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Background: Dual checkpoint inhibition with Anti-PD-1 and anti-CTLA4 checkpoint inhibitors have proven to be effective in several malignancies but their potential role in numerous rare solid cancers is yet to be established. This study presents the first results of ipilimumab and nivolumab in the non-epithelial ovarian tumor cohort (#13) of the SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) trial. Methods: DART is a prospective, open-label, multicenter/multi-cohort phase 2 clinical trial of ipilimumab (1mg/kg intravenously every 6 weeks) plus nivolumab (240mg intravenously every 2 weeks). This cohort included several histologies grouped for statistical analysis. The primary endpoint was objective response rate (ORR) (RECIST v1.1) (confirmed complete (CR) and partial responses (PR)); progression-free survival (PFS), overall survival (OS), stable disease (SD) >6 months, and toxicity are secondary endpoints. Results: Seventeen evaluable patients (median age, 64 years) were analyzed. The subtypes of non-epithelial ovarian cancer were: granulosa cell (47%, n=8), carcinosarcoma or malignant mixed Mullerian tumor (MMMT; 35%, n=6), one each for Wolffian duct, yolk sac, and Sertoli-Leydig cell. There were 2 responses in the 8 patients with granulosa cell (ORR of 25% in the granulosa cell tumors): 1CR (79% regression [due to lymph node < 1.0cm], 59 month PFS, juvenile type) and 1 PR (79% regression, 51+ month PFS, adult type). 6/8 patients remain alive (PFS 52-1774 days). In contrast, carcinosarcomas showed no responses. One patient with Sertoli-Leydig cell tumor had a 22% response and 341 day PFS. Overall ORR was 12% (2/17), clinical benefit rate (CBR; no progression > 6months) of 29.4%. The median PFS was 3.5 months, median OS was 42.5 months. The most common adverse events were fatigue (52.9%, n=9) and hypothyroidism (35.3%, n=6). Grade 3-4 adverse events occurred in 47.1% of patients (n=8). There were 3 adverse events (17.6%) that led to discontinuation, of which 2 (11.8%) were grade 3-4. There were no grade 5 adverse events. Conclusion: Ipilimumab plus nivolumab in non-epithelial ovarian cancer resulted in an ORR of 12% (with 2 of 8 patients with granulosa ovarian tumors showing a durable CR and PR [both, >4 years)) and CBR of 29.4%, with durable responses seen. In contrast there were no responses in the carcinosarcoma group. One patient with Sertoli Leydig cell tumor suggested a possible benefit. Correlative studies to determine response and resistance markers are ongoing. Expanded prospective studies in granulosa tumor but not carcinosarcoma are warranted. Citation Format: Young Kwang Chae, Megan Othus, Sandip Pravin Patel, Kelly J. Wilkinson, Emily M. Whitman-Purves, Jayanthi Lea, John M. Schallenkamp, Nabil Adra, Leonard J. Appleman, Mitchell Alden, Jessica Thomes Pepin, John A. Ellerton, Andrew Poklepovic, Adam Walter, Murtuza M. Rampurwala, William R. Robinson, Liam Il-Young Chung, Christine M. McLeod, Helen X. Chen, Elad Sharon, Howard Streicher, Christopher W. Ryan, Charles D. Blanke, Razelle Kurzrock. A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: the non-epithelial ovarian tumor cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT161.

