Systemic Therapy Research Articles

Is pancreatic adenosquamous carcinoma (PASC) a surgical disease? A large healthcare system review

IntroductionPancreatic cancer represents an increasing cause of cancer-related deaths. Pancreatic adenosquamous carcinoma (PASC) is a rare subtype of pancreas cancer. Optimal treatment is not well-defined. This review aims to provide a detailed analysis of the natural history, management, and outcomes of the patients with PASC within a single large healthcare system. Materials and methodsA large healthcare database was used to retrospectively identify all patients with histological diagnosis of PASC from 2010 to 2020. The cohort was evaluated as a whole and according to the following management modalities: operative, non-metastatic non-operative, and patients with metastatic disease. Abstracted data included patient characteristics, oncologic characteristics at presentation, and details of surgical and non-surgical treatment. ResultsIn total, 60 patients with PASC were identified. All patients had confirmed histopathological diagnosis of PASC. Mean age at the time of diagnosis was 70.9 years, and 28 patients were male (46.7 %). Most patients presented with pancreas head tumors (60 %). Thirty-four patients presented with non-metastatic disease (56.6 %). The operative group consisted of 17 patients (28.3 %). Most patients received adjuvant systemic therapy (70.6 %). Majority of patients experienced recurrence (76.5 %), with median time to recurrence at 6.5 months. Median overall survival in the operative group was 19.1 months. Seventeen patients with non-metastatic disease (28.3 %) did not undergo resection. Median overall survival of this cohort was 3.3 months. Systemic chemotherapy was used in 8 patients. Approximately half of patients with non-metastatic disease (9/17) did not receive any treatment due to rapid physical deterioration or poor functional status at baseline. Median survival for the non-treatment group was 1.7 months. At presentation, 26 patients (43.3 %) had metastatic disease. Most common site of metastasis was the liver. Median survival for patients with metastatic disease was 3.1 months. DiscussionPASC is a distinct entity from glandular PDAC, and it appears to be a more aggressive disease process. Complete resection confers survival benefit but is not curative. Furthermore, few patients undergo surgery, even with seemingly resectable disease. Systemic therapy administration is limited in many patients due to physiologic decline. Dismal clinical course and poor survival is universal among all patients who do not undergo any treatment modality, regardless of metastatic status. Globally grim prognosis appears to be due early systemic effects, disease progression and lack of effective systemic therapy. ConclusionsPASC remains a poorly understood cancer and portends particularly poor prognosis. It is associated with a rapid clinical decline, poor response to systemic therapy, early recurrence, and poor overall survival. However, ability to treat with surgery and chemotherapy may best prolong survival. SynopsisPancreatic adenosquamous carcinoma (PASC) is a rare subtype of pancreatic cancer. In this study, we evaluated 60 patients with PASC. PASC is a systemic disease characterized by rapid clinical decline, poor response to systemic therapy, early recurrence, and poor survival. Despite resection or systemic therapy, patients succumb rapidly.

Efficacy and safety of lenvatinib combined with anti-PD-1 antibodies plus GEMOX chemotherapy as non-first-line systemic therapy in advanced gallbladder cancer

BackgroundLenvatinib, programmed cell death 1 (PD-1) antibodies, and gemcitabine and oxaliplatin (GEMOX) chemotherapy have shown significant antitumor activity as first-line therapy against biliary tract cancer. This study evaluated their efficacy and safety as non-first-line therapy in advanced gallbladder cancer (GBC).MethodsPatients with advanced GBC who received lenvatinib combined with anti-PD-1 antibodies and GEMOX chemotherapy as a non-first-line therapy were retrospectively analyzed. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR) and safety.ResultsA total of 36 patients with advanced GBC were included in this study. The median follow-up time was 11.53 (95% confidence interval (CI): 2.2–20.9) months, and the ORR was 36.1%. The median OS and PFS were 15.1 (95% CI: 3.2–26.9) and 6.1 (95% CI: 4.9–7.2) months, respectively. The disease control rate (DCR) and clinical benefit rate (CBR) were 75% and 61.1%, respectively. Subgroup analysis demonstrated that patients with programmed cell death-ligand 1 (PD-L1) expression had significantly longer PFS and OS than those without PD-L1 expression. Additionally, patients with a neutrophil–lymphocyte ratio (NLR) < 5.57 had a longer OS than those with an NLR ≥ 5.57. All patients experienced adverse events (AEs), with 61.1% experiencing grade 3 or 4 AEs, including myelosuppression (13.9%) and fatigue (13.3%), alanine transaminase or aspartate transaminase levels (8.3%), and diarrhea (8.3%). No grade 5 AEs were reported.ConclusionAnti-PD-1 antibodies combined with lenvatinib and GEMOX chemotherapy are effective and well-tolerated as a non-first-line therapy in advanced GBC. PD-L1 expression and baseline NLR may potentially predict treatment efficacy.

