Receipt Of Immunotherapy Research Articles

Disparities in Survival Outcomes Among Patients With Metastatic Melanoma in Texas: Implications for Policy and Interventions in the Era of Immune Checkpoint Inhibitors.

Disparities exist in the length and quality of survival from melanoma. This study evaluated, in a Texas cohort, patient factors associated with melanoma survival and examined if newer immune-oncologic agents extend survival compared with conventional therapies. A retrospective analysis of patients diagnosed with metastatic melanoma from 2011 to 2018 in the Texas Cancer Registry database. Multivariable Cox proportional hazard regression was used to evaluate patient characteristics associated with cancer-specific survival (CSS) and overall survival (OS). The patient cohort was then grouped based on receipt of first-line immunotherapy or other therapies. The association between receipt of immunotherapy and survival was assessed with Kaplan-Meier analysis and inverse probability treatment weighted Cox regression. There were 1372 patients with metastatic melanoma. Factors associated with increased melanoma mortality risk (CSS) included being male (HR: 1.13, 95% CI: 1.02-1.26), non-Hispanic black (HR: 1.28, 95% CI: 1.13-1.45), living in poorer counties (HR: 1.40, 95%CI: 1.20-1.64), and having multimorbidity (HR: 1.35, 95% CI: 1.05-1.74). All minority races and Hispanics had poorer OS compared with non-Hispanic Whites. Patients who received first-line immunotherapy had significantly longer median (interquartile range) survival (CSS: 27.00 [21.00 to 42.00] mo vs. 16.00 [14.00 to 19.00] mo; OS: 22.00 [17.00 to 27.00] mo vs. 12.00 [11.00 to 14.00] mo). They also had reduced mortality risk (HR for CSS: 0.80; 95% CI: 0.73-0.88; P <0.0001; HR for OS: 0.76; 95% CI: 0.69-0.83; P <0.0001) compared with the nonimmunotherapy cohort. This study showed differences in risks from melanoma survival based on patient demographic and clinical characteristics. Low socioeconomic status increased mortality risk, and first-line immunotherapy use favored survival. Health policies and tailored interventions that will promote equity in patient survival and survivorship are essential for managing metastatic melanoma.

The impact of demographics and socioeconomic status on the receipt of immunotherapy for stage III melanoma

BackgroundThere is limited data examining potential disparities in the receipt of immunotherapy among patients with stage III melanoma. MethodsWe performed a retrospective cohort review using the National Cancer Database (NCDB) including adult patients with stage III melanoma between 2004 and 2017. We compared receipt of immunotherapy based on demographic and socioeconomic factors for patients diagnosed 2004–2014 and 2016–2017, before and after FDA approval of immune checkpoint blockade. Results12,099 patients were included. The proportion of stage III patients who received immunotherapy significantly increased over time, from 24.0 % in 2004–2014 to 43.7 % in 2016–2017 (p < 0.001). There was a significant difference in patients who receive immunotherapy based on age (p < 0.001), insurance (p < 0.001), facility location (p < 0.001).On multivariable analysis, increased odds of immunotherapy receipt were found in patients with diagnosis in 2016–2017 (adjusted odds ratio (aOR) 3.3, 95 % CI 2.9–3.7), younger age (65–80 years aOR 0.43, 95 % CI 0.35–0.52), Hispanic ethnicity (aOR 1.5, 95 % CI 1.1–2.1), and private insurance (not insured aOR 0.67, 95 % CI 0.52–0.85). ConclusionsAlthough narrowing, gaps persist in the receipt of immunotherapy after FDA approval. Understanding disparities in the receipt of immunotherapy will aid in understanding barriers to treatment and ensuring patients have equitable access to advanced care.

Tumor lysate particle only vaccine (TLPO) vs. Tumor lysate particle-loaded, dendritic cell vaccine (TLPLDC) to prevent recurrence in resected stage III/IV melanoma patients: Results of a phase I/IIa trial

BackgroundThe autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is produced from dendritic cells (DC) loaded ex vivo with autologous tumor lysate (TL). TLPLDC has been shown to decrease recurrence in resected Stage III/IV melanoma patients in a Phase IIb trial. The TL particle only (TLPO) vaccine is produced by loading of yeast cell wall particles with autologous TL and direct injection allowing for in vivo DC loading. We have compared the TLPO and TLPLDC vaccines in an embedded Phase I/IIa trial of a larger Phase IIb trial of the TLPLDC vaccine. MethodsPatients rendered clinically disease-free after surgery were randomized 2:1 to receive the TLPO or TLPLDC vaccine and followed for recurrence and death. Patients had scheduled intradermal inoculations at 0, 1, 2, 6, 12, and 18 months after enrollment. Kaplan-Meier and log-rank analysis were used to compare disease-free survival (DFS) and overall survival (OS) in an intention-to-treat (ITT) analysis. ResultsSixty-three patients were randomized, 43 TLPO and 20 TLPLDC. Patients randomized to the TLPO arm were more likely to be female (37.2% vs. 10.0 %, p = 0.026), but otherwise no significant clinicopathological differences were identified. No differences in related adverse events (AE) were found between treatment arms. At a median follow-up of 20.5 months, the DFS (60.8% vs. 58.7 %, p = 0.714) and OS (94.6% vs. 93.8 %, p = 0.966) were equivalent between the TLPO and TLPLDC groups, respectively. No statistical differences were found in subgroup analyses between vaccine types, which accounted for receipt of immunotherapy and the use of G-CSF pre-blood draw. ConclusionsIn a randomized, double-blind Phase I/IIa trial, there were no differences in DFS or OS in resected Stage III/IV melanoma patients receiving adjuvant TLPO versus TLPLDC vaccines. Given manufacturing advantages, further efficacy testing of TLPO is warranted in a Phase III trial.