Introduction: Dual checkpoint inhibitor therapy with nivolumab and ipilimumab has been FDA-approved for a number of different cancers including melanoma, recurrent NSCLC, and hepatocellular carcinoma. However, their role in the treatment of ACC and other salivary gland carcinomas is not well established. Methods: We performed a Simon’s two-stage prospective single-institution phase II clinical trial of nivolumab (240 mg intravenously every 2 weeks for 16 weeks, then 480 mg every 4 weeks) with ipilimumab (1 mg/kg intravenously every 6 weeks), both of which were provided until intolerable toxicity or disease progression. Two cohorts were analyzed: patients with metastatic/recurrent ACC and patients with other salivary gland cancers. The primary endpoint was median progression-free survival (PFS) based on RECIST and immune-related RECIST (irRECIST) criteria; secondary endpoints were overall response rate (ORR), overall survival (OS), and toxicity. Results: Patients with ACC (n=19) and other salivary gland carcinomas (total n=5; parotid gland adenocarcinoma (n=3), salivary duct carcinoma (n=1), and myoepithelial carcinoma (n=1)) were enrolled between May 2017 and July 2019. Among the patients with ACC, the median OS was 30.0 months (95% confidence interval (CI) 15.3 months to not reached), the median PFS was 8.3 months (95% CI 5.5 - 30.0 months), and the disease control rate (DCR) was 53% (10/19). The ORR in the ACC group was 5% (CR 0%, n=0; confirmed PR 5%, n=1) using both RECIST and irRECIST criteria, with one patient having continued stable disease at the time of trial conclusion. In the salivary gland tumor cohort, the median OS was 10.4 months (95% CI 6.21 months to not reached), the median PFS time was 6.21 months (95% CI 2.83 months to not reached), and the DCR was 40% (2/5). The ORR in this cohort was 0% using both RECIST and irRECIST criteria. Across both cohorts, platelet counts above the joint cohort’s median were significantly associated with better OS (p=0.032) and PFS (p=0.046). Additionally, although not significant, there was a trend for improved OS and PFS among patients with neutrophil-to-lymphocyte ratios >5 (OS p=0.42, PFS p=0.25) and above median neutrophil counts (OS p=0.24, PFS p=0.18). Four patients with ACC underwent circulating tumor DNA sequencing, resulting in the identification of two MYB-NFIB translocations, one NOTCH1 Cys1383 frameshift mutation, one MTOR N1760K mutation, and one PDGFRA copy number gain. Common immune-related toxicities include fatigue (54%), lymphocytopenia (46%), and anemia (42%) with lymphocytopenia being the most common grade III/IV adverse event. Conclusion: In patients with recurrent or metastatic ACC and other salivary gland neoplasms, combination nivolumab with ipilimumab resulted in moderate disease control. Further studies are warranted to validate our findings. Citation Format: Young Kwang Chae, Richard Duan, Liam Il-Young Chung, Youjin Oh, Maria Matsangou, Mark Agulnik, Victoria Villaflor, Devalingam Mahalingam. Phase II study of nivolumab and ipilimumab for treatment of metastatic/recurrent adenoid cystic carcinoma (ACC) of all anatomic sites of origin and other malignant salivary gland tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT165.

Background: Dual checkpoint inhibition with Anti-PD-1 and anti-CTLA4 checkpoint inhibitors have shown to be efficacious in many malignancies, but its potential role in various rare solid cancers is yet to be established. Small cell ovarian carcinoma, hypercalcemic type (SCCOHT) is a rare tumor characterized by loss of SMARC 2/4 function and so presents a novel paradigm for the treatment of SWI/SNF pathway deficient tumors (Petar Jelinic et al., 2018; Marc Tischkowitz et al., 2020). This study presents the first results of ipilimumab and nivolumab used in the SCCOHT cohort (#49) of the SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) trial. Methods: DART is a prospective, open-label, multicenter/multi-cohort phase 2 clinical trial of ipilimumab (1mg/kg intravenously every 6 weeks) plus nivolumab (240mg intravenously every 2 weeks). The primary endpoint includes objective response rate (ORR) (RECIST v1.1) (confirmed complete (CR) and partial responses (PR)). Secondary endpoints include progression-free survival (PFS), overall survival (OS), stable disease (SD) >6 months, and toxicity. Results: Five evaluable patients (median age 30) with SCCOHT were analyzed. Objective response rate was 20% (1 CR with 100% regression). The patient with CR has a duration of response (DoR) and OS of 35+ months. Another patient, showed unconfirmed PR with 81% regression (DoR 4 months), this patient went on to have confirmed iCR (CR confirmed by iRECIST) at around 24 months and has OS of 38+ months. At 12 months, 3 patients remain alive and 1 patient remains progression free; overall median PFS was 1.8 months (1.0-∞); median OS was 24 months (4.5-∞). The most common adverse events were fatigue, nausea, pruritus, dry mouth, maculo-papular rash and aspartate aminotransferase elevation (50%, n=2, respectively). There were two incidents (33.3%) of grade 3-4 adverse events. None of the adverse events led to discontinuation. There were no grade 5 adverse events. Conclusion: Ipilimumab plus nivolumab in five patients with the ultra-rare small cell ovarian carcinoma (hypercalcemic type) resulted in one CR durable at 35+ months and one unconfirmed PR with 81% regression. This is the first prospective study demonstrating efficacy of nivolumab and ipilimumab in this rare disease. Correlative studies to determine response and resistance markers are ongoing. Expanded prospective studies in small cell ovarian histologies are needed. Citation Format: Young Kwang Chae, Megan Othus, Sandip P. Patel, Raid Aljumaily, Khine Z. Win, Tanya Pejovic, Sajeve S. Thomas, William R. Robinson, Liam Il-Young Chung, Christine M. McLeod, Helen X. Chen, Elad Sharon, Howard Streicher, Christopher W. Ryan, Charles D. Blanke, Razelle Kurzrock. A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: the small cell carcinoma of the ovary, hypercalcemic type cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT163.

