Use Of Multimodal Therapy Research Articles

Current management practices of de novo oligometastatic breast cancer: Real-world data from a physician survey.

1104 Background: De novo oligometastatic breast cancer (oligo-mBC) is generally defined as < 5 lesions at the time of diagnosis and represent a steadily increasing subset of metastatic cancers. Several retrospective studies demonstrated prolonged overall survival (OS) for select patients with oligo-mBC when treated with multimodality therapy (chemotherapy, surgery, and radiation). However, randomized trials that tested surgical resection of the primary tumor, or radiation of oligometastases (including recurrent and de novo disease) showed no OS benefit. No randomized trials to date have tested all 3 treatment modalities combined (as used with curative intent in early-stage disease). Current NCCN guidelines do not include specific recommendations for de novo oligo-mBC, the St Gallen International guidelines allow multimodality therapy for carefully selected patients. We surveyed practicing medical oncologists through the ASCO survey pool regarding their use of multimodality therapy in de novo oligo-mBC. Methods: An online survey was sent to the ASCO Research survey pool (N=999) between 11/14/23 – 12/29/23, 193 ASCO members completed the survey. Data was confidential and anonymous. Results: The majority (76-79%) of respondents recommend starting with palliative systemic chemotherapy. If patients have a response to initial chemotherapy, 42-54% recommend ablative radiation to all residual lesions, and 38-52% recommended surgical resection of the primary tumor. Overall, multimodality therapy is recommended sometimes by 29-36%, often by 19-29%, almost never by 32-41%, and never by 2-7% of respondents. Recommendations varied by disease subtype (Table). Conclusions: These survey data indicate varied practices in the treatment of de novo oligo-mBC. This highlights the need for future randomized clinical trials to investigate whether there may be survival benefit by receptor subtype in de novo oligo-mBC treated with curative intent multimodality therapy as used in locally advanced cancers. [Table: see text]

Abstract 4822: Disparities in receiving non-surgical therapy impact outcomes in non-metastatic gastric cancer in Louisiana

Abstract Background: Given the history of evolving medical therapies and advancements in cancer treatments over the last decades, resectable gastric cancer has presented multiple strategies for care. Previous literature indicates historically decreased use of multimodal therapies in minority populations. This study aims to evaluate Louisiana patient populations for rates of definitive treatment, inequities in access to care, and evaluating its impact on the outcomes of minorities and underserved population. Methods: Patients with non-metastatic primary invasive gastric cancer, with T2-4 or any T status with positive lymph nodes, were identified in the Louisiana Tumor Registry using ICD-O codes and AJCC staging system. Receipt of non-surgical therapy was modeled using logistic regression. Overall survival (OS) was modeled using a Cox proportional hazards model. Results: The study included 561 patients, of which 37.6% (n=211) did not receive surgical treatment and 16.2% (n=91) did not receive non-surgical therapy. A subset of the cohort received no definitive treatment, (6.8%, n=38). In a demographic only multivariable model, adjusting for age, sex, and race, age 70 and over [OR (95%CI) =0.18 (0.08-0.42), p<0.001] and female sex [OR (95%CI) =0.48 (0.28-0.85), p=0.011] was associated with decreased rates of non-surgical therapy. Black [OR (95%CI) = 0.54 (0.31-0.93), p=0.027] and Hispanic [OR (95%CI) = 0.38 (0.13-1.08), p=0.070] race was associated with decreased receipt of non-surgical therapies. However, after adjusting for domestic partner, insurance status, rurality, area poverty, and surgery status, racial disparities were no longer significant compared to whites: Black [OR (95% CI) = 0.59 (0.33-1.06), p=0.075]; Hispanic [OR (95% CI) = 0.52 (0.17-1.66), p=0.272]. In multivariable analyses, receipt of surgery [HR (95% CI) = 0.3 (0.23 - 0.38), p<0.001) and any non-surgical therapy [HR (95% CI) = 0.43 (0.31 - 0.60), p<0.001) were associated with increased overall survival. Conclusion: A significant number of patients did not receive all modalities of the multidisciplinary treatment that is recommended for patients with non-metastatic gastric adenocarcinoma. Black patients and females are less likely to receive non-surgical modalities for gastric cancer in Louisiana, which is, at least, partially driven by socioeconomic determinants. Identifying patients with these risk factors is a crucial step in allocating resources to increase access the care and improve outcomes. Citation Format: Conner D. Hartupee, Kyla Maupin, Denise M. Danos, Omeed Moaven. Disparities in receiving non-surgical therapy impact outcomes in non-metastatic gastric cancer in Louisiana [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4822.

