Neoadjuvant relatlimab and nivolumab in resectable melanoma.

Relatlimab and nivolumab combination immunotherapy improves progression-free survival over nivolumab monotherapy in patients with unresectable advanced melanoma1. We investigated this regimen in patients with resectable clinical stage III or oligometastatic stage IV melanoma (NCT02519322). Patients received two neoadjuvant doses (nivolumab 480 mg and relatlimab 160 mg intravenously every 4 weeks) followed by surgery, and then ten doses of adjuvant combination therapy. The primary end point was pathologic complete response (pCR) rate2. The combination resulted in 57% pCR rate and 70% overall pathologic response rate among 30 patients treated. The radiographic response rate using Response Evaluation Criteria in Solid Tumors 1.1 was 57%. No grade 3-4 immune-related adverse events were observed in the neoadjuvant setting. The 1- and 2-year recurrence-free survival rate was 100% and 92% for patients with any pathologic response, compared to 88% and 55% for patients who did not have a pathologic response (P = 0.005). Increased immune cell infiltration at baseline, and decrease in M2 macrophages during treatment, were associated with pathologic response. Our results indicate that neoadjuvant relatlimab and nivolumab induces a high pCR rate. Safety during neoadjuvant therapy is favourable compared to other combination immunotherapy regimens. These data, in combination with the results of the RELATIVITY-047 trial1, provide further confirmation of the efficacy and safety of this new immunotherapy regimen.

Impact of Cancer Care Regionalization on Patient Volume.

BACKGROUND: Cancer centers are regionalizing care to expand patient access, but the effects on patient volume are unknown. This study aimed to compare patient volumes before and after the establishment of head and neck regional care centers (HNRCCs). METHODS: This study analyzed 35,394 unique new patient visits at MD Anderson Cancer Center (MDACC) before and after the creation of HNRCCs. Univariate regression estimated the rate of increase in new patient appointments. Geospatial analysis evaluated patient origin and distribution. RESULTS: The mean new patients per year in 2006-2011 versus 2012-2017 was 2735 ± 156 patients versus 3155 ± 207 patients, including 464 ± 78 patients at HNRCCs, reflecting a 38.4 % increase in overall patient volumes. The rate of increase in new patient appointments did not differ significantly before and after HNRCCs (121.9 vs 95.8 patients/year; P = 0.519). The patients from counties near HNRCCs, showed a 210.8 % increase in appointments overall, 33.8 % of which were at an HNRCC. At the main campus exclusively, the shift in regional patients to HNRCCs coincided with a lower rate of increase in patients from the MDACC service area (33.7 vs. 11.0 patients/year; P = 0.035), but the trend was toward a greater increase in out-of-state patients (25.7 vs. 40.3 patients/year; P = 0.299). CONCLUSIONS: The creation of HNRCCs coincided with stable increases in new patient volume, and a sizeable minority of patients sought care at regional centers. Regional patients shifted to the HNRCCs, and out-of-state patient volume increased at the main campus, optimizing access for both local and out-of-state patients.

Clinical activity of checkpoint inhibitors in angiosarcoma: A retrospective cohort study.

BACKGROUND: Systemic treatments for angiosarcoma remains an area of unmet clinical need. The authors conducted this retrospective study to assess the clinical activity of checkpoint inhibitors in patients with angiosarcoma. The primary objective was to assess the objective response rate, and the secondary objective was to assess the progression-free and overall survival durations and disease control rate. METHODS: Patient data were obtained using The University of Texas MD Anderson Cancer Center Tumor Registry database. The final study population was refined to only include patients who had undergone pembrolizumab monotherapy. The objective response rate was evaluated using RECIST/irRECIST version 1.1. Progression-free survival and overall survival were defined as the time from the initiation of immunotherapy to disease progression or recurrence, death, or last follow-up and to death or last follow-up, respectively. RESULTS: The final cohort comprised 25 patients. Most patients had metastatic disease (72%) and had undergone at least two lines of systemic therapy (80%) before starting pembrolizumab. The objective response rate was 18%, whereas the disease control rate was 59%. The median progression-free survival duration was 6.2 months and was not significantly different between the cutaneous (4.7 months) and visceral angiosarcoma (6.2 months) groups (p = .42). The median overall survival duration was 72.6 months. Toxicities were recorded for eight patients, with fatigue, anemia, constipation, and rash being the most common. CONCLUSIONS: Pembrolizumab shows durable clinical activity in angiosarcoma. These findings suggest that checkpoint inhibition as monotherapy or combination therapy is likely to have a high probability of success.© 2022 American Cancer Society. LAY SUMMARY: This is the largest retrospective study to assess the clinical activity of checkpoint inhibitor monotherapy in angiosarcomas. The study includes an adequate number of patients with visceral angiosarcoma that enabled to obtain meaningful clinical insights that were previously unavailable. Our findings indicate an improvement in progression-free survival with pembrolizumab that is comparable to other active agents in angiosarcoma. Pembrolizumab monotherapy in angiosarcomas also has a favorable tolerability profile. Our findings emphasize the need for prospective studies to evaluate the activity of pembrolizumab monotherapy and combination therapy.

