American Joint Cancer Committee Research Articles

776. THREE-FIELD LYMPHADENECTOMY IN ESOPHAGEAL CANCER: EXPERIENCE OF A PORTUGUESE TERTIARY CENTER

Abstract Background The American Joint Committee for Cancer (AJCC) and the Japanese Esophagus Society (JES) differ in the N classification for esophageal cancer, with the former considering the presence of disease in the supraclavicular lymph nodes as M1, and the latter classifying it as loco-regional disease in thoracic esophageal tumors. Patients who would be excluded from a curative intent treatment strategy by the AJCC classification may be candidates for surgery with lymphadenectomy of nodal groups 101 and 104 (JES). Our goal is to understand the impact of three-field lymphadenectomy on morbidity, loco-regional control and overall survival in patients with esophageal cancer. Methods A retrospective cohort study was conducted using data from a prospective database from a single center, which included all consecutive patients undergoing esophagectomy for cancer with either two-field total thoracic lymphadenectomy or three-field lymphadenectomy, between January 2019 and December 2023. Three-field lymphadenectomy was performed for clinical supraclavicular and recurrent nerve nodal involvement and for proximal third tumors. We assessed the morbidity and mortality of both types of surgery, and loco-regional and distant recurrence and overall survival for both groups. Results Of the 279 esophagectomies for cancer, 137 were included for analysis. The median age was 65 years, with 84% males. 58,4% had squamous cell carcinoma and 41,6% adenocarcinoma. 34.3% of the patients had a 3-field lymphadenectomy, 27,7% of these for supraclavicular N+ and 34% for recurrent nerve N+. Conclusion In this large single-center cohort, patients with significant lymph node involvement, treated with esophagectomy and three-field lymphadenectomy, demonstrated comparable loco-regional control and overall survival to more favorable cases, with no statistically significant increase in morbidity and mortality.

Evaluation of prognostic factors for oral tongue squamous cell carcinoma: Significance of intratumoral tumor-infiltrating lymphocytes, lymph node ratio, and depth of invasion.

132 Background: Oral tongue squamous cell carcinoma (SCC) is an aggressive malignancy with a variable prognosis. Identifying reliable prognostic factors is crucial for developing personalized treatment strategies and improving patient outcomes. This study examined the prognostic significance of clinicopathological factors in oral tongue SCC. Methods: A retrospective cohort study was conducted on 192 patients who underwent surgical resection at Asan Medical Center between 2010 and 2017. Clinicopathological data, including age at diagnosis, American Joint Committee of Cancer (AJCC) 8th edition stages, depth of invasion (DOI), extranodal extension (ENE), intratumoral and stromal (invasive front) tumor-infiltrating lymphocytes (TILs), lymphovascular invasion (LVI), margin status, metastatic-to-examined lymph nodes ratio (LNR), number of metastatic lymph nodes, perineural invasion (PNI), sex, size, tumor budding, tumor differentiation, tumor-to-stromal ratio (TSR), and worst pattern of invasion (WPOI) were analyzed. The total cohort, early-stage group, and late-stage group were analyzed separately. Results: Most variables showed significant associations with the survival rate. The multivariate Cox proportional hazard models for the total cohort showed significant results for intratumoral TILs, DOI grade, and LNR. However, other factors failed to show statistical significance. Intratumoral TIL was the only consistently potent factor for survival in all study groups. Conclusions: Our findings highlight the need for increased focus on the prognostic significance of intratumoral TILs. The DOI grade and LNR were also powerful prognostic factors, especially in late-stage tongue SCCs. Our data suggest that the prognostic significance of certain variables, such as the WPOI, may have been overestimated in the literature, thereby warranting a reassessment of the currently utilized prognostic markers in oral tongue SCC.

Eyelid/Periocular Sebaceous Gland Carcinoma in 500 Eyes: Analysis Based on 8th Edition American Joint Cancer Committee Classification