Background: According to a consensus document from the International Society for Heart and Lung Transplantation (ISHLT), adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are listed as ‘special circumstances’ for lung transplantation (Weill D et al., 2015). There have been five reported studies of lung transplantation in carefully selected subsets of patients with multifocal lung adenocarcinoma (Raemdonck DV et al., 2016; Glanville AR et al., 2018). The 5-year survival rate of bilateral sequential lung transplantation was estimated at over 50% in patients with multifocal BAC, invasive adenocarcinoma, and NSCLC (Ahmad U et al., 2012; Paloyan EB et al., 2000; Zorn GL et al., 2003; de Perrot M et al., 2004). In 1999, a case series reported a post-transplant recurrence-free survival of 23 to 56 months in three patients (Garver RI et al., 1999). There is also an unmet need for patients who have lung-limited metastasis after successful treatment for primary tumors such as sarcomas or colorectal cancer (CRC). As with liver transplantation for CRC patients who have liver-confined metastases (Dueland S et at., 2020; Hernandez-Alejandro R et al., 2022), the applicability of lung transplantation in lung-limited metastasis patients should be explored. Methods: This is a prospective registration trial to evaluate outcomes of patients who undergo lung transplantation for the treatment of the select groups of medically refractory cancers (primary lung cancers or metastatic cancers in lungs). Overall survival (OS), disease-free survival (DFS), allograft rejection (AR) and allograft survival (AS) will be monitored as well as molecular and genetic biomarkers to investigate the correlation with prognosis. The study duration will be 10 years including surveillance. Recruitment to occur during the first 5 years of the study. The goal is to enroll 175 participants through the Lurie Comprehensive Cancer Center of Northwestern University. Essential Criteria: The tumor should be without any involvement of mediastinal lymph nodes involvement confirmed by endobronchial ultrasound (EBUS) or mediastinoscopy. The patient who are resistant or refractory to or without available standard of care treatment options or experimental treatment options that are known to increase survival outcome. Study cohorts: • Cohort A: Primary lung cancers - Examples include, but not limited to, invasive mucinous/non-mucinous non-small cell lung cancers and multifocal carcinomas. • Cohort B: Metastatic cancers to the lung only - Examples include, but not limited to, germ cell tumors, head & neck tumors, colorectal tumors, renal cell tumors, testicular cancers. Clinical trial registry number: NCT05671887. Enrollment began November 16, 2022. Trial is open and recruiting as of January 12, 2023. Citation Format: Young Chae, Liam Il-Young Chung, Rade Tomic, Ankit Bharat. Double lung transplant registry aimed for lung-limited malignancies (DREAM) - a prospective registry study of bilateral lung transplantation for medically refractory cancers confined to the lungs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT051.

