Fragmentation of Care in Patients with Peritoneal Metastases Undergoing Cytoreductive Surgery.

BACKGROUND: The delivery of multimodal treatment at a high-volume center is known to optimize the outcomes of gastrointestinal malignancies. However, patients undergoing cytoreductive surgery (CRS) for peritoneal metastases often must 'fragment' their surgical and systemic therapeutic care between different institutions. We hypothesized that this adversely affects outcomes. PATIENTS AND METHODS: Adults undergoing CRS for colorectal or appendiceal adenocarcinoma at our institution between 2016 and 2022 were identified retrospectively and grouped by care network: 'coordinated care' patients received exclusively in-network systemic therapy, while 'fragmented care' patients received some systemic therapy from outside-network providers. Factors associated with fragmented care were also ascertained. Overall survival (OS) from CRS and systemic therapy-related serious adverse events (SAEs) were compared across the groups. RESULTS: Among 85 (80%) patients, 47 (55%) had colorectal primaries and 51 (60%) received fragmented care. Greater travel distance [OR 1.01 (CI 1.00-1.02), p = 0.02] and educational status [OR 1.04 (CI 1.01-1.07), p = 0.01] were associated with receiving fragmented care. OS was comparable between patients who received fragmented and coordinated care in the colorectal [32.5 months versus 40.8 months, HR 0.95 (CI 0.43-2.10), p = 0.89] and appendiceal [31.0 months versus 27.4 months, HR 1.17 (CI 0.37-3.74), p = 0.55] subgroups. The frequency of SAEs (7.8% versus 17.6%, p = 0.19) was also similar. CONCLUSIONS: There were no significant differences in survival or SAEs based on the networks of systemic therapy delivery. This suggests that patients undergoing CRS at a high-volume center may safely receive systemic therapy at outside-network facilities with comparable outcomes.

Dietary fat in relation to all-cause mortality and cancer progression and death among people with metastatic colorectal cancer: Data from CALGB 80405 (Alliance)/SWOG 80405.

Data on diet and survival among people with metastatic colorectal cancer are limited. We examined dietary fat in relation to all-cause mortality and cancer progression or death among 1149 people in the Cancer and Leukemia Group B (Alliance)/Southwest Oncology Group (SWOG) 80405 trial who completed a food frequency questionnaire at initiation of treatment for advanced or metastatic colorectal cancer. We examined saturated, monounsaturated, total and specific types (n-3, long-chain n-3 and n-6) of polyunsaturated fat, animal and vegetable fats. We hypothesized higher vegetable fat intake would be associated with lower risk of all-cause mortality and cancer progression. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI). Over median follow-up of 6.1 years (interquartile range [IQR]: 5.3, 7.2 y), we observed 974 deaths and 1077 events of progression or death. Participants had a median age of 59 y; 41% were female and 86% identified as White. Moderate or higher vegetable fat was associated with lower risk of mortality and cancer progression or death (HRs comparing second, third and fourth to first quartile for all-cause mortality: 0.74 [0.62, 0.90]; 0.75 [0.61, 0.91]; 0.79 [0.63, 1.00]; P trend: .12; for cancer progression or death: 0.74 [0.62, 0.89]; 0.78 [0.64, 0.95]; 0.71 [0.57, 0.88]; P trend: .01). No other fat type was associated with all-cause mortality and cancer progression or death. Moderate or higher vegetable fat intake may be associated with lower risk of cancer progression or death among people with metastatic colorectal cancer.

Role of Tumor-informed Personalized Circulating Tumor DNA Assay in Informing Recurrence in Patients With Peritoneal Metastases From Colorectal and High-grade Appendix Cancer Undergoing Curative-intent Surgery.