Cardiovascular risks of systemic corticosteroid therapy

Cardiovascular risks of systemic corticosteroid therapy

A Systematic Review of Phase II/III Trials of Hypofractionated versus Conventionally Fractionated Radiation Therapy in Stage III Non-Small Cell Lung Cancer Patients

Introduction: This systematic review evaluated whether curative intent hypofractionated radiation therapy improved survival (primary endpoint) as compared to standard conventionally fractionated radiation therapy for stage III non-small cell lung cancer (NSCLC) patients. Toxicity was also examined as a secondary endpoint. Methods: Electronic bibliographic databases were searched from 1 January 1990 to 31 March 2024. Phase II and phase III trials were included to assess survival (primary outcome) and toxicity (secondary outcome) for newly diagnosed stage III NSCLC patients. Results: Eight phase II trials (n = 349 participants), 3 randomized phase II trials (n = 382 participants), and 5 randomized phase III trials (n = 811 participants), for a total of 1542 participants, were identified. The published trials were heterogeneous, with a wide variety of dose prescriptions. A wide range of survivals (median survival 13.6 months–42.5 months) and toxicities such as grade 3 or higher esophagitis (0–42%) and grade 3 or higher pneumonitis (0–18%) were reported. Conclusions: There is no level 1 evidence to date that suggests that any hypofractionated regimen (dose escalated or not) improves survival as compared to conventionally fractionated radiation. The published phase III trials have been powered for superiority (not equivalence) for the hypofractionated arm. Toxicity with hypofractionated regimens may be similar to conventionally fractionated regimens when normal tissue radiotherapy constraints are kept within tolerance limits. It is unclear how the use of systemic therapy may negatively affect radiation toxicity with hypofractionated radiation therapy.

Effects of Tralokinumab on Clinical and Laboratory Indexes in Atopic Dermatitis: A 24-Week Real-World Study.

Background: Tralokinumab, a monoclonal anti-IL-13 antibody, is approved for treating atopic dermatitis (AD). Real-world data on its effectiveness and safety are limited. Objective: To evaluate the real-world effectiveness and safety of tralokinumab and the transition of laboratory indexes during 24-week treatment for AD patients. Methods: This retrospective study included 104 patients with moderate-to-severe AD treated with tralokinumab 300 mg every 2 weeks after primary 600 mg. Clinical and laboratory indexes were assessed until week 24. Results: At week 24, achievement rates of Eczema Area and Severity Index 75 (EASI 75), EASI 90, and investigator's global assessment 0 out of 1 in systemic therapy-naïve patients, 83.3%, 72.2%, and 44.4%, respectively, were higher than those in systemic therapy-experienced patients, 46.7%, 20.0%, and 6.7%, respectively. Serum levels of immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and lactate dehydrogenase (LDH) significantly decreased at week 24, whereas neutrophil-to-lymphocyte ratio (NLR) and systemic inflammation response index (SIRI) significantly decreased at week 12 from baseline. Twenty-nine patients (27.9%) experienced mild treatment-emergent adverse events. Conclusions: Tralokinumab treatment showed prosperous therapeutic effects and good tolerability in real-world practice for AD, with higher effectiveness in patients without prior systemic therapy compared with those with prior systemic therapy. Tralokinumab treatment significantly decreased clinical and laboratory indexes, EASI, Peak Pruritus-Numerical Rating Scale, IgE, TARC, LDH, NLR, and SIRI.

The Prognostic Significance of Tumoral Melanosis.