PurposeTo analyze the presentation and outcomes of eyelid and periocular sebaceous gland carcinoma (SGC) based on prognostic stage of the 8th edition of American Joint Committee on Cancer (AJCC) classification. DesignRetrospective clinical cohort study Methods• Setting: Quaternary referral center• Study population: 500 eyes of 499 patients with SGC• Intervention: Excisional biopsy, chemotherapy, Orbital exenteration• Main outcome measures: Tumor recurrence, lymph node metastasis, systemic metastasis, and death based on AJCC prognostic staging ResultsThe mean age at presentation with SGC was 57 years (55 years; range, 26 to 82 years). Based on the 8th edition of AJCC classification, tumors belonged to Stage 0 (n=13, 3%), I (n=158, 32%), II (n=269, 54%), III (n=48, 9%), and IV (n=12, 2%). At a mean follow-up of 26 months (median, 10 months; range, <1 to 192 months), tumor recurrence, lymph node metastasis, systemic metastasis, and disease-related death were seen in 39 (10%), 65 (16%), 33 (8%), and 33 (8%) patients respectively. Tumor recurrence rates did not differ significantly between the stages (p=0.472). The 5-year Kaplan-Meier estimates of regional lymph node metastasis, systemic metastasis, and metastasis-related death were higher for stage II (12%, 11%, and 12%, respectively), III (69%, 25%, and 42%, respectively) and IV (70%, 100%, and 100%, respectively) compared to stage I (0%, 6%, and 6%, respectively). Cox proportional analysis revealed a greater hazard ratio (HR) for lymph node metastasis in stage II (HR, 3.498; 95% CI, 0.200 to 10.200; p<0.022), III (HR, 95% CI, 24.836; 8.733 to 70.631; p<0.001), and IV (HR, 53.731; 95% CI, 15.418 to 187.253; p<0.001), systemic metastasis in stage III (HR. 13.895; 95% CI, 3.871 to 49.874; p<0.001) and IV (HR, 81.465; 95% CI, 22.267 to 298.051; p<0.001) and for disease-related death in stage III (HR, 9.182; 95% CI, 2.743 to 30.728; p<0.001) and IV (HR, 85.237; 95% CI, 25.331 to 287.422; p<0.001), compared to stage I. ConclusionThe prognostic staging of the 8th edition AJCC classification predicts the prognosis of patients with eyelid and periocular SGC, which worsens with the advancing stage. The high incidence of lymph node and systemic metastasis accounts for mortality in these patients.

Sex-specific aspects in patients with oropharyngeal squamous cell carcinoma: a bicentric cohort study

BackgroundOropharyngeal squamous cell carcinoma (OPSCC) is the only subgroup of head neck cancer that presents with an increased incidence. Gender-specific studies in other cancer entities have revealed differences in treatment response and prognosis. However, only limited data in OPSCC according to gender and human papillomavirus (HPV) status exist. Therefore, we aimed to investigate sex-specific differences in OPSCC and how these may be distributed in relation to HPV and other risk factors.MethodsThis retrospective, bicentric study included 1629 patients with OPSCC diagnosed between 1992 and 2020. We formed subgroups based on TNM status, American Joint Cancer Committee 8th edition (AJCC8), HPV status, treatment modality (surgery (± radio(chemo)therapy (RCT) vs. definitive RCT) and patient-related risk factors and investigated gender differences and their impact on patients survival via descriptive-,uni- and multivariate analysis.ResultsWith the exception of alcohol abuse, no significant differences were found in risk factors between men and women. Females presented with better OS than males in the subgroup T1-2, N + , independent of risk factors (p = 0.008). Males demonstrated significant stratification through all AJCC8 stages (all p < 0.050). In contrast, women were lacking significance between stage II and III (p = 0.992). With regard to therapy (surgery (± R(C)T) – vs. definitive RCT) women treated with surgery had better OS than men in the whole cohort (p = 0.008). Similar results were detected in the HPV-negative OPSCC sub-cohort (p = 0.042) and in high-risk groups (AJCC8 stage III and IV with M0, p = 0.003).ConclusionSex-specific differences in OPSCC represent a health disparity, particularly according to staging and treatment, which need to be addressed in future studies.

Retinoblastoma in Asia: Clinical Presentation and Treatment Outcomes in 2112 Patients from 33 Countries

PurposeTo describe the clinical presentation and treatment outcomes of children diagnosed with retinoblastoma (RB) in the year 2017, throughout Asia. DesignMulti-national prospective study including treatment-naïve patients diagnosed with retinoblastoma in Asia during 2017 and followed up thereafter. ParticipantsA total of 2112 patients (2797 eyes) from 96 RB treatment centers in 33 Asian countries. InterventionChemotherapy, radiotherapy, enucleation, orbital exenteration Main Outcome MeasuresEnucleation and death ResultsWithin the cohort, 1021 (48%) patients were from South Asia (SA), 503 (24%) from East Asia (EA), 310 (15%) from South-East Asia (SEA), 218 (10%) from West Asia (WA) and 60 (3%) from Central Asia (CA). Mean age at presentation was 27 months (median, 23 months; range, <1 to 261 months). There were 1195 (57%) males and 917 (43%) females. The most common presenting complaints were leukocoria (72%) and strabismus (13%). Based on 8th edition American Joint Committee for Cancer, tumors were staged as cT1 (n=441; 16%), cT2 (n=951; 34%), cT3 (n=1136; 41%), cT4 (n=267; 10%), N1 (n=48; 2%), and M1 (n=129; 6%) at presentation. RB was treated with intravenous chemotherapy in 1450 (52%) eyes and 857 (31%) underwent primary enucleation. Three-year Kaplan-Meier estimates for enucleation and death were 33% and 13% for CA, 18% and 4% for EA, 27% and 15% for SA, 32% and 22% for SEA, 20% and 11% for WA (p<0.0001 and p<0.0001), respectively. ConclusionAt the conclusion of this study, there was a significant heterogeneity in treatment outcomes of RB between the regions of Asian continent. East Asia displayed better outcomes with higher rates of globe and life salvage, while South-East Asia had poorer outcomes compared to the rest of Asia.