Outcomes of Immunotherapy in Sinonasal Mucosal Melanoma Patients With Recurrent and Metastatic Disease.

Sinonasal mucosal melanoma (SNMM) is a rare malignancy with poor prognosis and high recurrence rate. In those with recurrence, survival is dismal. Immunotherapy is an emerging area of investigation; however, there is a scarcity of data on immunotherapy outcomes in SNMM patients with recurrence. We report outcomes of immunotherapy in recurrent SNMM patients with distant versus nondistant recurrence. Fifty-four patients with recurrent SNMM were identified, and 31 (57.4%) had distant recurrence. One-year overall survival (OS) following recurrence was 47.5% (95% confidence interval [CI]: 34.0%-60.9%), with a median survival of 2.8 years (95% CI: 2.0-5.3). In those with distant recurrence, receipt of immunotherapy was associated with better OS compared to those without immunotherapy (hazard ratio [HR] = 0.29 [95% CI: 0.12-0.68], P = .004). While patients with nondistant recurrence (n = 23), who received immunotherapy (n = 6) had worse OS compared to those who did not receive immunotherapy (HR = 4.76 [95% CI: 1.36, 15.89], P = .02). LEVEL OF EVIDENCE: Level IV.

Immunotherapy in stage IV non-small cell lung cancer according to racial characteristics and community of residence.

e20621 Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer mortality worldwide. The advent of immunotherapy has transformed treatment paradigms for NSCLC. However, the use and effectiveness and immunotherapy may differ across racial groups and other sociodemographic factors, including sex, comorbidities, and community of residence. Our study analyzed disparities in immunotherapy receipt and overall survival among patients with stage IV NSCLC. Methods: Patients diagnosed with stage IV NSCLC from 2014 through 2016 were identified using the Surveillance Epidemiology, and End Results (SEER)-Medicare linked dataset. Immunotherapy receipt was compared across racial groups: non-Hispanic Whites, Blacks, Asians, Hispanics, and Native Americans. A multivariable logistic regression model evaluated associations between immunotherapy receipt and demographic and clinical variables including age, sex, marital status, Charlson comorbidity index, and histology. A multivariable Cox proportional hazards model assessed associations between these variables and overall survival. Results: Among 21,444 patients, the majority (78.6%) were White, while 10.7% were Black, 4.9% were Asian, 1.6% were Hispanic, and 0.2% were Native American. The efficacy of immunotherapy treatment was present across races, associating with better overall survival versus no immunotherapy (adjusted HR: 0.54, 95% CI: 0.49-0.59). After accounting for community of residence, race remained a significant factor in immunotherapy receipt (type 3 p-value: 0.028). Further adjustment for other covariates revealed that Black patients had significantly lower odds of receiving immunotherapy than White patients (adjusted OR: 0.64, 95% CI: 0.47-0.87). While Hispanics and Asians also had lower rates of receiving immunotherapy, these differences were not statistically significant. Asian patients exhibited higher overall survival compared to other races (adjusted HR: 0.88, 95% CI: 0.82-0.95). Conclusions: Use of immunotherapy for stage IV NSCLC is substantially lower among Blacks and other minority groups compared to Whites, indicating racial disparities in access to novel lung cancer treatments. Patients treated in urban areas are more likely to receive immunotherapy, underscoring the need to expand consistent access to efficacious treatments for advanced NSCLC. Ensuring equal access to effective treatments such as immunotherapy, regardless of race or community of residence, has the potential to improve outcomes and reduce racial disparities in lung cancer survival.

Understanding the Association Between Social Determinants of Health and Receipt of Immunotherapy for Melanoma.

In this review article, we sought to elucidate how the social determinants of health, including socioeconomic status, education, neighborhood or physical environment, access to healthcare, and race/ethnicity, affect the likelihood of receiving immunotherapy, a novel and expensive treatment for melanoma.&nbsp; Methods: The PubMed database was queried up to May 2023, for studies pertaining to health disparities in melanoma, including studies examining the utilization of immunotherapy agents for the treatment of melanoma across various social determinants of health. Disparities in the utilization of immunotherapy exist across various social determinants. A total of 10 studies were found to report on disparities in receipt of immunotherapy. These studies reported an association between insurance status, education level, socioeconomic status, as well as proximity to a cancer research center, and a lower likelihood of receiving immunotherapy. As the number of novel immunotherapy drugs grows, it is important to understand the various disparities affecting the delivery of immunotherapy across social determinants. The findings from this study can help to drive public health policy aimed at addressing inequities in the treatment of melanoma as well as other cancers.&nbsp; &nbsp; J Drugs Dermatol. 2024;23(5):311-315. doi:10.36849/JDD.7803.