Tumoral melanosis (TM) is a histological term to describe a nodular aggregation of macrophages containing melanin pigment (melanophages) that is devoid of viable melanocytes. It is most often identified in skin, where it may be appreciated clinically as a pigmented lesion; however, it can also be found in other organs such as lymph nodes. The presence of TM is usually thought to signify the presence of a regressed melanoma or other pigmented tumor. Until recently, it was a relatively uncommon finding; however, with the use of effective systemic therapies against melanoma, its occurrence in histological specimens is more frequent. We identified and reviewed all histopathological diagnoses of TM at any organ site reported at a single institution from 2006 to 2018. TM cases were paired with non-TM cases of cutaneous melanoma through propensity score matching at a 1:2 ratio, and their survival outcomes were compared. The clinical outcomes examined included recurrence-free survival (RFS), distant disease-free survival (DDFS), melanoma-specific survival (MSS), and overall survival (OS). TM was reported in 79 patients. Their median age was 65 years (range 22-88), with a 2:1 male predominance (51 out of 79, 65%). The most common organ involved was the skin (67%), with a third of all cases localized to a lower limb (36%). TM had a strong association with the presence of melanoma (91%) and regression at other sites of melanoma (54%), suggesting that it is part of a systemic immune response against melanoma. Most patients with TM either previously or subsequently developed histologically confirmed melanoma in the same anatomical region as the TM (89%). Thirty-five TM patients were matched with 70 non-TM cases. Patients with melanoma who developed TM without prior regional or systemic therapy showed improved MSS (p = 0.03), whereas no statistically significant differences were observed in terms of RFS, DDFS, and OS. TM usually occurs in the context of a previous or subsequent cutaneous melanoma and is associated with improved MSS. It is important that TM is recognized by pathologists and documented in pathology reports.

Cancer Immunotherapy Trials Network 12: Pembrolizumab in HIV-Associated Kaposi Sarcoma.

Cancer Immunotherapy Trials Network 12 demonstrated safety of pembrolizumab in treating advanced cancer in people with HIV. Here, we report results of the Kaposi sarcoma (KS) cohort. In this multicenter phase I trial, we enrolled participants with HIV-associated KS on antiretroviral therapy with CD4+ ≥50 cells/μL and HIV plasma RNA <200 copies/mL. Pembrolizumab 200 mg intravenously was administered once every 3 weeks for up to 35 cycles. The primary end point was safety, and the secondary end point was KS response by modified AIDS Clinical Trials Group Criteria. Thirty-two cisgender men enrolled with baseline median CD4+ T-cell count of 274 cells/µL. All but nine participants had received previous systemic KS therapy. Participants received a median of 11 cycles of pembrolizumab (range, 1-35). Sixty-six percent had grade ≥1 treatment-emergent adverse events, including one death from polyclonal KS herpesvirus-related B-cell lymphoproliferation. Thirty-one percent had ≥one immune-mediated AEs (imAEs) with 25% requiring systemic steroids. In 29 participants with evaluable KS, the overall response rate (ORR) was 62.1% (95% CI, 42.3 to 79.3) and did not differ by CD4+ T-cell count. ORR in the eight participants with evaluable disease without previous KS therapy was 87.5% (95% CI, 47.3 to 99.7). Median duration of response (DOR) was not reached, and the Kaplan-Meier estimate of DOR of ≥12 months was 92.3% (95% CI, 56.6 to 98.8). Median progression-free survival was 28.2 months (95% CI, 4.2 to noncalculable). Pembrolizumab yielded a high rate of durable responses in HIV-associated KS. imAEs were successfully managed with standard guidelines.

Association of Participation in Medicare's Oncology Care Model With Spending, Utilization, and Quality Outcomes Among Commercially Insured and Medicare Advantage Members.

The Oncology Care Model (OCM), a value-based payment model for traditional Medicare beneficiaries with cancer, yielded total spending reductions that were outweighed by incentive payments, resulting in net losses to the Centers for Medicare & Medicaid Services. We studied whether the OCM yielded spillover effects in total episode spending, utilization, and quality among commercially insured and Medicare Advantage (MA) members, who were not targeted by the program. This observational study used administrative claims from a large national payer, yielding 157,189 total patients with commercial insurance or MA with solid malignancies who initiated 229,376 systemic anticancer therapy episodes before (2012-2015) and during (2016-2021) the OCM at 125 OCM-participating practices (a subset of total OCM practices) and a 1:10 propensity-matched set of 860 non-OCM practices. We used difference-in-differences analyses to assess the association between the OCM and total episode spending, defined as medical spending during a 6-month episode. Secondary outcomes included hospitalization and emergency department (ED) utilization and quality measures. From the pre-OCM to the OCM period, mean total episode payments increased from $45,504 in US dollars (USD) to $46,239 USD for OCM-participating practices, and increased from $50,519 USD to $58,591 USD for non-OCM practices (adjusted difference-in-differences -$6,287 USD [95% CI, -$10,076 USD to -$2,498 USD], P = .001). The OCM was associated with adjusted spending decreases for both high-risk (-$6,756 USD [95% CI, -$10,731 USD to -$2,781 USD], P = .001) and low-risk (-$4,171 USD [95% CI, -$7,799 USD to -$543 USD], P = .025) episodes. OCM-associated spending reductions were strongest for outpatient (-$5,243 USD [95% CI, -$8,589 USD to -$1,897 USD], P = .002) and infused/injected anticancer drug (-$3,031 USD [95% CI, -$5,193 USD to -$869 USD], P = .006) spending. There were no associations between OCM participation and changes in hospital or ED utilization nor quality of care. The OCM was associated with reductions in spending for nontargeted members, a spillover effect.