COVID-19 infection and its consequences among surgical oncology patients: A systematic analysis, meta-analysis and meta-regression.

We conducted this meta-analysis to address the outcomes in cancer patients after oncologic surgery during COVID-19 pandemic. The primary endpoint was the COVID-19-related mortality rate. Higher body mass index was significantly and negatively associated with higher all-cause mortality and in-hospital COVID-19 infection rates. Male sex, preoperative respiratory disease, and smoking history were positively and significantly associated with increased all-cause mortality rates. Furthermore, male sex was positively and significantly associated with the COVID-19 infection rate.

Determinants of patient-reported xerostomia among long-term oropharyngeal cancer survivors.

BACKGROUND: This study was conducted to identify clinicodemographic risk factors for xerostomia among long-term oropharyngeal cancer (OPC) survivors. METHODS: This cross-sectional study included 906 disease-free, adult OPC survivors with a median survival duration at the time of survey of 6 years (range, 1-16 years); self-reported xerostomia scores were available for 877 participants. Study participants had completed curative treatment between January 2000 and December 2013 and responded to a survey administered from September 2015 to July 2016. The primary outcome variable was cancer patient-reported xerostomia measured with the MD Anderson Symptom Inventory Head and Neck Cancer Module. Clinicodemographic risk factors for moderate to severe xerostomia were identified via multivariable logistic regression. RESULTS: Moderate to severe xerostomia was reported by 343 of the respondents (39.1%). Female sex (odds ratio [OR], 1.82; 95% CI, 1.22-2.71; P = .003; Bayesian false-discovery probability [BFDP] = 0.568), high school or lower education (OR, 1.73; 95% CI, 1.19-2.52; P = .004; BFDP = 0.636), and current cigarette smoking at the time of survey (OR, 2.56; 95% CI, 1.19-5.47; P = .016; BFDP = 0.800) were risk factors for moderate to severe xerostomia, and bilateral intensity-modulated radiotherapy (IMRT) combined with proton therapy and ipsilateral IMRT were protective. CONCLUSIONS: In this large xerostomia study, modern radiotherapy was a protective factor, and continued cigarette smoking at the time of survey, female sex, and high school or lower education were identified as other contributing risk factors associated with moderate to severe xerostomia. Importantly, these findings need to be confirmed in prospective studies. These results can inform future research and targeted patient-centered interventions to monitor and manage radiation therapy-associated xerostomia and preserve quality of life among patients with OPC.

Elective neck dissection versus observation in patients with head and neck cutaneous squamous cell carcinoma.

BACKGROUND: The survival benefit of elective neck dissection (END) for patients with cutaneous squamous cell carcinoma (cSCC) of the head and neck and no evidence of regional metastasis (cN0) has never been reported. The aim of this study was to determine the effect of END on patient survival. METHODS: The authors included patients with head and neck cSCC who had undergone primary surgery from 1995 to 2017. The primary end point was survival, and the secondary end points were the incidence of occult regional disease and regional disease control. To assess the impact of END on survival, the authors used multivariable Cox proportional hazards models with propensity score and matching techniques for internal validation. RESULTS: A total of 1111 patients presented with no evidence of nodal disease; 173 had END, and 938 were observed. Adjuvant radiotherapy to the neck was administered to 101 patients (9%). END resulted in a 5-year overall survival rate of 52%, whereas the rate was 63% in the observation group (P = .003 [log-rank]). The 5-year disease-free survival rate for patients undergoing END was similar to that for the observation group (73% vs 75%; P = .429). A multivariate regression model showed that the performance of END was not associated with improved rates of overall, disease-specific, or disease-free survival; similarly, among patients with advanced disease (T3-4), those who underwent END did not have improved survival rates. CONCLUSIONS: Among patients with cSCC of the head and neck, observation of the neck nodes resulted in noninferior survival rates in comparison with END at the time of primary surgery. Further studies are required to elucidate the role of END in patients with advanced disease.

