Performance of a targeted methylation-based multi-cancer early detection test by race and ethnicity.

Disparities in cancer screening and outcomes based on factors such as sex, socioeconomic status, and race and ethnicity in the United States are well documented. A blood-based multi-cancer early detection (MCED) test that detects a shared cancer signal across multiple cancer types and also predicts the cancer signal origin was developed and validated in the Circulating Cell-free Genome Atlas study (CCGA; NCT02889978). CCGA is a prospective, multicenter, case-control, observational study with longitudinal follow-up (overall N = 15,254). In this pre-specified, exploratory, descriptive analysis, test performance was evaluated among racial and ethnic groups. Overall, 4077 participants comprised the independent validation set with confirmed cancer status (cancer: n = 2823; non-cancer: n = 1254). Participants were stratified into the following racial/ethnic groups: Black (non-Hispanic), Hispanic (all races), Other (non-Hispanic), Other/unknown and White (non-Hispanic). Cancer and non-cancer participants were predominantly White (n = 2316, 82.0% and n = 996, 79.4%, respectively). Across groups, specificity for cancer signal detection ranged from 98.1% [n = 103; 95% CI: 93.2-99.5%] to 100% [n = 85; 95% CI: 95.7-100.0%]. The sensitivity for cancer signal detection across groups ranged from 43.9% [n = 57; 95% CI: 31.8-56.7%] to 63.0% [n = 192; 95% CI: 56.0-69.5%] and generally increased with clinical stage. The MCED test had consistently high specificity and similar sensitivity across racial and ethnic groups, though results are limited by sample size for some groups. Results support the broad applicability of this MCED test and clinical implementation on a population scale as a complement to standard screening.

Municipal Pathways in Response to COVID-19: A Strategic Management Perspective on Local Public Administration Resilience.

This paper aims to understand the different resilience pathways local governments may take during moments of crisis, specifically focusing on the COVID-19 pandemic. Through survey responses from local administrations in Wallonia, Belgium, we consider how varied contexts led to different strategic resilience pathways. These pathways range from static (i.e., no strategy) to innovative change. Our findings highlight that digital technology solutions may play a role in supporting resilience across the different pathways. Therefore, we adapt strategic public management literature to suggest propositions for future research to test the specific role that digital technologies play in supporting resilience within local administrations.

Documentation of medical marijuana use in cancer patients.

PURPOSE: Medical marijuana is often used as adjuvant therapy in cancer patients for symptom management, although limited evidence-based studies evaluating its efficacy or safety exist. Similar to over-the-counter medications, supplements, or herbal products, documentation of medical marijuana is important to monitor efficacy, potential adverse effects, or interactions. The objective of this quality improvement study was to improve the consistency of medical marijuana documentation in cancer patients by assessing current practices; educating healthcare team members about the importance of documentation and newly established documentation process; and evaluating the new documentation process. METHODS: This three-part quality improvement study was approved by the Institutional Review Board. In part I, a voluntary survey was sent via email to Cancer Center healthcare personnel to assess the current documentation process of medical marijuana. In part II, a best practice process for documenting medical marijuana in the electronic medical record was established. Medical marijuana was to be listed as a historical medication in the medication list. In-person and electronic education sessions were offered to Cancer Center clinical staff. The education emphasized the importance of documenting medical marijuana use and provided a detailed process for electronic medical record documentation. A pre- and post-test to assess understanding was also included. Part III was a retrospective chart review to evaluate documentation practices of certified medical marijuana users in the Cancer Center. Patients included in the study were greater than 18 years old and certified for medical marijuana use on or after 1 January 2018. Department of Corrections patients were excluded. Descriptive statistics were used for data analysis. RESULTS: The survey results in part I demonstrated a lack of consistency in the documentation of medical marijuana in the Cancer Center. The pre- and post-test scores measured in part II showed a significant improvement in understanding after education was provided. The average pre-test score was a 61 and post-test score was 88, indicating an average increase of 27 points. A larger increase in test scores was observed in those attending the in-person education than the online sessions (p < 0.002). The results of the retrospective chart review in part III revealed 56 patients who met inclusion criteria, but only 39 patients were alive and evaluated at the time of the retrospective chart review. Of the 39 patients, 22 never completed the patient registration process and therefore, would never have been able to obtain medical marijuana. Seven patients had medical marijuana properly documented in their medication list and 10 patients were missing documentation in the medication list, showing room for improvement in documentation practices. CONCLUSIONS: This quality improvement study led to the implementation of medical marijuana documentation in the medication list. Education increased healthcare team members understanding of medical marijuana utilization and the importance of documentation.