Tailored management of advanced thyroid cancer patients treated with lenvatinib or vandetanib: the role of a multimodal approach.

In differentiated/poorly differentiated (DTC/PDTC) or medullary thyroid cancer (MTC) treated with kinase inhibitors (KIs), additional treatments (ATs) can be performed in selected cases. We retrospectively analysed all the ATs performed in our center in KI-treated TC patients, evaluating the subsequent KI modulation, the local PD in case of loco-regional procedure (LRP) and the AT-related complications. DTC/PDTC patients with or without progressive disease before the first AT (PD and NO PD GROUP, respectively) were analysed separately. In our center, 32 ATs (30 LRPs and 2 radioactive iodine treatments) were performed in 14 DTC/PDTC patients and 4 MTC subjects after the start of systemic therapy with lenvatinib or vandetanib (27 and 5 ATs, respectively). Brain was the most treated site (11/30 LRPs) and external beam radiation was the most employed LRP (18/30 LRPs). KIs dose reduction or discontinuation of KI therapy (at least transient) was performed after 50% of ATs in DTC/PDTC NO PD GROUP. The KI was maintained at the same dosage after 75% and 50% of the ATs performed in DTC/PDTC PD GROUP and MTC, respectively. During the follow-up, local PD was detected after 14 LRPs. Local progression-free survival (LPFS) was significantly shorter in DTC/PDTC PD GROUP in comparison to NO PD GROUP (12 month-LPFS 91.7% versus 15.2%); in patients with MTC, 12 month-LPFS was 50%. AT-related AEs were mostly G1-G2. In selected DTC/PDTC without previous PD and treated with a multimodal strategy, local disease control is generally maintained regardless the KI dose modulation. In DTC/PDTC patients with previous limited PD and in MTC subjects, the choice of performing a LRP and continue the ongoing KI therapy must consider the risk of early local progression. AT-related AEs in KI treated patients were mild in most cases.

Racial disparities in hepatocellular carcinoma (HCC) treatment and survival: A SEER-Medicare analysis.

144 Background: Between 2017-2022, approved systemic therapies for HCC increased from 1 to 10. Studies have shown racial disparities in overall survival (OS), but no studies have evaluated disparities in new systemic treatments. Methods: We identified patients in SEER-Medicare data diagnosed with HCC in 2014-2019 with claims through 2020. We identified demographics, liver disease type, cirrhosis complications (e.g, jaundice), diagnosis stage, receipt of local therapies (e.g, resection) and receipt of systemic therapies (e.g, sorafenib). We described cohort characteristics by race. OS and receipt of treatment were analyzed using Cox and logistical regression models adjusted for the above covariates. Results: The study included 8,257 patients (77.7% White, 11.9% Asian, 9.1% Black, 0.9% American Indian). Median OS for all patients was 9.1 months. Compared to White patients, Black patients had worse OS (hazard ratio [HR] 1.36, p= &lt;.0001). Black patients receiving no treatment (HR 1.24, p=0.002) and local therapy first (HR 1.29, p=0.003) also had worse survival, while Black patients receiving systemic therapy first had similar OS (HR 1.08, p=0.62) to White patients. Black patients were less likely than White patients to receive any treatment (odds ratio [OR]: 0.64, p=&lt;.0001) or curative treatment if they had early stage-HCC (OR 0.49, p=0.013), but had no difference in receipt of a new systemic therapy if receiving any systemic therapy (OR 0.72, p=0.19) (Table). Compared to White patients, Asian patients had better OS among all patients (HR 0.91, p=0.04) and among patients receiving local therapy first (HR 0.89), but similar OS among patients receiving no treatment (HR 0.90, p=0.13) or systemic therapy first (HR 1.07, p=0.60). Asian patients were as likely as White patients to receive any treatment (OR 1.07, p=0.43), curative treatment for early-stage HCC (OR 0.94, p=0.70) and novel therapies if receiving systemic therapy (OR 1.10, p=0.70). Conclusions: As new HCC therapies emerged, there were racial disparities in OS and receipt of any treatment or local therapies, but not in receipt of new systemic treatments. Targeted interventions are essential to address these disparities and ensure equitable access to care. Treatment and survival disparities, by race. All PatientsN=8,218 White N=6412 Black N=747 Asian or Pacific Islander N=983 American Indian/Alaskan Native* N=76 Median Overall survival, months 9.1 9.5 5.6 10.1 8.3 No treatment, n (%) 3213 (39.1) 2510 (39.2) 348 (46.6) 330 (33.6) 25 (32.9) Systemic first, n (%) 894 (10.9) 693 (10.8) 85 (11.4) 103 (10.5) 13 (17.1) Local first, n (%) 4111 (50.0) 3209 (50.0) 314 (42.0) 550 (56.0) 38 (50.0) Of patients with early-stage HCC, those who received curative treatment, n (%) 749 (41.7) &gt;542 (&gt;41.5) 43 (29.3) 147 (45.2) &lt;11 (&lt;40.0) Of patients receiving systemic therapy, those who got a novel therapy, n (%) 763 (44.3) &gt;581 (&gt;43.9) 63 (40.9) 103 (46.0) &lt;11 (&lt;50.0)