Risk Stratification of Pancreatic Ductal Adenocarcinoma Patients Undergoing Curative-Intent Surgery after Neoadjuvant Therapy.

Clinical prognostic criteria using preoperative factors were not developed for post-neoadjuvant therapy (NAT) surgery of pancreatic ductal adenocarcinoma (PDAC). We aimed to identify preoperative factors associated with overall survival (OS) in PDAC patients who underwent post-NAT curative-intent surgery and develop risk stratification criteria. Consecutive PDAC patients who underwent post-NAT curative-intent surgeries between 2007 and 2020 were retrospectively analyzed. Demographic, laboratory, surgical, and histopathologic variables were collected. Baseline, preoperative, and interval changes of computed tomography (CT) findings proposed by the Society of Abdominal Radiology and the American Pancreatic Association were analyzed. Cox proportional hazard analysis was used to select preoperative variables associated with OS. We developed risk stratification criteria composed of the significant preoperative variables, i.e., post-NAT response criteria. We compared the discrimination performance of post-NAT response criteria with that of post-NAT pathological (yp) American Joint Cancer Committee TNM staging system. One hundred forty-five PDAC patients were included. Stable or increased tumor size on CT (hazard ratio [HR], 2.58; 95% confidence interval [CI], 1.58 to 4.21; p < 0.001) and elevated preoperative carbohydrate antigen 19-9 (CA19-9) level (HR, 1.98; 95% CI, 1.11 to 3.55; p=0.021) were independent factors of OS. The OS of the patient groups stratified by post-NAT response criteria which combined changes in tumor size and CA19-9 showed significant difference (p < 0.001). Such stratification was comparable to ypTNM staging in discrimination performance (difference of C-index, 0.068; 95% CI, -0.012 to 0.142). "Any degree of decrease in tumor size on CT" and CA19-9 normalization or staying normal were independent favorable factors of OS. The combination of the two factors discriminated OS comparably to ypTNM staging.

A dynamic nomogram integrated with blood inflammation markers for predicting overall survival in patients with upper tract urothelial carcinoma.

Upper tract urothelial carcinoma (UTUC) is a relatively rare disease with a poor prognosis. A growing body of evidence demonstrates that inflammation and the inflammatory microenvironment play a crucial role in tumorigenesis and tumor progression. Our aim was to evaluate the prognostic value of blood inflammation markers and develop a prediction model that incorporates inflammation markers in order to predict overall survival (OS) of UTUC. We included 304 localized UTUC patients from two medical institutions who had undergone radical nephroureterectomy (RNU) (167 in the training cohort, 137 in the validation cohort). Univariate and multivariate Cox regression analyses were performed to screen the prognostic factors, and a nomogram and a web-based calculator were generated based on these predictors. The Harrell's concordance index (C-index), the area under the receiver operating characteristic (ROC) curve, the calibration curve, and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. Independent predictors incorporated in the nomogram were pathological stage, surgical margin, albumin-to-globulin ratio (AGR), and hemoglobin-to-red cell distribution width ratio (HRR). The c-index value was 0.726 in the training cohort and 0.761 in the validation cohort. The area under the ROC of the nomogram at 1-, 3- and 5-year in the training and validation sets were 0.765, 0.755, 0.763, and 0.791, 0.833, 0.802, respectively. Both the internal and external validation calibration plots showed a subtle distinction between the predicted and the actual probabilities. And it appears to provide incremental benefits for clinical decision-making in comparison to the American Joint Committee of Cancer (AJCC) staging system. In patients with UTUC after RNU, lower preoperative AGR and HRR were independent predictors of inferior survival. In addition, we created a novel blood inflammation marker-based dynamic nomogram that may be useful for surgeons or oncologists in risk stratification and patient selection for more intensive therapy and closer follow-up.

