Rechallenges without desensitization following platinum-based chemotherapy reactions.

BACKGROUND: There is increasing interest in non-desensitization protocols as a potential way to reintroduce chemotherapy following hypersensitivity reactions (HSR). OBJECTIVE: To provide insight into the potential utility of non-desensitization reintroduction, particularly at institutions where allergy consultation may not be available. METHODS: For 70 patients with platinum HSR who underwent rechallenge with standard (≤2 hours), extended (1-bag, 1-step, 4-6 hours), or titrated (4-to-5-bag and -step, 6-7.5 hours) infusions between 1/2014 and 7/2019, demographics and clinical characteristics were reviewed and initial and breakthrough reactions (BTR) were graded using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Tolerance (no BTR) and completion (dose completed despite BTR) were compared using Fisher's exact test. RESULTS: Patients (mean [standard deviation] age 57 [13] years, initial HSR grade 2 [1]), were rechallenged with standard (n = 8), extended (n = 23), or titrated (n = 22) infusions after oxaliplatin HSR; and standard (n = 5) or titrated (n = 12) after carboplatin HSR. Tolerance and completion were higher for extended versus (vs) standard (tolerance-87%-vs-8%, p < 0.005; completion-96%-vs-38%, p < 0.005) and titrated versus standard (tolerance-76%-vs-8%, p < 0.005; completion-79%-vs-38%, p < 0.05) infusions. CONCLUSIONS: Extended and titrated infusions may increase reintroduction safety compared to standard infusions. Further investigation into extended infusions may provide a safe alternative to standard infusions in patients who may not have access to desensitization at their institution.

Assessing Unique Risk Factors for COVID-19 Complications Among Cancer Patients: A Multi-ethnic Cohort Study.

A myriad of organ-specific complications have been observed with COVID-19. While racial/ethnic minorities have been disproportionately burdened by this disease, our understanding of the unique risk factors for complications among a diverse population of cancer patients remains limited. This is a multi-institutional, multi-ethnic cohort study evaluating COVID-19 complications among cancer patients. Patients with an invasive cancer diagnosis and confirmed SARS-CoV-2 infection were identified from March to November 2020. Demographic and clinical data were obtained and a multivariate logistic regression was employed to evaluate the impact of demographic and clinical factors on COVID-19 complications. The study endpoints were evaluated independently and included any complication, sepsis, pulmonary complications and cardiac complications. A total of 303 patients were evaluated, of whom 48% were male, 79% had solid tumors, and 42% were Hispanic/Latinx (Hispanic). Malignant hematologic cancers were associated with a higher risk of sepsis (OR 3.93 (95% CI 1.58-9.81)). Male patients had a higher risk of sepsis (OR 4.42 (95% CI 1.63-11.96)) and cardiac complications (OR 2.02 (95% CI 1.05-3.89)). Hispanic patients had a higher odds of any complication (OR 2.31 (95% CI 1.18-4.51)) and other race was associated with a higher odds of cardiac complications (OR 2.41 (95% CI 1.01-5.73)). Clinically, fever, cough, and ≥2 co-morbidities were independently significantly associated with any complication. This analysis evaluated covariates that can significantly predict a myriad of complications among a multi-ethnic cohort of cancer patients. The conclusions drawn from this analysis elucidate a mechanistic understanding of differential illness severity from COVID-19.

Phase I prospective trial of TAS-102 (trifluridine and tipiracil) and radioembolization with 90Y resin microspheres for chemo-refractory colorectal liver metastases.