Real-world event-free survival (rwEFS) and overall survival (rwOS) in elderly patients with resected locoregionally advanced head and neck squamous cell carcinoma (LA HNSCC) in the US.

375 Background: Surgery followed by adjuvant radiotherapy (RT) ± systemic therapy (ST) is often recommended for patients (pts) with resectable LA HNSCC with curative intent. This study assessed rwEFS, rwOS, and the correlation between rwEFS and rwOS in elderly pts (≥66 years old at diagnosis) with resected LA HNSCC to better understand unmet needs and inform future clinical trial designs. Methods: This retrospective cohort study utilized linked SEER-Medicare data (2007–2019). Pts with newly diagnosed stage III-IVB (AJCC 6/7th) LA HNSCC (larynx, hypopharynx, oral cavity, or oropharynx) who underwent surgery as primary treatment within 4 months of diagnosis were included. Index date was defined as the primary treatment initiation date. rwEFS was defined as time from index date to first recurrence or death, whichever occurred first. rwOS was defined as time from index date to death. Baseline (12 months prior to index date) factors associated with rwEFS and rwOS were assessed using a Cox proportional hazards model. Correlation between rwEFS and rwOS was assessed using the normal scores rank correlation. Results: A total of 526 pts met the selection criteria (median follow-up: 24.3 months). The median (interquartile range) age at initial diagnosis was 72.6 (68.6-78.8) years, 63.9% were male, 79.5% were white, and 6.1% had stage IVb disease. HPV status and smoking status were not available. Over half of pts received adjuvant RT ± ST following resection. Median rwEFS and 5-year rwEFS were 8.0 months (95% CI: 6.4, 9.2) and 16.3%, respectively. Median rwOS was 32.6 months (95% CI: 26.2, 42.3), with a 5-year rwOS of 37.8%. Older age, primary hypopharynx disease (vs. oropharynx), and higher Charlson Comorbidity Index scores were associated with significantly shorter rwOS. Additionally, surgery followed by RT ± ST (vs. surgery only) and less advanced tumor stage were associated with significantly longer rwEFS and rwOS. The correlation between rwEFS and rwOS was moderate and significantly positive (r = 0.68 [95% CI: 0.62, 0.74], p&lt;0.001). Conclusions: Real-world survival outcomes were modest among elderly pts with surgically managed LA HNSCC, highlighting a population with significant unmet need where more effective therapies are needed. rwEFS was found to have a significant, positive correlation with rwOS, supporting EFS as a predictor for OS in this patient population. Primary treatment and association with rwEFS and rwOS. 1,2,3 Treatment Pattern N (%) HR (95% CI) - rwEFS HR (95% CI) - rwOS Surgery Only 144 (27.4%) - - Surgery followed by RT 172 (32.7%) 0.60 (0.47, 0.78)* 0.77 (0.58, 1.03) Surgery followed by RT + ST 128 (24.3%) 0.49 (0.36, 0.66)* 0.50 (0.34, 0.72)* RT or RT+ST followed by surgery 66 (12.5%) 0.66 (0.47, 0.93)* 0.80 (0.55, 1.18) 1 Treatment modalities with N&lt;11 were not reported. 2 *denotes p &lt; 0.05. 3 denotes reference group.