Examining crossover and postprotocol therapies in first-line immunotherapy trials in non-small cell lung cancer.

Immune checkpoint inhibitor (ICI) therapy has led to significant improvement in outcomes for patients with nononcogene-driven advanced non-small cell lung cancer (NSCLC). The rate of crossover and receipt of postprotocol ICI in frontline trials for advanced NSCLC has not been systematically evaluated. ClinicalTrials.gov was used to identify phase 3 studies evaluating the use of immunotherapy or combination chemoimmunotherapy against chemotherapy alone in the frontline management of advanced NSCLC. Data on outcomes, rate of crossover and/or subsequent post-protocol receipt of immunotherapy, and the start dates of these clinical trials were then extracted. Twenty-three frontline trials in nononcogene-driven advanced NSCLC were identified. Six trials with ICI monotherapy/dual ICI therapy and 17 trials evaluating chemotherapy/ICI in first-line advanced NSCLC were included in the analysis. The crossover rate ranged 0% to 54% in ICI monotherapy/dual ICI trials and 0% to 52% in chemotherapy/ICI trials. Nineteen of 23 trials provided information on subsequent postprotocol therapies. Among the trials not allowing crossover, postprotocol ICI was administered to 17% to 45.8% of patients. Information regarding the eventual receipt of ICI therapy was available for 22 of 23 trials. Of 6631 patients, 2507 (37.8%) randomized to the control arm eventually received ICI therapy. The rate of crossover and postprotocol ICI use was low in frontline trials for first-line NSCLC incorporating ICI. Given the proven improved overall survival of ICI in a broad population, there is a need to ensure availability of this life-prolonging therapy in future trials, either by crossover treatment or postprotocol administration.

High-volume facilities are significantly more likely to use guideline-adherent systemic immunotherapy for metastatic Merkel cell carcinoma: implications for cancer care regionalization.

Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer with a high rate of mortality. While still relatively rare, the incidence of MCC has been rapidly rising in the US and around the world. Since 2017, two immunotherapeutic drugs, avelumab and pembrolizumab, have been FDA-approved for the treatment of metastatic MCC and have revolutionized outcomes for MCC. However, real-world outcomes can differ from clinical trial data, and the adoption of novel therapeutics can be gradual. We aimed to characterize the treatment practices and outcomes of patients with metastatic MCC across the US. A retrospective cohort study of adult cases of MCC in the National Cancer Database diagnosed from 2004 to 2019 was performed. Multivariable logistic regressions to determine the association of a variety of patient, tumor, and system factors with likelihood of receipt of systemic therapies were performed. Univariate Kaplan-Meier and multivariable Cox survival regressions were performed. We identified 1017 cases of metastatic MCC. From 2017 to 2019, 54.2% of patients received immunotherapy. This increased from 45.1% in 2017 to 63.0% in 2019. High-volume centers were significantly more likely to use immunotherapy (odds ratio 3.235, p = 0.002). On univariate analysis, patients receiving systemic immunotherapy had significantly improved overall survival (p < 0.001). One-, 3-, and 5-year survival was 47.2% (standard error [SE] 1.8%), 21.8% (SE 1.5%), and 16.5% (SE 1.4%), respectively, for patients who did not receive immunotherapy versus 62.7% (SE 3.5%), 34.4% (SE 3.9%), and 23.6% (SE 4.4%), respectively, for those who did (Fig. 1). In our multivariable survival regression, receipt of immunotherapy was associated with an approximately 35% reduction in hazard of death (hazard ratio 0.665, p < 0.001; 95% CI 0.548-0.808). Our results demonstrate that the real-world survival advantage of immunotherapy for metastatic MCC is similar to clinical trial data. However, many patients with metastatic disease did not receive this guideline-recommended therapy in our most recent study year, and use of immunotherapy is higher at high-volume centers. This suggests that regionalization of care to high-volume centers or dissemination of their practices, may ultimately improve patient survival.

Immunotherapy utilization in stage IIIA melanoma: less may be more.

Immunotherapy agents are approved for adjuvant treatment of stage III melanoma; however, evidence for survival benefit in early stage III disease is lacking. Current guidelines for adjuvant immunotherapy utilization in stage IIIA rely on clinician judgment, creating an opportunity for significant variation in prescribing patterns. This study aimed to characterize current immunotherapy practice variations and to compare patient outcomes for different prescribing practices in stage IIIA melanoma. Patients with melanoma diagnosed from 2015-2019 that met American Joint Committee on Cancer 8th edition criteria for stage IIIA and underwent resection were identified in the National Cancer Database. Multiple imputation by chained equations replaced missing values. Factors associated with receipt of adjuvant immunotherapy were identified. Multivariable Cox proportional hazards regression compared overall survival across groups. Of 4,432 patients included in the study, 34% received adjuvant immunotherapy. Patients had lower risk-adjusted odds of receiving immunotherapy if they were treated at an academic center (OR=0.48, 95%CI=0.33-0.72, p<0.001 vs. community facility) or at a high-volume center (OR=0.69, 0.56-0.84, p<0.001 vs. low-volume). Immunotherapy receipt was not associated with risk-adjusted survival (p=0.095). Moreover, patients treated at high-volume centers experienced longer overall risk-adjusted survival than those treated at low-volume centers (HR=0.52, 0.29-0.93, p=0.030). Risk-adjusted survival trended toward being longer at academic centers than at community centers, but the difference was not statistically significant. Academic and high-volume centers utilize significantly less adjuvant immunotherapy in stage IIIA melanoma than community and low-volume centers without compromise in overall survival. These findings suggest that this population may benefit from more judicious immunotherapy utilization.