Inclusion of extranodal extension in the lymph node classification of cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: The prognostic performance of the recently updated American Joint Committee on Cancer lymph node classification of cutaneous head and neck squamous cell carcinoma (HNSCC) has not been validated. The objective of this study was to assess the prognostic role of extranodal extension (ENE) in cutaneous HNSCC. METHODS: This was a retrospective analysis of 1258 patients with cutaneous HNSCC who underwent surgery with or without adjuvant therapy between 1995 and 2019 at The University of Texas MD Anderson Cancer Center. The primary outcome was disease-specific survival (DSS). Local, regional, and distant metastases-free survival were secondary outcomes. Recursive partitioning analysis (RPA) and a Cox proportional hazards regression model were used to assess the fitness of staging models. RESULTS: No significant differences in 5-year DSS were observed between patients with pathologic lymph node-negative (pN0) disease (67.4%) and those with pN-positive/ENE-negative disease (68.2%; hazard ratio, 1.02; 95% CI, 0.61-1.79) or between patients with pN-positive/ENE-negative disease and those with pN-positive/ENE-positive disease (52.7%; hazard ratio, 0.57; 95% CI, 0.31-1.01). The RPA-derived model achieved better stratification between high-risk patients (category III, ENE-positive with >2 positive lymph nodes) and low-risk patients (category I, pN0; category II, ENE-positive/pN1 and ENE-negative with >2 positive lymph nodes). The performance of the RPA-derived model was better than that of the pathologic TNM classification (Akaike information criterion score, 1167 compared with 1176; Bayesian information criterion score, 1175 compared with 1195). CONCLUSIONS: The number of metastatic lymph nodes and the presence of ENE are independent prognostic factors for DSS in cutaneous HNSCC, and incorporation of these factors in staging systems improves the performance of the American Joint Committee on Cancer lymph node classification.

Nodal Recurrence is a Primary Driver of Early Relapse for Patients with Sentinel Lymph Node-Positive Melanoma in the Modern Therapeutic Era.

BACKGROUND: Management of patients with sentinel lymph node (SLN)-positive melanoma has changed dramatically over the last few years such that completion lymph node dissection (CLND) has become uncommon, and many patients receive adjuvant immunotherapy or targeted therapy. This study seeks to characterize patterns and predictors of early recurrence in this setting. PATIENTS AND METHODS: All patients with primary cutaneous melanoma undergoing sentinel lymph node biopsy (SLNB) between 3/2016 and 12/2019 were identified. The subset with a positive SLN who did not undergo CLND were examined for further analysis of outcomes and predictors of recurrence. RESULTS: Overall, 215 patients with SLN-positive melanoma who did not have CLND were identified. Adjuvant systemic therapy was administered to 102 (47%), with 93% of this subset receiving immunotherapy (n = 95). Median follow-up from SLNB was 20 months (IQR 12-28.5 months), and 57 patients (27%) recurred during this time. The SLN basin was the most common site of recurrence (n = 38, 67% of recurrence), with isolated nodal recurrence being the most common first site of recurrent disease (n = 22, 39% of recurrence). On multivariable analysis, lymphovascular invasion (LVI) of the primary tumor, two or more involved nodes, and > 1 mm nodal deposit were independently associated with higher rates of nodal relapse. CONCLUSIONS: Nodal recurrence is a primary driver of early disease relapse for patients with SLN-positive melanoma who do not undergo CLND in the era of effective adjuvant systemic therapy. LVI, ≥ 2 nodes, or > 1 mm nodal disease identifies patients at particularly high risk of nodal relapse.

Association between postoperative complications and long-term oncologic outcomes following total laryngectomy: 10-year experience at MD Anderson Cancer Center.