Background: Globally, cancer results in 10.08 million deaths per year. A single blood-based screening tool that detects multiple cancer types could greatly reduce cancer burden. We aim to systematically review and statistically examine both the accuracy and applicability of blood-based MCED tests to strategize their utilization in improving cancer detection. Methods: Original articles were searched from Pubmed, Cochrane, and Embase for blood-based screening tests analyzing multiple cancer types and asymptomatic human subjects. We excluded studies with small sample size (n Findings: Of 1,074 records screened, 10 case-control and 6 cohort studies were analyzed, most of which utilized cfDNA-based diagnostic tests. Ten cfDNA studies selected for meta-analysis had a joint sensitivity of 0.66 (95%CI 0.54-0.75) and specificity of 0.98 (0.94-0.99) with an area under the curve of 0.883. For cohort studies, the joint positive and negative predictive values were 0.96 (0.29-1.00) and 0.81 (0.37-0.97) respectively. Sensitivity was higher for advanced staged cancers (III/IV 0.84 (0.84-0.86)) with breast cancer having the lowest sensitivity (0.42 (0.31-0.55)). Sensitivity and specificity were not affected by study type, gender, or assay type. Lastly, accuracy of tumor origin prediction was 0.792 (0.64-0.91) without significant differences across cancer types. Interpretation: Given high sensitivities and specificities, MCED tests show promise as additional screening tools. Although there exist multiple barriers to their application in clinic, MCED tests may improve patient outcomes for cancers with no conventional screening tools. Future prospective studies with large and diverse populations are warranted. Summarization of meta-analysis results on cfDNA based multi cancer early detection tests Sensitivity Specificity DOR PPV NPV No. of study included 10 10 10 4 4 Events/Total 5778/10033 14797/15020 Experimental group: 5778/6001 901/1373 10148/11216 Control group: 4202/19052 Proportion (95% CI) 0.652 [0.537; 0.751] 0.978 [0.936; 0.992] 69.290 [25.208; 190.457] 0.961 [0.293; 0.999] 0.812 [0.365; 0.970] Heterogeneity (p value) 98% ( Citation Format: Joo Hee Park, Youjin Oh, Liam Il-Young Chung, Richard Duan, Trie A. Djunadi, Sung Mi Yoon, Zunairah Shah, Chan Mi Jung, Ilene Hong, Leeseul Kim, Young Kwang Chae. Systematic review and meta-analysis of the accuracy and applicability of blood-based multi-cancer early detection (MCED) in the general population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 783.

Background: Radiomics is an emerging tool that involves the extraction of high-throughput features from medical images. These quantitative values can be used to develop predictive models for clinical characteristics and treatment outcomes. We evaluated radiomic features-based models as imaging biomarkers in NSCLC patients. Methods: 71 patients with NSCLC treated with immunotherapy who had pretreatment CT chest with contrast were retrospectively evaluated. The main tumor and 1cm-thick peritumoral space surrounding the tumor were manually segmented using LIFEx software (IMIV/CEA, Orsay, France) by four physicians. Of 255 radiomic features collected, those with >0.4 of Fleiss’ kappa coefficient were selected. The Random Forest (RF) algorithm with mixed effects was used to develop multi-reader models and assess feature importance. The dataset was divided into a training set (75%) and a test set (25%). Bootstrapping with 1,000 iterations was conducted to estimate the model performance. Durable disease control was defined as having no progression of diseases per RECIST 1.1 up to 24 weeks from starting immunotherapy. Results: Among 71 patients, 35 (49.3%) are female and 36 (50.7%) are male. The median age was 66. 48 (67.6%) adenocarcinoma, 13 (18.3%) squamous cell carcinoma, and 10 (14.1%) other histologic types were included. 22 radiomic features were included based on importance in the prediction models from both the tumor and peritumoral space. Each model is trained to predict patients’ durable disease control, TTF1 expression, PD-L1 expression, histology (adenocarcinoma or not), and Neutrophils Lymphocyte Ratio (NLR; greater than 5 or not) status. The statistical results from the models to predict clinical outcomes are shown in Table. Conclusion: The radiomic features-based models lack accuracy in predicting clinical characteristics and outcomes. Further validation with larger cohorts is warranted. Statistics of radiomics-based models in predicting clinical characteristics and treatment outcomes Durable Disease Control(Yes/No)(n=64) TTF1 expression(Yes/No)(n=62) Histology(Adeno/Other)(n=71) NLR(>=5/ Citation Format: Jisang Yu, Yury Velichko, Hyeonseon Kim, Moataz Soliman, Nicolo Gennnaro, Leeseul Kim, Youjin Oh, Trie Arni Djunadi, Jeeyeon Lee, Liam Il-Young Chung, Sungmi Yoon, Zunairah Shah, Soowon Lee, Cecilia Nam, Timothy Hong, Rishi Agrawal, Pascale Aouad, Young Kwang Chae. Radiomics-based machine learning models to predict progression and biomarker status in non-small cell lung cancer (NSCLC) patients treated with immunotherapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5619.

