Institute Cancer Center Research Articles

Molecular markers of metastatic disease in KRAS-mutant lung adenocarcinoma

Prior studies characterized the association of molecular alterations with treatment-specific outcomes in KRAS-mutant (KRASMUT) lung adenocarcinoma (LUAD). Less is known about the prognostic role of molecular alterations and their associations with metastatic disease. We analyzed clinicogenomic data from 1817 patients with KRASMUT LUAD sequenced at the Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering Cancer Center (MSKCC). Patients with metastatic (M1) and nonmetastatic (M0) disease were compared. Transcriptomic data from The Cancer Genome Atlas (TCGA) were investigated to characterize the biology of differential associations with clinical outcomes. Organ-specific metastasis was associated with overall survival (OS). KEAP1 (DFCI: OR= 2.3, q= 0.04; MSKCC: OR= 2.2, q= 0.00027) and SMARCA4 mutations (DFCI: OR= 2.5, q= 0.06; MSKCC: OR= 2.6, q= 0.0021) were enriched in M1 versus M0 tumors. On integrative modeling, NRF2 activation was the genomic feature most associated with OS. KEAP1 mutations were enriched in M1 versus M0 tumors independent of STK11 status (KEAP1MUT/STK11WT: DFCI OR= 3.0, P= 0.0064; MSKCC OR= 2.0, P= 0.041; KEAP1MUT/STK11MUT: DFCI OR= 2.3, P= 0.0063; MSKCC OR= 2.5, P= 3.6× 10-05); STK11 mutations without KEAP1 loss were not associated with stage (KEAP1WT/STK11MUT: DFCI OR= 0.97, P= 1.0; MSKCC OR= 1.2, P= 0.33) or outcome. KEAP1/KRAS-mutated tumors with and without STK11 mutations exhibited high functional STK11 loss. The negative effects of KEAP1 were compounded in the presence of bone (HR= 2.3, P= 4.4× 10-14) and negated in the presence of lymph node metastasis (HR= 1.0, P= 0.91). Mutations in KEAP1 and SMARCA4, but not STK11, were associated with metastatic disease and poor OS. Functional STK11 loss, however, may contribute to poor outcomes in KEAP1MUT tumors. Integrating molecular data with clinical and metastatic-site annotations can more accurately risk stratify patients.

MemU-Net: A new volumetric dose prediction model using deep learning techniques in radiation treatment planning

Objective:Automatic radiation treatment planning systems are gaining significance nowadays. This paper presents a novel deep learning architecture for automatically generating the radiotherapy dose information given to the cancer patients. Methods:A new deep learning architecture MemU-Net is proposed. MemU-Net incorporates the principles of two existing deep learning architectures: Memnet, which was proposed for image restoration, and U-Net, which was proposed for biomedical image segmentation. The proposed model is first trained and tested with the public dataset (OpenKBP). The predicted dose distributions are evaluated based on dosimetric values and Dose volume histogram measures. The results are compared with the predictions made by a standard 3D U-Net, Residual U-Net, Dense U-Net and 3D GAN. The statistical significance of the proposed model is tested by computing the paired t-test P-values. Finally the proposed model is trained and tested on a private dataset collected from MVR Cancer Center and Research Institute. The model performance was evaluated by plotting DVHs and analyzing dosimetric values. Results:The dose distributions of MemU-Net shows superiority in performance compared to other models. MemU-Net had a lower mean absolute error of the predicted and ground truth doses than other models for all targets and OARs except spinal cord. The dosimetric measures of the MemU-Net outperformed the state of the art models except in the case of D0.1cc of OARs. Conclusion:A new variant of U-Net, MemU-Net is proposed, that performs better than the state of the art models, in the dose prediction domain in radiotherapy.

Improving Empiric Antibiotic Therapy Among Cancer Patients With Acute Cholangitis

