Definitive Radiotherapy is a Viable Treatment for Locally Advanced Basal Cell Carcinoma Otherwise Requiring Radical or Disfiguring Resection.

BACKGROUND: Standard treatment for basal cell carcinoma (BCC) is surgical resection. However, a subset of locally advanced BCCs may be unresectable, or surgery would result in unacceptable functional or cosmetic defects. Outcomes after definitive radiotherapy for locally advanced BCC in the contemporary era are not well established. OBJECTIVE: We sought to determine locoregional control and disease specific survival after definitive radiotherapy for locally advanced BCC. METHODS: Patients with locally advanced BCC treated with definitive radiotherapy between 2005-2020 from 4 academic tertiary care institutions were included. Locally advanced BCCs were defined as patients with unresectable disease, or locations where margin negative resection would lead to unacceptable cosmetic or functional deficit. Additionally, a set of 5 risk factors (size ≥4 cm, the presence of bone invasion, PNI, immunocompromised patient, and recurrent disease) was separately defined and outcomes were investigated. RESULTS: 608 locally advanced BCC cases were identified, of which 140 were treated with definitive radiotherapy. Median follow up was 22.9 months (1.5-207.2 months). 101 (72.1%) tumors were treated with upfront definitive radiotherapy, while 39 (27.9%) were treated for a recurrence. 5-year Kaplan-Meier estimated locoregional control was 78%. The majority of locoregional failures were local recurrences (95.5%). Larger tumor diameter was a risk factor for locoregional failure (p=0.045), while recurrent disease was not (p=0.29). Cumulative incidence of BCC related mortality at 5 years was 9.5%. Patients with 0 risk factors had a 5-year FF-LRF of 92.4%, whereas those with 1+ risk factors had a 5-year FF-LRF of 68.5% (p=0.004). CONCLUSION: Definitive radiotherapy for locally advanced BCC has excellent locoregional control, with tumor size representing the only risk factor for recurrence in this study.

Intramedullary Metastases to Conus Medullaris: A Review of the Literature with a Case Illustration.

Introduction: Intramedullary metastases to the conus medullaris spinalis (IMCM) pose a rare problem in neurosurgical oncology and are usually encountered as a complicated clinical scenario in the setting of advanced systemic malignancy with poor overall survival. Despite the progress in interdisciplinary oncological care, their management remains complicated. Research Question: We performed a PRISMA-guided literature search to achieve a pooled analysis of all previously reported IMCM cases that contained detailed clinical data on this problem to investigate the currently employed management options and respective outcomes. We obtained a clinical vignette and performed a comprehensive narrative review of IMCM management. Materials and Methods: The PubMed/MEDLINE/Google Scholar, Cochrane and Embase databases were systematically searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All relevant publications retrieved were subjected to full-text analysis in detail and pertinent information was extracted. Results: The most common systemic primary tumor site as the origin of IMCM was the lung, followed by the breast. Overall, the pooled median survival was 6 months (range 0.5-36 months). Patients who received both surgery and radiation therapy had the longest overall survival (OS) (mean 9.9 months) and those who received no oncological treatment (neither surgery nor adjuvant therapy) had the shortest OS (mean 3.6 months). In cases where surgical resection was performed as part of the treatment plan for metastases, those with partial tumor resection had a more favorable neurological outcome than patients who underwent aggressive gross total resection. Conclusions: Based on the results of our analysis, we find that diligent microsurgical resection (subtotal or total) followed by radiation therapy appears as an effective and suitable treatment in select patients with IMCM. When surgery is not feasible as part of the treatment algorithm, radiation therapy alone (conventional or radiosurgery) also appears to be a suitable treatment option that confers a benefit to the patient.

Helminth-derived metabolites induce tolerogenic functional, metabolic, and transcriptional signatures in dendritic cells that attenuate experimental colitis.