BACKGROUND: Extrahepatic disease progression limits clinical efficacy of Yttrium-90 (90Y) radioembolization (TARE) for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). Trifluridine and tipiracil (TAS-102) has overall survival benefit for patients with refractory mCRC and may be a radiosensitizer. METHODS: Sequential lobar TARE using 90Y resin microspheres in combination with TAS-102 in 28-day cycles were used to treat adult patients with bilobar liver-dominant chemo-refractory mCRC according to 3 + 3 dose escalation design with a 12-patient dose expansion cohort. Study objectives were to establish safety and determine maximum tolerated dose (MTD) of TAS-102 in combination with TARE. RESULTS: A total of 21 patients (14 women, 7 men) with median age of 60 years were enrolled. No dose limiting toxicities were observed. Treatment related severe adverse events included cytopenias (10 patients, 48%) and radioembolization-induced liver disease (2 patients, 10%). Disease control rate in the liver lobes treated with TARE was 100%. Best observed radiographic responses were partial response for 4 patients (19%) and stable disease for 12 patients (57%). CONCLUSIONS: The combination of TAS-102 and TARE for patients with liver-dominant mCRC is safe and consistently achieves disease control within the liver. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02602327 (first posted 11/11/2015).

Multidisciplinary Management of Pancreatic Cancer.

At JADPRO Live Virtual 2021, presenters reviewed the epidemiology of pancreatic cancer, treatment options for patients with different stages of pancreatic cancer, and the most common symptoms and complications related to pancreatic cancer and their management in a collaborative practice model.

The Additional Diagnostic Benefit of Pancreatic Cancer Molecular Profiling After Germline Testing.

OBJECTIVES: Germline genetic testing is universally recommended for patients with pancreatic cancer to guide therapeutic selection, but tumor molecular profiling (TMP) is not. We aimed to determine the real-world additional diagnostic benefit of TMP after germline testing for detecting therapeutically actionable alterations. METHODS: Medical records and genetic test reports were reviewed for all patients who underwent germline testing and TMP at the University of California San Francisco during January 2016-January 2020. The detection rate of actionable alterations with germline testing alone was compared to that with both germline testing and TMP. RESULTS: Among 738 eligible patients, 144 (20%) met study criteria. Germline testing detected 10 actionable alterations in 10 patients. Tumor molecular profiling identified 3 new therapeutic targets among these 10 patients and 45 targets in 41 additional patients, increasing the number of patients with actionable findings from 10 (7%) to 51 (35%). Most actionable alterations (35/58, 60%) involved genes associated with the Homologous Recombination DNA Damage Repair pathway. CONCLUSIONS: Tumor molecular profiling after germline testing increased the detection of actionable alterations by 5-fold. Tumor molecular profiling is a necessary complement to germline genetic testing to fully inform therapeutic decision making for all patients with pancreatic cancer.

COVID-19 Outcomes Among Patients With Cancer: Observations From the University of California Cancer Consortium COVID-19 Project Outcomes Registry.

BACKGROUND: The risks associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated illness, coronavirus disease 2019 (COVID-19), among patients with a cancer diagnosis have not been fully characterized. This study leverages data from a multi-institutional cohort study, the University of California Cancer COVID Consortium, to evaluate outcomes associated with SARS-CoV-2 infection among patients with cancer. METHODS: Clinical data were collected from March to November 2020 and included patient demographics, cancer history and treatment, SARS-CoV-2 exposure and testing, and COVID-19 clinical management and outcomes. Multivariate ordinal logistic regression permitting unequal slopes was used to evaluate the impact of demographic, disease, and treatment factors on SARS-CoV-2 related hospitalization, intensive care unit (ICU) admission, and mortality. FINDINGS: Among all evaluated patients (n = 303), 147 (48%) were male, 118 (29%) were older adults (≥65 years old), and 104 (34%) were non-Hispanic white. A subset (n = 63, 21%) had hematologic malignancies and the remaining had solid tumors. Patients were hospitalized for acute care (n = 79, 26%), ICU-level care (n = 28, 9%), or died (n = 21, 7%) due to COVID-19. Patients with ≥2 comorbidities were more likely to require acute care (odds ratio [OR] 2.09 [95% confidence interval (CI), 1.23-3.55]). Cough was identified as a significant predictor of ICU hospitalization (OR 2.16 [95% CI, 1.03-4.57]). Importantly, mortality was associated with an active cancer diagnosis (OR 3.64 [95% CI, 1.40-9.5]) or advanced age (OR 3.86 [95% CI, 1.2-12.44]). INTERPRETATION: This study observed that patients with active cancer or advanced age are at an increased risk of death from COVID-19. These study observations can inform risk counseling related to COVID-19 for patients with a cancer diagnosis.