CT-Based Radiogenomics of P4HA3 Expression in Clear Cell Renal Cell Carcinoma

The sequencing of the renal cell carcinoma (RCC) genome identified several mutations with prognostic significance. Genomic analysis, collected in The Cancer Genome Atlas Research Network, revealed several clear cell renal cell carcinoma (ccRCC) gene mutations and gene expressions. Radiogenomics is a new branch of diagnostic imaging based on the association between imaging phenotypes and genomics of diseases. P4HA3 expression has recently been shown to correlate with increased aggressiveness of ccRCC, with poor prognosis, proliferation, migration, invasion, and metastases, suggesting P4HA3 as a prognostic marker and therapeutic target in ccRCC. The aim of this study is to investigate the computed tomography (CT) imaging phenotype of P4HA3 expression in ccRCC patients. In this retrospective study we enrolled 196 ccRCC patients divided into two groups: ccRCC patients with P4HA3 expression (n =13) and ccRCC patients without P4HA3 expression (n=183). Several imaging features were evaluated on preoperative CT scan. The statistical significance threshold was set at P<.05. A statistically significant association was found with larger primary tumor size (P=.033), tumor infiltration (P=.023), ill-defined tumor margins (P=.025), and advanced tumor stage American Joint Committee of Cancer (P=.014). This study demonstrates CT imaging features associated with P4HA3 expression in ccRCC. These results could contribute to better understand P4HA3 expression with a noninvasive approach and could be applied to the development of targeted therapies.

Development and validation of a diagnostic and prognostic model for lung metastasis of hepatocellular carcinoma: a study based on the SEER database.

Lung metastasis (LM) is a common occurrence in patients with hepatocellular carcinoma (HCC), and it is associated with a poorer prognosis compared to HCC patients without LM. This study aimed to identify predictors and prognostic factors for LM in HCC patients as well as develop diagnostic and prognostic nomograms specifically tailored for LM in HCC patients. A retrospective analysis was conducted on HCC patients from the Surveillance, Epidemiology, and End Results (SEER) database, covering the period from 2010 to 2015. The study employed multivariate logistic regression analysis to identify risk factors associated with LM in HCC patients. Additionally, multivariate Cox proportional hazards regression analysis was utilized to investigate prognostic factors for HCC patients with LM. Subsequently, two nomograms were developed to predict the risk and prognosis of LM in HCC patients. The performance of the nomograms was evaluated through calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). This retrospective study included a total of 5,934 patients diagnosed with HCC, out of which 174 patients were diagnosed with LM. Through multivariate logistic regression analysis, several independent risk factors for LM in HCC patients were identified, including tumor grade, tumor size, American Joint Committee for Cancer (AJCC) T stage, and AJCC N stage. Furthermore, multivariate Cox analysis revealed that tumor grade, delayed treatment, surgery, and radiation were independent prognostic factors for HCC patients with LM. To assess the predictive power of the developed nomograms, calibration curves, receiver operating characteristic (ROC) analysis, and decision curve analysis (DCA) were employed. The findings demonstrated that the nomograms exhibited satisfactory performance in both the training and validation sets. Additionally, the prognostic nomogram effectively stratified HCC patients with LM into low- and high-risk groups for mortality. These two nomograms optimally predicted the risk and prognosis of LM in HCC patients. Both nomograms have satisfactory performance. This would help clinicians to make accurate clinical decisions.

P50 Exploring unmet needs and attitudes to skin self-examination in melanoma survivors: EUNASS study

Abstract A melanoma diagnosis can have significant emotional and psychosocial impact, yet little guidance exists on how best to support individuals following initial diagnosis. This multicentre UK study aimed to evaluate the baseline needs of melanoma survivors and assess attitudes towards practising skin self-examination (SSE) to inform the development of intervention(s) that best support patients with melanoma beyond diagnosis. A prospective multicentre questionnaire study was conducted across four UK sites, including adults diagnosed with American Joint Cancer Committee (AJCC version 8) stage I–III primary cutaneous melanoma. Participants were invited within 3–12 months of their initial diagnosis to self-complete an electronic questionnaire (using Qualtrics software) evaluating unmet needs, which included the Functional Assessment of Cancer Therapy—Melanoma (FACT-M), Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF), Melanoma specific unmet needs (SF-36), Sun Protection Behaviour Scale (SPBS), Skin Self-Examination (SSE) benefits and barriers scale, and European Quality of Life 5 Dimensions (EQ-5D). STATA 17 was used for the data analysis. Overall, 252 participants were recruited and 55 excluded for failure to provide any responses. The sample was predominantly male (56.3%) and White (100%), with high educational qualifications (52.1%) and not in paid/self-employment (53.2%). Sites of primary melanoma included the trunk (n = 61; 31.0%), head/neck (n = 45; 22.8%), arm (n = 44; 22.3%), leg (n = 33; 16.8%), hands/feet (n = 10; 5.1%) and genitals (n &amp;lt; 5; &amp;lt; 2.5%). SSE barrier and benefit scales had median scores of 29 [interquartile range (IQR) 27–32] and 27 (IQR 22–32), respectively, indicating positive attitudes towards SSE; however, several barriers exist, including identifying abnormal moles and associated anxiety. The majority of participants (56.4%) were identified as having at least one unmet care need, most commonly with regard to information on recurrence risk (37.1%) and SSE (33.0%). The FACT-M, FACT-M trial outcome index and FACT-G (general) had median scores of 26 (IQR 12–38; n = 180), 16 (IQR 6–22, n = 183) and 21 (IQR 8–29; n = 180), respectively. Participants had a median EQ-5D score of 0.92 [IQR 0.86–1.0; full health = 1.0 (n = 189)] and 59.9% were identified as having less than full health. This multicentre UK study indicates that melanoma survivors experience low quality of life within the first year of their diagnosis. Routine collection of melanoma-specific patient-reported outcome measures could improve the patient experience by stratifying patients to receive appropriate supportive care. Focused educational tools guiding sun protection habits and SSE are needed to reduce the risk of further melanomas. Future qualitative data will support an evidence base to develop supportive tools, enabling patients to take an active role in self-management.