OBJECTIVE: To investigate the role of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay in informing recurrence in patients with peritoneal metastases (PM) from colorectal (CRC) and high-grade appendix (HGA) cancer after curative cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). BACKGROUND: Over 50% of patients with CRC/HGA-PM recur after optimal CRS-HIPEC. The limited sensitivity of axial imaging and diagnostic biomarkers is a significant cause of delay in the detection of recurrence and initiation of further therapies. Plasma ctDNA has a promising role in monitoring response to treatment and/or recurrence after primary cancer resection. METHODS: Patients with CRC/HGA-PM who underwent curative CRS-HIPEC and serial postresection ctDNA assessments were included. Patients with rising postoperative ctDNA levels were compared with those with stable, undetectable ctDNA levels. Primary outcomes were the percentage of patients with recurrence and disease-free survival (DFS). Secondary outcomes were overall survival, ctDNA sensitivity, lead time, and performance of ctDNA compared with carcinoembryonic antigen. RESULTS: One hundred thirty serial postresection ctDNA assessments [median 4, interquartile range (IQR), 3 to 5] were performed in 33 patients (n = 13 CRC, n = 20 HGA) who underwent completeness of cytoreduction-0/1 CRS with a median follow-up of 13 months. Of the 19 patients with rising ctDNA levels, 90% recurred versus 21% in the stable ctDNA group (n = 14, < 0.001). Median DFS in the rising ctDNA cohort was 11 months (IQR, 6 to 12) and not reached in the stable ( P = 0.01). A rising ctDNA level was the most significant factor associated with DFS (hazard ratio: 3.67, 95% CI: 1.06-12.66, P = 0.03). The sensitivity and specificity of rising ctDNA levels in predicting recurrence were 85% and 84.6%, respectively. The median ctDNA lead time was 3 months (IQR, 1 to 4). Carcinoembryonic antigen was less sensitive (50%) than ctDNA. CONCLUSIONS: This study supports the clinical validity of serial ctDNA assessment as a strong prognostic biomarker in informing recurrence in patients with CRC/HGA-PM undergoing curative resection. It also holds promises for informing future clinical trial designs and further research.

Intra-operative Radiation Therapy for Colorectal or Anal Cancer at Risk for Margin-Positive Resection: Initial Results of a Single-Institution Registry.

PURPOSE: Pelvic recurrence of rectal or anal cancers is associated with considerable morbidity and mortality. We report our initial experience with an aggressive intra-operative radiotherapy (IORT) program. METHODS: Patients with locally advanced or recurrent rectal or anal cancers considered to have a high likelihood of R1 or R2 resection after multi-disciplinary review underwent surgical excision and IORT using a high-dose-rate afterloader (Ir-192) and HAM applicator. Endpoints included local or distant recurrence, and acute and late toxicity graded using the American College of Surgeons (ACS) NSQIP and the LENT-SOMA scale. RESULTS: Twenty-one patients, largely with prior history of both pelvic external beam radiotherapy (EBRT, median 50.4 Gy) and surgical resection, underwent excision with IORT (median dose 12.5 Gy, range 10-15). Median follow-up was 20 months. Twelve (57%) patients had failure at the IORT site. Freedom from failure (FFF) within the IORT field was associated with resection status (FFF at 1 year 75% for R0 vs 15% for R1/2, p = 0.0065) but not re-irradiation EBRT or IORT dose (p > 0.05). Twelve, 5, and 13 patients experienced local, regional, and distant failure, respectively; 3 (14%) patients were disease-free at last follow-up. The most frequent acute toxicity was sepsis/abscess (24%). One patient (5%) required a ureteral stent; no patients developed neuropathy attributable to IORT. CONCLUSIONS: In patients treated with excision and IORT for locally recurrent cancer, R0 resection is a critical determinant of local control. For patients with R1/2 resection, poor disease-free outcomes warrant consideration of a different treatment strategy.

PI3K Pathway Alterations in Peritoneal Metastases are Associated with Earlier Recurrence in Patients with Colorectal Cancer Undergoing Optimal Cytoreductive Surgery.