Subcutaneous metastasis from recurrent basaloid squamous cell carcinoma of the esophagus.

BACKGROUND: Esophageal cancer is the 11th most common cause of cancer mortality in the United States. It is aggressive in nature and has an ability to spread rapidly through direct extension, lymphatic spread, or hematogenously. With an estimated incidence of 1%, cutaneous metastases from esophageal cancer are extremely rare. CASE PRESENTATION: In this case study and review, we describe a case of recurrent esophageal basaloid squamous cell carcinoma presenting as multiple, rapidly progressing and tender subcutaneous nodules. A 69-year-old male with history of basaloid squamous cell carcinoma of the esophagus treated with concurrent chemoradiation, presented to his oncologist with complaints of a large, painful nodule at the nape of his neck approximately two years after completing treatment. On further examination, he was noted to have multiple, well circumscribed, solid, tender nodules on his abdominal wall along with a painful nodule on the pulp of his index finger. Histopathology from all sites revealed skin infiltration by high-grade invasive basaloid subtype of squamous cell carcinoma, similar to patient's prior known and treated primary esophageal cancer. Further imaging work up showed extensive metastatic disease involving lung, liver, and brain. CONCLUSION: Esophageal squamous cell carcinoma rarely metastasize to the skin. Subcutaneous nodules can be the first presentation of recurrent disease. The lesions are commonly confused with skin infections and treated inappropriately with antibiotics, leading to delay in diagnosis of recurrent disease. Early biopsy of suspicious lesions should be performed, especially in patients with history of cancer, such that prompt diagnosis and treatment can occur to maximize patient outcomes.

Potential role of rituximab in metastatic castrate-resistant prostate cancer.

Nearly all men with prostate cancer who are treated with androgen deprivation therapy develop disease progression. There is considerable evidence to suggest that CXCL 13 released by tumor cells leads to B-cell infiltration into the prostate cells. This B-cell infiltration has been postulated to play a role in development of disease progression following androgen-deprivation therapies. We present a case of a patient who achieved remission of metastatic castrate-resistant prostate cancer after receiving rituximab and bendamustine for the treatment of follicular lymphoma. The findings in this report suggest that further investigation is warranted for utilizing B-cell targeted therapy in delaying progression of castrate-resistant prostate cancer.

Physician-pharmacist collaboration for oral chemotherapy monitoring: Insights from an academic genitourinary oncology practice.

BACKGROUND: Oral chemotherapy is being routinely used in metastatic castrate-resistant prostate and renal cell cancer. Although convenient, these drugs require monitoring for adherence, toxicity, and drug interactions to maximize outcomes. Oncology pharmacists have the training and expertise that place them in an optimal position to collaboratively provide medication therapy management. METHODS: A board-certified oncology pharmacist, working in collaboration with a medical oncologist, initiated an oral chemotherapy-monitoring program. The pharmacist provided education, completed medication therapy management; monitored for adherence and toxicity; and recommended treatment of toxicity and supportive care issues. Patient encounters included one of the following: collaboration with medical oncologist visit, pharmacist visit, or telephone or email follow-up between visits. RESULTS: From December 2012 to May 2014, the pharmacist had 123 encounters with 20 patients with either metastatic prostate (n = 17) or renal cell cancer (n = 3). All patients were males (median age 80 years). Most encounters were clinic visits, in collaboration with physician visit or alone (52%); 36% were telephone encounters, and 11.3% were email follow-ups. Medication-related problems were identified in 25% of the 315 assessments made. Problems included: adverse drug reactions, 40%; inappropriate therapy, 20%; and noncompliance, 18%. Recommendations included: modification of laboratory monitoring, 25%; cancer or non-cancer therapy modification, 12%; drug discontinuation, 6.9%. Non-cancer therapy-related drug information and coordination of care accounted for 30% of recommendations. CONCLUSION: Our program led to identification of a number of potentially clinically significant issues for patients on oral chemotherapy and demonstrated the benefit of the pharmacist in the multidisciplinary team to assist in addressing them.