Abstract Introduction Acute cholangitis (AC) is a hepatobiliary infection that requires prompt antibiotic therapy. Providers have to rely on empiric antibiotic guidelines, before receiving culture results. These antibiotic guidelines require routine surveillance of the biliary microbial flora and resistance patterns found in cultures to increase accuracy and appropriateness of empiric therapy. This is particularly essential in cancer patients who are more likely to be exposed to various antibiotics, potentially creating unique bactobilia, and fungobilia selection pressures that are different from the general patient population and require empiric therapy to halt AC progression to septicemia, shock, or mortality. This unique population is poorly researched and primary literature is relatively scarce. Methodology A retrospective chart review was performed to identify all patients between the age of 18 and 85 years who met the criteria for positive biliary culture and were treated for AC using empiric antibiotic treatment at the H. Lee Moffitt Cancer Center and Research Institute from January 2012 to January 2019. The patient information and laboratory results were analyzed to identify the microbial spectrum and drug resistance in bile cultures of cancer patients. Aim The aim of the study is to review the microbial patterns and characteristics of AC in immunocompromised patients with cancer. Results Pancreatic carcinomas and cholangiocarcinoma were most prevalent malignancies among patients. Although most bile cultures were polymicrobial, further analysis indicated Enterococcus species. Streptococcus species, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans were the most common isolates. Conclusions Cholangitis in cancer patients develops because of cholestasis from cancer obstructing the biliary flow mostly because of pancreatic cancer, cholangiocarcinoma, and metastatic cancer to the porta hepatis. Empiric antibiotic therapy should include broad-spectrum coverage for usual enteric flora.

History and Role of Quality Accreditation.

Accreditation has played a major role in the evolution of health care quality as well as the structure and organization of American medicine. In its earliest iterations, accreditation aimed to set a minimum standard of care, and now more prominently sets standards for high quality, optimal patient care. There are several institutions that provide accreditations that are relevant to colorectal surgery including the American College of Surgeons (ACS) Commission on Cancer, National Cancer Institute Cancer Center Designation, National Accreditation Program for Rectal Cancer, and the ACS Geriatrics Verification Program. While each program has unique criteria, the aim of accreditation is to assure high-quality evidenced-based care. In addition to these benchmarks, these programs provide avenues for collaboration and research between centers and programs.

Monitoring the Implementation of Tobacco Cessation Support Tools: Using Novel Electronic Health Record Activity Metrics.

Clinical decision support (CDS) tools in electronic health records (EHRs) are often used as core strategies to support quality improvement programs in the clinical setting. Monitoring the impact (intended and unintended) of these tools is crucial for program evaluation and adaptation. Existing approaches for monitoring typically rely on health care providers' self-reports or direct observation of clinical workflows, which require substantial data collection efforts and are prone to reporting bias. This study aims to develop a novel monitoring method leveraging EHR activity data and demonstrate its use in monitoring the CDS tools implemented by a tobacco cessation program sponsored by the National Cancer Institute's Cancer Center Cessation Initiative (C3I). We developed EHR-based metrics to monitor the implementation of two CDS tools: (1) a screening alert reminding clinic staff to complete the smoking assessment and (2) a support alert prompting health care providers to discuss support and treatment options, including referral to a cessation clinic. Using EHR activity data, we measured the completion (encounter-level alert completion rate) and burden (the number of times an alert was fired before completion and time spent handling the alert) of the CDS tools. We report metrics tracked for 12 months post implementation, comparing 7 cancer clinics (2 clinics implemented the screening alert and 5 implemented both alerts) within a C3I center, and identify areas to improve alert design and adoption. The screening alert fired in 5121 encounters during the 12 months post implementation. The encounter-level alert completion rate (clinic staff acknowledged completion of screening in EHR: 0.55; clinic staff completed EHR documentation of screening results: 0.32) remained stable over time but varied considerably across clinics. The support alert fired in 1074 encounters during the 12 months. Providers acted upon (ie, not postponed) the support alert in 87.3% (n=938) of encounters, identified a patient ready to quit in 12% (n=129) of encounters, and ordered a referral to the cessation clinic in 2% (n=22) of encounters. With respect to alert burden, on average, both alerts fired over 2 times (screening alert: 2.7; support alert: 2.1) before completion; time spent postponing the screening alert was similar to completing (52 vs 53 seconds) the alert, and time spent postponing the support alert was more than completing (67 vs 50 seconds) the alert per encounter. These findings inform four areas where the alert design and use can be improved: (1) improving alert adoption and completion through local adaptation, (2) improving support alert efficacy by additional strategies including training in provider-patient communication, (3) improving the accuracy of tracking for alert completion, and (4) balancing alert efficacy with the burden. EHR activity metrics were able to monitor the success and burden of tobacco cessation alerts, allowing for a more nuanced understanding of potential trade-offs associated with alert implementation. These metrics can be used to guide implementation adaptation and are scalable across diverse settings.