BACKGROUND: Colorectal cancer with peritoneal metastasis (CRC-PM) represents a biologically heterogeneous disease; yet little is known regarding the impact of tumor biology on survival outcomes following optimal cytoreductive surgery (CRS). We analyzed the frequency of alterations in cancer signaling pathways in patients with CRC-PM and their impact on recurrence-free survival (RFS) following optimal CRS. METHODS: Thirty-five consecutive CRC-PM patients who underwent optimal CRS/HIPEC and next generation sequencing of peritoneal metastases were included in the study. Alterations in eight cancer-related signaling pathways were analyzed: Wnt/APC, p53, RTK-RAS, PI3K, TGF-B, Notch, Myc, and cell cycle. The association of pathway alterations with RFS and OS following optimal cytoreduction was estimated using Cox proportional hazard modeling. RESULTS: The most frequently altered pathways were Wnt/APC (63%), p53 (63%), RTK-RAS (60%), and PI3K (23%). Among optimally cytoreduced patients with CRC-PM, PI3K pathway alterations were an independent predictor of worse RFS (hazard ratio 3.2, 95% confidence interval CI 1.3-8.3, p = 0.01) with a clinically meaningful impact on median months to recurrence (5 vs. 13 months, p = 0.02). Alterations in p53, Wnt, and RTK-RAS pathways were not significantly associated with a difference in RFS following CRS. Alterations in the four pathways were not associated with differences in OS following CRS (median OS was 50 (interquartile range 23-80) months). CONCLUSIONS: In patients with CRC-PM, PI3K pathway alterations are associated with earlier recurrence following optimal CRS, which may represent a distinct molecular subtype. This novel finding can tailor clinical trials by using PIK3CA-directed interventions to reduce risk of recurrence after optimal CRS.

Mutational profiles and prognostic impact in colorectal and high-grade appendiceal adenocarcinoma with peritoneal metastases.

BACKGROUND: Next-generation sequencing (NGS) personalizes cancer treatments. In this study, we analyze outcomes based on NGS testing for colorectal cancer (CRC) and high-grade appendiceal adenocarcinoma (HGA) with peritoneal metastases. METHODS: Retrospective review of genomic analyses and outcomes in patients with CRC or HGA with peritoneal metastases at a high-volume center from 2012 to 2019. RESULTS: Ninety-two patients (57 CRC, 35 HGA) were identified. Overall survival was longer for CRC (52.8 vs. 30.5 months, p = 0.03), though rates of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) were similar. Multiple genes were more frequently mutated in CRC, including KRAS (51% vs. 29%, p = 0.04), TP53 (47% vs. 20%, p < 0.01), and APC (46% vs. 6%, p < 0.01). For CRC, multivariate regression showed an increased hazard ratio (HR) with increasing peritoneal cancer index (1.06 [1.01-1.11], p = 0.02) and a decreased HR following CRS/HIPEC (0.30 [0.11-0.80], p = 0.02). PIK3CA mutation associated with significantly increased HR (3.62 [1.06-12.41], p = 0.04), though only in non-CRS/HIPEC patients. Multivariate analysis in the HGA group showed a benefit following CRS/HIPEC (0.18 [0.06-0.61], p = 0.01) and for mucinous disease (0.38 [0.15-0.96], p = 0.04), while there was an increased HR with TP53 mutation (6.89 [2.12-22.44], p < 0.01). CONCLUSION: CRC and HGA with peritoneal spread have distinct mutational profiles. PIK3CA and TP53 mutations are associated with survival for CRC or HGA with peritoneal metastases, respectively.

Phase II Prospective, Open-Label Randomized Controlled Trial Comparing Standard of Care Chemotherapy With and Without Sequential Cytoreductive Interventions for Patients with Oligometastatic Foregut Adenocarcinoma and Undetectable Circulating Tumor Deoxyribose Nucleic Acid (ctDNA) Levels.

