NCCN Guidelines® Insights: Merkel Cell Carcinoma, Version 1.2024.

The NCCN Guidelines for Merkel Cell Carcinoma (MCC) provide recommendations for diagnostic workup, clinical stage, and treatment options for patients. The panel meets annually to discuss updates to the guidelines based on comments from expert review from panel members, institutional review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new page for locally advanced disease in the setting of clinical node negative status, entitled "Clinical N0 Disease, Locally Advanced MCC." This new algorithm page addresses locally advanced disease, and the panel clarifies the meaning behind the term "nonsurgical" by further defining locally advanced disease. In addition, the guideline includes the management of in-transit disease and updates to the systemic therapy options.

Basal Cell Skin Cancer, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States. Due to the high frequency, BCC occurrences are not typically recorded, and annual rates of incidence can only be estimated. Current estimated rates are 2 million Americans affected annually, and this continues to rise. Exposure to radiation, from either sunlight or previous medical therapy, is a key player in BCC development. BCC is not as aggressive as other skin cancers because it is less likely to metastasize. However, surgery and radiation are prevalent treatment options, therefore disfigurement and limitation of function are significant considerations. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) outline an updated risk stratification and treatment options available for BCC.

Demographic variations and time to initiation of adjunct treatment following surgical resection of anaplastic astrocytoma in the United States: a National Cancer Database analysis.

BACKGROUND AND AIMS: The aim of this study was to analyze the trends, demographic differences in the type and time to initiation (TTI) of adjunct treatment AT following surgery for anaplastic astrocytoma (AA). MATERIAL AND METHODS: The National Cancer Database (NCDB) was queried for patients diagnosed with AA from 2004 to 2016. Cox proportional hazards and modeling was used to determine factors influencing survival, including the impact of time to initiation (TTI) of adjuvant therapy. RESULTS: Overall, 5890 patients were identified from the database. The use of combined RT + CT temporally increased from 66.3% (2004-2007) to 79% (2014-2016), p < 0001. Patients more likely to receive no treatment following surgical resection included elderly (> 60 years old), hispanic patients, those with either no or government insurance, those living > 20 miles from the cancer facility, those treated at low volume centers (< 2 cases/year). AT was received following surgical resection within 0-4 weeks, 4.1-8 weeks, and > 8 weeks in 41%, 48%, and 3%, respectively. Compared to patients who received RT + CT, patients were likely to receive RT only as AT either at 4-8 weeks or > 8 weeks after the surgical procedure. Patients who received AT within 0-4 weeks had the 3-year OS of 46% compared to 56.7% for patients who received treatment at 4.1-8 weeks. CONCLUSION: We found significant variation in the type and timing of adjunct treatment following surgical resection of AA in the United States. A considerable number of patients (15%) received no AT following surgery.

Radiosurgery fractionation and post-treatment hemorrhage development for intact melanoma brain metastases.

PURPOSE: To assess, for intact melanoma brain metastases (MBM), whether single-fraction stereotactic radiosurgery (SRS) versus fractionated stereotactic radiotherapy (fSRT) is associated with a differential risk of post-treatment lesion hemorrhage (HA) development. METHODS: A single institution retrospective database review identified consecutive patients with previously unresected MBM treated with robotic SRS/fSRT between 2013 and 2021. The presence of lesion HA was determined by multi-disciplinary imaging review. Dosimetric variables were reported as biologically effective doses using an α/ß ratio of 2.5 (BED2.5). Statistical analysis was performed using mixed effect logistic regression for post-treatment HA and Cox frailty modeling for local control (LC). RESULTS: The cohort included 48 patients with 226 intact MBM treated with SRS/fSRT. Of lesions without prior HA, 63 of 133 lesions (47.4%) receiving SRS demonstrated evidence of post-treatment HA versus 2 of 24 lesions (8.3%) treated with fSRT (p = 0.01). A larger maximum BED2.5 was observed in lesions developing HA compared to no HA (238.3 Gy vs. 211.4 Gy; p = 0.022). 12-month LC was 65.7% (95% CI 37.2-87.3%) and 77.5% (95% CI 58.5-91.2%) for lesions demonstrating pre-treatment and post-treatment HA, respectively, with no local failure events observed within 12 months for non-hemorrhagic lesions (p < 0.001). CONCLUSION: We found an increased incidence of post-treatment HA for intact MBM receiving a larger maximum BED2.5, which was significantly higher for single fraction treatments within our cohort. The presence of lesion HA, either pre- or post-treatment, was indicative of inferior LC. Further investigations of optimal dose and fractionation schedules for treatment of MBM in the era of immunotherapy are warranted.

