph node dissection in 23.8% which was central in 13.9%, and central and lateral in 9.9%. 90.1% were papillary thyroid cancer, 7.9% (8 patients) were follicular carcinoma and 2 patients had Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Following the 8th AJCC classification,64% were T1, 12.9% T2, and 20.8% were T3 . Microcarcinoma represented 39.6% of cases, and 15.8% had lymph node involvement, while 1 patient had distance metastasis. Multifocality, bilaterality, vascular invasion, and capsular thyroid invasion were seen in 30.7%,15.8%,7.9%, and 17.8% respectively. As for risk stratification according to the American thyroid association (ATA) system, the initial risk was low, intermediate, and high in 41.6%,35.6%, and 10.9% respectively and data were insufficient for risk stratification in 11.9% of patients. 99% were stage I TNM and RAI therapy was done in 88.1% of patients. In analysis AYA patients aged >30 had more capsular invasion and lymph node involvement (p<0.05), and AYA patients with follicular thyroid carcinoma had more thyroid capsular invasion (p<0.05). These data give us a profile of AYA patients in the Algerian population. In our study, patients with follicular carcinoma had more capsular invasion and patients aged< 30 years had more capsular invasion and lymph node involvement.

Survival analysis following enucleation for uveal melanoma.

To determine survival outcomes following enucleation for uveal melanoma. To compare these outcomes with the 8th edition AJCC classification and determine the influence of cytogenetics, using Fluorescent in situ Hybridisation (FISH), on survival. To determine whether failure to gain sufficient sample for cytogenetics using Fine Needle Aspiration Biopsy (FNAB) correlates with survival. All patients undergoing primary enucleation for uveal melanoma at Moorfields Eye Hospital between 2012 and 2015 were included. Clinical, pathological, cytological and survival data were analysed for all patients. In total, 155 subjects were included. Mean age at enucleation was 65.9 years (SD 14.13). 88 (56.8%) patients died at a mean of three (SD 1.9) years following enucleation. Of these, 52 (33.5%) died from metastatic melanoma, 16 (10.3%) from other causes and 20 (12.9%) causes of death were unknown. Cumulative incidence analysis demonstrated AJCC grade, chromosome 8q gain and monosomy three all predict metastatic mortality. The greatest 5-year mortality rate (62%, SD10.1%) was in those with both chromosome abnormalities and AJCC stage III (Stage IV patients excluded due to low numbers). Largest basal diameter and chromosome status, both independently (p = 0.02 and p < 0.001) predicted metastatic mortality on multivariable regression analysis. Those who had an insufficient sample of cells gained during FNAB (n = 16) had no different prognosis. This study confirms, in this population, the poor survival of patients enucleated for uveal melanomas. It confirms the prognostic utility of adding AJCC grade to cytogenetic information. It demonstrates that the lack of sample in patients undergoing FNAB is not related to prognosis.

Validation of the TNM-8 AJCC Classification for HPV-Positive Oropharyngeal Cancers in Patients Undergoing Trans-Oral Robotic Surgery (TORS)

High-risk human papillomaviruses (HPV) are associated with some oropharyngeal squamous cell carcinomas (OPSCC) and confer a significant prognostic factor. HPV-OPSCC have better survival outcomes compared to HPV negative tumours. The new TNM-8 AJCC staging (2018) is specific to HPV-associated OPSCC. In the re-classification study by the ‘International Collaboration on Oropharyngeal Cancer Network for Staging’, 98% of HPV-OPSCC patients were treated with primary chemo-radiation. The aim of our study was to validate the TNM-8 AJCC classification in HPV-OPSCC treated primarily with surgery (trans-oral robotic surgery or open). There were 102 patients with HPV-OPSCC treated between July 2009 and December 2014 at the Royal Adelaide Hospital. The median age was 57 years (range: 38-83) and mostly males (84.5%). 27.2% were active smokers and 50.5% reformed smokers. Early T stage cancer accounted for 72.8% (T1/2). Primary treatment was with surgery (TORS or open) and adjuvant therapy (70%) while primary chemo-radiation was the treatment for 30% of patients. Kaplan-Meier and Cox regression analyses were performed for both the 7th and 8th AJCC staging systems. The re-classification of this cohort to the AJCC 8th edition staging system resulted in a change of 54 patients from stage 4 to stages 1 and 2. This was mainly an effect of changes with N2a and N2b nodal disease being reclassified to N1 and demonstrates the prognostic effect of HPV in OPSCC. Survival outcomes were comparable with the ICON-S data. The new TNM-8 classification is therefore validated in a cohort treated, predominantly with primary surgery and adjuvant therapy. Funding Statement: None. Declaration of Interests: All authors declare no conflicts of interest. Ethics Approval Statement: Ethical approval was obtained from the CALHN REC, South Australia (Ref 13,407) to analyse clinical data on TORS.