Improving the assessment and documentation of systemic cancer therapy–related toxicity in the ambulatory oncology setting.

221 Background: Accurate documentation of systemic cancer therapy toxicity is crucial for patient safety and effective treatment management. However, achieving consistent and comprehensive documentation remains challenging. While the use of electronic patient-reported outcomes (ePROs) is becoming standard in clinical practice, small community-based practices lack the resources to implement this strategy. This project aims to offer alternative methods for implementing patient-reported outcomes in such practices and utilize this information to enhance the documentation of systemic cancer therapy toxicities using the CTCAE (Common Terminology Criteria for Adverse Events). Methods: We conducted a quality improvement project targeting the adequate assessment and documentation of graded toxicity assessments among healthcare providers. Interventions included implementing a patient-reported outcome survey created using the National Cancer Institute PRO-CTCAE form builder, which patients completed while waiting to be seen by the provider. Additionally, we educated providers on how to use the CTCAE grading tool available in Cerner. Rates of documented graded toxicity assessment using the CTCAE system were evaluated among 71 patients aged 18 years or older receiving systemic cancer therapy and attending follow-up appointments at the Seton Cancer Clinic. Data were collected from electronic medical records both before and after the intervention, with 50 patients assessed pre-intervention and 21 patients assessed post-intervention. Results: The implementation of the patient-reported outcome survey and the utilization of the CTCAE grading tool available in Cerner facilitated a more consistent and comprehensive assessment and documentation process. Post-intervention, the rate of documented graded toxicities increased significantly; the percentage of patients with documented graded toxicities increased from 4% pre-intervention to 80% post-intervention. The intervention also improved the workflow efficiency and the accuracy of toxicity assessments in the oncology clinic. Conclusions: These findings highlight the importance of implementing strategies to improve the assessment and documentation of systemic cancer therapy-related toxicity, especially in small community-based practices where resources may be limited. Continued monitoring and periodic data collection will be essential for sustaining these improvements.

Real World Evidence Study to Assess Incidence, Treatment Patterns, Clinical Outcomes, and Health Care Resource Utilization in Early-Stage, High-Risk HER2-Negative Breast Cancer in Alberta, Canada

BackgroundData are needed to improve the current understanding of the epidemiology of patients with high-risk, HER2-negative, early breast cancer (eBC) (hormone receptor positive [HR+]/HER2-negative BC and triple-negative BC [TNBC]). Patients and MethodsThis retrospective longitudinal cohort study used real-world, population-level data that included all individuals newly diagnosed with high-risk, HER2-negative eBC in Alberta, Canada, between 2010 and 2019. Data on treatment, laboratory results and pathology findings were collected through electronic health records and administrative databases. ResultsThe annual cumulative incidence of high-risk, HER2-negative eBC ranged from 6% to 9% of all incident BC cases. Individuals with TNBC were more likely to be younger, had stage II disease, grade 3 histology and received systemic therapy at a community centre (P < .05) compared to individuals with HR+/HER2-negative eBC. Only 14% of individuals diagnosed in 2010-2017 underwent germline BRCA testing postdiagnosis. Neoadjuvant systemic therapy was given to 37% of individuals. Adjuvant systemic therapy use increased from 77% (2012-2015) to 84% (2019). The 5-year overall survival (OS) from initiation of adjuvant systemic therapy or date of surgery (for individuals who did not receive adjuvant systemic therapy) was 77% (95% CI: 75-79). OS was significantly worse among individuals who were older, had grade 3 histology, had stage III disease, or had nodal involvement (P < .05). OS among individuals with TNBC between 2016 and 2019 who initiated adjuvant capecitabine was markedly worse compared to the overall cohort (2-year OS: 70% vs. 89%). ConclusionOutcomes analyses in this high-risk, HER2-negative eBC population suggest a continued unmet clinical need.