Atypical presentation of fever as hypersensitivity reaction to oxaliplatin.

Oxaliplatin, a third-generation, platinum-based agent is widely used, most commonly in the FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) regimen, which is the first-line therapy in metastatic colorectal adenocarcinoma and adjuvant chemotherapy in stage III colorectal cancer. Platinum-based products are well known for causing hypersensitivity reactions. Fever associated with oxaliplatin-hypersensitivity reactions typically follows a specific pattern. It usually starts during the oxaliplatin infusion or immediately after (within hours instead of days) and happens after several administrations (mean 2-25) with unpredictable clinical presentations. We report a case of oxaliplatin-induced hypersensitivity reaction manifesting as fever but with unusual presentation than the aforementioned features.

Impact of a pharmacist-led oral chemotherapy-monitoring program in patients with metastatic castrate-resistant prostate cancer.

BACKGROUND: With the introduction of oral chemotherapy, the paradigm for cancer treatment is shifting. Use of oral chemotherapy agents offers a non-invasive option for patients with metastatic castrate-resistant prostate cancer. However, these medications are not without challenges including strict adherence for optimal effects, novel toxicity profiles, frequent lab parameter monitoring, high cost, and proper handling and disposal methods. Pharmacists are positioned to play a key role in providing patients with the education required to assure an optimal treatment course is carried out. METHODS: Two cohorts of patients receiving abiraterone, bicalutamide, or enzalutamide for metastatic castrate-resistant prostate cancer seen in our outpatient cancer center 21 months before and 24 months after the implementation of a pharmacist-led oral chemotherapy-monitoring program in December of 2012 were retrospectively compared. Patients were evaluated for number of interventions, adherence to lab parameter monitoring, and overall time on each therapy. RESULTS: Of the 64 patients identified, 31 patients fulfilled inclusion criteria. A significant increase in the average number of interventions per patient (6.9 vs. 2.6; P = 0.004) and adherence to lab parameter monitoring (10 vs. 3; P = 0.04) in the post-program implementation cohort was found. However, no significant difference in overall time on therapy (10.3 vs. 8.1; P = 0.341) between the two groups was observed. CONCLUSION: These results suggest a potential opportunity exists to maximize oral chemotherapy treatment outcomes with the addition of a formalized monitoring program directed by an oncology pharmacist.

Critical analysis of contemporary clinical research in muscle-invasive and metastatic urothelial cancer: a report from the Bladder Cancer Advocacy Network Clinical Trials Working Group.

BACKGROUND: There have been no improvements in the treatment of metastatic urothelial cancer in the past several decades. A census of contemporary clinical research in this disease was performed to identify potential barriers and opportunities. METHODS: These authors performed a search for clinical trials exploring interventions in muscle-invasive and metastatic urothelial cancer, using the ClinicalTrials.gov registry. Data extracted from the registry included title, recruitment status, interventions, sponsor, phase, enrollment, study design, and study sites. RESULTS: Among 120 eligible trials exploring interventions in muscle-invasive and metastatic urothelial cancer, 73% were phase 2 and 73% were nonrandomized. The majority (63%) involved treatment in the metastatic disease state. The median planned enrollment size per trial was 45 patients (interquartile range, 47 patients). The majority of trials (55%) involved ≤ 3 study sites. Trials most commonly explored interventions in the first-line metastatic (30%) or second-line metastatic (37%) settings. Targeted therapeutics were studied in 58% of the trials. Among 56 trials that completed enrollment, the median time to complete accrual was 50 months (range, 10-109 months), and these trials enrolled a median of 40 patients per trial (interquartile range, 44 patients). CONCLUSIONS: The majority of contemporary clinical trials in muscle-invasive and metastatic urothelial cancer are small, nonrandomized, phase 2 trials involving 1 to 3 study sites. Enhanced communication and collaboration among the urothelial cancer community, and other stakeholders, is needed to facilitate the design and conduct of trials capable of expediting progress in this disease.