ASO Visual Abstract: Effect of Hospital Cancer Designation on Use of Multimodal Therapy and Survival of Patients with Metastatic Colorectal Cancer: A State-Wide Analysis.

ASO Visual Abstract: Effect of Hospital Cancer Designation on Use of Multimodal Therapy and Survival of Patients with Metastatic Colorectal Cancer: A State-Wide Analysis.

Effect of Hospital Cancer Designation on use of Multimodal Therapy and Survival of Metastatic Colorectal Cancer: A State-Wide Analysis.

Stage IV colorectal cancer (CRC) often requires multidisciplinary approach. However, multimodal treatment options (receipt of >1 type of treatment) may not be uniformly delivered across health systems. We characterized the association between center-level cancer center designation and receipt of multimodal treatment and survival. The Texas Cancer Registry was used to identify patients diagnosed with stage IV CRC from 2004-2017. We identified those who received care at either: a National Cancer Institute-designated (NCI-D), an American College of Surgeons-Commission on Cancer-designated (ACS-D), or an undesignated facility. We used multivariable logistic regression and Cox regression for analysis to assess receipt of one or more treatment modality and 5-year overall survival. Of 19,355 patients with stage IV CRC, 2955 (15%) received care at an NCI-D facility and 5871 (30%) received multimodal therapy. Both NCI-D (odds ratio [OR] 1.64; 95% confidence interval [CI] 1.49-1.81) and ACS-D (OR 1.37; 95% CI 1.27-1.48) were associated with increased likelihood of multimodal therapy compared with undesignated centers. NCI-D also was associated with significantly improved survival (hazard ratio [HR] 0.74; 95% CI 0.70-0.78), although ACS-D was associated with a modest improvement in survival (HR 0.95; 95% CI 0.92-0.99). Receipt of multimodal therapy was strongly associated with improved survival (HR 0.61; 95% CI 0.59-0.63). In patients with stage IV CRC, treatment at ACS-D and NCI-D facilities was associated with increased use of multimodality therapy and improved survival. However, only a small proportion of patients have access to these specialized centers, highlighting a need for expanded access to multimodal therapies at other centers.

Has management of locally advanced intrahepatic cholangiocarcinoma evolved with the evidence? Trends and practice patterns from the National Cancer Database.

464 Background: Intrahepatic cholangiocarcinoma (IHC) is often advanced at presentation. Mounting evidence suggests a limited role for surgical resection in the setting of multifocal hepatic and regional lymph node involvement in favor of initial treatment with systemic therapy. We sought to characterize trends and practice patterns in the management of patients with locally advanced IHC without distant extrahepatic metastasis. Methods: We queried the National Cancer Database (NCDB) for patients with IHC between 2004-2020. Patients with inadequate data quality, carcinoma in situ, other primary cancers prior to IHC diagnosis, distant metastasis (M1), unknown M status (MX), and no treatment were excluded. Lymph node involvement was categorized using clinical N stage to reflect clinical decision-making. Due to AJCC staging updates and coding limitations, subgroup analysis of patients with multifocal disease (T2bNXM0 in the 7th AJCC edition) was confined to 2010-2017. A two-sided Cochran-Armitage test was used to evaluate time trends and Kaplan Meier methods were used to summarize overall survival (OS). Results: Of 11,368 patients treated for IHC without distant metastasis between 2004-2020, 2,467 / 10,183 (24%) with clinical lymph node staging had positive nodes; the subgroup with multifocal disease comprised 1,384 patients staged T2bNXM0 between 2010-2017. Overall, 36% of patients received formal resection as first treating modality and 59% received systemic or radiation therapy first. The use of perioperative chemotherapy in combination with formal resection increased from 39% pre 2010 to 70% in 2018-2020 (p<0.001), most often delivered post-operatively: 49% received adjuvant, 13% neoadjuvant, and 8% both in 2018-2020. Among those with clinically positive lymph nodes, there was a decreasing trend in upfront resection (p<0.001) and an increase in systemic or radiation therapy first (p<0.001). Similarly, in the multifocal disease subgroup analysis, the proportion of upfront formal resection trended down from 33% in 2010 to 12% in 2017 (p<0.001). Across the entire cohort, median OS improved from 16 months (IQR 15, 18) to 27 months (IQR 26, 29) for patients diagnosed 2018-2019 compared to <2010. Conclusions: Over the last decade, increasing evidence has demonstrated unfavorable outcomes of surgical resection in locally advanced IHC even without distant extrahepatic disease, and supported the use of multimodality therapy. The most significant overall trends have been increasing use of perioperative systemic therapy in combination with formal resection compared to resection alone and an improvement in overall survival. On subgroup analysis, there was a significant and appropriate trend away from resection as first treatment modality for patients with clinically positive lymph nodes or multifocal disease.