DS09 (P50) Exploring Unmet Needs and Attitudes to Skin ­Self-examination in melanoma survivors: EUNASS study

Abstract A melanoma diagnosis can have significant emotional and psychosocial impact, yet little guidance exists on how best to support individuals following initial diagnosis. This multicentre UK study aimed to evaluate the baseline needs of melanoma survivors and assess attitudes towards practising skin self-examination (SSE) to inform the development of intervention(s) that best support patients with melanoma beyond diagnosis. A prospective multicentre questionnaire study was conducted across four UK sites, including adults diagnosed with American Joint Cancer Committee (AJCC version 8) stage I–III primary cutaneous melanoma. Participants were invited within 3–12 months of their initial diagnosis to self-complete an electronic questionnaire (using Qualtrics software) evaluating unmet needs, which included the Functional Assessment of Cancer Therapy—Melanoma (FACT-M), Fear of Cancer Recurrence Inventory—Short Form (FCRI-SF), Melanoma-specific unmet needs (SF-36), Sun Protection Behaviour Scale (SPBS), Skin Self-Examination (SSE) benefits and barriers scale and European Quality of Life 5 Dimensions (EQ-5D). STATA 17 was used for the data analysis. Overall, 252 participants were recruited and 55 excluded for failure to provide any responses. The sample was predominantly male (56.3%) and White (100%), with high educational qualifications (52.1%) and not in paid/self-employment (53.2%). Sites of primary melanoma included the trunk (n = 61; 31.0%), head/neck (n = 45; 22.8%), arm (n = 44; 22.3%), leg (n = 33; 16.8%), hands/feet (n = 10; 5.1%) and genitals (n &amp;lt; 5; &amp;lt; 2.5%). Skin self-examination barriers and benefits scales had median scores of 29 [interquartile range (IQR) 27–32] and 27 (IQR 22–32), respectively, indicating positive attitudes towards SSE; however, several barriers exist, including identifying abnormal moles and associated anxiety. The majority of participants (56.4%) identified as having at least one unmet care need, most commonly with regard to information on recurrence risk (37.1%) and SSE (33.0%). The FACT-M, FACT-M trial outcome index and FACT-G (general) had median scores of 26 (IQR 12–38; n = 180), 16 (IQR 6–22, n = 183) and 21 (IQR 8–29; n = 180), respectively. Participants had a median EQ-5D score of 0.92 [IQR 0.86–1.0; full health = 1.0 (n = 189)], and 59.9% were identified as having less than full health. This multicentre UK study indicates that melanoma survivors experience low quality of life within the first year of their diagnosis. Routine collection of melanoma-specific patient-reported outcome measures could improve the patient experience by stratifying patients to receive appropriate supportive care. Focused educational tools guiding sun protection habits and SSE are needed to reduce the risk of further melanomas. Future qualitative data will support an evidence base to develop supportive tools, enabling patients to take an active role in self-management.

Early Stage Melanoma of the Vermillion with Mucosal Melanoma in Situ: A Clinical Conundrum

BackgroundMelanoma is a predominantly cutaneous malignancy associated with sun exposure. Mucosal melanoma is rare and carries a distinct pathogenesis from cutaneous tumors. The vermillion of the lip is a unique site that divides cutaneous from mucosal tissues. Tumors arising on the dry aspect are classified as cutaneous and those of the wet aspect are mucosal. The distinction is importation in tumor staging as all mucosal melanomas are classified as T3-T4b under the current 8th edition American Joint Committee of Cancer (AJCC) guidelines.MethodsWe describe a case of early stage melanoma of the vermillion with associated mucosal melanoma in situ. We discuss nuances of management at this site and the distinctions between cutaneous versus mucosal melanomas with a review of the literature.ResultsOur patient was treated surgically with 2-3 cm margins. Residual melanoma in situ was present at the mucosal margin on final pathology which required a second surgery for margin revision. The case was discussed at tumor board with recommendation for no further treatment.ConclusionsThe nuances between the vermillion and mucosal lip must be understood for appropriate staging and treatment of melanomas. The paucity of literature on melanomas affecting this site render management decisions challenging. Multidisciplinary discussion is essential for guiding care.

