5-year Disease-specific Survival Research Articles

The Prognostic Role of Pre-Treatment Neutrophil-to-Lymphocyte Ratio in an Asian Cohort of Patients with Oropharyngeal Squamous Cell Carcinoma

Purpose: The neutrophil-to-lymphocyte ratio is a simple biomarker that reflects the balance between the systemic inflammatory and immunity status. Here we investigate the prognostic role of pre-treatment neutrophil-to-lymphocyte ratio (NLR) in an Asian cohort of oropharyngeal squamous cell carcinoma (OPSCC) patients. Methods: A retrospective review of OPSCC patients from a tertiary institution was conducted. The NLR was calculated from the haematological specimen taken within a month before treatment. Survival rates were estimated via the Kaplan–Meier method, and Cox proportional hazards regression was performed for univariable and multivariable analyses. The NLR cutpoint was determined using maximally selected log-rank statistics. Results: In a cohort of 148 OPSCC patients, 43% were p16-positive and 44% were p16-negative, with a median follow-up of 24 months. The p16-positive patients were younger (median age 62 vs. 67 years) and exhibited a lower prevalence of heavy smoking (47% vs. 69%). The p16-negative cases frequently presented at an advanced disease stage (74% vs. 41%), with a history of previous radiotherapy (26% vs. 3%). The p16-negative patients displayed a higher median NLR (2.91 vs. 2.49). The 3-year disease-specific survival (DSS) in p16-positive was higher compared to p16-negative patients (89.9% vs. 41.6%). The optimal NLR cutpoint was determined as 3.56 and predicted for decreased DSS (hazard ratio [HR] 2.59, p = 0.004). Multivariable analysis revealed smoking, high NLR ≥ 3.56, and p16-negativity as independent variables associated with poorer DSS and overall survival (OS) across the cohort. Conclusion: A high NLR is independently prognostic of poorer DSS in OPSCC, independent of p16 and smoking status. A NLR of more than 3.56 was highly prognostic for poorer survival and warrants further validation in larger cohorts of OPSCC.

Local Endoscopic Treatment of Low-Grade Urothelial Tumors in the Upper Urinary Tract—Oncological Outcome of a Consecutive Single-Center Series of 118 Patients

Background: Upper urinary tract urothelial tumors are mostly treated with the use of endoscopic laser ablation. The treatment is recommended when the tumor is low grade and non-invasive. Objective: The aim of the present study was to investigate the oncological outcome of patients treated endoscopically for low-grade (LG) upper tract urothelial carcinoma (UTUC). Methods: One hundred and eighteen consecutive patients with pTa LG UTUC initially treated with laser ablation from 2012–2022 at a single university hospital were included. Patient and tumor characteristics, treatment, and oncological outcomes were retrospectively registered from electronic medical journals. Survival analysis was performed using Kaplan–Meier and Nelson–Aalen plots. Results: The median number of local recurrences was 2 with a median time to first recurrence of 5 months (IQR: 2–46). The 2-year share of patients having no recurrence was 28.8%. The risk of recurrence was highest within the first 3 years following initial treatment. Two-year survival function with no progression and preserved renal unit was 67.9%. The two-year overall survival (OS) and disease-specific survival (DSS) were 84.2% and 97.1%. The 5-year OS and DSS were 59.1% and 94.1%. The median follow-up time for OS was 36 months (IQR: 20.3–58.8). Conclusions: In the patient series, we found that the risk of recurrence following laser ablation of LG UTUC was high; however, it was associated with a low risk of progression and high OS and DSS. Therefore, we conclude that treatment with laser ablation in patients with LG UTUC is safe, although frequent follow-up is needed to detect recurrence.

Rectal Cancer Watch & Wait Management: Experience of 545 Patients from the U.S. Rectal Cancer Research Group.