Abstract P4-07-14: Long-term Outcomes After 1 or 2-3 Lines of Neoadjuvant Therapy in Stage III Inflammatory Breast Cancer

Abstract Background: Inflammatory breast cancer (IBC) is associated with a poor prognosis. While many stage III IBC patients (pts) experience a sufficient response to first-line (1L) neoadjuvant chemotherapy (NAC) to permit subsequent surgical therapy, the prognostic significance of requiring additional NAC to enable resectability is unknown. We sought to describe the pathologic complete response (pCR) rates, breast cancer-free survival (BCFS) and overall survival (OS) among pts requiring 1 vs >1 lines of NAC prior to surgery. Methods: Upon IRB approval, pts with stage III IBC from 2 academic institutions (Dana-Farber Cancer Institute and MD Anderson Cancer Center) who received 1L or 2-3 lines (2-3L) of NAC prior to surgery were identified. Standard NAC regimens containing different drugs, such as AC-T or TCHP, were considered as 1L. Pts with locoregional progression or metastatic disease prior to surgery were excluded. Hormone receptor (HR), HER2 status, grade, and pCR, defined as no residual invasive cancer in the breast and the axilla, were evaluated. BCFS, defined as time from surgery to locoregional and/or distant recurrence, and OS, defined as time from surgery to death, were evaluated by the Kaplan-Meier method. Multivariable Cox models stratified by institution and containing the covariates pCR and tumor subtype were utilized to estimate the HR of 2-3L vs. 1L of therapy. Results: 808 eligible pts diagnosed between 1997 and 2020 were identified. 733 (91%) had 1L and 75 (9%) had 2-3L of NAC, and the median age was 50 years. 295 (37%) had HER2+, 282 (35%) HR+HER2-, 211 (26%) had HR-HER2- disease and for 20 (2%) pts, the receptor status was unknown. The median time from diagnosis to surgery was 6 months. Grade III disease, triple-negative and HER2-positive disease were more prevalent in pts receiving 2-3L of therapy (table). pCR was achieved in 178 (24%) pts receiving 1L of NAC, and in 14 (19%) pts receiving 2-3L of NAC. At 68 months of median follow-up, 417 (52%) pts experienced a recurrence with 376 in the 1L group and 41 in the 2-3L group. The 5-year BCFS was shorter for the 2-3L group compared to the 1L group (33% v 46%, HR=1.37; 95% CI:0.99-1.91). However, in 192 pts with a pCR, BCFS was similar, regardless of the number of NAC lines. There were 38 recurrences among 178 1L pts, and 3 recurrences among 14 2-3L pts, resulting in BCFS of 76% and 83% in 1L and 2-3L pts, respectively. Overall, there were 308 deaths, 276 deaths among 1L pts and 32 among 2-3L pts. The 5-yr OS estimate in 1L versus 2-3L pts was 60% versus 53% (HR=1.32, 95% CI: 0.91-1.93). Conclusion: Among pts with stage III IBC, pCR was observed among 24% who had 1L and 19% of pts who required 2-3L of NAC. BCFS and OS were comparable among pts with pCR after 1L and 2-3L. Our results suggest the need to continue to optimize current treatment strategies in IBC to improve pCR rates across all disease subtypes regardless of the number of lines of NAC required. Citation Format: Faina Nakhlis, Samuel Niman, Naoto T. Ueno, Elizabeth Troll, Sean Ryan, Eren Yeh, Laura Warren, Jennifer Bellon, Beth Harrison, Toshiaki Iwase, H. T. Carisa Le-Petross, Sadia Saleem, Mediget Teshome, Gary J. Whitman, Wendy Woodward, Beth Overmoyer, Sara Tolaney, Meredith Regan, Filipa Lynce, Rachel M. Layman. Long-term Outcomes After 1 or 2-3 Lines of Neoadjuvant Therapy in Stage III Inflammatory Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-14.

Self-esteem of acute leukemic children undergoing chemotherapy

Background Acute leukemia is a major malignancy in children. Multiagent chemotherapy protocols are the main treatment option for acute leukemia. Still chemotherapy has a significant effect on children's well-being, improving the physical, psychological, and social status of children, and also, it has a remarkable effect on self-image and self-esteem. Aim The aim was to assess self-esteem of acute leukemic children undergoing chemotherapy. Patients and methods A descriptive exploratory research design was used. The study was conducted at two pediatric oncology outpatient clinics at Tanta Cancer Center and National Cancer Institute at Cairo University. A purposive sample of 80 children with acute lymphoblastic leukemia was recruited. Their ages were between 10 and 16 years old. A structured interview questionnaire and Coopersmith Self-esteem Inventory were used, and IRB approval was obtained from the National Cancer Institute for performing this study. Results The age of half of the children (50%) ranged between 14 and 16 years, with mean±SD age of 13.21±1.62 years. Overall, 61.3% were males. Less than half of the children (47.5%) received intravenous chemotherapy, whereas 46.2% of the children had both oral and intravenous chemotherapy. More than half of the children (62.5%) had low self-esteem regarding general self, whereas the vast majority of children (90%) had low self-esteem regarding their social self-peers. All children had low self-esteem toward their home parents, whereas the highest percent (98.8%) of children had low self-esteem regarding their school academic. The vast majority children (98.8%) had low self-esteem regarding the lie scale. All dimensions of self-esteem were significantly correlated with total score of self-esteem. Conclusion Children with acute leukemia undergoing chemotherapy had low self-esteem regarding general self, home parents, school academic, and social peers. Self-esteem was negatively affected among school age and adolescent children with acute leukemia who underwent chemotherapy. Regarding the lie domain, most children always told the truth. Recommendations Training programs should be designed and constructed for nurses in how to assess self-esteem for children with acute leukemia. Empowerment program should be directed to children with acute leukemia and their caregivers to improve their self-esteem.