BACKGROUND: Postoperative complications are an independent predictor of poor survival across several tumors. However, there is limited literature on the association between postoperative morbidity and long-term survival following total laryngectomy (TL) for cancer. METHODS: We conducted a retrospective review of all TL patients at a single institution from 2008 to 2013. Demographic and clinical data were collected and analyzed, including postsurgical outcomes, which were classified using the Clavien-Dindo system. Multivariable Cox regression analyses were performed to identify factors associated with overall survival (OS) and disease-free survival (DFS). RESULTS: A total of 362 patients were identified. The mean age was 64 years, and the majority of patients were male (81%). The median follow-up interval was 21 months. Fifty-seven percent of patients had received preoperative radiation, and 40% had received preoperative chemotherapy. Fifty-seven percent of patients underwent salvage TL, and 60% underwent advanced reconstruction (45% free flap and 15% pedicled flap). A total of 136 patients (37.6%) developed postoperative complications, 92 (25.4%) of which were major. Multivariable modeling demonstrated that postoperative complications independently predicted shorter OS (hazard ratio [HR], 1.50; 95% CI, 1.16-1.96; P = .002) and DFS (HR, 1.36; 95% CI, 1.05-1.76; P = .021). Other independent negative predictors of OS and DFS included positive lymph node status, preoperative chemotherapy, comorbidity grade, and delayed adjuvant therapy. Severity of complication and reason for TL (salvage vs primary) were not shown to be predictive of OS or DFS. CONCLUSION: Postoperative complications are associated with worse long-term OS and DFS relative to uncomplicated cases. Patient optimization and timely management of postoperative complications may play a critical role in long-term survival.

Magnifying glass on spiradenoma and cylindroma histogenesis and tumorigenesis using systematic transcriptome analysis.

Spiradenoma and cylindroma are related sweat gland tumors. To delineate their histogenesis, gene profiles, and their potential drivers, we performed a whole-transcriptome sequencing analysis of fourteen samples of spiradenoma/cylindroma in comparison to normal samples. A total of 12 spiradenomas, 5 cylindromas, 3 hybrid spiradenomas/cylindromas and 2 adnexal carcinomas were included in this study. 1335 characteristic genes and transcripts expressed over all 14 spiradenoma/cylindroma tumors were identified, and two groups of expression profiles were observed. Highest upregulated top 7 gene signatures characterized benign tumors with developmental and differentiation related genes, and carcinomas with top 7 genes mainly related to signaling, reorganization and metabolism of membranes. Immunohistochemistry of protein expressions validated 4 upregulated genes (ODAM, HOXB13, MYB and SOX10) considered important and as potential biomarkers for spiradenomas and cylindromas. We further compared the transcriptome of eccrine adnexal tumors with the transcriptome of adenoid cystic carcinoma (ACC) to identify the overlapping genes that may indicate histogenesis. There were 36 specific genes overlapping between adnexal carcinomas and the epithelial-dominant subtype of ACC, and 27 specific genes overlapping benign adnexal tumors with the myoepithelial-dominant subtype of ACC, At this point there is no known specific biomarker to aid in the diagnosis of eccrine spiradenoma and cylindroma in small samples or biopsies within the context of morphological overlap with ACC. In conclusion, spiradenomas and cylindromas are characterized by overexpressed developmental genes, where LHX2 and activated WNT signaling possibly drive associated carcinomas.

Extrathyroidal Extension: Does Strap Muscle Invasion Alone Influence Recurrence and Survival in Patients with Differentiated Thyroid Cancer?

BACKGROUND: According to the 8th edition American Joint Committee on Cancer staging system, extrathyroidal extension (ETE) and primary tumor size remain the principle determinants of T stage. However, impact of gross ETE into strap muscles on survival remains controversial. PATIENTS AND METHODS: A retrospective review of 2084 patients with ≤ 4 cm nonmetastatic differentiated thyroid cancer who underwent surgery between 2000 and 2015 was conducted. Patients were divided into three groups according to degree of ETE: no ETE (group 1), ETE into perithyroidal soft tissue (group 2), and gross ETE into strap muscle (group 3). Survivals were analyzed using Kaplan-Meier method and compared using log-rank test. Factors predictive of survival were analyzed using Cox proportional hazard model. RESULTS: Ten-year disease-free survival (DFS) of patients in groups 1-3 was 90, 82, and 83%, respectively (p = 0.003). On multivariate analysis, age ≥ 55 years, male sex, and pathologic N1b category predicted significantly worse DFS, while ETE into perithyroidal soft tissue or gross strap muscle invasion did not predict worse DFS. Overall survival (p = 0.957) and disease-specific survival (p =0.910) were not significantly different between the three groups. There was a statistically significant difference in locoregional recurrence-free survival between groups 1 and 2 [HR 2.02, 95% CI 1.06-3.94]. CONCLUSION: Gross strap muscle invasion may not be an important survival prognostic factor for staging purposes. Although both gross strap muscle invasion and perithyroidal soft tissue extension may be predictive for locoregional recurrence, the distinction between them may not be as important for postoperative risk stratification.