The use of a watch and wait management strategy following a complete clinical response to neoadjuvant therapy for rectal cancer is increasing. However, insights into implementation, treatments, and outcomes, on a United States national level, are limited. To investigate and report on watch & wait management practices and outcomes in the US. Retrospective study. Multicenter. Stage II or III rectal cancer patients who underwent intentional watch & wait management between January 2015 and August 2022. Patient and tumor characteristics, neoadjuvant treatment and response, local cancer regrowth and metastasis, salvage surgery, overall and disease-specific survival. Among 545 patients from 33 centers, follow-up was 21 months (range, 9-37). Total neoadjuvant therapy or other types of neoadjuvant were used in 395 (72%) and 150 (28%) of patients, respectively. Estimated 3-year local regrowth rate was 23.8% (95% CI: 19.1-29.4%). Patients with local regrowth had higher distant metastases incidence (14.2% vs. 3.5%, p < 0.001). Salvage surgery was performed in 74/84 (88%) patients with local regrowth and included rectal resection in 66 (89%), and local excision in 8 (11%). Of 64 salvage resections with known pathology results, 58 (91%) were margin-negative. Overall, 3-year overall survival was 94.8% (95% CI: 90.5 - 97.2%) and 3-year disease specific survival 96.2% (95% Cl 91.8 - 98.2%). Patients with and without local regrowth exhibited 3-year overall survival of 83.6% (95% Cl 68.4 - 91.9%), and 97.7% (95% CI: 93.3 - 99.2%), respectively. Retrospective study. This multicenter study indicates that the watch & wait approach for locally advanced rectal cancer is feasible with acceptable outcomes across a variety of geographical regions and practice settings in the US. Local regrowth and distant metastasis rates were within published norms and salvage surgery proved effective. See Video Abstract.

Sinonasal Mucosal Melanoma Survival Outcomes, Recurrence Patterns, and Prognostic Factors: A Systematic Literature Review and Meta-analysis of Publications after 2000

Abstract Background Sinonasal mucosal melanoma (SNMM) comprises &lt;1% of all head and neck cancers but has one of the highest 5-year mortalities. Methods A systematic review and analysis using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta- Analyses) guidelines was conducted on SNMM survival, recurrence, and prognostic factors. Results A total of 2,379 abstracts were reviewed resulting in 90 studies describing 3347 SNMM patients. Patients were 49.65% male and 66.5 years old. Surgery plus radiation therapy, followed by surgery only, then radiation only were the most common treatments. Chemotherapy and immunotherapy were used in 418 patients and 101 respectively. The 2-, 3-, and 5-year overall survivals are 55.97, 40.09, and 30.35%, respectively. The 5-year disease-free survival and disease-specific survival are 25.56 and 38.04%. The 5-year local, regional, and distant recurrence-free survivals are 42.35, 81.64, and 44.65%. Mean survival after diagnosis was 26.99 months. Local (n = 650), regional (n = 226), and distant (n = 723) failure presented after 19.36, 6.35, and 12.42 months. Sites of metastasis were lung, liver, bone, brain, skin, kidney, and adrenal glands. Distant metastases, disease in the paranasal sinuses, and higher stage were noted to have worse survival outcomes. Positive margins did not significantly impact overall survival in 11/12 studies. Conclusion Overall survival over 20 years has remained poor with 70% of patients deceased in 5 years. About half of patients will develop distant failure and will thereafter rapidly decline. These data indicate need for advances in treatment of SNMM and new efforts with targeted immunotherapy offer a promising avenue toward improving survival outcomes.

Epidemiology and treatment outcome of nasopharyngeal carcinoma in a low-incidence population - a DAHANCA analysis in Denmark 2000-2018.

Nasopharyngeal carcinoma (NPC) is a rare disease and most studies have therefore been conducted in endemic areas. The aim of this study was to describe epidemiology and treatment outcomes of NPC in a population-based, non-endemic setting. Patients with NPC diagnosed in Denmark from 2000 to 2018 were identified in the Danish Head and Neck Cancer Study Group (DAHANCA) database. Clinical records were reviewed to obtain missing data and confirm outcome, histological subtypes, Epstein-Barr virus (EBV)-status, prognostic factors, and treatment. NPC was identified in 394 patients corresponding to age-standardized incidence rates of 0.5 and 0.2 per 100,000 in men and women, respectively. The 5-year overall (OS) and disease-specific survival (DSS) were 56 and 66%. In multivariate analysis, stage, smoking, and histology affected both OS and DSS, as patients with undifferentiated carcinomas had superior outcomes. Tumor EBV-status was determined in 221 patients, of whom 160 (72%) tested positive. EBV-positivity was associated with an improved OS in univariate analysis, but not after adjustment for relevant clinical factors. NPC is a rare malignancy in Denmark, and three in four patients have EBV-associated tumors. Tumor histology, smoking status, and stage, but not EBV-status, had independent prognostic impact on survival.

Racial and ethnic disparities in outcomes of diffuse large B cell lymphoma in adolescent and young adults: a SEER database analysis.