Real-world Use of Mogamulizumab Among Patients With Mycosis Fungoides and Sézary Syndrome Before and During COVID-19 in the United States

During the coronavirus disease 2019 (COVID-19) pandemic, professional organizations suggested extending dosing intervals for systemic cancer therapies to limit in-person visits. Mogamulizumab, indicated for adults with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after ≥1 prior systemic therapy, should be administered every 7 days of the first 28-day cycle (loading) and every 14 days of each subsequent cycle (maintenance) according to the approved prescribing information in the United States (US). This study examined the real-world use of mogamulizumab before and during the COVID-19 pandemic in the US. Using Symphony Health's Integrated Dataverse (IDV) database, adults with ≥1 diagnosis of MF or SS and ≥1 mogamulizumab claim between October 1, 2018 and December 22-, 2022 were identified. Patients in MF and SS cohorts were divided into 3 subgroups based on the date they initiated mogamulizumab treatment: pre-COVID-19 (October 1, 2018-March 31, 2020), COVID-19 Phase 1 (April 1, 2020-July 31, 2021), and COVID- 19 Phase 2 (August 1, 2021-December 22, 2022). During the study, 270 patients with MF and 337 patients with SS initiated mogamulizumab. The pre-COVID-19, COVID-19 Phase 1, and COVID-19 Phase 2 subgroups included 95, 81, and 94 patients with MF and 124, 119, and 94 patients with SS, respectively. In the MF cohort, mean loading dosing intervals were 13, 12, and 9 days for the pre-COVID-19, COVID-19 Phase 1, and COVID-19 Phase 2 subgroups, respectively, and mean maintenance dosing intervals were 16, 16, and 16 days, respectively. In the SS cohort, mean loading dosing intervals were 16, 11, and 11 days, and mean maintenance dosing intervals were 19, 18, and 16 days, respectively. For both cohorts, more patients in the COVID-19 Phase 1 and Phase 2 subgroups than in the pre-COVID-19 subgroup had gaps of ≤10 days between loading doses and ≤21 days between maintenance doses. In patients with MF and SS, loading dosing intervals in the pre-COVID-19 period were longer than the loading schedule per the approved prescribing information, but there was a trend towards closer concordance in the COVID-19 periods. Maintenance dosing intervals in patients with MF were consistently similar to the approved schedule across treatment periods, and in patients with SS became more closely aligned over time. Thus, dosing intervals for mogamulizumab in both loading and maintenance cycles do not appear to have been extended during the COVID-19 Phase 1 and Phase 2 periods compared with the pre-COVID-19 period, despite recommendations to extend dosing intervals for systemic cancer therapies during COVID-19.

Feasibility and safety of single-fraction sub-ablative radiotherapy with systemic therapy in colorectal cancer patients with ≤ 10 metastases: A multicenter pilot study (NCT05375708)

Colorectal cancer patients with ≤10 unresectable metastases were treated with single-fraction sub-ablative radiotherapy in addition to standard of care systemic therapy in a single-arm, open-label, multicenter, pilot study (SIRIUS) to assess feasibility and safety. Results indicate that radiotherapy combined with systemic therapy is feasible and safe in this population.

The time toxicity efficacy-effectiveness gap: A population-based study of stage III/IV non-small cell lung cancer (NSCLC) in Ontario, Canada.

133 Background: While patients enrolled in clinical trials tend to have superior cancer-specific outcomes relative to those in routine practice (the ‘’efficacy-effectiveness gap’’), it is unknown if this gap extends to time toxicity. While trial protocols can impose additional contact days, trial participants also tend to be healthier, perhaps needing fewer contact days. We sought to evaluate the time toxicity efficacy-effectiveness gap among patients with stage III/IV NSCLC. Methods: We created a population-based, retrospective cohort with health administrative data covering the population of Ontario, Canada (15.5 million), of adults aged ≥20 years diagnosed with stage III/IV NSCLC in 2014-2017 and died in 2014-2019, receiving palliative systemic anti-cancer drug(s) as part of a trial. We matched patients 1:1 to those who received the same drug(s) in the real world (post-approval) in the same line of treatment, and received the same total lines of therapy. We calculated contact days (days with healthcare contact outside the home) from diagnosis to death and measured overall survival. We plotted, normalized, and fitted with cubic splines the weekly percentage of contact days to obtain trajectories over the disease course. Results: We identified and matched 55 trial participants to 55 patients in routine practice. Trial participants were younger (median age, 62 vs 66 years), had fewer co-morbidities (hypertension, 35% vs 53%), and more often had de novo metastatic disease (82% vs 67%). Median lines of therapy were 2. Systemic therapy regimens most commonly included immunotherapy (n=41, 75%). Trial participants initiated systemic therapy sooner than in routine practice (median 2.0 vs 2.4 months). Trial participants had a longer overall survival (median 13.8 vs 11.6 months) and a similar number of contact days (median 79 vs 78 days). The percentage of contact days was lower in trial participants due to longer survival (median 19% vs 22%). Trial participants had similar acute/assisted institutional care contact days (median 19 vs 18 days), but more days with laboratory tests (median 23 vs 17 days), systemic therapy (median 9 vs 6 days), and radiotherapy visits (median 15 vs 11 days). Normalized trajectories for both cohorts followed a ‘’U-shape’’; the difference between the maximal peak and trough was smaller in trial participants. Conclusions: We describe a novel efficacy-effectiveness gap in time toxicity, in addition to the previously established efficacy-effectiveness gap in overall survival. Encouragingly, trial participants did not experience delays in treatment, and initiated treatments sooner than in routine practice. Among trial participants, the higher number of contact days for tests, and the shallower U-shaped curve (indicating frequent visits even when relatively well) indicate potential opportunities to decrease trial-related time toxicity.