Factors influencing receipt and time to treatment of immunotherapy relative to chemotherapy in stage III and stage IV melanoma.

Immunotherapies have changed the landscape of late-stage melanoma; however, data evaluating timely access to immunotherapy are lacking. A retrospective cohort study utilizing the National Cancer Database was conducted. Stage III and IV melanoma cases diagnosed between 2011 and 2018 that received systemic treatment with either immunotherapy or chemotherapy were included. Chemotherapy included BRAF/MEK inhibitors. Multivariable logistic regression models were utilized to evaluate factors associated with the likelihood of receiving immunotherapy as primary systemic treatment relative to chemotherapy; additionally, Cox proportional hazards models were utilized to incorporate time from diagnosis to primary systemic therapy into the analysis. The study population was comprised of 14,446 cases. The cohort included 12,053 (83.4%) immunotherapy and 2393 (16.6%) chemotherapy cases. In multivariable logistic regression analysis, factors significantly associated with immunotherapy receipt included population density, circle distance, year of diagnosis, Breslow thickness, and cancer stage. Immunotherapy timing was evaluated using multivariable Cox regression analysis. Minorities were less likely to receive timely immunotherapy than non-Hispanic Whites (HR 0.83, CI 0.74-0.93, p = 0.001). Patients at circle distances of 10-49 miles (HR 0.94, CI 0.89-0.99, p = 0.02) and ≥50 miles (HR 0.83, CI 0.77-0.90, p < 0.001) were less likely to receive timely immunotherapy. Patients traveling ≥10 miles and minorities have a decreased likelihood of receiving timely immunotherapy administration for primary systemic treatment. Future research is needed to identify what barriers and approaches can be leveraged to address these inequities.

Abstract B051: Immunotherapy treatment disparities: A TCR analysis of patients with cutaneous melanoma

Abstract Abstract Background: As the deadliest form of skin cancer, advanced-stage melanoma is a devastating disease. Encouragingly, after the introduction of systemic immunotherapy, the overall survival of metastatic melanoma has improved drastically. Immunotherapy is showing superior survival outcomes for patients with advanced stage melanoma, but access to novel immunotherapeutic drugs is not universal for all patients. Herein, we examined the association between various sociodemographic and economic factors and the likelihood of using immunotherapy for the treatment of melanoma in the state of Texas. Patients and Methods: In this retrospective cohort study, data from the Texas Cancer Registry for the years 2011-2018 was analyzed. The study population included 35963 patients, 18 years and older, diagnosed with cutaneous melanoma. As a primary study outcome, multivariable regression analysis was done to evaluate the association between patient characteristics and likelihood of receipt of immunotherapy. As secondary outcomes, the association between sociodemographic factors and likelihood of presentation with metastasis at diagnosis was examined. Finally, subgroup analysis evaluated general trends between Hispanic and non-Hispanic patients with melanoma. Results: A total of 933 patients underwent immunotherapy. Having metastasis at diagnosis was strongly associated with higher odds of receiving immunotherapy (penalized adjusted OR 28.690, 95% CI 23.470-34.350, p&amp;lt; .0001). Compared to having private insurance, patients were less likely to receive immunotherapy if they were uninsured, had Medicare, or had missing/unknown insurance status (penalized adjusted OR’s 0.700, 0.790, 0.130, p = 0.026, 0.027, and p &amp;lt; .0001 respectively). Hispanic ethnicity did not show a statistically significant association with likelihood of receipt of immunotherapy. Results from our multivariate model highlighted several factors associated with a higher likelihood of presenting with metastatic disease which included Hispanic ethnicity, black race, having no insurance, having Medicare, and belonging to the 10-20% and the 20-100% poverty level groups (p &amp;lt;0.05 for all). When compared to NHW’s, Hispanics with melanoma demonstrate a higher level of poverty, increased risk of metastasis at diagnosis, as well as higher likelihood of being uninsured and living in a border region (p &amp;lt; 0.001 for all). Conclusion: Immunotherapy has revolutionized the treatment of melanoma. As new immunotherapy drugs reach the market, disparities in utilization of immunotherapy are expected to increase. With this retrospective cohort study, we add to the growing body of evidence recognizing insurance status as a barrier to treatment with immunotherapy. Dermatologic health disparities affecting the Hispanic population underscore the importance of targeted interventions to overcome community level barriers to melanoma diagnosis and care. Finally, this study highlights the need to further evaluate different insurance types and their effect on receipt of immunotherapy. Citation Format: Fabiola G. Ramirez, Luis Alvarado, Alok Dwivedi, Jessica Chacon. Immunotherapy treatment disparities: A TCR analysis of patients with cutaneous melanoma [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B051.

Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI): One-Year Safety and Efficacy Outcomes from a Multicenter Phase I Trial

The combination of immunotherapy and single-fraction stereotactic radiosurgery (SRS) for treatment of metastatic brain disease has yielded symptomatic radiation necrosis rates as high as 20% (PMID: 29327059). Consequently, the Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI) multicenter phase I trial (registered at clinicaltrials.gov, NCT04047602) was created to address whether reduced-dose SRS can improve morbidity without compromising efficacy. In this report we present our one-year findings. Eligibility for RADREMI enrollment required brain metastases patients with: a) Histologically-confirmed primary malignancy, b) Receipt of immunotherapy within 30 days of SRS, c) 1-10 MRI-visible brain metastases, d) Estimated median survival of at least 6 months (via disease-specific graded prognostic assessment), and e) No history of whole brain radiation therapy. Reduced-dose SRS utilized 18 Gy for lesions 0-2 cm, 14 Gy for lesions 2.1-3 cm, and 12 Gy for lesions 3.1-4 cm. Symptomatic radiation necrosis was defined as imaging findings consistent with radiation necrosis combined with clinical symptoms requiring steroid administration and/or operative intervention. Local control was defined by Response Assessment in Neuro-Oncology (RANO) criteria. From December 18, 2019 to June 30, 2022, 54 lesions in 17 patients were treated on RADREMI with at least one-year of follow-up. One-year local control occurred in 52 of 54 lesions and in 15 of 17 patients, yielding control rates of 96% per lesion and 88% per patient. Radiographic radiation necrosis occurred in 2 of 54 lesions (4%). No symptomatic radiation necrosis occurred. Our findings of concurrent immunotherapy + reduced-dose SRS at one-year post-treatment revealed excellent local control (96%) with no symptomatic radiation necrosis, and minimal radiographic radiation necrosis. These results attest to the durability of the safety and efficacy of reduced-dose SRS with immunotherapy for metastatic brain disease.

Long-Term Survival in Patients with Brain-Only Metastatic Lung Cancer Undergoing Upfront Intracranial Stereotactic Radiosurgery and Definitive Treatment to the Thoracic Primary Site

To evaluate modern clinical outcomes for patients with brain-only metastatic lung cancer treated with intracranial stereotactic radiosurgery (SRS) with or without definitive treatment of the primary site. Patients with new diagnosis of lung cancer and synchronous brain-only metastatic disease treated with intracranial SRS were identified in a prospectively maintained, single institution database. Patients were stratified based on whether they did (Group A) or did not receive (Group B) definitive primary site treatment, defined by surgical resection or radiation therapy (RT) to a dose > 40 Gy. Patient demographics and treatment details were recorded. Intrathoracic, distant body, and intracranial progression, as well as overall survival (OS) and cancer-specific survival (CSS) were recorded, with 2- and 5-y rates estimated using the Kaplan-Meier method. Univariate (UVA) and multivariate analysis (MVA) were performed to determine predictors of OS. From 2008-2022, 107 patients were identified. 57 patients received definitive primary site treatment, of whom forty received upfront and seventeen received consolidative treatment at a median 9 months after diagnosis. 45 patients underwent fractionated RT to a median dose of 60 Gy (range 45-74 Gy), 9 underwent SBRT to a median dose of 50 Gy in 5 fractions (range 40-60 Gy), and 3 had lobectomy. Median follow-up was 2.7 y (A) and 1.2 y (B) (p<0.01). Median number of brain metastases was 1 (range 1-17; 82% 1-3 and 18% ≥ 4). There were no significant differences in patient age, sex, race, smoking status, histology, targetable mutations, AJCC T- or N-stage, receipt of systemic therapy, number or volume of brain metastases, neurologic deficits, or resected brain metastases between the groups. 82% (A) and 72% (B) of patients were T1-4N1-3, while 16% (A) and 24% (B) were T1-3N0. 32 (56%) patients in Group A received immunotherapy (ICI) versus 19 (38%) in Group B (p = 0.048). There were no differences in intracranial progression-free survival (PFS) (p = 0.17) or CNS-related death (p = 0.30) between groups. 2- and 5-y estimates for OS were 61.4% and 38.5% (A) versus 28.3% and 0% (B) (p = 0.002). 2- and 5-y CSS were 83.8% and 64.2% (A) versus 48.6% and 0% (B) (p = 0.002). 2- and 5-year intrathoracic PFS were 90% and 75% (A) versus 55% and 55% in (B) (p<0.01). 2- and 5-y distant body PFS were 49.3% and 32% (A) versus 17.3% and 0% (B) (p = 0.001). On UVA, definitive primary site treatment, receipt of immunotherapy, and young age were significant predictors of OS, and each of these remained significant on MVA. Definitive treatment to the thoracic primary site in patients with brain-only metastatic lung cancer after intracranial radiosurgery was associated with not only reduced rates of intrathoracic progression but also lower rates of distant systemic progression and improved overall and cancer-specific survival.