Intranasal delivery of sunitinib: A new therapeutic approach for targeting angiogenesis of glioblastoma

Glioblastoma multiforme (GBM) is one of the most vascular among solid tumors, and despite the use of multimodal therapies, the survival of these patients is poor. In order to target angiogenesis in GBM as a promising strategy, an antiangiogenic drug is required. This study was designed to evaluate the effects of sunitinib, a multityrosine kinase inhibitor with tumor proliferation and angiogenesis inhibitory properties, on GBM-bearing rats. Given the ineffective drug delivery to the brain due to the presence of the blood-brain barrier (BBB), intra-nasal (IN) drug delivery has recently been considered as a non-invasive method to bypass BBB. Therefore, in the current study, IN was used as an ideal method for the delivery of sunitinib to the brain, and the effects of this method were also compared to the OR administration of the sunitinib. GBM was induced in the brain of male Wistar rats, and they were randomly divided into 4 groups; IN-STB (sunitinib intranasal delivery), IN-sham (placebo intranasal delivery), OR-STB (sunitinib oral delivery) and OR-sham (placebo oral delivery). After the end of the treatment period, an MRI of animals' brains showed a reduction in tumor growth in the treatment groups. Immunohistochemistry revealed that sunitinib inhibits angiogenesis in GBM in both OR and IN delivery methods. Analysis of liver tissue and enzymes showed that IN delivery of sunitinib had less hepatotoxicity than the OR method. Overall, it was found that IN sunitinib delivery could be used as a potential non-hepatotoxic alternative for the treatment of GBM.

Hypothyroidism following Radiotherapy for Head and Neck Cancer: A Systematic Review of the Literature and Opportunities to Improve the Therapeutic Ratio.

(1) Background: Radiotherapy (RT) is a central component for the treatment of many head and neck cancers. In this systematic review of the literature, we aimed to characterize and quantify the published evidence on RT-related hypothyroidism, including estimated incidence, clinical risk factors, and dosimetric parameters that may be used to guide clinical decision making. Furthermore, we aimed to identify potential areas of improvement in the prevention and clinical management of RT-induced hypothyroidism, including the role of modern advanced therapeutic techniques. (2) Methods: We conducted a systemic review of the literature in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. PubMed and Google Scholar were searched to identify original research articles describing the incidence, mechanism, dosimetry, treatment, or prevention of radiation-related hypothyroidism for adults receiving RT for the treatment of head and neck cancers. The snowball method was used to identify additional articles. For identified articles, we tabulated several datapoints, including publication date, patient sample size, estimated hypothyroidism incidence, cancer site/type, follow-up period, radiation modality and technique, use of multimodality therapy, method of thyroid function evaluation, and proposed dosimetric predictors of hypothyroidism. (3) Results: One hundred and eleven articles met inclusion criteria, reflecting a range of head and neck cancer subtypes. There was a large variation in the estimated incidence of RT-related hypothyroidism, with a median estimate of 36% (range 3% to 79%). Reported incidence increased in later publication dates, which was likely related to improved screening and longer follow up. There were a wide variety of predictive metrics used to identify patients at high risk of hypothyroidism, the most common of which were volumetric and mean dosimetrics related to the thyroid gland (Vxx%, Dmean). More recently, there has been increasing evidence to suggest that the thyroid gland volume itself and the volume of the thyroid gland spared from high-dose radiation (VSxx) may better predict thyroid function after RT. There were no identified studies investigating the role of advanced radiotherapeutic techniques such as MRI-guided RT or particle therapy to decrease RT-related hypothyroidism. Conclusions: Hypothyroidism is a common toxicity resulting from therapeutic radiation for head and neck cancer with recent estimates suggesting 40-50% of patients may experience hypothyroidism after treatment. Dosimetric predictive models are increasingly able to accurately identify patients at risk of hypothyroidism, especially those utilizing thyroid VS metrics. Further investigation regarding the potential for advanced radiotherapeutic therapies to decrease RT-induced thyroid dysfunction is needed.

Association of social vulnerability on survival, treatment, and presentation in oral cavity cancer.