Data regarding racial disparities in the incidence, treatment, and outcomes of diffuse large B-cell lymphoma (DLBCL) is limited in the adolescent and young adult (AYA) population. We utilized the surveillance, epidemiology, and end-result (SEER) registry research plus database to evaluate racial/ethnic disparities in 8605 AYA patients with DLBCL. Race/ethnicity was categorized into three main subsets: non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), and 'other races' that included Hispanics (H), American Indian/Alaskan Native (AI/AN), Asian or Pacific Islander (A/PI). NHB were more likely to present with advanced stage disease (p < 0.001) and B symptoms (p < 0.001) and were less likely to receive chemotherapy(p < 0.001) compared to non-Hispanic white (NHW) patients and other races respectively. NHB patients had inferior 5-year disease specific survival (DSS) (70% vs 85% vs 80%, p < 0.001) and 5-year overall survival (OS) (66% vs 82% vs 77%, p < 0.001) compared to NHW and other races respectively. Black race was independently associated with both inferior DSS (HR 1.55, 95% CI 1.17-2.05, p = 0.002) and OS (HR 1.41, 95% CI 1.10-1.83, p = 0.007) after adjusting for age, gender, stage, presence of B symptoms, receipt of chemotherapy and radiation. NHB-DLBCL patients also had a lower 1-year relative survival rate (RSR) compared to NHW and other races. The low RSR in NHB patients persisted up to 5 years from diagnosis unlike NHW and other races. Our study shows that despite significant therapeutic advances in DLBCL over the last two decades, NHB AYA patients with DLBCL continue to have inferior survival outcomes compared to other ethnic and racial groups with disparities arising as early as the first year of diagnosis.

Margin-to-depth ratio as an independent prognostic factor in resected oral cavity squamous cell carcinoma: A nationwide cohort study

BackgroundThe prognostic significance of margin-to-depth ratio (MDR) in oral cavity squamous cell carcinoma (OCSCC) remains unclear, particularly in comparison to traditional margin status. We aimed to examine the association between MDR and clinical outcomes in a large Taiwanese cohort. MethodsA total of 18,324 patients with first primary OCSCC were categorized by margin status: positive (1013), <5 mm (8371), and ≥ 5 mm (8940). Disease-specific survival (DSS) and overall survival (OS) served as the main outcome measures. ResultsAfter excluding patients with positive margins (MDR = 0), the optimal MDR cutoff value for DSS and OS was 0.6. Patients with MDR > 0.6 showed significantly better 5-year DSS and OS rates (87 %, 81 %) compared to those with MDR ≤ 0.6 (71 %, 63 %) and MDR = 0 (53 %, 43 %). Multivariable analysis identified MDR ≤ 0.6 as independently associated with both DSS and OS in the entire cohort (hazard ratio [HR] = 1.34/1.32). This finding was consistent in the subgroups with surgical margins < 5 mm (HR = 1.39 for DSS and 1.38 for OS) and margins ≥ 5 mm (HR = 1.21 for both DSS and OS). In subgroups with surgical margins < 5 mm and ≥ 5 mm, an MDR > 0.6 was associated with better survival outcomes. ConclusionsAn MDR (cutoff: 0.6) is independently associated with prognosis in OCSCC, offering improved risk stratification compared to margin status alone. While MDR may guide surgical margin modification, further research is needed to determine whether MDR could serve as a postoperative indicator for adjuvant therapy in patients with close or clear margins.

Prognostic significance of adjuvant therapy and specific radiation dosages in Taiwanese patients with oral cavity cancer and extra-nodal extension: a nationwide cohort study