Grading Dysphagia as a Toxicity of Head and Neck Cancer: Differences in Severity Classification Based on MBS DIGEST and Clinical CTCAE Grades.

Clinician-reported toxicity grading through common terminology criteria for adverse events (CTCAE) stages dysphagia based on symptoms, diet, and tube dependence. The new dynamic imaging grade of swallowing toxicity (DIGEST) tool offers a similarly scaled five-point ordinal summary grade of pharyngeal swallowing as determined through results of a modified barium swallow (MBS) study. This study aims to inform clinicians on the similarities and differences between dysphagia severity according to clinical CTCAE and MBS-derived DIGEST grading. A cross-sectional sample of 95 MBS studies was randomly selected from a prospectively-acquired MBS database among patients treated with organ preservation strategies for head and neck cancer. MBS DIGEST and clinical CTCAE dysphagia grades were compared. DIGEST and CTCAE dysphagia grades had "fair" agreement per weighted κ of 0.358 (95% CI .231-.485). Using a threshold of DIGEST ≥ 3 as reference, CTCAE had an overall sensitivity of 0.50, specificity of 0.84, and area under the curve (AUC) of 0.67 to identify severe MBS-detected dysphagia. At less than 6 months, sensitivity was 0.72, specificity was 0.76, and AUC was 0.75 while at greater than 6 months, sensitivity was 0.22, specificity was 0.90, and AUC was 0.56 for CTCAE to detect dysphagia as determined by DIGEST. Classification of pharyngeal dysphagia on MBS using DIGEST augments our understanding of dysphagia severity according to the clinically-derived CTCAE while maintaining the simplicity of an ordinal scale. DIGEST likely complements CTCAE toxicity grading through improved specificity for physiologic dysphagia in the acute phase and improved sensitivity for dysphagia in the late-phase.

Complications, hospital length of stay, and readmission after total laryngectomy.

BACKGROUND: The purpose of this study was to describe the 30-day incidence of complications after total laryngectomy (TL) in a high-volume institution and their impact on the hospital length of stay (LOS) and readmission rates. METHODS: A retrospective cohort study of all patients who underwent TL at The University of Texas MD Anderson Cancer Center from January 1, 2010 through June 30, 2013 was conducted. The patient demographics, treatment history, LOS, and 30-day post-TL complications and readmissions were extracted from the medical record. Univariate associations were analyzed, and stepwise backward selection methods were used to fit multivariate models. RESULTS: Two hundred forty-five patients were included. Complications occurred in 83 patients (33.9%) and included 3 deaths (1.2%). Wound complications occurred in 53 patients (21.6%), and 34 were pharyngocutaneous fistulas (PCFs; 13.9% overall). Thirty-four patients (13.9%) were readmitted within 30 days. A multivariate analysis revealed the following: wound complications were associated with former (odds ratio [OR], 5.1; P = .03) and current smokers (OR, 5.8; P = .02), PCFs were associated with prior wide-field radiation (OR, 3.1; P = .01) but not prior narrow-field (larynx-only) radiation (OR, 1.4; P = .61), LOS was associated with the type of flap (P = .002) and postoperative hematomas (P = .05), and readmissions were associated with preoperative hypoalbuminemia (P = .003) and postoperative wound complications (P < .001). CONCLUSIONS: Complications occurred in approximately one-third of TL patients and particularly in patients with poor wound-healing risk factors such as prior smoking and radiation. As expected, LOS was longer among reconstructed patients. Readmission was associated with hypoalbuminemia and postoperative wound complications. These data can inform quality improvement efforts and the counseling of high-risk patients undergoing TL. Cancer 2017;123:1760-1767. © 2016 American Cancer Society.

Trans-oral robotic surgery and surgeon-performed trans-oral ultrasound for intraoperative location and excision of an isolated retropharyngeal lymph node metastasis of papillary thyroid carcinoma.