Patterns of Care and Data Quality in a National Registry of Black and White Patients with Merkel Cell Carcinoma.

Merkel Cell Carcinoma (MCC) is a rare cancer most commonly affecting White patients; less is known for Black patients. We aim to report presentation, treatment, and quality of registry data by race with a secondary endpoint of overall survival. We conducted a retrospective cohort analysis between 2006−2017 via the National Cancer Database of Black and White MCC patients with and without known staging information. Multivariable logistic, proportional odds logistic, and baseline category logistic regression models were used for our primary endpoint. Multivariable Cox regression was used to interrogate overall survival. Multiple imputation was used to mitigate missing data bias. 34,503 patients with MCC were included (2566 Black patients). Black patients were younger (median age 52 vs. 72, p < 0.0001), had higher rates of immunosuppression (28% vs. 14%, p = 0.0062), and were more likely to be diagnosed at a higher stage (proportional OR = 1.41, 95% CI 1.25−1.59). No differences were noted by race across receipt of definitive resection (DR), though Black patients did have longer time from diagnosis to DR. Black patients were less likely to receive adjuvant radiation. Black patients were more likely to have missing cancer stage (OR = 1.69, CI 1.52−1.88). Black patients had decreased adjusted risk of mortality (HR 0.73, 0.65−0.81). Given the importance of registry analyses for rare cancers, efforts are needed to ensure complete data coding. Paramount to ensuring equitable access to optimal care for all is the recognition that MCC can occur in Black patients.

Financial Toxicity in Women With Breast Cancer Receiving Radiation Therapy: Final Results of a Prospective Observational Study.

PURPOSE: We sought to quantify financial toxicity (FT) present in a prospective cohort of women with breast cancer (BC) receiving radiation therapy (RT), identify predictors of FT, correlate FT with health-related quality of life (QoL), and determine whether duration of RT is associated with FT. METHODS AND MATERIALS: Consecutive patients with stage I-III BC completed Functional Assessment of Cancer Therapy-G7 (FACT-G7), a tailored FT questionnaire, and Comprehensive Score for Financial Toxicity (COST) scoring within 1 month of RT completion. Lower scores on FACT-G7 (range, 0-28) and COST (range, 0-44) indicate worse QoL and FT. Group comparisons were performed with a 2-sample t test and χ2 tests for continuous and categorical variables, respectively. Pearson correlation was used to associate COST with FACT-G7. Linear and multiple regression were used to evaluate predictors of COST. RESULTS: One hundred eight enrolled patients were eligible for analysis with completed COST scores, including 56, 42, and 10 patients treated with long-, intermediate-, and short-course RT. Mean COST score was 28.6 and mean FACT-G7 was 18.4. Among patients treated with intermediate- and long-course RT (n = 98), marital status (higher COST associated with married status relative to other), medication cost (higher COST for no significant medication costs relative to significant medication costs), employment type (lower COST associated with disabled status or unemployed, higher COST with retired status relative to working), and surgery type (higher COST for lumpectomy relative to mastectomy) were significantly associated with COST score by multivariable analysis (all P values < .05). RT length group was not associated with COST (P = .79). COST and FACT-G7 were strongly correlated for the overall cohort (P < .0001). CONCLUSIONS: In this prospective study of women with BC receiving RT, distinct factors including surgery type were significantly associated with FT. FT was strongly correlated with health-related QoL. Increased characterization of the relationship between FT and health-related QoL for women with BC receiving RT and defining clinical predictors of FT may help guide future studies investigating optimal targeted interventions for patients with BC at high risk for FT.