BackgroundThe evidence for adjuvant chemoradiotherapy (CRT) of oral cavity squamous cell carcinoma (OCSCC) with extra-nodal extension (ENE) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. The guidelines further suggest a radiation dose ranging from 6000 to 6600 cGy. In this nationwide study, we sought to evaluate the prognostic significance of adjuvant therapy and the specific radiation dosage in Taiwanese patients with pure OCSCC and ENE.MethodsA retrospective analysis of 1577 OCSCC patients with ENE who underwent resection and received adjuvant CRT or radiotherapy (RT) between January 2011 and December 2020 was conducted.ResultsMultivariable analysis revealed that adjuvant RT, more than four pathologically positive nodes, and radiation dosage below 6000 cGy were independent risk factors for unfavorable 5-year disease-specific survival (DSS) and overall survival (OS). Comparing patients who received CRT (n = 1453) to those treated with RT (n = 124) before and after propensity score (PS) matching, the 5-year outcomes were as follows: before PS matching, DSS (54% versus 30%, p < 0.0001), OS (42% versus 18%, p < 0.0001); after PS matching (n = 111 in each group), DSS (52% versus 30%, p = 0.0016), OS (38% versus 21%, p = 0.0019). For patients who underwent CRT, the 5-year outcomes for different radiation dose groups (6600 − 7000 cGy, n = 1155 versus 6000 − 6500 cGy, n = 199) were as follows: before PS matching, DSS (52% versus 54%, p = 0.1904), OS (43% versus 46%, p = 0.1610); after PS matching (n = 199 in each group), DSS (55% versus 54%, p = 0.8374), OS (46.5% versus 46.3%, p = 0.7578).ConclusionsFor OCSCC patients with ENE, our study shows CRT improved survivals than RT alone, underscoring the clinical significance of chemotherapy. Patients undergoing CRT with irradiation doses ranging from 6000 to 6500 cGy exhibited comparable survival outcomes to those receiving doses of 6600–7000 cGy. This observation suggests that irradiation doses exceeding the 6600 cGy may not confer the survival advantage in these patients. Further research is needed to confirm our results and explore the optimal irradiation dose for managing these patients.

Zanubrutinib, obinutuzumab, and venetoclax for first-line treatment of mantle cell lymphoma with a TP53 mutation

AbstractTP53-mutant mantle cell lymphoma (MCL) is associated with poor survival outcomes with standard chemoimmunotherapy. Dual Bruton tyrosine kinase and BCL2-inhibition with or without anti-CD20 monoclonal antibody therapy has shown promising activity in TP53-mutant MCL. We conducted a multicenter, phase 2 study of zanubrutinib, obinutuzumab, and venetoclax (BOVen) in untreated patients with MCL with a TP53 mutation. Patients initially received 160 mg zanubrutinib twice daily and obinutuzumab. Obinutuzumab at a dose of 1000 mg was given on cycle 1 day 1, 8, and 15, and on day 1 of cycles 2 to 8. After 2 cycles, venetoclax was added with weekly dose ramp-up to 400 mg daily. After 24 cycles, if patients were in complete remission with undetectable minimal residual disease (MRD) using an immunosequencing assay, treatment was discontinued. The primary end point was met if ≥11 patients were progression free at 2 years. The study included 25 patients with untreated MCL with a TP53 mutation. The best overall response rate was 96% (24/25) and the complete response rate was 88% (22/25). Frequency of undetectable MRD (uMRD) at a sensitivity level of 1 × 10–5 and uMRD at a sensitivity level of 1 × 10–6 at cycle 13 was 95% (18/19) and 84% (16/19), respectively. With a median follow-up period of 28.2 months, the primary end point was met with a 2-year progression-free survival of 72%, and the 2-year disease-specific and overall survival were 91% and 76%, respectively. Common side effects were generally low grade and included diarrhea (64%), neutropenia (32%), and infusion-related reactions (24%). BOVen was well tolerated and met its primary efficacy end point in TP53-mutant MCL. These data support its use and further evaluation of the BOVen regimen in this high-risk population. This trial was registered at www.ClinicalTrials.gov as #NCT03824483.

Small-cell carcinoma in the head and neck region: A propensity score-matched analysis of the effect of surgery

Background Head and neck small-cell carcinoma (HNSmCC) is a rare and aggressive cancer with a high tendency for distant metastasis. It is treated with multimodal treatment involving chemotherapy. Occasionally, surgery is performed for the management of locoregional HNSmCC. However, the benefits of surgery in this context have not yet been elucidated. Therefore, in this study, we aimed to investigate whether surgery could improve the survival of patients with HNSmCC. Patients and methods We obtained data from patients with locoregional HNSmCC treated with chemoradiation therapy (CRT) from the Surveillance, Epidemiology, and End Results database. Patients who did and did not undergo surgery were matched using propensity scores. The overall survival (OS) and disease-specific survival (DSS) rates were estimated using the Kaplan-Meier method and tested using the log-rank test. Hazard ratios (HRs) were calculated using the Cox proportional hazard model. Results The 5-year OS rates of the patients who did and did not undergo surgery were 57.2% and 50.6%, respectively (P = 0.689); the corresponding 5-year DSS rates were 61.0% and 57.5% (P = 0.769). The adjusted HRs for surgery were 0.85 (95% confidence interval [CI]: 0.54–1.33) for OS and 0.87 (95% CI: 0.51–1.49) for DSS. Conclusion The addition of surgery to CRT did not improve the survival of patients with locoregional HNSmCC.