Abstracts Teaching Kitchen Research Conference Los Angeles, California October 18–19, 2022

Abstracts Teaching Kitchen Research Conference Los Angeles, California <i>October 18–19, 2022</i>

Developing a Collaborative, Team-Based Smoking Cessation Treatment Program in an Outpatient Oncology Setting.

Because clinical specialists often lack time and training to address secondary health issues such as smoking cessation, the National Cancer Institute Cancer Center Cessation Initiative (C3I) has mobilized cancer centers to develop systems for treating patients' tobacco dependence. One university-based cancer center was able to develop a program that formalized smoking treatment using a collaborative, multidisciplinary care team with overlapping expertise in cancer care, medication management, and tobacco cessation. Program planners delivered tobacco cessation services in the outpatient setting by automating identification of eligible patients using a tobacco registry in the electronic health records, directly involving oncology pharmacists in medication oversight, using dedicated tobacco treatment specialists to provide cessation services, and engaging oncologists through active communications protocols. Evaluators used Practical Robust Implementation and Sustainability Model as the guiding framework for a qualitative assessment of program development and implementation. Evaluators also measured provider satisfaction and utilization of services, program reach, and smoking cessation outcomes 6 months post enrollment. During the evaluation period (July 1, 2018-September 30, 2019), the smoking cessation program engaged 96% of eligible patients (n = 214 of 223 eligible); 82% of those enrolled in the program (n = 183). At 6-month follow-up, 29.1% of enrolled patients self-reported 30-day point prevalence abstinence (n = 53) and 34.9% (n = 64) reported 7-day point prevalence abstinence (intent-to-treat rates). Using a team-based approach that leverages individual expertise and interprofessional collaboration to provide patient-centered treatment, a smoking cessation program can identify and treat eligible patients in specialty clinics.

Treatments and Outcomes for Patients at Academic Cancer Centers with Myelodysplastic Syndrome (MDS) By Revised International Prognostic Scoring System (IPSS-R) Scores