Background: Among the recently developed blood-based multi-cancer early detection (MCED) tests, determining the location of tumors is pivotal to guiding appropriate treatment. We aim to systematically review and statistically examine the accuracy of tumor of origin prediction among blood-based MCED tests. Methods: Original articles were searched from Pubmed, Cochrane, and Embase that featured blood-based screening tests, multiple cancer types, and asymptomatic human subjects. We excluded studies with small samples (n Findings: Of 1,074 records identified and screened, 4 cohort studies were analyzed using cfDNA-based diagnostic tests. The accuracy of tissue-of-origin (TOO) prediction for 3,762 cancer samples across cancer types was 0.79 (95% CI 0.64 - 0.91). Among six cancer types, colorectal cancers had the highest accuracy, and liver & bile duct cancers had the lowest, although the difference was statistically insignificant (0.89 (95% CI 0.79-0.97) vs. 0.68 (95% CI 0.40-0.90)). Additionally, cases were most frequently misclassified as colorectal cancer (Table 1). Lastly, two studies reported increased prediction accuracies when two sites of origin were assigned rather than a single site. The information for localizing TOO was derived from methylation patterns of cfDNA in two studies, fragmentation profiles of cfDNA in another study, and protein markers in the other research. Interpretation: Our results demonstrate that the primary site of cancers was accurately discerned in 79% of cases by MCED tests. However, the performance varies across cancer types. Further research on performance according to cancer stages and in combination with other molecular profiling is warranted. Table 1. Events/Total Accuracy of prediction (95% CI) misclassification type freqeuncy Total 3,129/3,762 0.79 (0.64 - 0.91) Colorectal 638/723 0.89 (0.79 - 0.97) stomach & esophagus 26/553 breast 8/553 Breast 443/538 0.86 (0.64 - 0.99) colorectal 20/349 pancreas & GB 4/349 lung 4/349 Ovarian Breast 132/159 0.85 (0.62 - 0.99) colorectal 39/261 uterus 13/147 Pancreatic & GB 289/338 0.82 (0.69 - 0.93) colorectal 12/300 stomach & esophagus 10/300 Stomach & Esophagus 225/311 0.75 (0.48 - 0.95) colorectal 39/261 lung 10/261 Lung 530/656 0.72 (0.45 - 0.92) colorectal 29/560 head and neck 8/560 Liver & Bile duct 95/144 0.68 (0.40 - 0.90) colorectal 13/220 pancreatic & GB 8/220 Abbreviations: CI = confidence interval; GB = gallbladder Citation Format: Youjin Oh, Joo Hee Park, Liam Il-Young Chung, Richard Duan, Trie Arni Djunadi, Sung Mi Yoon, Zunairah Shah, Chan Mi Jung, Ilene Hong, Leeseul Kim, Horyun Choi, Young Kwang Chae. Systematic review and meta-analysis of the accuracy of tumor origin detection in blood-based multi-cancer early detection (MCED) in the general population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 784.