HIPEC as Up-Front Treatment in Locally Advanced Ovarian Cancer

Purpose: The main objective of the study is to evaluate the effect of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of naïve ovarian cancer women undergoing complete or near-complete cytoreduction by assessing the overall survival, the disease-specific survival, and the disease-free survival. The secondary objective is the identification of prognostic indicators of survival and recurrence of these patients. Patients—Methods: Retrospective study of treatment in naïve women with locally advanced ovarian cancer treated with cytoreductive surgery (CRS) and HIPEC and compared with those who were treated with cytoreduction alone. Clinicopathologic variables were correlated to overall survival, disease-specific survival, and disease-free survival using Kaplan–Meier method, and the multivariate Cox proportional hazards regression models. Results: 5- and 10-year overall survival, disease-specific survival, and disease-free survival rates were significantly higher in patients treated with CRS and HIPEC. These patients were 67% less likely to die from any cause (adjusted hazard ratio, aHR = 0.33, p = 0.001), 75% less likely to die from cancer (aHR = 0.25, p = 0.003), and 46% less likely to develop recurrence (aHR = 0.54, p = 0.041) compared to patients treated with CRS alone. Moreover, the poor performance status (aHR = 2.96, p &lt; 0.001), the serous carcinomas (aHR = 0.14, p = 0.007), and the morbidity (aHR = 6.87, p &lt; 0.001) were identified as independent indicators of poor overall survival. The degree of differentiation (aHR = 8.64, p = 0.003) was identified as the independent indicator of disease-specific survival (aHR = 4.13, p = 0.002), while the extent of peritoneal carcinomatosis (aHR = 2.32, p &lt; 0.001) as the independent indicator of disease-free survival. Conclusions: Treatment in naïve patients with locally advanced ovarian cancer undergoing CRS plus HIPEC appears to have improved overall, disease-specific, and disease-free survival.

Postoperative pathological findings and prognosis of early laryngeal and pharyngeal cancer treated with transoral surgery

ObjectiveTransoral surgery for early-stage pharyngeal and laryngeal cancer provides good local control and is less invasive than external incisions. Postoperative pathological findings are considered the most important indicators for determining postoperative treatment, but detailed criteria have not been established. In this study, we evaluated the impact of postoperative pathological findings on prognosis of patients undergoing transoral surgery. MethodsThis study included patients with oropharyngeal, hypopharyngeal, and supraglottic cancer who underwent transoral surgery at Gifu University Hospital from April 2016 to December 2023. Resection margins were pathologically evaluated with horizontal and vertical margins, and vascular invasion was evaluated in three categories: lymphatic invasion, venous invasion, and perineural invasion. The correlation between each postoperative pathological finding and prognosis was evaluated. ResultsA total of 70 cases were assessed in this study. Cases of horizontal margin positive were 38.6 %, and cases of vertical margin positive were 27.1 %. Prognoses were comparable to previous reports. Despite the high margin positive rate, the 5-year overall survival rate was 77.1 %. The 5-year disease-specific survival rate was 89.7 %, and the 5-year local control rate was 85.3 %. Notably, when evaluated by margin direction, cases with positive horizontal margins had significantly worse prognoses. Although no significant correlation was found between vascular invasion and prognosis, cases of venous invasion tended to have a higher local recurrence rate. ConclusionThis study suggests that transoral surgery has good prognosis despite a high positive-margin rate. However, detailed criteria for additional treatment have not been developed, and further case accumulation is required. Intriguingly, positive horizontal margins are correlated with significantly worse prognosis. This result may be related to a high risk of multiple cancers, and careful follow-up after surgery is recommended.