BACKGROUND: Metastatic adenocarcinomas of foregut origin are aggressive and have limited treatment options, poor quality of life, and a dismal prognosis. A subset of such patients with limited metastatic disease might have favorable outcomes with locoregional metastasis-directed therapies. This study investigates the role of sequential cytoreductive interventions in addition to the standard of care chemotherapy in patients with oligometastatic foregut adenocarcinoma. METHODS: This is a single-center, phase II, open-label randomized clinical trial. Eligible patients include adults with synchronous or metachronous oligometastatic (metastasis limited to two sites and amenable for curative/ablative treatment) adenocarcinoma of the foregut without progression after induction chemotherapy and having undetectable ctDNA. These patients will undergo induction chemotherapy and will then be randomized (1:1) to either sequential curative intervention followed by maintenance chemotherapy versus routine continued chemotherapy. The primary endpoint is progression-free survival (PFS), and a total of 48 patients will be enrolled to detect an improvement in the median PFS in the intervention arm with a hazard ratio (HR) of 0.5 with 80% power and a one-sided alpha of 0.1. Secondary endpoints include disease-free survival (DFS) in the intervention arm, overall survival (OS), ctDNA conversion rate pre/post-induction chemotherapy, ctDNA PFS, PFS2, adverse events, quality of life, and financial toxicity. DISCUSSION: This is the first randomized study that aims to prospectively evaluate the efficacy and safety of surgical/ablative interventions in patients with ctDNA-negative oligometastatic adenocarcinoma of foregut origin post-induction chemotherapy. The results from this study will likely develop pertinent, timely, and relevant knowledge in oncology.

Management of colorectal cancer during the COVID-19 pandemic: Recommendations from a statewide multidisciplinary cancer collaborative.

COVID-19 has resulted in significant disruptions in cancer care. The Illinois Cancer Collaborative (ILCC), a statewide multidisciplinary cancer collaborative, has developed expert recommendations for triage and management of colorectal cancer when disruptions occur in usual care. Such recommendations would be applicable to future outbreaks of COVID-19 or other large-scale disruptions in cancer care.

Racial differences in survival and response to therapy in patients with metastatic colorectal cancer: A secondary analysis of CALGB/SWOG 80405 (Alliance A151931).

BACKGROUND: The objective of this study was to evaluate the association between self-identified race and overall survival (OS), progression-free survival (PFS), and response to therapy among patients enrolled in the randomized Cancer and Leukemia Group B (CALGB)/SWOG 80405 trial. METHODS: Patients with advanced or metastatic colorectal cancer who were enrolled in the CALGB/SWOG 80405 trial were identified by race. On the basis of covariates (treatment arm, KRAS status, sex, age, and body mass index), each Black patient was exact matched with a White patient. The association between race and OS and PFS was examined using a marginal Cox proportional hazard model for matched pairs. The interaction between KRAS status and race was tested in the model. The association between race and response to therapy and adverse events were examined using a marginal logistic regression model. RESULTS: In total, 392 patients were matched and included in the final data set. No difference in OS (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.73-1.16), PFS (HR, 0.97; 95% CI, 0.78-1.20), or response to therapy (odds ratio [OR], 1.00; 95% CI, 0.65-1.52) was observed between Black and White patients. Patients with KRAS mutant status (HR, 1.31; 95% CI, 1.02-1.67), a performance statusscore of 1 (reference, a performance status of 0; HR, 1.49; 95% CI, 1.18-1.88), or ≥3 metastatic sites (reference, 1 metastatic site; HR, 1.67; 95% CI, 1.22-2.28) experienced worse OS. Black patients experienced lower rates and risk of grade ≥3 fatigue (6.6% vs 13.3%; OR, 0.46; 95% CI, 0.24-0.91) but were equally likely to be treated with a dose reduction (OR, 1.09; 95% CI, 0.72-1.65). CONCLUSIONS: No difference in OS, PFS, or response to therapy was observed between Black patients and White patients in an equal treatment setting of the CALGB/SWOG 80405 randomized controlled trial. LAY SUMMARY: Despite improvements in screening and treatment, studies have demonstrated worse outcomes in Black patients with colorectal cancer. The purpose of this study was to determine whether there was a difference in cancer-specific outcomes among Black and White patients receiving equivalent treatment on the CALGB/SWOG 80405 randomized clinical trial. In this study, there was no difference in overall survival, progression-free survival, or response to therapy between Black and White patients treated on a clinical trial. These findings suggest that access to care and differences in treatment may be responsible for racial disparities in colorectal cancer.

Cytoreductive Surgery for Selected Patients Whose Metastatic Gastric Cancer was Treated with Systemic Chemotherapy.