Implementation of an Embedded In-Clinic Genetic Testing Station to Optimize Germline Testing for Patients with Pancreatic Adenocarcinoma.

BACKGROUND: Germline genetic testing is universally recommended for patients with pancreatic cancer, but testing remains infrequent. In May 2018, we implemented a systematic patient intake workflow featuring an in-clinic genetic testing station (GTS) at the University of California San Francisco (UCSF) to expedite genetic counseling and facilitate sample collection. We sought to determine the impact of this innovation on rates of genetic counseling and testing. METHODS: Medical records, patient intake records, and genetic test reports were retrospectively reviewed for new patients with pancreatic cancer eligible for germline testing at UCSF from May 2018 to May 2019. Primary outcomes included the rate of offered genetic counseling and confirmed germline testing. Data were compared for periods before and after GTS implementation. Associations between demographic characteristics and testing rates were assessed. RESULTS: Genetic counseling/testing was offered to 209 (94%) of 223 eligible patients, and 158 (71%) completed testing (135 at UCSF, 23 elsewhere). Compared with a traditional referral-based genetic counseling model, confirmed testing increased from 19% to 71%, patient attrition between referral and genetics appointment decreased from 36% to 3%, and rate of pathogenic variant detection increased from 20% to 33%. Patients who were younger, identified as non-Hispanic White, and spoke English as a primary language were more likely to complete testing. CONCLUSIONS: Implementation of a systematic patient intake workflow and in-clinic GTS resulted in the highest reported real-world rate of germline testing for patients with pancreatic cancer. Health care disparities were identified and will guide future innovation. This report provides a model for other centers to create a similar testing infrastructure. IMPLICATIONS FOR PRACTICE: This study demonstrates that a systematic patient intake workflow and associated in-clinic genetic testing station improve delivery of genetic counseling and completion of germline testing for patients with pancreatic cancer. This study achieved, to the authors' knowledge, the highest real-world rate of confirmed genetic testing in this patient population. This article describes this innovation in detail to guide replication at other medical centers and facilitate guideline-concordant care for patients with pancreatic cancer. This infrastructure can also be applied to other cancers for which germline testing is recommended.

Planning for post-pandemic cancer care delivery: Recovery or opportunity for redesign?

The delivery of cancer care has never changed as rapidly and dramatically as we have seen with the coronavirus disease 2019 (COVID-19) pandemic. During the early phase of the pandemic, recommendations for the management of oncology patients issued by various professional societies and government agencies did not recognize the significant regional differences in the impact of the pandemic. California initially experienced lower than expected numbers of cases, and the health care system did not experience the same degree of the burden that had been the case in other parts of the country. In light of promising trends in COVID-19 infections and mortality in California, by late April 2020, discussions were initiated for a phased recovery of full-scale cancer services. However, by July 2020, a surge of cases was reported across the nation, including in California. In this review, the authors share the response and recovery planning experience of the University of California (UC) Cancer Consortium in an effort to provide guidance to oncology practices. The UC Cancer Consortium was established in 2017 to bring together 5 UC Comprehensive Cancer Centers: UC Davis Comprehensive Cancer Center, UC Los Angeles Jonsson Comprehensive Cancer Center, UC Irvine Chao Family Comprehensive Cancer Center, UC San Diego Moores Cancer Center, and the UC San Francisco Helen Diller Family Comprehensive Cancer Center. The interventions implemented in each of these cancer centers are highlighted, with a focus on opportunities for a redesign in care delivery models. The authors propose that their experiences gained during this pandemic will enhance pre-pandemic cancer care delivery.