Adenomatous Polyposis Coli Gene Mutations, Risk Factors, and Long-term Outcomes Associated With Desmoid Tumors in Patients With Familial Adenomatous Polyposis After Colectomy in Japan

Goals: To clarify the characteristics of desmoid tumors in Japanese patients with familial adenomatous polyposis after colectomy. Background: Few comprehensive reports have been published on desmoid tumors in Asian patients with familial adenomatous polyposis. Study: This retrospective study included the data of 81 patients with familial adenomatous polyposis who underwent surgery between 1978 and 2021. The adenomatous polyposis coli gene mutation sites, risk factors, and long-term outcomes associated with desmoid tumors in Japanese patients with familial adenomatous polyposis after colectomy were analyzed. Results: No association was observed between the gene mutation sites and desmoid tumor development in 40 patients who underwent genetic analyses. The rate of desmoid tumor development was 30.3% in 66 patients. Multivariate analysis revealed that age below 32 years at colectomy (hazard ratio = 5.491, 95% confidence interval 1.820-16.50, P &lt; 0.001) and familial adenomatous polyposis-related malignancies other than colorectal cancer (hazard ratio = 5.574, 95% confidence interval 2.075-14.98, P &lt; 0.001) were independent risk factors for desmoid tumor development following colectomy. The 10-year disease-specific survival and overall survival rates for desmoid tumors were 92.9% and 76.9%, respectively. The median surveillance duration was 90 months. Conclusions: Adenomatous polyposis coli gene mutation sites alone were not considered a factor for delaying or avoiding colectomy to prevent desmoid tumors in Japanese patients with familial adenomatous polyposis. The timing of colectomy and careful surveillance should be considered for managing patients at a high risk of developing desmoid tumors. Desmoid tumors in patients with familial adenomatous polyposis did not significantly impact prognosis, and pharmacological treatments are important for disease control.

Dedifferentiated liposarcoma of the extremities: a Korean multi-center study of 107 cases

BackgroundDedifferentiated liposarcoma of the extremities (DDL-E) is rare in comparison to that of the retroperitoneum. Its clinical features and surgical principle for resection margins at the dedifferentiated and the well-differentiated components are yet to be elucidated.MethodsThis retrospective multi-center study examined patients diagnosed with DDL-E from August 2004 to May 2023 at 5 sarcoma centers. Clinical features, oncologic outcomes, and prognostic factors were analyzed.ResultsA total of 107 patients were reviewed. The 5-year local recurrence free survival (LRFS), metastasis-free survival (MFS) and disease specific survival (DSS) were 84.7%, 78.6%, and 87.8%, respectively. Other primary malignancies and extrapulmonary metastasis were observed in 27 and 4 patients, respectively. The independent risk factor for local recurrence was R1/2 margin at the dedifferentiated component of the tumor. Metastasis was associated with tumor size in univariate analysis. The independent risk factor for DSS was tumor grade. Previous unplanned excision, de novo presentation, tumor depth, absence of the well-differentiated component, infiltrative border, R1/2 margin at the well-differentiated component were not associated with oncologic outcomes.ConclusionsThis is the largest study examining DDL-E to-date. Localized DDL-E has low potential for metastasis and carries an excellent prognosis. Other primary malignancy and extrapulmonary metastasis are more frequent in DDL-E, thus close monitoring of other sites during follow-up is recommended. While wide resection margin is the standard surgical approach for DDL-E, further investigation into moderated wide resection margin at the well-differentiated component is warranted.

Treatment strategy for cervical lymph node metastases from early-stage tongue and floor of the mouth squamous cell carcinoma using tumour budding and depth of invasion as predictors.

This study aimed to determine whether elective neck dissection can help improve outcomes in early-stage tongue and floor squamous cell carcinoma (SCC) by statistically analysing the relationship between information obtained from biopsy specimens and the incidence and prognosis of cervical lymph node metastasis (CLM). Biopsy specimens of 103 patients diagnosed with early cT1-T2 cancer of the tongue and floor of the mouth were included. Multivariate analysis showed that the three parameters significantly correlated with CLM, and univariate analyses showed that budding score (BS) ≥ 5 and pathological depth of invasion (pDOI) ≥ 5mm were independent risk factors for CLM. There were significant differences in the 5-year cumulative disease-specific survival between the BS < 5 and BS ≥ 5 groups, the pDOI < 5mm and pDOI ≥ 5mm groups, and the positive and negative budding and depth of invasion (BD) score groups. In early-stage tongue and floor of the mouth cancers with maximum tumour diameter ≤ 20mm, it may be necessary to treat occult CLM during initial surgery based on the following preoperative criteria: pDOI ≥ 5mm or BS ≥ 5 in biopsy specimens and DOI ≥ 8mm on imaging. The BD model exhibited the highest specificity and proved helpful for CLM prediction. pDOI ≥ 5mm and BS ≥ 5 were independent predictors of CLM and prognosis in early-stage tongue and floor of the mouth cancers with a maximum tumour diameter of 20mm.