BACKGROUND: The authors hypothesized that cytoreductive surgery (CRS, comprising gastrectomy combined with metastasectomy) in addition to systemic chemotherapy (SC) is associated with a better survival than chemotherapy alone for patients with metastatic gastric adenocarcinoma (MGA). METHODS: Patients with MGA who received SC between 2004 and 2016 were identified using the National Cancer Database (NCDB). Nearest-neighbor 1:1 propensity score-matching was used to create comparable groups. Overall survival (OS) was compared between subgroups using Kaplan-Meier analyses. Immortal bias analysis was performed among those who survived longer than 90 days. RESULTS: The study identified 29,728 chemotherapy-treated patients, who were divided into the following four subgroups: no surgery (NS, n = 25,690), metastasectomy alone (n = 1170), gastrectomy alone (n = 2248), and CRS (n = 620) with median OS periods of 8.6, 10.9, 14.8, and 16.3 months, respectively (p < 0.001). Compared with the patients who underwent NS, the patients who had CRS were younger (58.9 ± 13.4 vs 62.0 ± 13.1 years), had a lower proportion of disease involving multiple sites (4.6% vs 19.1%), and were more likely to be clinically occult (cM0 stage: 59.2% vs 8.3%) (p < 0.001 for all). The median OS for the propensity-matched patients who underwent CRS (n = 615) was longer than for those with NS (16.4 vs 9.3 months; p < 0.001), including in those with clinical M1 stage (n = 210). In the Cox regression model using the matched data, the hazard ratio for CRS versus NS was 0.56 (95% confidence interval [CI], 0.49-0.63). In the immortal-matched cohort, the corresponding median OS was 17.0 versus 9.5 months (p < 0.001). CONCLUSIONS: In addition to SC, CRS may be associated with an OS benefit for a selected group of MGA patients meriting further prospective investigation.

Novel Application of Iterative Hyperthermic Intraperitoneal Chemotherapy for Unresectable Peritoneal Metastases from High-Grade Appendiceal Ex-Goblet Adenocarcinoma.

BACKGROUND: Peritoneal metastases (PMs) from appendiceal ex-goblet adenocarcinoma (AEGA) are associated with a poor prognosis. While cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to prolong survival, the majority of patients are ineligible for complete cytoreduction. We describe a novel approach to the management of such patients with iterative HIPEC (IHIPEC). METHODS: Patients with signet ring/poorly differentiated AEGA with high Peritoneal Cancer Index (PCI) and extensive bowel involvement underwent IHIPEC with mitomycin C at 6-week intervals for a total of three cycles. Survival outcomes for these patients were compared with patients with high-grade appendiceal tumors matched for tumor burden who were treated with other conventional approaches, i.e. systemic chemotherapy only (SCO) or complete CRS + HIPEC. RESULTS: Between 2016 and 2019, seven AEGA patients with high PCI (median 32.5 [range 21-36]) underwent 18 IHIPEC cycles (median cycles per patient 3 [2-3]) in combination with systemic chemotherapy (median 2 lines [1-3], 12 cycles [10-28]). IHIPEC was delivered laparoscopically in 14/18 cases. Postoperatively, the median length of stay was 1 day (1-8 days), no procedure-related complications were reported, and five (28%) 90-day readmissions for bowel obstruction were documented. Median overall survival after IHIPEC was better compared with a matched group of patients (n = 16) receiving SCO (24.6 vs. 7.9 months; p = 0.005), and similar to those (n = 7) who underwent CRS + HIPEC (24.6 vs. 16.5 months; p = 0.62). CONCLUSIONS: IHIPEC in combination with systemic chemotherapy is tolerable, safe, and may be associated with encouraging survival outcomes compared with SCO in selected patients with high-grade, high-burden AEGA PM.

Race and Gender Differences in Awareness of Colorectal Cancer Screening Tests and Guidelines Among Recently Diagnosed Colon Cancer Patients in an Urban Setting.