Stereotactic radiosurgery for melanoma brain metastases: dose-size response relationship in the era of immunotherapy.

PURPOSE/OBJECTIVE(S): To determine, for intact melanoma brain metastases (MBM) treated with single-fraction stereotactic radiosurgery (SRS), whether planning parameter peripheral dose per lesion diameter (PDLDm, Gy/mm) and lesion control (LC) differs with versus without immunotherapy (IO). MATERIALS/METHODS: We performed a retrospective analysis of patients with intact MBM treated with SRS from 2008 to 2019. Cox-frailty models were constructed to include confounders selected by penalized Cox regression models with a LASSO selector. Interaction effect testing was used to determine whether a significant effect between IO and PDLDm could be demonstrated with respect to LC. RESULTS: The study cohort comprised 67 patients with 244 MBMs treated with SRS (30 patients with 122 lesions treated with both SRS and IO) were included. The logarithm of PDLDm was selected as a predictor of LC (HR 0.307, 95% CI 0.098-0.441), adjusting for IO receipt (HR 0.363, 95% CI 0.108-1.224). Interaction effect testing demonstrated a differential effect of PDLDm by IO receipt, with respect to LC (p = 0.048). Twelve-month LC rates for a 7.5 mm lesion receiving SRS (18 Gy) with IO versus without IO were 87.8% (95% CI 69.0-98.3%) versus 79.8% (95% CI 55.1-93.8%) respectively. CONCLUSION: PDLDm predicted LC in patients with small MBMs treated with single-fraction SRS. We found a differential effect of dose per lesion size and LC by immunotherapy receipt. Future studies are needed to determine whether lower doses of single-fraction SRS afford similarly effective LC for patients with small MBMs receiving immunotherapy.

Merkel Cell Carcinoma of the Head and Neck: Epidemiology, Pathogenesis, Current State of Treatment and Future Directions.

Merkel cell carcinoma (MCC) is a rare, cutaneous neuroendocrine malignancy with increasing incidence. The skin of the head and neck is a common subsite for MCC with distinctions in management from other anatomic areas. Given the rapid pace of developments regarding MCC pathogenesis (Merkel cell polyoma virus (MCPyV)-positive or virus-negative, cell of origin), diagnosis, staging and treatment, and up to date recommendations are critical for optimizing outcomes. This review aims to summarize currently available literature for MCC of the head and neck. The authors reviewed current literature, including international guidelines regarding MCC pathogenesis, epidemiology, diagnosis, staging, and treatment. Subsequently recommendations were derived including the importance of baseline imaging, MCPyV serology testing, primary site surgery, nodal evaluation, radiotherapy, and the increasing role of immune modulating agents in MCC. MCPyV serology testing is increasingly important with potential distinctions in treatment response and surveillance between virus-positive and virus-negative MCC. Surgical management continues to balance optimizing local control with minimal morbidity. Similarly, radiotherapy continues to have importance in the adjuvant, definitive, and palliative setting for MCC of the head and neck. Immunotherapy has changed the paradigm for advanced MCC, with increasing work focusing on optimizing outcomes for non-responders and high-risk patients, including those with immunosuppression.

Immune Status in Merkel Cell Carcinoma: Relationships With Clinical Factors and Independent Prognostic Value.