BACKGROUND: IPSS-R classifications are used to estimate risk of disease progression to acute myeloid leukemia (AML), overall survival (OS), and to guide treatment decisions for patients with MDS. Recent data show mutational profiles improve prognostic stratification of MDS. This study aims to describe the distribution of IPSS-R scores in patients with MDS and assess treatment patterns and clinical outcomes by IPSS-R scores. METHODS: A retrospective cohort study assessed real-world, patient-level data from adults diagnosed with MDS between 2010-2020 at the Huntsman Cancer Institute and Moffitt Cancer Center, both NCCN, NCI-designated Comprehensive Cancer Centers. Data were obtained via chart review from electronic medical records. IPSS-R scores were calculated at or within 30 days of diagnosis. Patients with an intermediate to very-high IPSS-R score (3.5-6+) comprised the higher risk (HR) cohort; those with low or very low-risk IPSS-R (0-3) comprised the lower risk (LR) cohort. Study variables were compared across cohorts. Progression-free survival (PFS), defined as physician documented disease progression, AML transformation, or death, was evaluated from initiation of medication therapy and was censored at lost to follow-up or initiation of second-line therapy. OS was also assessed from treatment initiation. Clinical outcomes, specifically PFS and OS, were assessed within the hypomethylating agent (HMA)-treated subgroup. The influence of common genetic alterations on clinical outcomes was evaluated. RESULTS: There were 369 patients included in this analysis. Distribution of IPSS-R scores was: 5% (n=18) very low, 18% (n=68) low, 26% (n=97) intermediate, 25% (n=94) high, and 25% (n=92) very high. The mean age of patients was 66 years (SD: 10.6). Males were 56% (n=208) of patients, 93% (n=342) were white, and 41% (n=141) were transfusion independent at diagnosis. Transfusion independence was more common in the LR cohort (47%, n=35) compared to the HR cohort (39%, n=106). Among NGS-tested patients, the TP53 gene was most frequently altered (30%, n=86), followed by ASXL1 (20%, n=58), TET2 (17%, n=50), and DNMT3A (15%, n=44). The HR cohort harbored more TP53 mutations (HR: n=78 [35%]; LR: n=8 [12%]) and fewer SF3B1 mutations (HR: n=11 [5%]; LR: n=14 [22%]). In the HR cohort, first-line HMAs were used to treat 81% (n=230) of patients for a median of 4 cycles, while 11% (n=32) received no MDS-directed therapy, and 7% (n=21) received other medications for treatment of MDS (e.g., clinical trial drug, hydroxyurea). In the LR cohort, HMAs were used to treat 51% (n=44) of patients for a median 5 cycles, 26% (n=22) received no MDS-directed therapy, & 23% (n=20) received other medications for treatment of MDS (e.g., clinical trial drug, hydroxyurea). Second-line treatment was received by 24% of patients (n=88) with HMAs as the most frequent therapy choice for both HR (19%, n=53) and LR (16%, n=14) patients. Lenalidomide was the second most common second-line therapy for both HR (1%, n=3) and LR (5%, n=4) patients. Stem-cell transplant (SCT) was pursued within the HR cohort both more frequently (n=157 [55%] vs. n=23 [27%]) and sooner (7.2 vs. 9.3 median months from diagnosis) compared to the LR cohort. Among HR patients treated with first-line HMA complete response (CR) was achieved by 11% (n=26) with a median duration of CR of 23.8 months that included 24 patients (92%) who received SCT. Among first-line HMA-treated patients (n=274), median PFS was shorter within the HR cohort (median 9.5 months) compared to the LR cohort (18.3 months). Similarly, among first-line HMA-treated patients (n=274) median OS was shorter for the HR cohort (18.8 months) compared to the LR cohort (25.6 months. Among HMA-treated HR patients (n=227), OS was shorter for TP53 mutated patients (median 14.3 vs. 26.8 months) compared to TP53 wildtype patients, and longer for ASXL1 mutated patients (median 51.8 vs. 16.3 months) compared to ASXL1 wildtype patients. CONCLUSIONS: In the first-line setting, HR patients have low likelihood of achieving and maintaining a complete response. Both HR and LR patients have a high likelihood of experiencing disease progression. In addition, few patients received second-line therapy. Therefore, a large unmet need exists for first and subsequent lines of therapy. Specific genetic profiles may influence treatment decisions. Future research will describe the IPSS-M classification system within the same cohort.

Hypoplastic MDS: Validation of the New World Health Organization 2022 Proposal

Introduction: Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic neoplasms that is characterized by ineffective hematopoiesis. The morphological diagnosis is essential and reveals a subset of patients with hypoplastic marrow, referred to as hypoplastic MDS (MDS-h) that is more recently being proposed as a distinct entity in the World Health Organization (WHO) 2022 proposal for myeloid neoplasms. MDS-h shares several features with aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH), thus, it needs a careful diagnostic approach, but also, the natural history of the disease is distinct than those with non-hypoplastic MDS (MDS-nh) warranting consideration for further subclassification. Here, we aim to study the characteristics and molecular profiling of MDS-h as opposed to the (MDS-nh), in addition to treatment and disease outcomes, and overall survival. Methods: We conducted a retrospective analysis of all patients diagnosed with MDS at the H. Lee Moffitt Cancer Center & Research Institute from our MDS database. Patients were divided into two groups: those with MDS-h, defined as bone marrow cellularity of less than 30%, and those with MDS-nh, with cellularity greater than 30%. We further subdivided patients based on the marrow blasts (<5% vs >=5%). Patients with MDS/MPN were excluded. Results: A total of 4037 patients with MDS were identified, of those, 403 (10%) were MDS-h. The median age at diagnosis was 65 and 68 for MDS-h and MDS-nh respectively (P= 0.03). In females, MDS-h was observed more compared to MDS-nh (41% vs 35%, P= 0.008). There was no difference in terms of IPSS-R, LGL clones, PNH clones, and history of autoimmune diseases. MDS-RS was more observed in MDS-nh. Interestingly, therapy-related MDS (t-MDS) was more observed in MDS-h (29% vs 20%, P <0.005). Patients with MDS-h had more thrombocytopenia, neutropenia and were more likely to be platelet transfusion dependent (31% vs 23% P=0.001). The following somatic mutations were found more frequently in MDS-nh compared to MDS-h: SF3B1 (P<0.005), SRSF2 (P<0.005), TET2 (P=0.004), and ASXL1 (P=0.02). There was a better response to ATG/CSA among MDS-h compared to MDS-nh (46% vs 21% P=0.019). On the contrary patients with MDS-nh were more likely to respond to lenalidomide when compared to patients with MDS-h (46% vs 22% P=0.001). There was no statistically significant difference in response to hypomethylating agents. The median overall survival (OS) for MDS-h was 41.6 months compared to 35 months in patients with MDS-nh (P=0.05). The HR for OS was 0.88 (P =0.057) adjusted for IPSS-R. There was no difference in the rate of AML transformation. Then, we further categorized patients based on the marrow blasts. Among MDS-h, 43% (170/400) had myeloblasts >=5% (MDS-EB), The median OS was 53 months for MDS-h with < 5% blasts (n=231) compared to 27 months for those with >= 5% blasts (n=170) (P < 0.005). Among all patients with MDS-EB, those with MDS-h (n= 170) had median OS of 27 month compared to 19 months for MDS-EB with MDS-nh (n=1465) (P=0.02). Conclusions: In summary, we conclude that MDS-h accounted for 10% of MDS cases. The OS for MDS-h is better than MDS-nh. Additionally, MDS-h tended to have lower frequency of splicing and epigenetic somatic mutations. Among MDS-h, patients with marrow myeloblasts >=5% clearly had inferior outcomes compared to those MDS-h with blasts <5%. Therefore, our findings support the new WHO 2022 proposal for MDS-h as a distinct entity with restriction to patients with marrow cellularity of <30% and marrow myeloblasts <5%.