Favorable Toxicity and Local Control with Ultrahypofractionated Radiation Therapy (UH-RT) for Melanoma of the Lower Genital Tract (LGT)

To report our experience using UH-RT +/- immunotherapy (IO) in women with melanoma of the LGT. We retrospectively identified 23 patients who received UH-RT to primary tumor for vulvovaginal melanoma from 2012 to 2022. Median age was 69 years (IQR: 62-76). Stage included localized, node positive, or metastatic. 18 (78%) had tumors involving the vagina/cervix and 5 (22%) had vulvar tumors. 6 patients had c-KIT mutations; 13 patients were wild-type; 4 patients were unknown. 12 (52%) were treated at initial presentation (cohort A) and 11 (48%) at local progression/recurrence following prior therapy (cohort B). In cohort A, most (n = 11) received concurrent IO. In cohort B, 3 recurred after surgery alone, 4 after systemic therapy alone and 4 after surgery and systemic therapy. RT consisted of 6 Gy x 6 (n = 11), 6 Gy x 5 (n = 10) and 5 Gy x 5-6 (n = 2) delivered to the primary tumor + 0.5 cm margin. Patients initiated IO either ≥3 months preRT (n = 8), concurrent with RT (n = 12) or ≥3 months following RT (n = 2). 1 patient in cohort B did not receive IO. Toxicity was graded using CTCAE v 5. Overall survival (OS) was measured from end of RT. Cumulative incidence of local progression was measured from end of RT. Kaplan-Meier method and Cox regression were used for survival analyses. Landmark method was used for timing of IO. Median follow-up as determined by reverse Kaplan-Meier method was 60 months (95% CI: 37-N/A). Overall incidence of acute/late grade 2+ toxicity for the entire cohort was 34%. Grade 2 acute toxicity included: dermatitis (n = 3), urinary (n = 2), vaginitis (n = 2) and diarrhea (n = 1). 3 patients experienced grade 3 acute dermatitis. 1 patient experienced late grade 2 vaginitis. No grade 3 or 4 toxicity was noted. No significant differences in toxicity were noted between RT regimens. Local disease control was achieved in 61% of patients. Local only, local and distant, and distant-only progression were seen in 17%, 22%, and 30% of patients respectively. 2-year cumulative incidence of local progression was 33% for the whole cohort, 28% for cohort A, and 36% for cohort B (p = 0.4). On UVA, factors associated with local progression were vulvar disease (p = 0.02) and c-KIT mutation (p = 0.011). No significant difference in local control was noted based on biologic effective dose (BED10 < = 48Gy vs >48Gy) (p = 0.06). Median OS for entire cohort, cohort A, and cohort B were 46, 72, and 30 months, respectively. 2-year survival (95% CI) was 67% (50%-91%), 73% (51%-100%), and 64% (41%-99%) respectively. On UVA, non-local disease at time of RT (p = 0.016) and receipt of IO ≥3 months prior to RT (p = 0.030) had worse OS. UH-RT+/- IO for melanoma of the LGT is well-tolerated with local disease control achieved in 61% of patients. Vulvar primary and c-Kit mutations were associated with worse local control. Additional follow-up may be necessary to determine the value of dose escalation.

Pretreatment Clinical Parameters Associated with Intracranial Progression Burden Following an Initial Stereotactic Radiosurgery Course in a Multi-Institutional Brain Metastases Cohort

While brain metastasis (BM) velocity is a valuable prognostic metric at time of intracranial progression (ICP), pre-SRS risk factors for post-SRS high-burden intracranial progression (ICP) remain poorly characterized. We hypothesized that pre-SRS clinical parameters are associated with subsequent high-burden (ICP), defined as either ≥5 (ICP5) or new/progressive ≥11 BMs (ICP11). All patients completing an initial SRS course for BMs at two institutions from 1/2015-12/2020 were retrospectively identified. Patients with prior whole brain radiation therapy (WBRT) and/or BM resection were eligible. Demographic and clinical parameters were collected. ICP was defined as any radiographic concern for distant and/or in-field progression per multidisciplinary consensus. Overall survival (OS) and freedom from ICP were estimated via the Kaplan Meier method. Cox models assessed association between parameters and freedom from ICP5 and ICP11. We identified 1383 patients completed SRS, with a median follow up of 8.7 months. Patients were 54.8% female, 45.6% with KPS ≥90, and a median of 63.4 years old. Primary tumor types included non-small cell lung (48.7%), breast (14.7%), and melanoma (8.5%). 46.9% had oligometastatic disease (≤5 metastatic foci: including BMs) at SRS, and 53.4% underwent SRS for >1 BM. 10.3% of patients had undergone prior WBRT and 26.1% surgical resection. 555 patients (40.1%) experienced ICP following SRS, of whom 72.6% had 1-4, 11.5% had 5-10, and 15.9% had ≥11 new/progressive BMs. Among patients with ICP, 6-month freedom from ICP was 35.5% (95% CI: 31.1-40.5%) for those with 1-4 BMs at time of ICP, 29.7% (95% CI: 20.4-43.3%) for 5-10 BMs, and 20.5% (95% CI: 13.5-30.1%) for ≥11 BMs (p = 0.016). Respective 12-month OS rates were 56.8% (95% CI: 52.1-61.9%), 46.0% (95% CI: 35.1-60.1%), and 38.7% (95% CI: 29.4-50.9%; p<0.001). Neurologic symptoms at time of ICP were observed in 21.1% of patients with 1-4 BMs, 28.1% with 5-10 BMs, and 50.0% with new/progressive ≥11 BMs (p<0.001). On multivariable analysis, superior freedom from high-burden ICP was associated with the following pre-SRS parameters: oligometastatic burden (ICP5: HR 0.68, 95% CI: 0.47-0.99; ICP11: 0.59; 95% CI: 0.36-0.97), no prior immunotherapy (ICP11: HR 0.57, 95% CI: 0.34-0.57), and a single BM at time of initial SRS (1 vs 2 BM, ICP 5: HR 0.51, 95% CI: 0.31-0.82; ICP11: HR 0.45, 95% CI: 0.24-0.84), while primary tumor type was not associated with ICP5 or ICP11. Pre-SRS parameters including polymetastatic burden, prior receipt of immunotherapy, and >1 BM were associated with post-SRS high-burden ICP. High burden ICP developed earlier following SRS completion and was associated with higher rates of neurologic decline and inferior OS.