BACKGROUND: Immunosuppression (IS) currently is not considered in staging for Merkel cell carcinoma (MCC). An analysis of the National Cancer Database (NCDB) was performed to investigate immune status as an independent predictor of overall survival (OS) for patients with MCC and to describe the relationship between immune status and other prognostic factors. METHODS: The NCDB was queried for patients with a diagnosis of MCC from 2010 to 2016 who had known immune status. Multivariable Cox proportional hazards models were used to define factors associated with OS. Secondary models were constructed to assess the association between IS etiology and OS. Multivariable logistic regression models were used to characterize relationships between immune status and other factors. RESULTS: The 3-year OS was lower for the patients with IS (44.6%) than for the immunocompetent (IC) patients (68.7%; p < 0.0001). Immunosuppression was associated with increased adjusted mortality hazard (hazard ratio [HR], 2.36, 95% confidence interval [CI], 2.03-2.75). The etiology of IS was associated with OS (p = 0.0015), and patients with solid-organ transplantation had the lowest 3-year OS (32.7%). Immunosuppression was associated with increased odds of greater nodal burden (odds ratio [OR], 1.70; 95% CI, 1.37-2.11) and lymphovascular invasion (OR, 1.58; 95% CI, 1.23-2.03). CONCLUSIONS: Immune status was independently prognostic for the OS of patients with localized MCC. The etiology of IS may be associated with differential survival outcomes. Multiple adverse prognostic factors were associated with increased likelihood of IS. Immune status, and potentially the etiology of IS, may be useful prognostic factors to consider for future MCC staging systems.

Trends in the Management Paradigms of Intracranial Meningioma.

Objective Intracranial meningiomas are the most common primary brain tumor. Treatment paradigms have evolved over time. There are limited number of population-based studies that examine this modern evolution. Here, we describe the trends of management of intracranial meningiomas using a national database. Methods The data were obtained from the National Cancer Database for the years 2004 to 2015, the collected variables included: patients' age, gender, insurance type, income, comorbidity score, the tumor size and grade, and treatment modality (observation, surgery, radiotherapy, or combination therapy). We performed statistical analyses to detect association between unique variables and outcomes. In addition, we performed mortality analyses for various treatment modalities. Results A total of 199,096 patients with a diagnosis of intracranial meningioma were included, the majority of patients were white females, mean age of 61 years, and half of the tumors were ≤ 3 cm. Observation was the most commonly used management modality followed by surgical resection, radiotherapy, and combination therapy. For the entire time period, there was an increased use of observation as a primary management method. Predictors of mortality included increased age, larger tumor size, higher tumor grade, treatment at a community hospital, and higher comorbidity scores. Conclusion Population-based studies of intracranial meningiomas are uncommon; our study is one of the few reports that examine the changes in the modern management paradigms of meningioma in the United States over time. Additionally, we shed light on the factors that affected survival of patients with this condition.

Embolization of Brain Arteriovenous Malformations With Versus Without Onyx Before Stereotactic Radiosurgery.

BACKGROUND: Embolization of brain arteriovenous malformations (AVMs) using ethylene-vinyl alcohol copolymer (Onyx) embolization may influence the treatment effects of stereotactic radiosurgery (SRS) differently than other embolysates. OBJECTIVE: To compare the outcomes of pre-SRS AVM embolization with vs without Onyx through a multicenter, retrospective matched cohort study. METHODS: We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Embolized AVMs treated with SRS were selected and categorized based on embolysate usage into Onyx embolization (OE + SRS) or non-Onyx embolization (NOE + SRS) cohorts. The 2 cohorts were matched in a 1:1 ratio using de novo AVM features for comparative analysis of outcomes. RESULTS: The matched cohorts each comprised 45 patients. Crude AVM obliteration rates were similar between the matched OE + SRS vs NOE + SRS cohorts (47% vs 51%; odds ratio [OR] = 0.837, P = .673). Cumulative probabilities of obliteration were also similar between the OE + SRS vs NOE + SRS cohorts (subhazard ratio = 0.992, P = .980). Rates of post-SRS hemorrhage, all-cause mortality, radiation-induced changes, cyst formation, and embolization-associated complications were similar between the matched cohorts. Sensitivity analysis for AVMs in the OE + SRS cohort embolized with Onyx alone revealed a higher rate of asymptomatic embolization-associated complications in this subgroup compared to the NOE + SRS cohort (36% vs 15%; OR = 3.297, P = .034), but the symptomatic complication rates were similar. CONCLUSION: Nidal embolization using Onyx does not appear to differentially impact the outcomes of AVM SRS compared with non-Onyx embolysates. The embolic agent selected for pre-SRS AVM embolization should reflect both the experience of the neurointerventionalist and target of endovascular intervention.