Creative Strategies Implemented During the Coronavirus Pandemic That Will Impact the Future of Cancer Care.

The coronavirus pandemic has significantly impacted operations at leading cancer centers across the United States. In the midst of the chaos, at least one silver lining has emerged: the development of new, creative strategies for delivering cancer care that are likely to continue post pandemic. The NCCN Best Practices Committee, which is composed of senior physician, nursing, and administrative leaders at NCCN Member Institutions, conducted a webinar series in June 2020 highlighting the most promising and effective strategies to date. Experts from NCCN Member Institutions participated in the series to share their experiences, knowledge, and thoughts about the future of cancer care.

Metastatic Pancreatic Cancer: ASCO Guideline Update.

PURPOSE: The aim of this work was to provide an update to the ASCO guideline on metastatic pancreatic cancer pertaining to recommendations for therapy options after first-line treatment. METHODS: ASCO convened an Expert Panel and conducted a systematic review to update guideline recommendations for second-line therapy for metastatic pancreatic cancer. RESULTS: One randomized controlled trial of olaparib versus placebo, one report on phase I and II studies of larotrectinib, and one report on phase I and II studies of entrectinib met the inclusion criteria and inform the guideline update. RECOMMENDATIONS: New or updated recommendations for germline and somatic testing for microsatellite instability high/mismatch repair deficiency, BRCA mutations, and TRK alterations are provided for all treatment-eligible patients to select patients for recommended therapies, including pembrolizumab, olaparib, larotrectinib, or entrectinib, or potential clinical trials. The Expert Panel continues to endorse the remaining recommendations for second-line chemotherapy, as well as other recommendations related to treatment, follow-up, and palliative care from the 2018 version of this guideline. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Safety at the Time of the COVID-19 Pandemic: How to Keep our Oncology Patients and Healthcare Workers Safe.

The novel coronavirus, SARS-CoV-2, was first detected as a respiratory illness in December 2019 in Wuhan City, China. Since then, coronavirus disease 2019 (COVID-19) has impacted every aspect of our lives worldwide. In a time when terms such as social distancing and flattening the curve have become a part of our vernacular, it is essential that we understand what measures can be implemented to protect our patients and healthcare workers. Undoubtedly, healthcare providers have had to rapidly alter care delivery models while simultaneously acknowledging the crucial unknowns of how these changes may affect clinical outcomes. This special feature reviews strategies on how to mitigate transmission of COVID-19 in an effort to reduce morbidity and mortality associated with the disease for patients with cancer without infection, for patients with cancer with COVID-19 infection, and for the healthcare workers caring for them, while continuing to provide the best possible cancer care. [Editor's Note: This article includes the most current information available at time of publication; however, recommendations regarding public safety and practice may change rapidly in this situation. Individuals should get the most up to date information from the CDC website.].

Postoperative Exacerbation of Oxaliplatin-induced Neurotoxicity in Gastrointestinal Cancers: A Case Series.

BACKGROUND/AIM: Oxaliplatin-induced neurotoxicity (OIN) can be severe and dose-limiting with clinically significant symptoms that persist for years. Few published reports have described postoperative exacerbation of OIN and more longitudinal data are needed to better characterize the phenomenon. PATIENTS AND METHODS: We identified 13 patients diagnosed with colon (n=7), rectal (n=4) or pancreatic (n=2) cancer who experienced postoperative OIN exacerbation at our medical center. Charts were reviewed for demographic and clinical data regarding OIN. RESULTS: OIN exacerbation was documented 0.5-7.0 months after the first surgery following oxaliplatin exposure, with a median duration of 10.6 months (range=1.4-86.1 months). OIN exacerbation persisted in 3/13 patients at last follow-up, and improved to pre-operative levels in 6/13 patients (with complete resolution in 4/13) within a median of 3.6 months from initial exacerbation. CONCLUSION: Given the widespread use of oxaliplatin in neoadjuvant and first-line treatment for gastrointestinal cancers, further study is warranted to prospectively and systematically define risks for postoperative OIN exacerbation.