Defining stage in mucinous tumours of the appendix with peritoneal dissemination: the importance of grading terminology: systematic review.

BackgroundMucinous appendiceal neoplasms with peritoneal dissemination (PD) show a wide spectrum of clinical behaviour. Histological grade has been correlated with prognosis, but no universally accepted histological grading has been established. The aim of this systematic review was to provide historical insight to understand current grading classifications, basic histopathological features of each category, and to define which classification correlates best with prognosis.MethodsMEDLINE and the Cochrane Library were searched for studies that reported survival across different pathological grades in patients with mucinous neoplasm of the appendix with PD treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. PRISMA guidelines were followed.ResultsThirty-eight studies were included. Ronnett’s classification was the most common (9 studies). Classifications proposed by the Peritoneal Surface Oncology Group International (PSOGI) (6 studies) and the seventh or eighth edition of the AJCC (7 studies) are gaining in popularity. Nine studies supported a two-tier, 12 a three-tier, and two a four-tier classification system. Three studies demonstrated that acellular mucin had a better prognosis than low-grade pseudomyxoma peritonei in the PSOGI classification or M1bG1 in the eighth edition of the AJCC classification. Four studies demonstrated that the presence of signet ring cells was associated with a worse outcome than high-grade pseudomyxoma peritonei in the PSOGI classification and M1bG2 in the eighth edition of the AJCC.ConclusionThere is a great need for a common language in describing mucinous neoplasms of the appendix with PD. Evolution in terminology as a result of pathological insight turns the four-tiered PSOGI classification system into a coherent classification option.

Genome-wide association study to reveal novel germline markers of melanoma survival.

9581 Background: Cutaneous melanoma (CM) is the most invasive form of skin cancer accounting for ̃80% of all skin cancer related deaths. While tumor staging (based on recent AJCC classification) is routinely used in prognostic assessment, a large fraction of the outcomes is not explained by AJCC staging system. This urges for the discovery of a more personalized prognostic surrogates. Growing evidence highlights the role of germline genetics in CM progression; yet, to date no systematic prognostic germline study has been conducted in melanoma. We performed the first genome-wide association analysis (GWAS) to identify germline variants associated with melanoma survival. Methods: A cases/case GWAS was performed using the Infinium global screening array (GSA v3.0) to genotype 1,117 stage 0-III melanoma patients with no history of immunotherapy treatments ascertained at New York University Langone Health (NYULH). We randomly divided the study cohort into a discovery (N=630) and a validation (N=487) sets and tested the association of &gt; 5 million imputed germline variants with melanoma overall survival (OS) by fitting Cox-proportional hazard ratio (HR) regression in an additive genetic model adjusting for sex, age at diagnosis, AJCC 8th staging, tumor anatomic sites, and top 3 principal components. Results: We found 151 independent variants associated with melanoma OS (p&lt; 5×10−5) in the discovery cohort. Two of these associations validated in the independent replication set ( Bonferroni threshold for 151 tests: p &lt; 0.003) with enhanced clinical and statistical significance in the pooled meta-analysis: rs4128212 [HR =2.47(1.75-3.48); p=2.2× 10−7], and rs13212644 [HR =2.59 (1.72-3.88); p=4.2× 10−6]. We further tested the combined effect of these two variants and found the presence of at least one risk allele of the variants associated with a substantially increased risk of death, surpassing GWAS level of significance (HR=3.74 (2.43-5.74); p=1.5×10−9). Conclusions: We present the results of first GWAS testing an association of germline variation with melanoma OS. Stemming from a unique patient population with extensive clinical follow-up data, we identified two prognostic germline loci with large HR effect size &gt;2.5 that were independently validated. The observed association is independent of established histopathologic markers. While rs4128212 was mapped to a putative cancer prognostic gene locus (PLPP4: phospholipid phosphatase 4), rs13212644 was an eQTL (expression quantitative trait loci) for GCLC (Glutamate-Cysteine Ligase Catalytic Subunit), a key regulator in glutathione synthesis previously linked with favorable melanoma survival. The significantly enhanced combined effect of these two loci (HR &gt;3.5; p&lt;5×10−9) indicates a great promise for their clinical utility as independent personalized predictive markers of melanoma progression.