Stereotactic Radiosurgery With Versus Without Embolization for Brain Arteriovenous Malformations.

BACKGROUND: Prior comparisons of brain arteriovenous malformations (AVMs) treated using stereotactic radiosurgery (SRS) with or without embolization were inherently flawed, due to differences in the pretreatment nidus volumes. OBJECTIVE: To compare the outcomes of embolization and SRS, vs SRS alone for AVMs using pre-embolization malformation features. METHODS: We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Patients were categorized into the embolization and SRS (E + SRS) or SRS alone (SRS-only) cohorts. The 2 cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was defined as AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiologic and symptomatic radiation-induced changes (RIC), and cyst formation. RESULTS: The matched cohorts each comprised 101 patients. Crude AVM obliteration rates were similar between the matched E + SRS vs SRS-only cohorts (48.5% vs 54.5%; odds ratio = 0.788, P = .399). Cumulative probabilities of obliteration at 3, 4, 5, and 6 yr were also similar between the E + SRS (33.0%, 46.4%, 56.2%, and 60.8%, respectively) and SRS-only (32.9%, 46.2%, 56.0%, and 60.6%, respectively) cohorts (subhazard ratio (SHR) = 1.005, P = .981). Cumulative probabilities of radiologic RIC at 3, 4, 5, and 6 yr were lower in the E + SRS (25.0%, 25.7%, 26.7%, and 26.7%, respectively) vs SRS-only (45.3%, 46.2%, 47.8%, and 47.8%, respectively) cohort (SHR = 0.478, P = .004). Symptomatic and asymptomatic embolization-related complication rates were 8.3% and 18.6%, respectively. Rates of post-SRS hemorrhage, all-cause mortality, symptomatic RIC, and cyst formation were similar between the matched cohorts. CONCLUSION: This study refutes the prevalent notion that AVM embolization negatively affects the likelihood of obliteration after SRS.

Stereotactic radiosurgery with versus without prior Onyx embolization for brain arteriovenous malformations.

OBJECTIVE: Investigations of the combined effects of neoadjuvant Onyx embolization and stereotactic radiosurgery (SRS) on brain arteriovenous malformations (AVMs) have not accounted for initial angioarchitectural features prior to neuroendovascular intervention. The aim of this retrospective, multicenter matched cohort study is to compare the outcomes of SRS with versus without upfront Onyx embolization for AVMs using de novo characteristics of the preembolized nidus. METHODS: The International Radiosurgery Research Foundation AVM databases from 1987 to 2018 were retrospectively reviewed. Patients were categorized based on AVM treatment approach into Onyx embolization (OE) and SRS (OE+SRS) or SRS alone (SRS-only) cohorts and then propensity score matched in a 1:1 ratio. The primary outcome was AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiological and symptomatic radiation-induced changes (RICs), and cyst formation. Comparisons were analyzed using crude rates and cumulative probabilities adjusted for competing risk of death. RESULTS: The matched OE+SRS and SRS-only cohorts each comprised 53 patients. Crude rates (37.7% vs 47.2% for the OE+SRS vs SRS-only cohorts, respectively; OR 0.679, p = 0.327) and cumulative probabilities at 3, 4, 5, and 6 years (33.7%, 44.1%, 57.5%, and 65.7% for the OE+SRS cohort vs 34.8%, 45.5%, 59.0%, and 67.1% for the SRS-only cohort, respectively; subhazard ratio 0.961, p = 0.896) of AVM obliteration were similar between the matched cohorts. The secondary outcomes of the matched cohorts were also similar. Asymptomatic and symptomatic embolization-related complication rates in the matched OE+SRS cohort were 18.9% and 9.4%, respectively. CONCLUSIONS: Pre-SRS AVM embolization with Onyx does not appear to negatively influence outcomes after SRS. These analyses, based on de novo nidal characteristics, thereby refute previous studies that found detrimental effects of Onyx embolization on SRS-induced AVM obliteration. However, given the risks incurred by nidal embolization using Onyx, this neoadjuvant intervention should be used judiciously in multimodal treatment strategies involving SRS for appropriately selected large-volume or angioarchitecturally high-risk AVMs.