12134 Background: Chronic diseases are a significant source of physical, emotional, mental, and social distress to not only patients but also their friends and family. Healthcare professionals (HCPs) also share in the burden as they strive to provide the best possible care. In particular, cancer patients face great burden as they grapple with the uncertainty of their futures. Given the respective difficulties associated with cancer treatment, fostering a collaborative environment in which patients, caregivers, and HCPs mutually encourage each other becomes necessary to improve the quality of life of everyone involved. This study aims to investigate factors that influence a healthy long-term care relationship between patients and HCPs. Methods: This study is a qualitative analysis of HCPs’ experiences with patients and their caregivers at a large metropolitan academic medical center. This study analyzed reflective essays written by HCPs as part of the Pacemakers initiative at the medical center, which seeks to empower HCPs, patients, and caregivers in creative ways along the management journey. The essays focused on HCPs’ participation in meaningful experiences with patients and caregivers such as patient/caregiver award ceremonies celebrating their resilience and hope. A total of 22 essays ( N = 22) were thematically analyzed by two independent coders to produce meaning-making codes and themes (italicized). Results: The presence of support networks ( n = 10) was very important for the patients and caregivers. Conveying solidarity ( n = 21) was also central in helping patients experience companionship and fellowship in their community with their medical team, family, and friends. It was also noted that little means much ( n = 10); small acts of kindness showing genuine interest led to meaningful interactions that provided encouragement for the patients. Compassion ( n = 19) and patient-centeredness ( n = 17) were important in fostering a receptive environment in which patients and caregivers felt heard. Celebrating and honoring the patients’ resilience ( n = 10) made patients feel recognized, and this process of celebration was also found to bolster a renewed sense of purpose for the HCPs ( n = 11). Conclusions: The results of this study highlight the importance of supporting patients and their caregivers holistically. Understanding and meeting this need through creative encouragement empowers not only the patients and caregivers but also the HCPs. Trust is built and patients are strengthened to pursue their health to the best of their abilities as HCPs show their deep care for their struggles and resiliency. This sacred experience of entrusting one’s life to another builds the best environment for healing and recovery. This study shares a glimpse of how to best support patients as well as HCPs in long-term care relationships.

11020 Background: Cancer treatment is a difficult process that not only affects the patients themselves, but also their caregivers and healthcare professionals (HCPs). A cancer diagnosis is often a life-changing experience for both patients and caregivers, who may feel vulnerable and stressed in the face of such a complex disease. HCPs in oncology, who are constantly present on the frontline between life and death, often experience emotional and physical exhaustion. Such burnout of HCPs can lead to adverse effects on patient care. Therefore, it becomes important to prevent and manage HCPs’ fatigue to not only improve patient care, but also HCPs’ quality of life. Methods: This study qualitatively examined the experiences of HCPs who collaboratively interacted with patients and caregivers in the clinical setting. The Pacemakers initiative was developed and piloted in a large urban academic medical center with the aim to promote creative encouragement and companionship among HCPs and patients/caregivers. HCPs held ceremonies with personal awards for patients/caregivers during their treatment course, and their experience with the ceremonies was evaluated qualitatively with a survey. A thematic analysis was subsequently performed on the HCPs’ reflective essays ( N = 22) to identify recurring themes (italicized) in their experiences. Results: In general, we found that the HCPs felt that they were benefiting from taking part in the creative patient encouragement ceremonies. Many described the experience as motivating or inspiring ( n = 15), highlighting how such collaboration renews optimism and prevents burnout. The HCPs also reported feeling acknowledged for their behind-the-scenes work and support ( n = 5) and grateful to be given the opportunity to acknowledge their patients and caregivers ( n = 13), as well. Another common theme was that the HCPs felt that they were able to connect emotionally ( n = 14) with the patients and caregivers, describing moments of shared laughter and tears. Lastly, the HCPs reported feeling a sense of togetherness with patients and caregivers ( n = 13), often describing the relationship as akin to a team or family, and many stated that they were able to develop a more personal connection ( n = 15) with patients and caregivers through the ceremonies. Conclusions: Overall, we find that the benefits of encouraging patients and caregivers extend to HCPs. The positive impact of identifying and celebrating small but meaningful joys in the clinical setting is considerable especially upon HCPs, who find such experiences to be rewarding and refreshing. HCP burnout is common in oncology, and the findings of this analysis suggest that inspiring mutual encouragement and fostering collaboration between HCPs, patients, and caregivers are critical in reducing and preventing such fatigue.