A step towards equitable clinical trial recruitment: a protocol for the development and preliminary testing of an online prostate cancer health information and clinical trial matching tool.

BACKGROUND: Recruitment of a diverse participant pool to cancer clinical trials is an essential component of clinical research as it improves the generalizability of findings. Investigating and piloting novel recruitment strategies that take advantage of ubiquitous digital technologies has become an important component of facilitating broad recruitment and addressing inequities in clinical trial participation. Equitable and inclusive recruitment improves generalizability of clinical trial outcomes, benefiting patients, clinicians, and the research community. The increasing prevalence of online connectivity in the USA and use of the Internet as a resource for medical information provides an opportunity for digital recruitment strategies in cancer clinical trials. This study aims to measure the acceptability, preliminary estimates of efficacy, and feasibility of the Trial Library intervention, an Internet-based cancer clinical trial matching tool. This study will also examine the extent to which the Trial Library website, designed to address the linguistic and literacy needs of broader patient populations, influences patient-initiated conversations with physicians about clinical trial participation. METHODS: This is a study protocol for a non-randomized, single-arm pilot study. This is a mixed methods study design that utilizes the statistical analysis of quantitative survey data and the qualitative analysis of interview data to assess the participant experience with the Trial Library intervention. This study will examine (1) acceptability as a measure of participant satisfaction with this intervention, (2) preliminary measure of efficacy as a measure of proportion of participants with documented clinical trial discussion in the electronic medical record, and (3) feasibility of the intervention as a measure of duration of clinical visit. DISCUSSION: The principles that informed the design of the Trial Library intervention aim to be generalizable to clinical trials across many disease contexts. From the ground up, this intervention is built to be inclusive of the linguistic, literacy, and technological needs of underrepresented patient populations. This study will collect essential preliminary data prior to a multi-site randomized clinical trial of the Trial Library intervention. TRIAL REGISTRATION: This study has received institutional approval from the Committee of Human Subjects Research at the University of California, San Francisco.

CA 19-9 Response: A Surrogate to Predict Survival in Patients With Metastatic Pancreatic Adenocarcinoma.

OBJECTIVE: The objective of this study was to determine the features of carbohydrate antigen (CA) 19-9 decline that correlates best with survival benefit in patients with metastatic pancreatic cancer. METHODS: This is a retrospective study of 225 patients with metastatic pancreatic cancer receiving first-line therapy. Analysis was performed by the Kaplan-Meier method and Cox-proportional hazards ratios. CA 19-9 decline was grouped into quartiles within different CA 19-9 baseline groups. Time to nadir and CA 19-9 decline at month-2 (M2) of therapy were evaluated for patients with a baseline level ≥1000 U/mL. RESULTS: No significant trend in survival was observed across baseline CA 19-9 levels. The greatest survival benefit was seen with a ≥75% decline to nadir. Among those with a ≥75% decline and baseline ≥1000 U/mL, 43 of 57 patients had a >50% decline at M2 of therapy and additional survival benefit was observed with a slower decline to nadir. Small sample sizes limited analysis of other baseline groups. CA 19-9 decline at M2 was not predictive. CONCLUSIONS: In patients with a CA 19-9 ≥1000 U/mL, serial CA 19-9 levels may be considered as a surrogate for serial imaging to evaluate treatment response, with a ≥75% decline indicating the greatest survival benefit. Survival was improved further in the setting of a slower decline to nadir with the highest benefit seen in patients with a nadir occurring at 4 months or longer.

Early Response Assessment in Pancreatic Ductal Adenocarcinoma Through Integrated PET/MRI.