Tumors in the cauda equina: A SEER analysis of tumor types and predictors of outcome.

Caudaequinatumors are histologically diverse. International Classification of Diseases for Oncology (ICD-O3) confers dedicated site code (C72. 1) for cauda equina. This code is excluded during analyses of other primary spinal cord tumors. In this retrospective study, the Surveillance, Epidemiology and End Results (SEER) data for primary cauda equina tumors (PCET, C72. 1) excluding the tumors of spinal meninges (C70. 1) from 1992 to 2015 were reviewed. Demographic characteristics, tumor types, and clinical outcomes were analyzed using univariable analysis. Overall survival was estimated using Kaplan-Meier methods and compared for age, histology and treatment type. 293 patients with PCET met inclusion criteria. The most common tumors comprised schwannoma (32%), myxopapillary ependymoma (21%), malignant ependymoma (22%). The median age at diagnosis was 50 years (range < 1 year to 98 years), 57% of patients were males. 77% of the patients underwent surgery. Median follow up time for these patients was 70 months. Of the 293 patients, 250 (85%) were living at the end of 2015. The cause of death was tumor or CNS related in 15 patients. 136 patients were followed for <5 years, of which 102 were censored and 34 died (11.6%) before 5 years. Using univariable analysis, age at diagnosis (Hazard Ratio, HR 1.05; confidence interval, CI 1.03-1.07; p < 0.001), malignant tumor type (HR 2.88, CI 1.15-7.19, p = 0.0239) and absence of surgical intervention (HR 2.54, CI1.26-5.11, p = 0.0092) were predictors of increased mortality. Although most patients did well, older age and lack of surgical intervention were associated with worse survival.

Tumor infiltrating lymphocyte grade in Merkel cell carcinoma: relationships with clinical factors and independent prognostic value.

INTRODUCTION: Surrogate markers of the host immune response are not currently included in AJCC staging for Merkel cell carcinoma (MCC), and have not been consistently associated with clinical outcomes. We performed an analysis of a large national database to investigate tumor infiltrating lymphocyte (TIL) grade as an independent predictor of overall survival (OS) for patients with MCC and to characterize the relationship between TIL grade and other clinical prognostic factors. MATERIAL AND METHODS: The NCDB was queried for patients with resected, non-metastatic MCC with known TIL grade (absent, non-brisk and brisk). Multivariable Cox regression modeling was performed to define TIL grade as a predictor of OS adjusting for other relevant clinical factors. Multinomial, multivariable logistic regression was performed to characterize the relationship between TIL grade and other clinical prognostic factors. Multiple imputation was performed to account for missing data bias. RESULTS: Both brisk (HR 0.55, CI 0.36-0.83) and non-brisk (HR 0.77, CI 0.60-0.98) were associated with decreased adjusted hazard of death relative to absent TIL grade. Adverse clinical factors such as 1-3 positive lymph nodes, lymphovascular invasion (LVI) and immunosuppression were associated with increased likelihood of non-brisk TIL relative to absent TIL grade (p values <.05). Extracapsular extension (ECS) was associated with decreased likelihood of brisk TIL relative to absent TIL grade (p<.05). DISCUSSION: Histopathologic TIL grade was independently predictive for OS in this large national cohort. Significant differences in the likelihood of non-brisk or brisk TIL relative to absent grade were present with regards to LVI, ECS and immune status. TIL grade may be a useful prognostic factor to consider in addition to more granular characterization of TIL morphology and immunophenotype.