The purpose of this study was to first characterize the prevalence of recall, recognition, and knowledge of colon cancer screening tests and guidelines (collectively, "awareness") among non-Hispanic black (NHB) and NH white (NHW) urban colon cancer patients. Second, we sought to examine whether awareness was associated with mode of cancer detection. Low awareness regarding colon cancer screening tests and guidelines may explain low screening rates and high prevalence of symptomatic detection. We examined recall, recognition, and knowledge of colorectal cancer (CRC) screening tests and guidelines and their associations with mode of cancer detection (symptomatic versus screen-detected) in 374 newly diagnosed NHB and NHW patients aged 45-79. Patients were asked to name or describe any test to screen for colon cancer (recall); next, they were given descriptions of stool testing and colonoscopy and asked if they recognized each test (recognition). Lastly, patients were asked if they knew the screening guidelines (knowledge). Overall, awareness of CRC screening guidelines was low; just 20% and 13% of patients knew colonoscopy and fecal test guidelines, respectively. Awareness of CRC screening tests and guidelines was especially low among NHB males, socioeconomically disadvantaged individuals, and those diagnosed at public healthcare facilities. Inability to name or recall a single test was associated with reduced screen-detected cancer compared with recall of at least one test (36% vs. 22%, p = 0.01). Low awareness of CRC screening tests is a risk factor for symptomatic detection of colon cancer.

Facilities that service economically advantaged neighborhoods perform surgical metastasectomy more often for patients with colorectal liver metastases.

BACKGROUND: Metastasectomy of isolated colorectal liver metastases (CRLM) requires significant clinical expertise and may not be readily available or offered. The authors hypothesized that hospitals that treat a greater percentage of patients from higher income catchment areas are more likely to perform metastasectomies regardless of patient or tumor characteristics. METHODS: Using the National Cancer Data Base, the authors classified facilities into facility income quartiles (FIQs) based on the percentage of patients from the wealthiest neighborhoods (by zip code). Quartile 1 included facilities with <2.1% of the patients residing within the highest income zip codes, quartile 2 included facilities with 2.2% to 15.6% of patients residing within the highest income zip codes, quartile 3 included facilities with 15.7% to 40.2% of patients residing within the highest income zip codes, and quartile 4 included facilities with 40.3% to 90.5% of patients residing within the highest income ZIP codes. Patient, tumor, and facility characteristics were analyzed using a multivariate logistic regression to identify associations between metastasectomy and FIQ. RESULTS: Patients with CRLM were more likely to undergo metastasectomy at facilities in the highest FIQ compared with the lowest FIQ (18% vs 11% in FIQ4; P = .001). This trend was not observed in the resection of primary tumors for nonmetastatic CRLM (rates of 95% vs 93%; P = .94). After adjusting for individual insurance status, distance traveled, zip code-level individual income, tumor, and host, patients who were treated at the highest FIQ facilities were found to be more likely to undergo metastasectomy (odds ratio, 1.29; 95% CI, 1.02-1.72 [P = .03]). CONCLUSIONS: Metastasectomy for CRLM is more likely to occur at facilities that serve a greater percentage of patients from high-income catchment areas, regardless of individual patient characteristics. This disparity uniquely affects those patients with advanced cancers for which specialized expertise for therapy is necessary.

"Let Go, Let God": A Qualitative Study Exploring Cancer Patients' Spirituality and Its Place in the Medical Setting.

This study explored the role of God and spirituality in cancer patients to gain deeper insight into how patients use their spirituality to cope during illness, including how they see the medical team meeting their spiritual needs. From our work, some naturally emerging themes included Finding God in Cancer and Healing, Spiritual Support Desired from Medical Community, Doctor as "Gift from God"?, and Communication and the Power of Talk. Cancer patients not only acknowledged a spiritual need, but a desire for it to be addressed by their medical team as part of their treatment.

Investigation of a multimedia, computer-based approach to improve knowledge, attitudes, self-efficacy, and receptivity to cancer clinical trials among newly diagnosed patients with diverse health literacy skills.