OBJECTIVE: The purpose of this study is to investigate early changes in 18F-FDG PET/MRI metrics after treatment in patients with advanced pancreatic ductal adenocarcinoma (PDAC) and to correlate those changes with eventual tumor response at standard-of-care CT. SUBJECTS AND METHODS: Thirteen patients with advanced PDAC underwent integrated FDG PET/MRI before and 4 weeks after treatment initiation. Patients were classified as responders or nonresponders according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at subsequent CT performed 8-12 weeks after treatment initiation. Changes in the primary tumor's maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) determined at PET and apparent diffusion coefficient (ADC) determined at DWI at 4 weeks were compared between responders and nonresponders. RESULTS: Seven patients had a partial response according to RECIST, and six did not. Responders displayed significantly greater decreases in MTV (p = 0.003) and TLG (p = 0.006) in the primary pancreatic tumor at 4 weeks. Responders also displayed a greater increase in the mean (p = 0.004) and minimum (p = 0.024) ADC of the primary tumors. Tumor size change at 4 weeks was not significantly different between responders and nonresponders (p = 0.11). PET responders enjoyed longer progression-free survival (PFS) (p = 0.0004) and overall survival (OS) (p = 0.013) than did nonresponders, using either a 60% reduction in MTV or 65% reduction in TLG as a threshold. MRI responders had significantly longer PFS (p = 0.0002) and OS (p = 0.027) than did nonresponders, using a 20% increase in either mean or minimum ADC as a threshold. CONCLUSION: Integrated PET/MRI can provide early response assessment in patients with advanced PDAC, thus potentially allowing early treatment adaptation in nonresponders.

Best practices for the treatment of metastatic pancreatic adenocarcinoma: the therapeutic landscape in 2017.

The vast majority of patients diagnosed with pancreatic adenocarcinoma have inoperable, most commonly metastatic, disease at the time of initial presentation, at which point systemic therapy becomes the mainstay of treatment. Although survival rates remain very poor in this clinical setting, patients currently have a greater number of therapeutic options available to them than ever before, and consequently individuals are more frequently able to be sequenced through multiple lines of treatment. In this review, we will provide an overview of the current treatment landscape for metastatic pancreatic cancer in 2017, focusing on best practices and the various factors that should be considered in selecting the most appropriate regimen for a given individual. Options for front-line therapy include both infusional 5-fluorouracil, leucovorin, irinotecan, oxaliplatin (FOLFIRINOX) and the combination of gemcitabine plus nab-paclitaxel; however, how to choose between these two regimens can sometimes pose a challenging problem, and some patients may not be suitable candidates for either. For patients who are robust enough to receive second-line therapy (and beyond), the selection of treatment depends in part on their prior treatment exposure; newer drugs such as nanoliposomal irinotecan (nal-IRI) (in combination with infusional 5-fluorouracil and leucovorin) are now approved by the United States Food and Drug Administration (FDA) specifically for use following disease progression on first-line gemcitabine-based therapy. Despite these welcome advances in standard of care treatment, patients should still be encouraged to participate in clinical trials whenever possible.

A case series of patients with HER2-overexpressed primary metastatic gastroesophageal adenocarcinoma.

BACKGROUND: Overexpression of the human epidermal growth factor 2 (HER2) is associated with an aggressive metastatic phenotype in patients with breast cancer but its prognostic impact is not well-characterized in gastroesophageal adenocarcinoma. PATIENTS AND METHODS: This is a retrospective series of three cases of HER2-positive gastroesophageal cancer. RESULTS: In this case series, we describe three patients presenting with widespread metastatic disease prior to development of symptoms from the primary tumor. Two patients presented with brain metastases, while one demonstrated lymphangitic spread to lungs. CONCLUSION: Pooled analyses of outcomes among sub-populations of contemporary trials are needed to better understand the natural history and prognostic impact of HER2 over-expression in patients with gastroesophageal cancers.