A Vocation of Palliation.

I consider myself a "late bloomer," since I never encountered the practice of palliative care during medical school in the Philippines, nor during my internal medicine residency in the USA. It was 3years into my first job after finishing residency, working both as a hospitalist and an urgent care physician, when I came to an early morning session on end-of-life care at a large medical society meeting. That talk changed my life. I now see palliative care as being more than a "profession" or a "medical specialty." It is my vocation, as serendipitous events called me into this line of work. For more than 5years now, I have been practicing palliative care, both in the inpatient and outpatient settings, at our institution's cancer center. In this article, I reflect on my experiences during fellowship, and how I continue to derive satisfaction and joy from teaching palliative care to different levels of learners and through the meaningful connections I form with patients and their loved ones.

Evaluation of tumor microenvironment and biomarkers of immune checkpoint inhibitor response in metastatic renal cell carcinoma

BackgroundImmunotherapy combinations including ipilimumab and nivolumab are now the standard of care for untreated metastatic renal cell carcinoma (mRCC). Biomarkers of response are lacking to predict patients who will have...

Reply.

We thank Dr. Lo for the interest in our manuscripts that explored the association of COVID-19 vaccination and mortality.[1, 2] As correctly pointed out, the study reflects the distribution of cirrhosis in the entire Veterans Health Administration without a referral or tertiary care bias.[1-3] Therefore, as expected, the majority of participants included in both studies had compensated cirrhosis. Our results showed that, among patients with compensated cirrhosis, postvaccination COVID-19 was associated with an 81% reduction in hazard of death [adjusted hazard ratio (aHR) 0.19, 95% confidence interval (CI) 0.08–0.45, p = 0.0001] and 84% reduction in COVID-19–related death (aHR 0.16, 95% CI 0.06–0.46, p = 0.0001).[1] Among patients with decompensated cirrhosis, postvaccination COVID-19 was associated with a 73% reduction in hazard of death (aHR 0.27, 95% CI 0.08–0.90, p = 0.03) but not COVID-19–related death (aHR 0.51, 95% CI 0.14–1.88, p = 0.31). We believe that the lack of significance with COVID-19–related death among participants with decompensated cirrhosis is likely a Type II error; the power to identify differences between postvaccination and unvaccinated COVID-19 in this subgroup was only 48.7%, and the sample size required to identify differences between the two groups with 80% power was 366, which was higher than our study sample. Our retrospective study was not designed to identify vaccine safety. However, a follow-up study from our group using data from the same cohort compared vaccination-induced immunity and infection-induced immunity among participants with cirrhosis and was adequately powered.[4] The vaccine-associated immunity group was fully vaccinated participants with cirrhosis with no documented severe acute respiratory syndrome coronavirus 2 infection. The infection-induced immunity group was unvaccinated participants who had prior COVID-19. A subgroup analysis among the participants with decompensated cirrhosis in this study showed that vaccine-induced immunity was associated with a reduction in odds of developing COVID-19 [adjusted odds ratio (aOR) 0.10, 95% CI 0.07–0.13, p < 0.0001] and symptomatic (aOR 0.49, 95% CI 0.35–0.70, p < 0.0001), moderate/severe/critical (aOR 0.42, 95% CI 0.26–0.69, p = 0.0004), and severe or critical COVID-19 (aOR 0.15, 95% CI 0.07–0.31, p < 0.0001) compared with infection-induced immunity. This study, done later in the pandemic, had a larger sample size and more outcomes to demonstrate statistical significance. The above findings suggest that COVID-19 vaccines appear to be protective among participants with decompensated cirrhosis in an adequately powered study cohort, but we agree with the need for more studies in this highly vulnerable population. Services supporting this research project were generated by the Virginia Commonwealth University Massey Cancer Center Biostatistics Shared Resource, supported, in part, with funding from National Institute of Health-National Cancer Institute Cancer Center Support Grant P30 CA016059. Nothing to report. The authors prepared this work in their personal capacity. The opinions expressed in this article are the author's own and do not reflect the view of the Department of Veterans Affairs or the United States government.