BACKGROUND: Enrollment in therapeutic cancer trials remains low, and is especially challenging for patients with low health literacy. The authors tested an interactive technology designed for patients with diverse health literacy skills with the aim of improving patient receptiveness, willingness, knowledge, self-efficacy, and positive attitudes regarding clinical trials. METHODS: Patients presenting for their first oncology appointment were eligible. Patients viewed an interactive teaching video concerning clinical trials that was adapted from the National Institutes of Health. Validated surveys assessing receptiveness, willingness, knowledge, self-efficacy, and positive attitudes regarding clinical trials were administered before and after the test. RESULTS: A total of 120 patients with cancer were enrolled. Approximately 80% were non-Hispanic white, 33% were female, 69% had >high school education, and 8% reported an income <$20,000. Approximately 33% scored within the low health literacy range. Changes between pretest and posttest demonstrated increases in knowledge (P < .001), self-efficacy (P < .001), and positive beliefs (P = .004); a slight decrease in willingness (P = .009); and no difference in patient receptivity (P = .31). Higher health literacy was associated with improved willingness (P = .049) and non-Hispanic white race was associated with improved receptivity (P = .034). CONCLUSIONS: Interactive technology that was designed for patients with diverse health literacy skills demonstrated the ability to improve knowledge, self-efficacy, and positive beliefs regarding cancer clinical trials. Contrary to the hypothesis of the current study, patients with lower health literacy did not appear to derive a greater advantage from this technology. There was no improvement noted with regard to patient willingness or receptivity, and clinical trial enrollment remained at historical institutional levels. Talking touchscreen technology has a potential role as an important element in informed decision making for patients, but likely needs to be coupled with more robust and multitargeted interventions.

A UGT1A1 genotype-guided dosing study of modified FOLFIRINOX in previously untreated patients with advanced gastrointestinal malignancies.

BACKGROUND: FOLFIRINOX (5-fluorouracil [5-FU], leucovorin, irinotecan, oxaliplatin) is an effective but toxic therapy for pancreatic cancer. UGT1A1 (UDP glucuronosyltransferase 1A1) eliminates the active metabolite of irinotecan. Polymorphisms reduce UGT1A1 activity, leading to toxicity. The primary objective was to determine the dose-limiting toxicity (DLT) rate in cycle 1 of modified FOLFIRINOX (mFOLFIRINOX) using genotype-guided dosing of irinotecan for the most common UGT1A1 genotypes (*1/*1, *1/*28) in advanced gastrointestinal malignancies, with expansion in pancreatic and biliary tract cancers. METHOD: 5-FU (2400 mg/m2 over 46 hours), leucovorin (400 mg/m2 ), oxaliplatin (85 mg/m2 ), and irinotecan were given every 14 days. Irinotecan doses of 180, 135, and 90 mg/m2 were administered for UGT1A1 genotypes *1/*1, *1/*28, and *28/*28, respectively. Prophylactic pegfilgrastim was omitted in cycle 1 for cohort 1 (tolerability by genotype), but was given in cohort 2 (tolerability by tumor type). Doses were tolerable if the upper limit of a 2-sided 80% confidence interval for DLT rate was ≤33%. RESULTS: In cohort 1, DLTs (most commonly febrile neutropenia, fatigue, diarrhea) occurred in 2/15 (13%), 3/16 (19%), and 4/10 (40%) patients with *1/*1, *1/*28, and *28/*28 genotypes, respectively. In cohort 2, 6/19 (32%) pancreatic and 4/19 (21%) biliary tract cancer patients experienced DLTs (most commonly fatigue, diarrhea, nausea/vomiting). In cohort 2, upper confidence limits of DLT rates exceeded 33%. Response rates were 38% in pancreatic and 21% in biliary tract cancers. CONCLUSION: On the basis of our prespecified criteria, tolerability of UGT1A1 genotype-guided mFOLFIRINOX was not established in pancreatic and biliary tract cancers. However, this regimen was effective.

Analyzing the clinical actionability of germline pharmacogenomic findings in oncology.