Association of Receipt of Systemic Treatment for Melanoma With Insurance Type in North Carolina.

Previous studies of hospital-based patients with metastatic melanoma suggest sociodemographic factors, including insurance type, may be associated with the receipt of systemic treatments. To examine whether insurance type is associated with the receipt of systemic treatment among patients with melanoma in a broad cohort of patients in North Carolina. We conducted a retrospective cohort study between 2011 and 2017 of patients with stages III-IV melanoma using data from the North Carolina Central Cancer Registry linked to Medicare, Medicaid, and private health insurance claims across the state. The primary outcome was the receipt of any systemic treatment, and the secondary outcome was the receipt of immunotherapy. A total of 372 patients met the inclusion criteria. The average age was 68 years old (interquartile range: 56-76) and 61% were male. Within the cohort 48% had Medicare only, 29% had private insurance, 12% had both Medicare and Medicaid, and 11% had Medicaid only. A total of 186 (50%) patients received systemic treatment for melanoma, 125 (67%) of whom received immunotherapy. The use of systemic therapy, including immunotherapy, increased significantly over time. Having Medicaid-only insurance was independently associated with a 45% lower likelihood of receiving any systemic treatment [0.55 (95% CI: 0.35, 0.85)] and a 43% lower likelihood of receipt of immunotherapy [0.57 (95% CI: 0.34, 0.95)] compared with private insurance. Stage III-IV melanoma patients with Medicaid-only insurance were less likely to receive systemic therapy or immunotherapy than patients with private insurance or Medicare insurance. This finding raises concerns about insurance-based disparities in treatment access.

Differences in Receipt of Immunotherapy Treatment Among Patients With Head and Neck Cancer

The US Food and Drug Administration approved immune checkpoint inhibitors (immunotherapy) for select cases of head and neck squamous cell carcinoma (HNSCC) in 2016. However, it is unclear whether there are clinical or sociodemographic differences among patients receiving immunotherapy as part of their care. Given the known disparities in head and neck cancer care, we hypothesized that there are differences in receipt of immunotherapy among patients with HNSCC based on clinical and nonclinical characteristics. To characterize clinical and nonclinical factors associated with receipt of immunotherapy among older patients with HNSCC. This retrospective cohort study included patients 65 years or older diagnosed with HNSCC (n = 4860) in a community oncology care setting. Electronic health records from Navigating Cancer were assessed from January 1, 2017, to April 30, 2022. Multivariable logistic regression was used to characterize clinical (tumor stage [localized vs advanced] and anatomical subsite [oropharyngeal vs nonoropharyngeal]) and nonclinical (age, smoking history, race and ethnicity, sex, and marital status) factors associated with receipt of immunotherapy. In the study cohort of 4860 patients, 3593 (73.9%) were men; 4230 (87.0%) were White and 630 (13.0%) were of other races. A total of 552 patients (11.4%) had received immunotherapy. After adjusting for covariates, in the final model, White patients with HNSCC had 80% increased odds of receiving immunotherapy (adjusted odds ratio [AOR], 1.80 [95% CI, 1.30-2.48]) compared with patients of other races. There were no statistically significant differences in the odds of receiving immunotherapy based on age, sex, or smoking history. Patients with nonoropharyngeal disease were significantly more likely to receive immunotherapy than those with oropharyngeal cancer (AOR, 1.29 [95% CI, 1.05-1.59]), as were those with advanced compared with local disease (AOR, 2.39 [95% CI, 1.71-3.34]). The findings of this cohort study suggest that among older patients with HNSCC, White patients may be more likely to receive immunotherapy as part of their care. Equitable access to immunotherapy and other treatment options will reduce cancer-related health disparities and improve survival of patients with HNSCC.