This study utilized a population database to investigate how social environments are associated with outcomes including stage at diagnosis, multimodal treatment, and disease-specific survival for oral cavity squamous cell carcinomas. Retrospective analysis of adults with oral cavity squamous cell carcinoma between 2007 and 2016 from the Surveillance, Epidemiology, End Results (SEER) registry was performed. The CDC's social vulnerability index (SVI) was used to characterize social vulnerability at the county level. Predictors of disease-specific survival, stage at diagnosis, and use of multimodal therapy were identified using Cox regression and logistic regression. Our analysis included 17 043 patients. On adjusted models, patients in the highest SVI quartile (most social vulnerability) exhibited worse disease-specific survival compared to the lowest quartile (HR 1.24, 95% CI 1.12-1.37, p < 0.001), and were more likely to be diagnosed at later stages (OR 1.24, 95% CI 1.11-1.38, p < 0.001) and less likely to receive multimodal therapy (OR 0.84, 95% CI 0.77-0.99, p = 0.037). High social vulnerability was associated with worse disease-specific survival and disease presentation in oral cavity cancer patients.

Glioblastoma Microenvironment and Invasiveness: New Insights and Therapeutic Targets.

Glioblastoma (GBM) is the most common and malignant primary brain cancer in adults. Without treatment the mean patient survival is approximately 6 months, which can be extended to 15 months with the use of multimodal therapies. The low effectiveness of GBM therapies is mainly due to the tumor infiltration into the healthy brain tissue, which depends on GBM cells' interaction with the tumor microenvironment (TME). The interaction of GBM cells with the TME involves cellular components such as stem-like cells, glia, endothelial cells, and non-cellular components such as the extracellular matrix, enhanced hypoxia, and soluble factors such as adenosine, which promote GBM's invasiveness. However, here we highlight the role of 3D patient-derived glioblastoma organoids cultures as a new platform for study of the modeling of TME and invasiveness. In this review, the mechanisms involved in GBM-microenvironment interaction are described and discussed, proposing potential prognosis biomarkers and new therapeutic targets.

Treatment, Management and Outcomes of Brain Metastasis in Adult Sarcoma

<h3>Purpose/Objective(s)</h3> Metastases from adult sarcomas often develop in the lungs, bone, and liver, yet brain metastases are less common. Few studies have discussed the incidence and prognosis of sarcoma brain metastases, and limited data exists regarding the differences in treatment patterns and outcomes by treatment modality. <h3>Materials/Methods</h3> We performed a retrospective analysis of sarcoma patients with a diagnosis of brain metastasis treated at our institution between 2009-2020. Baseline patient and tumor characteristics were analyzed. Patients were stratified based on treatment modality (surgery, radiosurgery, external beam radiotherapy (RT), and surgery plus RT). Outcome measures were rates of local failure (LF) and toxicities with different modalities. Univariate analysis was performed to study associations between clinical factors and our primary endpoints. <h3>Results</h3> A total of 22 patients with 103 brain metastases were included. Most common histologies were leiomyosarcoma (5 patients, 22%), pleomorphic sarcoma (4 patients, 18%), chondrosarcoma and round cell sarcoma (2 patients each, 9%). Of the 103 lesions included, 4 (18%) were solitary lesions with a median size of 1.7cc (range 0.3 – 12.0 cm). All patients received treatment, 4 underwent surgery alone (18%), 5 received RT alone, and 13 underwent surgery plus RT. Radiotherapy techniques included radiosurgery or external beam RT. 63 lesions (61%) were treated with stereotactic radiosurgery with a median dose of 24 Gy (range 15-60 Gy). The median OS was 62 months (95% CI 18-74). At 1 year, the cumulative incidence of local failure was 8.1% (95% CI 3.5% - 15.2%). Rates of LF differed by treatment modality – 5 failures occurred with surgery alone (20%), 2 with RT alone (3.4%), and 1 with surgery plus RT (1.1%). Grade I-IV toxicities were higher with surgery plus RT (n=13, 59%) compared to surgery (n=4, 18.1%) or RT alone (n=5, 18.1%). <h3>Conclusion</h3> Our study describes tumor presentation, management, and outcomes for metastatic intracranial sarcoma. We show that surgery and radiotherapy are effective modalities to utilize in management of these patients with low rates of local failure. Use of multimodal therapy (surgery plus RT) may further improve tumor control rates, though may be associated with higher rates of toxicities.

Gene therapy using genome-edited iPS cells for targeting malignant glioma.