BACKGROUND: Retropharyngeal metastases are uncommon but a well-known location for regional spread of well-differentiated thyroid carcinoma (WDTC). Surgeon-performed, trans-oral ultrasound (SP-TO-US) and trans-oral robot-assisted surgical (TORS) excision represent a unique combination of technology and techniques in the treatment of isolated retropharyngeal thyroid metastases. PATIENT FINDINGS: A patient with a history of T3N1b papillary thyroid carcinoma (PTC) previously treated with total thyroidectomy, left central and lateral neck dissection, and radioactive iodine presented with progressive elevations in serum thyroglobulin (Tg) from baseline of 0.2 to 0.6 µg/L. She was found to have an isolated 2.6 cm left retropharyngeal nodal metastasis on MRI that was confirmed to be PTC on fine needle aspiration biopsy. She underwent SP-TO-US for identification of the node in the operating room immediately prior to TORS excision. There were no complications. Additional radioactive iodine was administered. Post-treatment iodine scans revealed resolution of avid uptake in left retropharynx and return of Tg to 0.2 µg/L. SUMMARY: The combination of SP-TO-US and TORS represents a novel combination of technology and technique for treatment of isolated retropharyngeal metastasis in WDTC. Trans-oral ultrasound allows for rapid localization of the lesion in relation to the adjacent neurovascular structures in the parapharynx while the robot-assisted approach affords a safe and effective dissection through the improved visualization and dexterity in a small working space. Our patient had no complications and only short-term dysphagia that resolved after temporary diet alteration. Risks and long-term morbidities associated with classical approaches to the retropharynx including trans-cervical and trans-mandibular, particularly in a previously dissected field, are avoided through this trans-oral approach. CONCLUSIONS: Retropharyngeal metastases are a known location for regional spread of WDTC and are amenable to evaluation and biopsy using TO-US by both surgical and non-surgical providers. In cases where lateral neck dissection has already been performed or when traditional transcervical or transmandibular approaches to the retropharynx represent a comparatively extensive procedure for isolated metastases, SP-TO-US and TORS are safe and effective combination for surgical management of disease.

Outcomes for Patients With Head and Neck Sarcoma Treated Curatively With Radiation Therapy and Surgery.

PURPOSE: Soft tissue sarcomas (STSs) of the head and neck (H&N) are rare malignancies that are challenging to manage. We sought to describe the outcomes of patients treated with curative intent using combined surgery and radiation therapy (RT) for H&N STS. METHODS AND MATERIALS: We performed a single-institution retrospective review of patients with nonmetastatic STS of the H&N who were treated from 1968 to 2020. The Kaplan-Meier method was used to estimate disease-specific survival (DSS) and local control (LC). Multivariable analyses (MVAs) were conducted using Cox proportional hazards model. RESULTS: One hundred ninety-two patients had a median follow-up of 82 months. Tumors arose in the neck (n = 50, 26%), paranasal sinuses (n = 36, 19%), or face (n = 23, 12%). Most patients were treated with postoperative RT (n = 134, 70%). Postoperative RT doses were higher (median, 60 Gy; preoperative dose, 50 Gy; P < .001). Treatment sequence was not associated with LC (preoperative RT, 78% [63%-88%]; postoperative RT, 75% [66%-82%]; P = .48). On MVA, positive/uncertain margin was the only variable associated with LC (hazard ratio [HR], 2.54; 95% CI, 1.34-4.82; P = .004). LC was significant on MVA (HR, 4.48; 95% CI, 2.62-7.67; P < .001) for DSS. Patients who received postoperative RT were less likely to experience a major wound complication (7.5% vs 22.4%; HR, 0.28; 95% CI, 0.11-0.68; P = .005). There was no difference in the rate of late toxicities between patients who received preoperative or postoperative RT. CONCLUSIONS: H&N STS continues to have relatively poorer LC than STS of the trunk or extremities. We found LC to be associated with DSS. Timing of RT did not impact oncologic or long-term toxicity outcomes; however, preoperative RT did increase the chance of developing a major wound complication.

Neoadjuvant Chemotherapy Alone or Combined with EGFR-Directed Targeted Therapy or Anti-PD-1 Immunotherapy for Locally Advanced Lacrimal Sac and Nasolacrimal Duct Carcinomas.