BACKGROUND: Germline and tumor pharmacogenomics impact drug responses, but germline markers less commonly guide oncology prescribing. The authors hypothesized that a critical number of clinically actionable germline pharmacogenomic associations exist, representing clinical implementation opportunities. METHODS: In total, 125 oncology drugs were analyzed for positive germline pharmacogenomic associations in journals with impact factors ≥5. Studies were assessed for design and genotyping quality, clinically relevant outcomes, statistical rigor, and evidence of drug-gene effects. Associations from studies of high methodologic quality were deemed potentially clinically actionable, and translational summaries were written as point-of-care clinical decision support (CDS) tools and formally evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. RESULTS: The authors identified germline pharmacogenomic results for 56 of 125 oncology drugs (45%) across 173 publications. Actionable associations were detected for 12 drugs, including 6 that had germline pharmacogenomic information within US Food and Drug Administration labels or published guidelines (capecitabine/fluorouracil/dihydropyrimidine dehydrogenase [DPYD], irinotecan/uridine diphosphate glucuronosyltransferase family 1 member A1 [UGT1A1], mercaptopurine/thioguanine/thiopurine S-methyltransferase [TPMT], tamoxifen/cytochrome P450 [CYP] family 2 subfamily D member 6 [CYP2D6]), and 6 others were novel (asparaginase/nuclear factor of activated T-cells 2 [NFATC2]/human leukocyte antigen D-related ß1 [HLA-DRB1], cisplatin/acylphosphatase 2 [ACYP2], doxorubicin/adenosine triphosphate-binding cassette subfamily C member 2/Rac family small guanosine triphosphatase 2/neutrophil cytosolic factor 4 [ABCC2/RAC2/NCF4], lapatinib/human leukocyte antigen DQ α1 [HLA-DQA1], sunitinib/cytochrome P450 family 3 subfamily A member 5 [CYP3A5], vincristine/centrosomal protein 72 [CEP72]). By using AGREE II, the developed CDS summaries had high mean ± standard deviation scores (maximum score, 100) for scope and purpose (92.7 ± 5.1) and rigour of development (87.6 ± 7.4) and moderate yet robust scores for clarity of presentation (58.6 ± 25.1) and applicability (55.9 ± 24.6). The overall mean guideline quality score was 5.2 ± 1.0 (maximum score, 7). Germline pharmacogenomic CDS summaries for these 12 drugs were recommended for implementation. CONCLUSIONS: Several oncology drugs have actionable germline pharmacogenomic information, justifying their delivery through institutional pharmacogenomic implementations to determine clinical utility. Cancer 2018;124:3052-65. © 2018 American Cancer Society.

Association of externalizing religious and spiritual beliefs on stage of colon cancer diagnosis among black and white multicenter urban patient populations.

BACKGROUND: This study explores whether externalizing religious and spiritual beliefs is associated with advanced-stage colon cancer at initial oncology presentation and whether this association is stronger for blacks than for whites. METHODS: Patients who had newly diagnosed, invasive colon cancer were recruited at 9 sites in the Chicago metropolitan area. Eligible patients were non-Hispanic white or black, ages 30 to 79 years, and diagnosed with a primary invasive colon cancer. Patients were interviewed on prior screening and diagnosis. Social and attitudinal constructs were measured, including the God Locus of Health Control (GLHC) and Religious Problem Solving. The final response rate was 52% and included 407 patients. RESULTS: The median age was 59 years (range, 30-79 years), and 51% of participants were black. Cancer stage was available for 389 (96%) patients and was divided between late stage (stages III-IV; 60%) and early stage (stages I-II; 40%). Multivariate analysis indicated that patients in the highest tertile of scores on the GLHC were more likely have an advanced stage of disease at presentation (odds ratio, 2.14; 95% confidence interval, 1.00-4.59; P = .05) compared with those in the lowest tertile. No significant interaction was identified between race and GLHC scores for stage at presentation (P = .78). CONCLUSIONS: In a large sample of black and white individuals across diverse health care systems, higher scores on the GLHC predicted late disease stage at presentation. Although blacks had significantly higher GLHC scores, race was not associated with stage at presentation, nor was the association between GLHC and stage limited to blacks. Further work is needed to better understand this association and to develop interventions to better connect the religious and health care spheres. Cancer 2018;124:2578-87. © 2018 American Cancer Society.