Time to Next Systemic Therapy After Stereotactic Body Radiation Therapy for Oligoprogressive Metastatic Castrate-Resistant Prostate Cancer

Time to Next Systemic Therapy After Stereotactic Body Radiation Therapy for Oligoprogressive Metastatic Castrate-Resistant Prostate Cancer

P4.15D.02 Risk of Osteoporosis and Bone Fracture by Systemic Therapy in Lung Cancer Survivors

P4.15D.02 Risk of Osteoporosis and Bone Fracture by Systemic Therapy in Lung Cancer Survivors

Therapies for Central Serous Chorioretinopathy: A Report by the American Academy of Ophthalmology

To assess the safety and efficacy of the multiple therapeutic modalities for the treatment of central serous chorioretinopathy (CSCR). A literature search of English-language studies in the PubMed database with no date restrictions was last conducted in May 2024. The combined searches yielded 612 citations, 31 of which were selected for full-text review and for inclusion in this assessment. The panel methodologist assigned a level of evidence rating to each study. Six were assigned a level I rating, 23 were assigned a level II rating, and 2 were assigned a level III rating. Studies were categorized based on treatment modalities: laser-based therapy, intravitreal therapy, laser-based therapy versus intravitreal therapy, and systemic therapies. Within those categories, they were separated based on treatments for acute versus chronic CSCR. One level I study showed that photodynamic therapy (PDT) using half-dose verteporfin for acute CSCR led to a significant decrease in subretinal fluid (SRF) with 95% of treated patients having no SRF at 12 months compared with 58% of untreated eyes with acute CSCR (P= 0.001). Anatomically, the mean CFT at 1 year was significantly lower in the treated group (161 ± 65 μm) versus the observation group (278 ± 92 μm) (P= 0.001). A second level I study compared half-dose verteporfin PDT versus 30%-dose verteporfin PDT and found that 94.6% in the half-dose PDT group had no SRF at 12 months compared with 75.4% in the 30%-dose PDT group (P= 0.004). The noninferiority of the 30%-dose PDT compared with half-dose PDT was not demonstrated. The VICI trial was a level I study that found no benefit with the use of mineralocorticoid antagonism with eplerenone for the treatment of chronic CSCR. With respect to the primary outcome of visual acuity (VA), the VICI trial found no significant difference at 12 months: 79.5 letters in the placebo group and 80.4 letters in the eplerenone group (P= 0.24). In general, the results from the other evaluated studies were inconsistent and thus inconclusive. There were no level I studies that supported the role of intravitreal anti-VEGF injections or systemic beta-blockers for patients with CSCR. A small level I study showed potential efficacy of Helicobacter pylori therapy for CSCR. There is evidence to support half-dose PDT for the treatment of acute CSCR regarding anatomic improvement, but less robust evidence supports improvement in VA or sustained anatomic benefit beyond 12 months. Intravitreal anti-VEGF injections and oral beta-blockers demonstrate inconsistent anatomic and visual benefits in patients with CSCR. The mineralocorticoid antagonist eplerenone has not been demonstrated as efficacious for treatment of chronic CSCR. The treatment of H.pylori infection may have some anatomic and visual benefit in the treatment of either acute or chronic CSCR. Acute CSCR resolves spontaneously without treatment in most eyes. Proprietary or commercial disclosure may be found after the references.

EP.06G.12 The Fibrosis Around the Pulmonary Artery Is Associated with Difficulty in Dissection During Surgery after Systemic Therapy

EP.06G.12 The Fibrosis Around the Pulmonary Artery Is Associated with Difficulty in Dissection During Surgery after Systemic Therapy