Omission of Completion Lymph Node Dissection in Sentinel Node Biopsy Positive Head and Neck Cutaneous Melanoma Patients.

Recent studies evaluating patients with a positive sentinel lymph node biopsy (SLNB+) show no melanoma-specific survival difference between patients undergoing lymph node basin surveillance and completion lymph node dissection (CLND). This has been broadly applied, despite underrepresentation of head and neck (HN) cutaneous melanoma patients. We evaluated whether this was upheld in the HN melanoma cohort. Patients with HN melanoma with a SLNB+ were selected from the National Cancer Database (NCDB) from 2012 to 2019. Overall survival (OS) of patients who underwent SLNB only versus SLNB + CLND were compared. Subgroup analyses were performed based on pathologic N (pN) and receipt of immunotherapy. Adjusted hazard ratio (aHR) and 95% confidence interval (CI) were calculated. Analysis of 634 patients with multivariable Cox regression showed no difference in OS in SLNB only versus SLNB + CLND cohorts (hazard ratio [HR] 1.13; 95% confidence interval [CI] 0.71-1.81; p = 0.610). Charlson-Deyo score (CDS) 1 versus 0 (HR 1.70; 95% CI 1.10-2.63; p = 0.016), pN2+ versus pN1 (HR 1.74; 95% CI 1.23-2.45; p = 0.002), and lymphovascular invasion (LVI) versus no (HR 2.07; 95% CI 1.34-3.19; p = 0.001) were associated with worse prognosis. Subgroup analysis by pN showed no OS benefit for CLND in either pN1 (HR 1.04; 95% CI 0.51-2.10; p = 0.922) or pN2+ (HR 1.31; 95% CI 0.67-2.57; p = 0.427) patients or in patients who received immunotherapy (HR 1.32; 95% CI 0.54-3.22; p = 0.549). This study of SLNB + HN melanoma patients showed no OS difference in SLNB only versus SLNB + CLND. Further studies need to be performed to better define the role of CLND.

Immunotherapy Treatment Disparities: A Texas Cancer Registry Analysis of Patients with Cutaneous Melanoma.

As the deadliest form of skin cancer, advanced-stage melanoma is a devastating disease. Encouragingly, with the introduction of immunotherapy, the overall survival of metastatic melanoma has improved drastically. However, access to novel immunotherapeutic drugs is not universal for all patients. Herein, we examined the association between various sociodemographic factors and the likelihood of using immunotherapy for melanoma treatment. This is a retrospective cohort study using the Texas Cancer Registry data for the years 2011-2018. Multivariable regression analysis was done to evaluate the association between patient characteristics and likelihood of receipt of immunotherapy. The association between sociodemographic factors and likelihood of presentation with metastasis at diagnosis was also examined. Having metastasis at diagnosis was strongly associated with higher odds of receiving immunotherapy (penalized adjusted OR 28.690, 95% CI 23.470-34.350, p < .0001). Compared to having private insurance, patients were less likely to receive immunotherapy if they were uninsured, had Medicare, or had missing/unknown insurance status (penalized adjusted OR's 0.700, 0.790, 0.130, p = .026, 0.027, and p < .0001 respectively). Results from our multivariate model highlighted several factors associated with a higher likelihood of presenting with metastatic disease which included Hispanic ethnicity and black race. Dermatologic disparities affecting the Hispanic population underscore the importance of targeted interventions to overcome community level barriers to melanoma treatment and diagnosis. This study highlights the need to further evaluate different insurance types and their effect on receipt of immunotherapy.

Immunochemotherapy or chemotherapy alone in primary central nervous system lymphoma: a National Cancer Database analysis

AbstractDebate remains over the role of rituximab, a large molecule with reduced central nervous system (CNS) penetration, in therapy for primary CNS lymphoma (PCNSL). Since 2013, the National Cancer Database has distinguished between chemotherapy and immunotherapy for frontline treatment. In this setting, rituximab would be the only standard frontline immunotherapy. We examined factors associated with the receipt of immunotherapy using a multivariate regression model for relative risk, with a random intercept to account for the hospital-specific treatment selection process. Patients were matched using a 1:1 propensity score to limit possible confounders, and overall survival (OS) was compared in the matched cohort. We identified 4691 patients with PCNSL diagnosed between 2013 and 2018. The use of immunotherapy has increased from 45% in 2013 to 76% in 2018. Immunotherapy use was associated with sociodemographic variables and local (hospital level) preference rather than clinical factors. The main factors associated with reduced use of immunotherapy included male sex, Black race or Hispanic ethnicity (compared with White non-Hispanic), HIV+ status, treatment in a lower-volume hospital, and earlier year of diagnosis. We matched 2830 patients for the survival analysis. Receipt of immunotherapy was associated with a significantly better OS (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.67-0.83). There was heterogeneity according to age, because the advantage of immunotherapy was more pronounced for patients aged ≤75 years (HR, 0.71; 95% CI, 0.63-0.80) than for those older than 75 years (HR, 0.87; 95% CI, 0.70-1.08). Overall, our findings support the current trend toward rituximab use, although a nuanced approach should be adopted when treating older patients.