International, Multi-Institutional Evaluation of Practice Patterns and Outcomes for Recurrent and Metastatic Sinonasal Undifferentiated Carcinoma

Abstract Objectives The aims of this study were to analyze the clinical characteristics of patients with recurrent and metastatic sinonasal undifferentiated carcinoma (SNUC) and evaluate the current treatment strategies to help guide future management. Design This is a retrospective cohort study. Setting The study was conducted at six international tertiary treatment centers. Participants Patients with documented diagnoses of recurrent or metastatic SNUC since 1983 were included in the study. Main Outcome Measures Patient demographics and clinical characteristics were collected. Primary outcome measures included disease-specific survival (DSS), overall survival (OS), and time to recurrence (TTR) following initial treatment. Further univariable and multivariable analyses were performed to assess for prognostic factors. Results A total of 97 patients with a mean (standard deviation [SD]) age of 52.4 (15.6) were identified, 15 of whom presented with metastatic SNUC and 90 of whom developed recurrence. Management in both populations was widely variable. For patients with metastatic disease, the 1-year DSS probability was 33.3% (95% confidence interval [CI], 10.8–100%). For patients with recurrent SNUC, the 1- and 5-year DSS probabilities were 45.7% (95% CI, 31.9–65.6%) and 8.6% (95% CI, 2.9–25.3%), respectively. The median (interquartile range [IQR]) TTR was 8 months (3–18.5 months). Multivariable analyses revealed a significant association between orbital involvement on initial presentation and TTR (hazard ratio [HR] = 3.28; 95% CI, 1.45–7.42; p = 0.004). Conclusions To our knowledge, this is the first study addressing metastatic and recurrent SNUC based on a large patient cohort. Orbital extension of the primary SNUC may predict a higher probability of recurrence following treatment, suggesting the possible utility of a more aggressive treatment in this subgroup of patients. A heterogenous patient population and wide variability in management emphasize the challenges in standardizing care; however, dismal survival rates demonstrate the necessity for further evaluation of current approaches to improve evidence-based recommendations.

Solar elastosis correlates with high tumor mutation burden and better 5-year disease-specific survival in patients with stage II/III melanoma

ObjectiveTo evaluate the relation between solar elastosis and tumor mutation burden (TMB) in a large clinically annotated cohort of stage II and III melanoma patients. MethodsPrimary cutaneous melanomas from 469 AJCC (8th edition) stage II and III patients with clinical annotation including outcome at 5 years of diagnosis were histopathologically evaluated for solar elastosis. Next-generation sequencing assay MSK-IMPACTTM was employed to determine TMB. Analysis by Fisher’s exact test, chi-square, and Kruskal-Wallis were performed, as well as uni- and multivariate logistic regression. ResultsTumors stratified by low and high TMB showed marked and statistically significant differences in presence and extent of associated solar elastosis. Lower risk patient stage (II versus III by AJCC 8th edition) as well as better 5-year melanomaspecific survival (as binary variable of controls-survivors versus cases-dead of disease at 5 years of diagnosis) were associated with severe solar elastosis. On univariate and multivariate logistic regression models, severe solar elastosis predicted significantly decreased odds of dying of melanoma within 5 years of diagnosis (OR 0.60, 95% CI 0.39-0.89; and OR 0.42, 95% CI 0.20-0.83, respectively; both p<0.05) ConclusionThe association of solar elastosis to TMB and 5-year melanoma specific survival points to its potential as a biomarker of clinical relevance that can be assessed by routine histopathology.

Survival and Patterns of Relapse of Cutaneous Squamous Cell Carcinoma With Large Nerve Perineural Spread After Skull Base Surgery and/or Radiation Therapy