The effect of omission of adjuvant radiotherapy after neoadjuvant chemotherapy and breast conserving surgery with a pathologic complete response.

OBJECTIVE(S): Neoadjuvant chemotherapy (NAC) is a standard of care for locally advanced breast cancers. Adjuvant radiotherapy (RT) after NAC is an area of active research. We hypothesize overall survival (OS) is not altered by omitting RT in women with a pathologic complete response (pCR) to NAC after breast conserving survery (BCS). METHODS: Patients from the National Cancer Database who underwent NAC, BCS, and had a pCR were included. Inflammatory disease, <6 months follow up, and unknown variables were excluded. Descriptive statistics characterized the retained cohort. Logistic regression analyzed the influence of variables on the rate of RT omission. Cox proportional hazard modeling analyzed the influence of prognostic variables on OS. RESULTS: Of 5383 women included, 364 (7%) omitted RT. 5-year OS was 94.1% with RT, 93% without. RT omission was most likely in women >70yo (adjusted OR2.4, 95%CI 1.58-3.65, p < .0001;reference 40-49 yo), Hispanic (AOR 1.73, 95%CI 1.19-2.52, p = .0044; reference non-Hispanic), ≥20 miles from treatment facility (20-49 miles; AOR 1.45, 95%CI 1.09-1.93, p = .0109: >50 miles; AOR 2.02, 95%CI 1.42-2.87, p < .0001;reference 0-19 miles), grade 1 (AOR 4.29, 95%CI 2.16-8.51, p < .0001; reference grade 3), and clinical T4 disease (AOR 3.17, 95%CI 1.74-5.79, p = .0002; reference T0/1). Women ≥60yo (60-69: AHR 2.33, 95%CI 1.41-3.83, p = .0009:70+:AHR 2.4, 95%CI 1.24-4.62, p = .0092; reference 40-49) and with N1 and N3 disease (N1: AHR 1.67, 95% CI 2.28-3.24, p = .0034; N3: AHR3.37,95%CI2.01-5.65,p < .0001) showed increased death. Triple-positive (AHR 0.18, 95%CI 0.07-0.43, p = .0002) and HER2+ patients (AHR 0.44, 95%CI 0.30-0.64, p < .0001) had improved OS compared to triple-negative disease. No survival difference was seen with omission of RT (log-rank test: p = .1783; Cox model AHR 1.33, 95%CI 0.76-2.31, p = .3181). CONCLUSION: Women ≥70, of Hispanic origin, living ≥20 miles from treatment facility, and grade 1 disease were more likely to omit RT. HER2+ patients had favorable OS, while older age and N3 disease were negative prognostic factors. Omitting RT after a pCR to NAC and BCS was not found to affect OS.

Immune status and the efficacy of radiotherapy on overall survival for patients with localized Merkel cell carcinoma: An analysis of the National Cancer Database.

BACKGROUND: Immunosuppressed (IS) patients with Merkel cell carcinoma (MCC) have worse outcomes compared to immunocompetent (IC) patients, and it is unclear if adjuvant radiotherapy (RT) is beneficial for these patients. We sought to determine the effect of immune status on adjuvant RT efficacy regarding overall survival (OS) for patients with localized MCC. METHODS: This was an observational study of National Cancer Database (NCDB) identifying patients with stage I/II or III MCC with known immune status diagnosed from 2010 to 2014. The median follow-up time was 29 months. OS was described using Kaplan-Meier methods and compared for subgroups by immune status and adjuvant RT using log-rank tests, multivariable Cox regression and interaction effect testing. RESULTS: A total of 2049 IC and 255 IS patients were included. Adjuvant RT was associated with decreased hazard of death for stage I/II MCC (HR 0.65, CI 0.54-0.78) adjusting for factors including immune status. Interaction effect testing did not demonstrate a significant difference in the effect of adjuvant RT on OS between IC and IS status in either stage I/II or III MCC (both P values > 0.05). CONCLUSIONS: In this observational study, adjuvant RT was associated with decreased hazard of death for patients with stage I/II MCC regardless of immune status. Adjuvant RT should be considered for both IS and IC patients with localized MCC.