Inflammatory bowel diseases (IBD) are chronic inflammatory diseases in which abdominal pain, bloody diarrhea, weight loss, and fatigue collectively result in diminished quality of patient life. The disappearance of intestinal helminth infections in Western societies is associated with an increased prevalence of IBD and other immune-mediated inflammatory diseases. Evidence indicates that helminths induce tolerogenic dendritic cells (tolDCs), which promote intestinal tolerance and attenuate intestinal inflammation characteristic of IBD, but the exact mechanism is unclear. Helminth-derived excretory-secretory (HES) products including macromolecules, proteins, and polysaccharides have been shown to modulate the antigen presenting function of DCs with down-stream effects on effector CD4 + T cells. Previous studies indicate that DCs in helminth-infected animals induce tolerance to unrelated antigens and DCs exposed to HES display phenotypic and functional features of tolDCs. Here, we identify that nonpolar metabolites (HnpM) produced by a helminth, the murine gastrointestinal nematode Heligmosomoides polygyrus bakeri (Hpb), induce tolDCs as evidenced by decreased LPS-induced TNF and increased IL-10 secretion and reduced expression of MHC-II, CD86, and CD40. Furthermore, these DCs inhibited OVA-specific CD4 + T cell proliferation and induced CD4 + Foxp3 + regulatory T cells. Adoptive transfer of HnpM-induced tolDCs attenuated DSS-induced intestinal inflammation characteristic of IBD. Mechanistically, HnpM induced metabolic and transcriptional signatures in BMDCs consistent with tolDCs. Collectively, our findings provide groundwork for further investigation into novel mechanisms regulating DC tolerance and the role of helminth secreted metabolites in attenuating intestinal inflammation associated with IBD. Summary Sentence: Metabolites produced by Heligmosomoides polygyrus induce metabolic and transcriptional changes in DCs consistent with tolDCs, and adoptive transfer of these DCs attenuated DSS-induced intestinal inflammation.

Standardizing Retrospective Observational Research in Cutaneous Squamous Cell Carcinoma: Expert Panel Guidelines from ITSCC.

Importance: Cutaneous squamous cell carcinoma (CSCC) is the second most common malignant disease in the US. Although it typically carries a good prognosis, a subset of CSCCs are highly aggressive, carrying regional and distant metastatic potential. Due to its high incidence, this aggressive subset is responsible for considerable mortality, with an overall annual mortality estimated to equal or even surpass melanoma. Despite this morbidity, CSCC is excluded from national cancer registries, making it difficult to study its epidemiology and outcomes. Therefore, the bulk of the CSCC literature is composed of single-center and multi-institutional retrospective cohort analyses. Given variations in reporting measures and analyses in these studies, interpretability between studies and the ability to pool results are limited. Objective: To define standardized reporting measures for retrospective CSCC studies. Findings: An expert panel was convened to determine standardized guidelines for recording and analyzing retrospective CSCC data. A total of 13 dermatologists and dermatologic surgeons with more than 5 years of posttraining experience and considerable experience with performing CSCC outcomes research were recruited to the panel. Consensus recommendations were achieved for CSCC retrospective study reporting measures, definitions, and analyses. Conclusions and Relevance: The recommendations in this report present the potential to standardize future CSCC retrospective studies. With such standardization, future work may have greater interstudy interpretability and allow for pooled analyses.

CD73 Is an Immunometabolic Biomarker of Poor Prognosis in Patients With Primary Cutaneous Squamous Cell Carcinoma and Hematologic Malignancy.

BACKGROUND: Impaired immunity may drive the increased incidence and aggression of cutaneous squamous cell carcinoma (cSCC) in patients with hematologic malignancy; however, precise mechanisms and prognostic biomarkers remain undefined. CD73 maintains elevated immunosuppressive adenosine levels and is associated with poor prognosis in several tumor microenvironments. OBJECTIVE: Identify poor outcome biomarkers in patients with cSCC and hematologic malignancy. MATERIALS AND METHODS: Differentially expressed genes in tumors from patients with hematologic malignancy experiencing good (n = 8) versus poor (n = 7) outcomes were identified by NanoString analysis. Results were validated at the protein level using CD73 immunohistochemistry in cSCC patients with (n = 38) and without (n = 29) hematologic malignancy. RESULTS: Forty-eight genes were differentially expressed in tumors from patients with hematologic malignancy experiencing good versus poor outcomes. CD73 gene expression was >2-fold higher in patients with poor versus good outcomes or normal skin. Significantly increased CD73 protein levels were observed in cSCC tumors with poor versus good outcomes from patients with hematologic malignancies (p < .01), whereas no differences were noted in tumors with poor versus good outcomes from patients without hematologic malignancies (p = .49). CONCLUSION: CD73 is highly expressed in poor prognosis cSCC from patients with hematologic malignancy and may represent a useful biomarker and potential therapeutic target.

Family Planning Experiences and Challenges of Mohs Fellowship Trainees.