Efficacy and feasibility of Apatinib and S-1 as a novel oral induction therapy in locally advanced head and neck squamous cell carcinoma: an exploratory phase 2 open-label, single-arm trial.

The current standard nonsurgical treatment for locally advanced head and neck squamous cell cancer (LA-HNSCC) is concomitant chemoradiotherapy (CRT). Neoadjuvant chemotherapy combined with CRT has been explored in HNSCC patients and is an acceptable strategy. However, the occurrence of adverse events (AEs) restricts its application. We conducted a clinical study to explore the efficacy and feasibility of a novel induction therapy with orally administered apatinib and S-1 in LA-HNSCC. This nonrandomized, single-arm, prospective clinical trial included patients with LA-HNSCCs. The eligibility criteria included histologically or cytologically confirmed HNSCC, with at least one radiographically measurable lesion detected by magnetic resonance imaging (MRI) or computerized tomography (CT) scan, age 18-75 years, and a diagnosis of stage III to IVb according to the 7th edition of the American Joint Committee of Cancer (AJCC). Patients received induction therapy with apatinib and S-1 for three cycles (3 weeks/cycle). The primary endpoint of this study was the objective response rate (ORR) to induction therapy. The secondary endpoints included progression-free survival (PFS), overall survival (OS), and AEs during induction treatment. From October 2017 to September 2020, 49 patients with LA-HNSCC were screened consecutively and 38 were enrolled. The median age of the patients was 60 years (range, 39-75). Thirty-three patients (86.8%) had stage IV disease according to the AJCC staging system. The ORR after induction therapy was 97.4% (95% confidence interval [CI]: 86.2%-99.9%). the 3-year OS rate was 64.2% (95% CI: 46.0%-78.2%) and 3-year PFS was 57.1% (95% CI: 40.8%-73.6%). The most common AEs during induction therapy were hypertension and hand-foot syndrome, which were manageable. Apatinib combined with S-1 as novel induction therapy for LA-HNSCC patients resulted in a higher-than-anticipated ORR and manageable adverse effects. With the associated safety profile and preferable oral administration route, apatinib combined with S-1 is an attractive exploratory induction regimen in outpatient settings. However, this regimen failed to show a survival benefit. https://clinicaltrials.gov/show/NCT03267121, identifier NCT03267121.

Renal Pelvic Urothelial Carcinoma With Invasion Into Renal Medulla Can Be Redefined as pT2 to Improve Correlation With Survival

According to the American Joint Cancer Committee, pT3 renal pelvic carcinoma is defined as tumor invading the renal parenchyma and/or peripelvic fat and is the largest pT category, with notable survival heterogeneity. Anatomical landmarks within the renal pelvis can be difficult to discern. Using glomeruli as a boundary to differentiate renal medulla invasion from renal cortex invasion, this study aimed to compare patient survival of pT3 renal pelvic urothelial carcinoma on the basis of the extent of renal parenchyma invasion and, thereafter, determine whether redefining pT2 and pT3 improves pT correlation with survival. Cases with primary renal pelvic urothelial carcinoma were identified through a review of pathology reports from nephroureterectomies completed at our institution from 2010 to 2019 (n = 145). Tumors were stratified by pT, pN, lymphovascular invasion, and invasion of the renal medulla versus invasion of the renal cortex and/or peripelvic fat. Overall survival between groups was compared using Kaplan-Meier survival models and Cox regression multivariate analysis. pT2 and pT3 tumors had similar 5-year overall survival, with multivariate analysis demonstrating an overlap between hazard ratios (HRs) for pT2 (HR, 2.20; 95% CI, 0.70-6.95) and pT3 (HR, 3.15; 95% CI, 1.63-6.09). pT3 tumors with peripelvic fat and/or renal cortex invasion had a 3.25-fold worse prognosis than pT3 tumors with renal medulla invasion alone. Furthermore, pT2 and pT3 tumors with only renal medulla invasion had similar overall survival, whereas pT3 tumors with peripelvic fat and/or renal cortex invasion had a worse prognosis (P = .00036). Reclassifying pT3 tumors with only renal medulla invasion as pT2 yielded greater separation between survival curves and HR. Thus, we recommend redefining pT2 renal pelvic carcinoma to include renal medulla invasion and restricting pT3 to peripelvic fat and/or renal cortex invasion to improve the prognostic accuracy of pT classification.

UNDIFFERENTIATED PLEOMORPHIC SARCOMA: PROGNOSTIC FACTORS IN 42 EXTREMITY CASES.