Editorial Comment

No AccessJournal of UrologyAdult Urology1 Sep 2022Editorial CommentThis article comments on the following:DNA Methylation Urine Biomarkers Test in the Diagnosis of Upper Tract Urothelial Carcinoma: Results from a Single-Center Prospective Clinical Trial Lee A. Hugar, Scott M. Gilbert, and Roger Li Lee A. HugarLee A. Hugar Moffitt Cancer Center and Research Institute, Tampa, Florida More articles by this author , Scott M. GilbertScott M. Gilbert Moffitt Cancer Center and Research Institute, Tampa, Florida More articles by this author , and Roger LiRoger Li Moffitt Cancer Center and Research Institute, Tampa, Florida More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002748.01AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Editorial Comment." The Journal of Urology, 208(3), p. 578

EP01.03-008 Lung Cancer Screening Patients Experiences and Satisfaction: Quantitative and Qualitative Findings From a Survey Study

In 2015, H. Lee Moffitt Cancer Center & Research Institute (MCC) launched a lung cancer screening program for high-risk individuals based on National Comprehensive Cancer Network guidelines. To identify successes and barriers of this program from the patient perspective, we conducted a survey study to measure patient experiences and satisfaction with lung cancer screening.

Dose escalation based on 18F-FDG PET/CT response in definitive chemoradiotherapy of locally advanced esophageal squamous cell carcinoma: a phase III, open-label, randomized, controlled trial (ESO-Shanghai 12)

IntroductionDefinitive chemoradiotherapy has established the standard non-surgical treatment for locally advanced esophageal cancer. The standard dose of 50–50.4 Gy has been established decades ago and been confirmed in modern trials. The theorical advantage of better local control and technical advances for less toxicity have encouraged clinicians for dose escalation investigation. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) have the potential to tailor therapy for esophageal patients not showing response to CRT and pioneers the PET-based dose escalation.Methods and analysisThe ESO-Shanghai 12 trial is a prospective multicenter randomized phase 3 study in which patients are randomized to either 61.2 Gy or 50.4 Gy of radiation dose by PET response. Both groups undergo concurrent chemoradiotherapy with paclitaxel/cisplatin regimen for 2 cycles followed by consolidation chemotherapy for 2 cycles. Patients with histologically confirmed ESCC [T1N1-3M0, T2-4NxM0, TxNxM1 (Supraclavicular lymph node metastasis only), (AJCC Cancer Staging Manual, 8th Edition)] and without any prior treatment of chemotherapy, radiotherapy or surgery against esophageal cancer will be eligible. The primary endpoints included overall survival in PET/CT non-responders (SUVmax > 4.0) and overall survival in total population. Patients will be stratified by standardized uptake volume, gross tumor volume and tumor location. The enrollment could be ended, when the number of PET/CT non-responder reached 132 and the total population reached 646 for randomization.Ethics and disseminationThis trial has been approved by the Fudan University Shanghai Cancer Center Institutional Review Board. Trial results will be disseminated via peer reviewed scientific journals and conference presentations.Trial registration The trial was initiated in 2018 and is currently recruiting patients. Trial registration number NCT03790553.