BACKGROUND: There is a paucity of literature describing family planning challenges faced by Mohs fellows. OBJECTIVE: To characterize perceptions about and experiences with family planning, fertility, lactation, and parental leave and identify ways to support parental health and family planning for Mohs fellows. MATERIALS AND METHODS: A voluntary, anonymous survey was distributed to Mohs surgeons who recently completed fellowship. RESULTS: In total, 116 Mohs surgeons completed the survey. Their mean age was 34.5 years old, and more were female ( n = 81, 69.8%) than male ( n = 35, 30.2%). Most had children before completion of their Mohs training ( n = 73, 62.9%). The most significant barrier to having children during fellowship was "loss of education or training time." Over 20% ( n = 23) of respondents or their partner had experienced infertility. Half of the 20 respondents ( n = 10) who breastfed or pumped did not have a convenient place to do so. CONCLUSION: This study elucidates trainee perceptions and gaps in parental support for Mohs fellowship trainees. In addition, barriers to implementing a universal family planning policy in Mohs surgery are discussed.

Characteristics of Hispanic patients with nonmelanoma skin cancer undergoing Mohs micrographic surgery: a review of the literature.

BACKGROUND: Nonmelanoma skin cancer (NMSC) is the most common cancer worldwide and is frequently treated with Mohs micrographic surgery (MMS); however, data regarding characteristics of Hispanic patients undergoing MMS for NMSC are limited. OBJECTIVE: To review the characteristics of Hispanic patients undergoing MMS for NMSC in the United States. METHODS: A systematic review of PubMed articles from inception through September 2022 providing data for Hispanic patients undergoing MMS for NMSC was completed. RESULTS: Overall, six publications met inclusion criteria and provided data for 2,856 Hispanic patients that underwent MMS for 2,955 NMSCs. Results demonstrate 60% of Hispanic patients were male, and the majority of NMSCs were basal cell carcinoma (BCC) (71%), followed by squamous cell carcinoma (SCC) (21%). Additionally, a larger percentage of pigmented BCC was found in the Hispanic population. While there is conflicting data in the literature, Hispanic patients may also have larger MMS defects when controlled for additional variables. Finally, over 64% of NMSCs in Hispanic patients were in high-risk locations. CONCLUSION: Literature regarding the characteristics of Hispanic patients undergoing MMS for NMSC demonstrates most patients were male, BCC was the most common tumor subtype, and the majority of NMSCs were in high-risk locations.

Evaluating Rates of Positive Margins After Standard Excision of Cutaneous Adnexal Malignancies.

BACKGROUND: It is recommended to excise adnexal neoplasms with standard local excision or Mohs micrographic surgery (MMS), although many occur on high-risk sites such as the head and neck (H&N) and exhibit subclinical extension. Minimal evidence exists on the efficacy of standard excisions for these tumors. OBJECTIVE: To evaluate the rate of positive surgical margins after standard excision of adnexal tumors. METHODS: Retrospective cohort study of cutaneous adnexal malignancies from the National Cancer Database diagnosed from 2004 to 2019. RESULTS: The authors identified a total of 4,402 cases treated with standard excision. Tumors on the H&N were approximately twice as likely as those on the trunk and extremities (T&E) to be excised with positive margins (odds ratio 2.146, p < .001), with the highest estimated rate for eccrine adenocarcinoma (12.1%, SE: 2.3%). The subtype with the highest positive margin rate on the T&E was microcystic adnexal carcinoma (8.0%, SE: 2.9). Positive margins were associated with poorer overall survival on multivariable survival analysis (hazard ratio 1.299, p = .015). CONCLUSION: The authors present subtype- and site-specific positive margin rates for adnexal tumors treated with standard excision, which suggest that tumors on the H&N and some T&E subtypes, should be considered for MMS.

Overall Survival After Mohs Surgery for Early-Stage Merkel Cell Carcinoma.