Soft tissue undifferentiated pleomorphic sarcoma (UPS) in extremities is considered a rare neoplasm, corresponding to 5% of soft tissue sarcomas (STS) today. The objective was to evaluate prognostic factors related to death, local recurrence (LR), and impact on survival rates. A retrospective study including 42 patients with UPS in extremities treated surgically in a single center. Comparisons were made between demographic data, characteristics of the neoplasia, and treatment. Between the variables with statistical significance, logistic regression analysis was used. Survival rates were evaluated using Kaplan-Meier plots. To compare the effect of variables on survival rates, the Log-Rank test was used. Age group of patients was from 25 to 85 years (mean 58 years), with a mean follow-up of 29.6 months. The variables with the highest effect on survival rates were sizes larger than 15 cm (T4) with p = 0.01, presence of metastatic lesions, and prognostic stage IV according to the American Joint Committee of Cancer (AJCC) with p < 0.001. The mean survival was 25.9 months. Metastasis and stage IV of AJCC were associated with a reduction in patient survival (17.8 months) with Log-Rank test p < 0.001. Conclusion: The main factors of poor prognosis related to mortality and reduction of survival of UPS in extremities were metastatic lesions and stage IV of AJCC. Level of Evidence III, Retrospective Study.

Varied Histomorphological Presentations of Appendiceal Neoplasms: A Case Series of Eight Cases

During routine histopathological study of appendicular specimens, we identified eight cases of appendiceal tumours, including five cases of Low-grade Appendiceal Mucinous Neoplasms (LAMN) and three cases of adenocarcinoma. Among the adenocarcinoma cases, one was a rare colorectal type adenocarcinoma in an older male and two were mucinous adenocarcinoma which includes a case of signet ring cell rich type. These tumours were classified and staged according to the recent WHO classification (5th edition) and the eighth edition of the American Joint Committee of Cancer (AJCC) staging manual. The median age in our series was 60 years. Serum markers were evaluated in two cases of Pseudomyxoma Peritonei (PMP), which showed elevated levels of CA-125 and CA 19.9 in each case. In this case series, three patients were initially diagnosed with acute appendicitis, one case as mucocele, two cases underwent surgery for ovarian malignancy, one patient was operated for an incisional hernia, and one patient was diagnosed with acute intestinal obstruction after clinical and radiological investigations. Histopathological examination confirmed the diagnosis of appendicular neoplasms in these eight cases. Meticulous histopathological examination of all appendectomy specimens is important for the proper diagnosis of appendicular neoplasms and to predict their severity. This will help surgeons plan further treatment to increase the patient's survival rate.

Development and validation of a prognostic model to predict the prognosis of patients with colorectal gastrointestinal stromal tumor: A large international population-based cohort study.

Colorectal gastrointestinal stromal tumors (GISTs), mesenchymal malignancy, only accounts for about 6% of GISTs, but prognosis is generally poor. Given the rarity of colorectal GISTs, the prognostic values of clinicopathological features in the patients remain unclear. Nomograms can provide a visual interface to help calculate the predicted probability of a patient meeting a specific clinical endpoint and communicate it to the patient. We included a total of 448 patients with colorectal GISTs diagnosed between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. For nomogram construction and validation, patients in the SEER database were divided randomly into the training cohort and internal validation cohort at a ratio of 7:3, while 44 patients with colorectal GISTs from our hospital patient data set between 2010 to 2016 served as the external validation cohort. The OS curves were drawn using the Kaplan-Meier method and assessed using the log-rank test. And, Fine and Gray's competing-risks regression models were conducted to assess CSS. We performed univariate and multivariate analyses to select prognostic factors for survival time and constructed a predictive nomogram based on the results of the multivariate analysis. Through univariate and multivariate analyses, it is found that age, primary site, SEER stage, surgery, and tumor size constitute significant risk factors for OS, and age, primary site, histological grade, SEER stage, American Joint Committee for Cancer (AJCC) stage, surgery, and tumor size constitute risk factors for CSS. We found that the nomogram provided a good assessment of OS and CSS at 1-, 3- and 5- year in patients with colorectal GISTs. The calibration plots for the training, internal validation and external validation cohorts at 1-, 3- and 5- year OS and CSS indicated that the predicted survival rates closely correspond to the actual survival rates. We constructed and validated an unprecedented nomogram to predict OS and CSS in patients with colorectal GISTs. The nomogram had the potential as a clinically predictive tool for colorectal GISTs prognosis, and can be used as a potential, objective and additional tool for clinicians in predicting the prognosis of colorectal GISTs patients worldwide. Clinicians could wield the nomogram to accurately evaluate patients' OS and CSS, identify high-risk patients, and provide a baseline to optimize treatment plans.

Regression Derived Staging Model to Predict Overall and Disease Specific Survival in Patients With Major Salivary Gland Carcinomas With Independent External Validation.