Glioblastoma is characterized by diffuse infiltration into the normal brain. Invasive glioma stem cells (GSCs) are an underlying cause of treatment failure. Despite the use of multimodal therapies, the prognosis remains dismal. New therapeutic approach targeting invasive GSCs is required. Here, we show that neural stem cells (NSCs) derived from CRISRP/Cas9-edited human-induced pluripotent stem cell (hiPSC) expressing a suicide gene had higher tumor-trophic migratory capacity compared with mesenchymal stem cells (MSCs), leading to marked in vivo antitumor effects. High migratory capacity in iPSC-NSCs was related to self-repulsive action and pathotropism involved in EphB-ephrinB and CXCL12-CXCR4 signaling. The gene insertion to ACTB provided higher and stable transgene expression than other common insertion sites, such as GAPDH or AAVS1. Ferroptosis was associated with enhanced antitumor immune responses. The thymidylate synthase and dihydroprimidine dehydrogenase expressions predicted the treatment efficacy of therapeutic hiPSC-NSCs. Our results indicate the potential benefit of genome-edited iPS cells based gene therapy for invasive GSCs. Furthermore, the present research concept may become a platform to promote clinical studies using hiPSC.

Stereotactic radiotherapy (10 Gy X 3) for canine nonlymphomatous intranasal tumors is associated with prolonged survival and minimal risk of severe radiotoxicity.

To describe oncologic outcomes following administration of a uniform stereotactic radiotherapy protocol (SRT; 10 Gy X 3) for canine intranasal tumors and to identify whether any clinical or dosimetric factors were predictive of event-free or overall survival time (EFST or OST). 129 dogs. In this single-institution retrospective study, the medical records database was searched for canine nonlymphomatous intranasal tumors treated with 10 Gy X 3 SRT between August 2013 and November 2020. Findings regarding adverse effects and outcomes were analyzed overall, for dogs grouped on the basis of life stage (mature adult, senior, or end of life), and for treatment-related or tumor-related variables to identify potential predictors of outcome. After SRT, most dogs clinically improved with minimal acute radiotoxicity. The median EFST was 237 days; median OST was 542 days. Receipt of other tumor-directed therapies before or after SRT was associated with improved EFST in senior dogs (hazard ratio [HR], 0.416) and improved OST in mature adult (HR, 0.241) and senior dogs (HR, 0.348). In senior dogs, administration of higher near-minimum radiation doses was associated with improved EFST (HR, 0.686) and OST (HR, 0.743). In senior dogs, chondrosarcoma was associated with shorter OST (HR, 7.232), and in dogs at end of life, having a squamous cell or transitional carcinoma was associated with worse EFST (HR, 6.462). This SRT protocol results in improved quality of life and prolonged OST for dogs of all life stages. Radiation protocol optimization or use of multimodal therapy may further improve outcomes.

ELEVATE – evaluating Temozolomide and Nivolumab in patients with advanced unresectable previously treated oesophagogastric adenocarcinoma with MGMT methylation: study protocol for a single arm phase II trial

BackgroundFor patients with oesophagogastric adenocarcinoma, surgery is the only curative option and despite the use of multimodality therapy, which combines it with chemotherapy and/or radiotherapy, more than 50% of patients will relapse and die. Many UK patients present with advanced disease which is already inoperable or metastatic at diagnosis. For these patients, standard care chemotherapy only offers them survival of less than a year. Nivolumab, a checkpoint blockade inhibitor, has been found to work in some advanced cancers. It is proposed, for those where immunotherapy hasn’t worked, that these immunologically evasive tumours need to be sensitized to immunotherapy drugs to allow them to act.MethodsELEVATE is a single arm phase II trial testing the overall response to nivolumab following temozolomide treatment in patients with advanced unresectable previously treated adenocarcinoma which is O6-methylguanine-DNA-methyltransferase (MGMT) methylated. 18 patients are being recruited from UK secondary care sites. To be eligible, participants must have been treated with at least 3 months of platinum and fluoropyrimidine chemotherapy. Participants will receive 50 mg/m2 temozolomide continuously for 3 months. If their disease progresses during the 3 months, they will stop temozolomide and start nivolumab at a dose of 240mg every 2 weeks. If there is no progression after 3 months the participant will continue taking temozolomide in combination with nivolumab. All treatment will stop once the participant progresses on nivolumab. The primary endpoint is the best overall response to nivolumab, using both Response Evaluation Criteria in Solid Tumours version 1.1 and immunotherapy modified Response Evaluation Criteria in Solid Tumours. Secondary endpoints include progression-free survival, overall survival, and quality of life.DiscussionELEVATE will provide evidence for whether giving nivolumab after temozolomide in patients with previously treated advanced oesophagogastric adenocarcinoma is safe and biologically effective prior to future randomised trials.Trial registrationsEudraCT Number: 2020-004771-41(issued 01 October 2020); ISCRTN11398887(registered 14 July 2021).