Importance: Merkel cell carcinoma (MCC) is a rare cutaneous malignant neoplasm with increasing incidence and high mortality. Although it is accepted that the optimal treatment for localized tumors is surgical, the data surrounding the optimal surgical approach are mixed, and current National Comprehensive Cancer Network guidelines state that Mohs micrographic surgery (MMS) and wide local excision (WLE) can both be used. The current National Comprehensive Cancer Network guidelines do not advocate a preference for MMS or WLE and suggest that they can be used interchangeably. Objective: To evaluate the association of surgical approach with overall survival after excision of localized T1/T2 MCC. Design, Setting, and Participants: This retrospective cohort study used the National Cancer Database to assess adults with T1/T2 MCC who were diagnosed between January 1, 2004, and December 31, 2018, with pathologically confirmed, negative regional lymph nodes and treated with surgery. The National Cancer Database includes all reportable cases from Commission on Cancer-accredited facilities. Data analysis was performed from October 2022 to May 2023. Exposure: Surgical approach. Main Outcomes and Measures: Overall survival. Results: A total of 2313 patients (mean [SD] age, 71 [10.6] years; 1340 [57.9%] male) were included in the study. Excision with MMS had the best unadjusted survival, with mean (SE) survival rates of 87.4% (3.4%) at 3 years, 84.5% (3.9%) at 5 years, and 81.8% (4.6%) at 10 years vs 86.1% (0.9%) at 3 years, 76.9% (1.2%) at 5 years, and 60.9% (2.0%) at 10 years for patients treated with WLE. Patients treated with narrow-margin excision had similar survival as those treated with WLE, with mean (SE) survival rates of 84.8% (1.4%) at 3 years, 78.3% (1.7%) at 5 years, and 60.8% (3.6%) at 10 years. On multivariable survival analysis, excision with MMS was associated with significantly improved survival compared with WLE (hazard ratio, 0.59; 95% CI, 0.36-0.97; P = .04). High-volume MCC centers were significantly more likely to use MMS over WLE compared with other centers (odds ratio, 1.99; 95% CI, 1.63-2.44; P < .001). Conclusions and Relevance: In this cohort study, the use of MMS (compared with WLE) was associated with significantly improved survival for patients with localized MCC with pathologically confirmed negative lymph nodes treated with surgery. These data suggest that Mohs surgery may provide a more effective treatment for MCC primary tumors than conventional WLE, although the lack of randomization and potential for selection bias in this study highlight the need for future prospective work evaluating this issue.

Ablative radiotherapy improves survival but does not cure autochthonous mouse models of prostate and colorectal cancer.

BACKGROUND: Genetically engineered mouse models (GEMMs) of cancer are powerful tools to study mechanisms of disease progression and therapy response, yet little is known about how these models respond to multimodality therapy used in patients. Radiation therapy (RT) is frequently used to treat localized cancers with curative intent, delay progression of oligometastases, and palliate symptoms of metastatic disease. METHODS: Here we report the development, testing, and validation of a platform to immobilize and target tumors in mice with stereotactic ablative RT (SART). Xenograft and autochthonous tumor models were treated with hypofractionated ablative doses of radiotherapy. RESULTS: We demonstrate that hypofractionated regimens used in clinical practice can be effectively delivered in mouse models. SART alters tumor stroma and the immune environment, improves survival in GEMMs of primary prostate and colorectal cancer, and synergizes with androgen deprivation in prostate cancer. Complete pathologic responses were achieved in xenograft models, but not in GEMMs. CONCLUSIONS: While SART is capable of fully ablating xenografts, it is unable to completely eradicate disease in GEMMs, arguing that resistance to potentially curative therapy can be modeled in GEMMs.

Mice can be used to model the types of cancer seen in people to investigate the effects of cancer therapies, such as radiation. Here, we apply radiation therapy treatments that are able to cure cancer in humans to mice that have cancer of the prostate or colorectum. We show that the mice do not experience many side effects and that the tumours reduce in size, but in some cases show progression after treatment. Our study demonstrates that mice can be used to better understand how human cancers respond to radiation treatment, which can lead to the development of improved treatments and treatment schedules.

Defining and quantifying histopathologic risk factors for regional and distant metastases in a large cohort of vulvar squamous cell carcinomas.