BACKGROUND/AIMS: We describe our findings in patients with locally advanced lacrimal sac and nasolacrimal duct (NLD) carcinoma who received neoadjuvant systemic therapy. METHODS: We identified patients with locally advanced primary lacrimal sac/NLD carcinoma treated with neoadjuvant systemic intravenous therapy at our institution during 2017-2019. RESULTS: The study included seven patients, four men and three women; the mean age was 60.4 years (range: 43-76). All patients had locally advanced disease with significant orbital soft tissue invasion with or without skull base invasion making eye-sparing surgery not feasible as an initial step. Three patients had poorly differentiated squamous cell carcinoma; two, invasive carcinoma with basaloid and squamous features; one, high-grade carcinoma with features suggestive of sebaceous differentiation; and one, undifferentiated carcinoma. The neoadjuvant regimens were cisplatin and docetaxel (n = 1); carboplatin and docetaxel (n = 1); paclitaxel and cetuximab (n = 1); carboplatin, paclitaxel, and cetuximab (EGFR inhibitor) (n = 2); cisplatin, docetaxel, and pembrolizumab (anti-PD-1 immunotherapy) (n = 1); and carboplatin, paclitaxel, and pembrolizumab (n = 1). All patients had radiologic disease regression, and one patient had radiologic near-complete response. After neoadjuvant therapy, all patients underwent wide local excision and adjuvant concurrent chemoradiation. Two patients had a complete pathologic response. At a median follow-up period of 13 months after chemoradiation (range, 8-54 months), all patients were alive without evidence of disease. One patient had nodal metastasis treated with lymph node dissection and adjuvant chemoradiation. CONCLUSIONS: Neoadjuvant systemic therapy can shrink tumors in patients with locally advanced primary lacrimal sac/NLD carcinoma with orbital or skull base invasion.

Durable local control with hypofractionated radiation therapy for unresectable or metastatic melanoma.

Background and purpose: As patients with advanced melanoma live longer in the context of systemic therapy advancements, better strategies for durable control of bulky tumors are needed. In this study, we evaluated if dose-escalated hypofractionated radiation therapy (HFRT) can provide durable local control and improve tumor-associated symptoms in patients with unresectable or bulky metastatic melanoma for whom stereotactic ablative radiotherapy (RT) approaches are not feasible due to tumor size or location. Materials and methods: We retrospectively reviewed 49 patients with unresectable or bulky metastatic melanoma who were treated to a total of 53 tumor targets with 12-17 fractions HFRT at our institution between 2015-2022. Clinical scenarios included: unresectable, locoregional only disease (26 %); oligometastatic disease (<3 total sites, 17 %); oligoprogressive disease (<3 sites progressing, 17 %); and aggressive palliation (>5 known sites of disease or with at least 3 sites progressing, 40 %). Results: Of the 53 HFRT targets, 91 % (n = 48) had radiographic evidence of response as defined by either stabilization (6 %, n = 3), decreased size (74 %, n = 39), or decreased FDG avidity (11 %, n = 6). Of the 43 symptomatic patients, 98 % (n = 42) had symptomatic improvement. One -year local control was 79 %, with 2-year progression-free and overall survival of 33 % and 39 % respectively. The most common acute toxicities were radiation dermatitis (16 %, n = 8) or a pain flare (14 %, n = 7). Late toxicities were uncommon and typically grade 1. Conclusion: HFRT provides favorable local control and symptomatic relief with limited toxicity in tumors not amenable to surgical resection or stereotactic ablative RT.

Immune checkpoint inhibitors for treatment of periorbital squamous cell carcinoma.

PURPOSE: To report on the outcomes of immunotherapy in patients with locally advanced periorbital squamous cell carcinoma. METHODS: We performed a retrospective chart review of seven consecutive patients with locally advanced periorbital cutaneous squamous cell carcinoma treated with anti-PD-1 immunotherapy. Treatments and therapeutic outcomes were reviewed. RESULTS: Of the seven patients, six were treated with cemiplimab, and one was treated with pembrolizumab. Five patients were treated with immunotherapy as neoadjuvant therapy before planned surgical resection; two patients received immunotherapy for treatment of advanced recurrent lesions deemed unresectable following multiple previous excisions and radiation therapy. In all seven patients, measurable clinical and/or radiologic response was observed. CONCLUSIONS: Our findings support the emerging role of anti-PD-1 immunotherapy in the management of locally advanced periorbital cutaneous squamous cell carcinoma.