Successful Management of an Oligometastatic Nsclc Patient with Multimodal Therapy

Non-small cell lung cancer (NSCLC) is more often diagnosed at an advanced stage and carries a poor prognosis. Recently, according to the new version of AJCC staging system published in 2018, oligometastatic disease has been integrated as an intermediate stage between non-metastatic and metastatic forms. The prognosis of oligometastatic NSCLC was significantly improved by the use of multimodal therapy, including chemotherapy, targeted therapies, immunotherapy, surgery and stereotactic radiotherapy. However, there is little evidence regarding the optimal sequence of these modalities in the management of patients with oligometastatic disease. We describe here a case study of a patient diagnosed with metachronous oligometastatic NSCLC, successfully managed by multimodal therapy based on stereotactic radiotherapy, chemotherapy, immunotherapy and standard radiotherapy for local control. Furthermore, randomized prospective studies would be of capital interest, including multi-centre patient studies and evaluation of several treatment strategies.

Clinical characteristics and outcomes of adult alveolar rhabdomyosarcoma (ARMS) patients on front-line therapies: An MD Anderson Cancer Center (MDACC) case series.

e23548 Background: Rhabdomyosarcomas are the most common soft tissue sarcoma in children, and the prognosis of pediatric ARMS has improved with the use of multi-modality therapies. However, ARMS in adults is rare, and long-term outcomes continue to be poor. This study aimed to evaluate clinical outcomes of an adult ARMS population on different front-line systemic chemotherapies, particularly the vincristine/doxorubicin/ifosfamide (VDI) regimen. Methods: Adult fusion-positive confirmed ARMS patients over the age of 18 years (y) treated at MDACC from 2004 to 2018 were identified in our patient registry. Descriptive clinical statistics including staging, front-line chemotherapy, multimodal therapy usage, and survival analyses were performed. Results: 49 patients were identified, with mean age of 34.9 y (range 18y - 67y), and 53% were male. Most patients were white (53%, 26 pts), and the most common primary tumor site was the parameningeal space (63%; 31 pts). Patients were either intermediate (67%) or high clinical risk (33%). Most patients were IRSG clinical group IIIa (36%), IIIb (20%) or IV (33%) and were classified clinical stage 3 (49%) or 4 (33%). Of all patients at diagnosis, 71% had nodal disease and 32% were metastatic. Radiotherapy and surgery were given with upfront chemotherapy in 33 pts (67%) and 24 pts (49%) respectively, with 19 patients receiving both. Median OS for the entire cohort was 3.6 years. Doxorubicin containing chemotherapy regimens trended to worse OS than non-doxorubicin containing regimens (2.3 yrs vs 4.0 yrs, p = 0.355). Comparing patients who received VDI (19 pts) vs non-VDI (30 pts; 13 received Actinomycin D, 12 received doxorubicin in different regimens, and 5 received neither), median OS was 1.8 yrs vs 3.8 yrs (p = 0.283) respectively. There were similar number of front-line chemotherapy cycles (8.5 vs 9.5 cycles), high clinical risk (26% vs 37%) and metastatic disease (21% vs 36%) in the VDI vs non-VDI cohorts. Patients receiving upfront radiation had improved survival (3.7 vs 1.5 yr, p = 0.01), but this is likely confounded by those with metastases being less likely to receive upfront radiation. Conclusions: In this single center retrospective analysis of adult ARMS patients, survival outcomes continue to be similar to historical outcomes. There was no statistically significant OS difference in patients who did or did not receive doxorubicin containing front-line chemotherapy regimens, or in particular VDI therapy, although there was a trend to decreased OS. However, limitations to this study include limited sample size, non-randomization to treatment selection, and possible biases in patient selection for different chemo regimens. Based on these observations, randomized prospective studies are necessary to delineate which frontline chemotherapy regimen is most beneficial in this rare tumor in adults.