BACKGROUND: Vulvar squamous cell carcinoma (vSCC) is a rare tumor with a good prognosis when treated at a localized stage. However, once regional/distant metastasis occurs, vSCC can be rapidly fatal. Thus, it is important to identify tumor prognostic features so that high-risk cases can be prioritized for further diagnostic workup and treatment. OBJECTIVE: To estimate the risk of regional/distant metastasis at presentation and sentinel lymph node status for vSCC based on histopathologic characteristics. METHODS: A retrospective cohort study of 15,188 adult vSCC cases from the National Cancer Database diagnosed from 2012 to 2019. RESULTS: We provide specific estimates of the risk of clinically positive nodes and metastatic disease at presentation and sentinel lymph node positivity according to tumor size, moderate/poor tumor differentiation, and lymph-vascular invasion. These histopathologic factors were all significantly associated with the tested clinical outcomes in a multivariable analysis. Moderate (hazard ratio, 1.190; P < .001) and poor differentiation (hazard ratio, 1.204; P < .001) and lymph-vascular invasion (hazard ratio, 1.465; P < .001) were also associated with significantly poorer overall survival. LIMITATIONS: Data on disease-specific survival not available in the data set. CONCLUSIONS: We demonstrate the association of the histopathologic characteristics of vSCC with clinically important outcomes. These data may provide individualized information when discussing diagnostic/treatment recommendations, particularly regarding sentinel lymph node biopsy. These data may also guide future staging and risk stratification efforts for vSCC.

Gender Differences in Clinical Practice and Medicare Reimbursement Among Mohs Surgeons.

OBJECTIVE: To evaluate Medicare reimbursement and clinical activity between male and female dermatologic surgeons. MATERIALS AND METHODS: A retrospective review of the Medicare Provider Utilization and Payment data from 2018 was performed for all dermatologists performing MMS. Provider gender, place of service, number of services, and average payment per service was recorded for all relevant procedure codes. RESULTS: Women represented 31.5% of the 2,581 surgeons who performed MMS in 2018. Women were paid significantly less than men (mean difference, -$73,033). On average, women performed 123 fewer cases than their male counterparts. When surgeons were stratified by productivity, remuneration was the same. CONCLUSION: Remuneration from CMS was disparate between male and female dermatologic surgeons, which may be attributed to submission of fewer charges by women. Further efforts are necessary to better evaluate and address causes for this discrepancy, because greater parity of opportunity and pay would greatly benefit this subspecialty of dermatology.

Assessing Rates of Positive Surgical Margins After Standard Excision of Vulvar Melanomas.

BACKGROUND: Vulvar melanoma is a rare malignancy with frequent recurrence and poor prognosis. National guidelines recommend wide local excision of these tumors with allowances for narrower margins for anatomic and functional limitations, which are common on specialty sites. There is presently a lack of data of margin positivity after standard excision of vulvar melanomas. OBJECTIVE: We aim to evaluate the rate of positive margins after standard excision of vulvar melanomas. MATERIALS AND METHODS: Retrospective cohort study of surgically excised vulvar melanomas from the NCDB diagnosed from 2004 to 2019. RESULTS: We identified a total of 2,226 cases. Across surgical approaches and tumor stages, 17.2% (Standard Error [SE]: 0.8%) of cases had positive surgical margins. Among tumor stages, T4 tumors were most commonly excised with positive margins (22.9%, SE: 1.5%). On multivariable survival analysis, excision with positive margins was associated with significantly poorer survival (Hazard Ratio 1.299, p = .015). CONCLUSION: We find that positive margin rates after standard excision of vulvar malignancies are higher than for other specialty site melanomas. Our data suggest that use of surgical approaches with complete margin assessment may improve local control and functional outcomes for patients with vulvar melanoma as they have for patients with other specialty site melanomas.

Applying Occam's Razor and Descending the Reconstructive Ladder: The Modified Cheek Advancement Flap for Reconstruction of Nasal Defects.

Nasal reconstruction has important functional and cosmetic considerations, as proper repair of nasal defects is necessary to maintain function of the nasal airway and to recreate the normal appearance of this central facial structure. Cheek advancement flaps provide matched, mobile, and highly vascularized tissue for the reconstruction of nasal defects, allowing for the concealment of incisions within natural creases in a one-stage approach. However, cheek advancement flaps are often underutilized for nasal reconstruction because of their difficulty in restoring nasal contour. We describe reconstruction of 19 nasal dorsal and sidewall defects 0.8 to 3 cm in size. We incorporated a periosteal anchoring suture to maintain/restore nasal contour and additionally removed a half standing cone inferior to the defect to prevent encroachment of the nasal ala or alar crease. All patients were evaluated at least 3 months postoperatively. In all patients, we were able to restore concavity of the nasofacial sulcus, preserve the biconvex nasal tips, prevent alar flaring and retraction, and conserve the alar groove. All patients had excellent functional and cosmetic outcomes. We believe this modified cheek advancement flap provides functionally and aesthetically superior results and can be considered as a first-line approach for repair of nasal dorsal and sidewall defects in subselected patients.