Updated International Society of Geriatric Oncology COVID-19 working group recommendations on COVID-19 vaccination among older adults with cancer

Updated International Society of Geriatric Oncology COVID-19 working group recommendations on COVID-19 vaccination among older adults with cancer

Abstract 5886: Pre-treatment adiposity measured by computed tomography and survival of women with high-grade serous ovarian cancer

Abstract The association of body mass index (BMI) with survival of women with ovarian cancer remains unclear due to mixed epidemiological evidence. This may be due, in part, to the fact that BMI is an imperfect measure of body fat as BMI does not distinguish weight from lean muscle versus adipose tissue. Here, we investigated the association of adiposity measured by computed tomography (CT) with survival among the most common histotype of ovarian cancer, high-grade serous ovarian cancer (HGSOC). The present study included 383 women diagnosed with HGSOC from 2008 to 2019 who were evaluated at H. Lee Moffitt Cancer Center and Research Institute and had pre-treatment computed tomography scans available for analysis. The sliceOmatic v5.0 rev13 (Tomovision, Magog, Canada) medical image analysis software and accompanying ABACS module for segmentation was used to quantify subcutaneous (SAT), visceral (VAT), and intermuscular adipose tissue (IMAT) from the third lumbar (L3) axial slice including the transverse processes. We used Cox proportional hazard regression to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for the association of each measure of adiposity with overall survival (OS) and recurrence-free survival (RFS) while adjusting for age at diagnosis, stage, race and ethnicity, and first-line treatment. The degree of ascites was included in the VAT models as ascites fluid density can mask VAT. We also assessed these associations within first-line treatment groups (upfront chemotherapy [n=147], upfront surgery [n=236]). In the overall study population, we observed a positive but not statistically significant association with OS and RFS for the highest vs. lowest tertile of IMAT (HR= 1.18, 95% CI=0.83, 1.67 and HR=1.16, 95% CI=0.85, 1.58, respectively). Among women who received upfront surgery, the highest tertile of IMAT was associated with a 57% increased risk of recurrence compared to the lowest tertile (HR=1.57, 95% CI=1.04, 2.37), while the association between IMAT and OS was similar to the findings in the overall population (HR=1.14, 95% CI=0.73, 1.78). No association was observed between IMAT and OS or RFS among women who received upfront chemotherapy. No associations with OS or RFS were observed for SAT or VAT overall or within first-line treatment groups. In summary, we observed inferior RFS among HGSOC patients with higher IMAT. These findings suggest that IMAT measured from standard-of-care imaging may represent a biomarker of recurrence among HGSOC patients, and incorporating lifestyle and behavioral changes (e.g., diet, exercise) to decrease IMAT may be warranted for this patient population. Citation Format: Christelle Colin-Leitzinger, Daniel Jeong, Mahmoud Abdalah, Rikki Cannioto, Jing-Yi Chern, Evan Davis, Robert Gillies, Melissa McGettigan, Jaileene Perez-Morales, Natarajan Raghunand, Sweta Sinha, Olya Stringfield, Rajwantee Tirbene, Matthew Schabath, Lauren C. Peres. Pre-treatment adiposity measured by computed tomography and survival of women with high-grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5886.

Real-World Adherence to Patient-Reported Outcome Monitoring as a Cancer Care Quality Metric.

Routine collection of patient-reported outcomes (PROs) for patients with advanced solid malignancies is an evidence-based practice and critical component of high-quality cancer care, but real-world adherence is poorly characterized. We sought to describe real-world adherence to PRO monitoring and its potential predictors. We conducted a retrospective cross-sectional study using deidentified electronic health record data from a National Cancer Institute Cancer Center, encompassing one academic and two community sites. Participants included individuals with lung cancer receiving systemic therapy from January 1 to December 31, 2019. The primary outcome was patient-level adherence, defined as the proportion of treatment visits during which a PRO questionnaire (spanning symptoms, functional status, and global quality-of-life domains) was completed within 30 days. Practice-level performance was calculated as unadjusted mean patient-level adherence. We modeled patient-level adherence using multivariable ordinary least squares regression and identified covariates associated with adherence using a significance threshold of P < .05. In 2019, there were 18,604 encounters for 1,105 patients with lung cancer (mean [standard deviation] age 65.8 [10.2] years; 621 [56.2%] female; 216 [19.6%] Black) receiving systemic therapy. The mean patient-level PRO adherence ranged from 27.2% to 70.0% across sites and was 49.4% overall. Advanced age (≥ 65 years) and Black or African American race were negatively associated with PRO adherence (P < .01). Across this real-world cohort of patients undergoing treatment for lung cancer, adherence to PRO monitoring lagged that achieved in seminal clinical trials, with potential age- and race-based disparities, demonstrating an implementation gap that could be addressed with standardized reporting of an adherence-based quality metric.