Comparison of Multimodal Therapies and Outcomes Among Patients With High-Risk Prostate Cancer With Adverse Clinicopathologic Features

The optimal management strategy for high-risk prostate cancer and additional adverse clinicopathologic features remains unknown. To compare clinical outcomes among patients with high-risk prostate cancer after definitive treatment. This retrospective cohort study included patients with high-risk prostate cancer (as defined by the National Comprehensive Cancer Network [NCCN]) and at least 1 adverse clinicopathologic feature (defined as any primary Gleason pattern 5 on biopsy, clinical T3b-4 disease, ≥50% cores with biopsy results positive for prostate cancer, or NCCN ≥2 high-risk features) treated between 2000 and 2014 at 16 tertiary centers. Data were analyzed in November 2020. Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy boost (BT) with ADT. Guideline-concordant multimodal treatment was defined as RP with appropriate use of multimodal therapy (optimal RP), EBRT with at least 2 years of ADT (optimal EBRT), or EBRT with BT with at least 1 year ADT (optimal EBRT with BT). The primary outcome was prostate cancer-specific mortality; distant metastasis was a secondary outcome. Differences were evaluated using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression models. A total of 6004 men (median [interquartile range] age, 66.4 [60.9-71.8] years) with high-risk prostate cancer were analyzed, including 3175 patients (52.9%) who underwent RP, 1830 patients (30.5%) who underwent EBRT alone, and 999 patients (16.6%) who underwent EBRT with BT. Compared with RP, treatment with EBRT with BT (subdistribution hazard ratio [sHR] 0.78, [95% CI, 0.63-0.97]; P = .03) or with EBRT alone (sHR, 0.70 [95% CI, 0.53-0.92]; P = .01) was associated with significantly improved prostate cancer-specific mortality; there was no difference in prostate cancer-specific mortality between EBRT with BT and EBRT alone (sHR, 0.89 [95% CI, 0.67-1.18]; P = .43). No significant differences in prostate cancer-specific mortality were found across treatment cohorts among 2940 patients who received guideline-concordant multimodality treatment (eg, optimal EBRT alone vs optimal RP: sHR, 0.76 [95% CI, 0.52-1.09]; P = .14). However, treatment with EBRT alone or EBRT with BT was consistently associated with lower rates of distant metastasis compared with treatment with RP (eg, EBRT vs RP: sHR, 0.50 [95% CI, 0.44-0.58]; P < .001). These findings suggest that among patients with high-risk prostate cancer and additional unfavorable clinicopathologic features receiving guideline-concordant multimodal therapy, prostate cancer-specific mortality outcomes were equivalent among those treated with RP, EBRT, and EBRT with BT, although distant metastasis outcomes were more favorable among patients treated with EBRT and EBRT with BT. Optimal multimodality treatment is critical for improving outcomes in patients with high-risk prostate cancer.

Management of Intractable Symptoms in Oncologic Care.

For patients undergoing evaluation and treatment of cancers, symptom management is a critical component of their treatment plan. For some patients, symptoms may become intractable or refractory to common therapies. Here, we review treatment options for these severe symptom conditions. Medication options and regimens have improved to treat refractory symptoms. Medications can be tailored to treat chemotherapy-induced nausea and vomiting based on current guidelines. Interventions such as venting gastrostomy can mitigate symptoms associated with malignant bowel obstruction, when life expectancy is long enough to realize this benefit. Opiates can reduce refractory dyspnea, consistent with guidelines from the American Thoracic Society. Interventional therapies for intractable pain, such as neurolytic blocks and intrathecal pumps, have shown promise in managing symptoms when traditional therapies have been ineffective. Refractory symptoms can be managed in cancer care. The use of multimodal therapies delivered by interdisciplinary teams appears to be the most effective way to approach these clinical situations.

The role of surgery in the management of locally advanced and metastatic thymoma: a narrative review.

Thymic epithelial tumors (TETs) are rare neoplasms. While treatment guidelines for early stage TETs are well established, treatment for advanced and locally invasive and metastatic TETs (Masaoka stage IVa/IVb) is varied. Many studies examining outcomes in this patient population are single institution, retrospective studies with small sample sizes. Further complicating study of advanced TETs is that Masaoka stage IVa/IVb describes a wide variety of disease heterogeneity, and includes both thymoma and thymic carcinoma. Thus, recommendations for treatment strategies vary widely. Surgical resection with an R0 resection is a key component of treatment for early stage TETs, however the utility of surgery and appropriate surgical approach for patients with locally invasive disease is debated and ranges from local metastasectomy to extrapleural pneumonectomy (EPP). The use of multimodal therapies, including adjuvant and neoadjuvant radiation and chemoradiation, are important for patients with locally advanced disease, however identifying patients who would most benefit from each strategy has been challenging. In this review we examined the literature to provide treatment strategies for advanced TETs. Surgery with an R0 resection should be attempted in all risk appropriate patients. Multimodal therapies are likely beneficial to patients particularly with locally advanced disease, and neoadjuvant therapies may increase likelihood of R0 resection. Further investigation is necessary to identify optimal treatment strategies for patients with locally advanced TETs.