Extrapulmonary small cell carcinoma: Prognostic factors, patterns of care, and overall survival.

BACKGROUND: Extrapulmonary small cell carcinoma is a rare malignancy with scarce data. Treatment paradigms extrapolate from pulmonary small cell carcinoma and single institution studies. We analyzed the epidemiology, patterns of care, prognostic factors, and overall survival (OS) of EPSCC patients. METHODS: The cohort included EPSCC. Patients with <2 months follow-up, unknown demographic/treatment variables were excluded. Descriptive statistics were performed to characterize the cohort. Kaplan-Meier methods were used to estimate OS. Cox proportional hazard modeling was done to analyze the influence of prognostic variables on OS. RESULTS: 5747 patients were included. Median OS was 1.2 years. Head and neck (HR: 0.60, 95% CI 0.53-0.67, p < 0.0001) and breast (HR: 0.69, 95% CI 0.53-0.89, p = .0046) were associated with improved OS; gastrointestinal (HR: 1.19, 95% CI 1.09-1.29, p < .0001) worse OS; and gynecologic (HR: 1.04, 95% CI 0.92-1.17, p = .5660) showing no difference, all compared to genitourinary (reference). Surgery was associated with improved overall survival (HR: 0.84, 95% CI 0.79-0.91, p=<.0001). Chemoradiation showed a decreased HR (HR: 0.91, 95% CI 0.83-0.99, p = .0363) when compared to chemotherapy alone (reference). CONCLUSION: EPSCC occurs throughout the body with poor survival. Anatomic subsite was predictive for survival. Surgical resection may improve survival. Concurrent chemoradiation appears to improve survival over chemotherapy alone.

Stereotactic radiosurgery for central neurocytomas: an international multicenter retrospective cohort study.

OBJECTIVE: Central neurocytomas (CNs) are uncommon intraventricular tumors, and their rarity renders the risk-to-benefit profile of stereotactic radiosurgery (SRS) unknown. The aim of this multicenter, retrospective cohort study was to evaluate the outcomes of SRS for CNs and identify predictive factors. METHODS: The authors retrospectively analyzed a cohort of patients with CNs treated with SRS at 10 centers between 1994 and 2018. Tumor recurrences were classified as local or distant. Adverse radiation effects (AREs) and the need for a CSF shunt were also evaluated. RESULTS: The study cohort comprised 60 patients (median age 30 years), 92% of whom had undergone prior resection or biopsy and 8% received their diagnosis based on imaging alone. The median tumor volume and margin dose were 5.9 cm3 and 13 Gy, respectively. After a median clinical follow-up of 61 months, post-SRS tumor recurrence occurred in 8 patients (13%). The 5- and 10-year local tumor control rates were 93% and 87%, respectively. The 5- and 10-year progression-free survival rates were 89% and 80%, respectively. AREs were observed in 4 patients (7%), but only 1 was symptomatic (2%). Two patients underwent post-SRS tumor resection (3%). Prior radiotherapy was a predictor of distant tumor recurrence (p = 0.044). Larger tumor volume was associated with pre-SRS shunt surgery (p = 0.022). CONCLUSIONS: Treatment of appropriately selected CNs with SRS achieves good tumor control rates with a reasonable complication profile. Distant tumor recurrence and dissemination were observed in a small proportion of patients, which underscores the importance of close post-SRS surveillance of CN patients. Patients with larger CNs are more likely to require shunt surgery before SRS.