The aim of our study was to evaluate survival and patterns of relapse for patients with perineural spread (PNS) of cutaneous squamous cell carcinoma (cSCC), who have undergone curative intent skull base surgery and/or radiation therapy. In addition, we modified the classification of zone 2 disease into 2a and 2b and reported the respective outcome. A review of a prospective database of patients who received diagnoses of PNS of cSCC and were treated with curative intent skull base surgery and/or radiation therapy between the years of 2013 and 2020 was conducted. Kaplan-Meier methods were used to estimate relapse-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). Cox proportional hazard modeling was performed to test associations between patient factors and survival outcomes. Eighty patients with a median follow-up of 36 months were included in the study. The 5-year RFS was 61% (95% CI, 48%-71%), the DSS was 77% (95% CI, 63%-86%), and OS was 67% (95% CI, 53%-78%). In multivariable modeling, involvement of 2 or more nerves was strongly associated with worse 5-year RFS (HR, 4.0; P ≤ .001), DSS (HR, 4.5; P = .004), and OS (HR, 4.3; P = .002). Age group (≥65 years) (HR, 5.1; P = .010) and immune compromise (HR, 10.7; P = .001) were strongly associated with worse OS but not DSS or RFS. The majority of relapses (60%) occurred at the local skin sites. Our study demonstrated surgery followed by radiation therapy was safe and effective in the management of cSCC with PNS. We did not detect a difference in outcome between zones 2a and 2b though further study is required. The most common mode of relapse was at the skin epidermis and/or adjacent dermis highlighting the importance of adequate local skin dose delivery.

The prognostic value of the 8th American Joint Committee on cancer anatomic and prognostic stage groups for penile cancer: A multicenter collaboration study

ObjectiveThe aim of this study was to investigate the value of 8th American Joint Committee on Cancer (AJCC) anatomic and prognostic stage groups for penile cancer patients and explore whether there is room for improvement. MethodsThe clinical and histopathologic data from 16 centers between 2000 and 2021 were assessed according to the 8th AJCC anatomic and prognostic stage groups. Kaplan–Meier plots were used to estimate the disease-specific survival (DSS) of the patients. The accuracy of the staging systems was investigated using the Harrell's concordance index (C-index). ResultsThe 5-year DSS rates for patients with stages 0is/a, I, IIA, IIB, IIIA, IIIB, and IV (stage 0 to stage IV) disease were 100 %, 98.9 %, 85.5 %, 81.1 %, 65.8 %, 34.4 %, and 23.2 %, respectively (p0is/a–I=0.798, pI–IIA<0.001, pIIA–IIB=0.486, pIIB–IIIA<0.001, pIIIA–IIIB<0.001, pIIIB–IV=0.004, ptotal<0.001). According to the modified model 1 system, the 5-year DSS rates without survivorship overlap for patients with stages 0is/a, I, II, IIIA, IIIB, and IV disease were 100 %, 98.9 %, 87.8 %, 65.8 %, 34.4 %, and 23.2 %, respectively (p0is/a–I=0.798, pI–II<0.001, pII–IIIA=0.002, pIIIA–IIIB<0.001, pIIIB–IV=0.004, ptotal<0.001). Similarly, according to the modified model 2 system, the 5-year DSS rates without survivorship overlap for patients with stages 0is/a, I, II, IIIA, IIIB, and IV disease were 100 %, 99.0 %, 85.8 %, 65.8 %, 34.4 %, and 23.2 %, respectively (p0is/a–I=0.757, pI–II<0.001, pII–IIIA=0.008, pIIIA–IIIB<0.001, pIIIB–IV=0.004, ptotal<0.001). The C-index of the simple modified staging systems were not inferior to those of the AJCC anatomic and prognostic stage groups. These results were confirmed by the bootstrap internal validation. ConclusionThere is still room for improvement about 8th AJCC anatomic and prognostic stage groups. The improved models, which are more concise and convenient, had a similar predictive value.

The Surgical Management of Intracranial Metastasis Secondary to Follicular Cell-Derived Thyroid Carcinoma.

Intracranial metastases (ICM) from follicular cell-derived thyroid carcinoma (FCDTC) are rare and are associated with a poor prognosis. The objective of this study is to report our experience in the surgical management of patients with ICM secondary to FCDTC. Patients with FCDTC who underwent surgical resection of an ICM were identified at our institution from 1998 to 2018. Thirty-two patients were included in this study. Nineteen patients (59%) had involvement of the brain parenchyma only, 8 (25%) had a dural-based metastasis, 3 (9%) had a calvarial metastasis with dural extension, and 2 (6%) had a skull base metastasis with dural extension. In patients who had an R0-1 resection, the estimated lesional control at the site of resection was 91% at 3 years. However, overall ICM control was 37% at 3 years due to the progression of other ICM lesions. The 1-year disease-specific survival (DSS) was 87% and 5-year DSS was 37%. ICM management in FCDTC is based on the size, number, and location of metastatic lesions. Complete resection of ICM may provide lesional control at the site of resection, however, DSS is poor due to the presence of other ICMs and metastases at multiple distant sites.