PURPOSEThe current American Joint Cancer Committee (AJCC) staging system for salivary gland tumors does not include histology and grade in its classification despite their proven prognostic importance. We planned to analyze if a modified staging system integrating these two factors into the staging improves prognostic performance and then validate it externally.MATERIALS AND METHODSFrom SEER database (2000-2018), patients with major salivary gland carcinoma who underwent surgical resection between 2004 and 2015 were analyzed. Histologies were recoded into two groups based on grade and type of histology into “Low Aggression” and “High aggression” groups. Cox proportional hazards model was used to identify predictor variables for overall survival and disease-specific survival and models were generated based on least absolute shrinkage and selection operator regression. Model performance was evaluated by Akaike Information Criterion, concordance index and calibration plot. The best model chosen was externally validated from our hospital database of patients who underwent surgery for salivary gland tumor between January 1, 2012 to December 31, 2019.RESULTSSix thousand two hundred forty-six patients were analyzed with a median follow up of 58 months. Age > 65 years, male sex, metastatic disease, Histological Stratification, Grade of tumor, AJCC stage and Primary Site were the significant factors influencing overall survival and disease-specific survival. By least absolute shrinkage and selection operator regression method, Correlation analysis and Interaction testing by multiple regression, AJCC stage and Histological Risk stratification were used for generating four models, out of which the best model was selected by Akaike Information Criterion, C index and calibration plot. This model was then externally validated in our hospital database of 269 patients.CONCLUSIONWe propose an externally validated modified salivary gland staging system that incorporates histology and grade of tumor for improved hazard discrimination among patient subgroups.

A Decade of Robotic-Assisted Radical Nephrectomy with Inferior Vena Cava Thrombectomy: A Systematic Review and Meta-Analysis of Perioperative Outcomes.

Open radical nephrectomy with inferior vena cava thrombectomy (O-CT) is standard management for renal cell carcinoma with inferior vena cava thrombus. First reported a decade ago, robotic-assisted radical nephrectomy with inferior vena cava thrombectomy (R-CT) is a minimally invasive option for this disease. We aimed to perform a systematic review to assess the safety and feasibility of R-CT in terms of perioperative outcomes and compare the outcomes between R-CT and O-CT. The PubMed®, Scopus®, Cochrane Central Register of Controlled Trials and Web of ScienceTM databases were searched using the free-text and MeSH terms "renal cell carcinoma," "inferior vena cava," "thrombosis" or "thrombus," "robot" and "thrombectomy." Studies reporting perioperative outcomes of R-CT and studies comparing R-CT with O-CT were included. The review was done in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search retrieved 28 articles describing R-CT, including 7 comparative studies. This systematic review included 1,375 patients, out of which 329 patients were in single-arm studies and 1,046 patients were in comparative studies. Of the 329 patients who underwent R-CT, 14.7% were level I, 60.9% level II, 20.4% level III and 2.5% level IV thrombus. Operative time ranged from 150 to 530 minutes; blood transfusion was administered in 38.2% (126). The overall complication rate was 30.3% (99). R-CT, in comparison to O-CT, was associated with a lower blood transfusion rate (18.4% vs 64.3%, p=0.002) and a lower complication rate (14.5% vs 36.7%, p=0.005). Major complication and 30-day mortality rates were similar in both groups. R-CT has acceptable perioperative outcomes in carefully selected patients. Compared with O-CT, R-CT is associated with a lower blood transfusion rate and fewer overall complications. In experienced hands with carefully selected patients, R-CT is feasible and safe, with acceptable outcomes; however, selection bias limits definitive inference of these results, and optimal patient selection criteria remain to be described.

Re-introduction of T-VEC Monotherapy in Recurrent Melanoma is Effective.

Talimogene laherparepvec (T-VEC) is a modified herpes simplex virus type 1, which can be administered intralesionally in patients with stage IIIB/C-IVM1a (American Joint Committee of Cancer; AJCC 7th edition) unresectable melanoma. In the case of disease recurrence, T-VEC can be re-introduced for the same category of patients. Five patients with recurrent disease after a prior achieved complete response (CR) recommenced treatment with T-VEC monotherapy at the Netherlands Cancer Institute. We collected data on response, adverse events and baseline characteristics. All 5 patients that were re-treated with T-VEC presented with in-transit metastases on the lower limb. Median age at baseline was 72.1 years with a median follow-up time of 30.4 months. Histologically proven CR was achieved after a median of 8 T-VEC courses on the initial exposure. Duration of response (time between first CR and recurrence) varied between 3.8 and 14.2 months. All 5 patients achieved a histologically and/or positron emission tomography/computed tomography proven CR again after re-introduction of T-VEC with a median of 5 courses. One patient (20%) developed a second recurrence and is currently still on treatment with T-VEC. No patients developed distant metastases. Grade 1 adverse events occurred in all patients. Mostly, these consisted of fatigue, influenza-like symptoms and injection site pain. Response to re-introduction of T-VEC monotherapy in this select patient population is promising. This real world data on re-introduction of T-VEC monotherapy in stage IIIB/C-IVM1a melanoma suggests T-VEC could be a treatment option for chronic disease control.