Prevalence of fertility discussions between young adult colorectal cancer survivors and their providers.

3518 Background: Clinical guidelines indicate that oncologists should discuss potential treatment-induced infertility with patients with reproductive potential. Due to tumor location and use of multimodal therapies, young adults with colorectal cancer (CRC) are at heightened risk for treatment-related infertility. Methods: An online, cross-sectional survey was administered in collaboration with a national patient advocacy organization for young adult CRC survivors (currently under age 50). Survivors were asked to indicate if a doctor had ever talked to them about potential problems with their ability to have children after treatment and if they banked eggs/embryos (females) or sperm (males) prior to their cancer therapy. Those who reported that they did not preserve fertility were asked to indicate why ( not sure; I chose not to; I did not know this was an option; I wanted to, but could not afford it; and I wanted to, but my treatment would not allow it). Results: A total of 234 colon (N=86) or rectal (N=148) cancer survivors were included in the study (male [61.9%] and White [77.9%; table]). Most respondents were diagnosed with stage 2 cancer (55.8% colon, 61.6% rectal). Over half of male and female survivors reported that their doctor did not talk to them about problems with their ability to have children after treatment, and 75% did not bank eggs/embryos or sperm prior to their cancer therapy. Of those, over 20% endorsed ‘I wanted to, but could not afford it’ and over 20% endorsed ‘I did not know this was an option’. Conclusions: Most CRC survivors in this study reported never having a fertility discussion with their provider, suggesting that survivors are not receiving, or cannot recall, comprehensive and guideline-concordant cancer care. In addition, one-fifth were not aware of preservation options, suggesting potential healthcare and/or provider-level barriers to appropriate fertility counseling. Fertility preservation cost is another barrier to the appropriate delivery of care. Providers must ensure that patients receive timely fertility discussions covering options to preserve fertility to mitigate this late effect of cancer treatment to ensure optimal quality of life for CRC patients with reproductive potential.[Table: see text]

Abstract PS11-34: Time to completion of breast cancer treatment and survival

Abstract Background:Modern breast cancer (BC) treatment involves the use of multimodality therapy. Treatment delays are common and can be multifactorial. There are few studies examining the association between the duration of the time from diagnosis to completion of all acute BC treatment modalities and survival. This study is designed to determine if there is an association between time to complete treatment and survival. Study Design:A retrospective analysis was performed using data from The National Cancer Database (NCDB) to determine whether an association exists between the duration of time from diagnosis to completing all acute BC treatment (surgery, chemotherapy and radiation therapy) and survival. A second analysis was performed to determine if the association between treatment duration and survival varies by receptor status. Results:The NCDB data from BC patients diagnosed in 2010 was analyzed. The inclusion criteria included less than 80 years of age with a single cancer diagnosis, Stage I through III invasive breast cancer who required treatment with surgery, chemotherapy and radiation therapy. A total of 28,284 patients were included in the analysis. Median follow-up was 5.8 years. The order of treatment included 20,772 patients had treatment in the order of surgery, chemotherapy and radiation therapy and 7,512 patients had treatment order chemotherapy, surgery and radiation therapy. A Cox proportional hazards model was developed and identified a cut off showing the risk of delaying completion of all treatment beyond 38 weeks was associated with decrease in overall survival. This was statistically significant with an adjusted hazard Ratio of 1.21. This cut off of 38 weeks was found to be significant regardless of receptors type. The statistically significant Hazard ratios for receptor subtypes include: Triple negative (HR: 1.188, 95%CI: 1.06-1.34), ER+PR+Her2- (HR: 1.22, 95%CI: 1.09-1.36), ER-PR-Her2+ (HR: 1.29, 95%CI: 1.004-1.67) and ER+PR+Her2+ (HR: 1.32, 95%CI: 1.01-1.72). The patients with treatment duration greater than 38 weeks were comprised of 4768(63.47%) neo-adjuvant chemotherapy patients and 8191 (39.43%) of the surgery first group. Conclusion: Efforts to improve the efficiency of multimodality BC treatment and reduce treatment delays should be a priority to optimize BC patient outcomes. Citation Format: Debra Ann Pratt, Talia Burneikis, Chao Tu, Stephen R. Grobmyer. Time to completion of breast cancer treatment and survival [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-34.