Multi-cancer early detection test sensitivity for cancers with and without current population-level screening options.

There are four solid tumors with common screening options in the average-risk population aged 21 to 75 years (breast, cervical, colorectal, and, based on personalized risk assessment, prostate), but many cancers lack recommended population screening and are often detected at advanced stages when mortality is high. Blood-based multi-cancer early detection tests have the potential to improve cancer mortality through additional population screening. Reported here is a post-hoc analysis from the third Circulating Cell-free Genome Atlas substudy to examine multi-cancer early detection test performance in solid tumors with and without population screening recommendations and in hematologic malignancies. Participants with cancer in the third Circulating Cell-free Genome Atlas substudy analysis were split into three subgroups: solid screened tumors (breast, cervical, colorectal, prostate), solid unscreened tumors, and hematologic malignancies. In this post hoc analysis, sensitivity is reported for each subgroup across all ages and those aged ⩾50 years overall, by cancer, and by clinical cancer stage. Aggregate sensitivity in the solid screened, solid unscreened, and hematologic malignancy subgroups was 34%, 66%, and 55% across all cancer stages, respectively; restricting to participants aged ⩾50 years showed similar aggregate sensitivity. Aggregate sensitivity was 27%, 53%, and 60% across stages I to III, respectively. Within the solid unscreened subgroup, aggregate sensitivity was >75% in 8/18 cancers (44%) and >50% in 13/18 (72%). This multi-cancer early detection test detected cancer signals at high (>75%) sensitivity for multiple cancers without existing population screening recommendations, suggesting its potential to complement recommended screening programs.Clinical trial identifier: NCT02889978.

Geriatric risk factors for serious COVID-19 outcomes among older adults with cancer: a cohort study from the COVID-19 and Cancer Consortium.

BACKGROUND: Older age is associated with poorer outcomes of SARS-CoV-2 infection, although the heterogeneity of ageing results in some older adults being at greater risk than others. The objective of this study was to quantify the association of a novel geriatric risk index, comprising age, modified Charlson comorbidity index, and Eastern Cooperative Oncology Group performance status, with COVID-19 severity and 30-day mortality among older adults with cancer. METHODS: In this cohort study, we enrolled patients aged 60 years and older with a current or previous cancer diagnosis (excluding those with non-invasive cancers and premalignant or non-malignant conditions) and a current or previous laboratory-confirmed COVID-19 diagnosis who reported to the COVID-19 and Cancer Consortium (CCC19) multinational, multicentre, registry between March 17, 2020, and June 6, 2021. Patients were also excluded for unknown age, missing data resulting in unknown geriatric risk measure, inadequate data quality, or incomplete follow-up resulting in unknown COVID-19 severity. The exposure of interest was the CCC19 geriatric risk index. The primary outcome was COVID-19 severity and the secondary outcome was 30-day all-cause mortality; both were assessed in the full dataset. Adjusted odds ratios (ORs) and 95% CIs were estimated from ordinal and binary logistic regression models. FINDINGS: 5671 patients with cancer and COVID-19 were included in the analysis. Median follow-up time was 56 days (IQR 22-120), and median age was 72 years (IQR 66-79). The CCC19 geriatric risk index identified 2365 (41·7%) patients as standard risk, 2217 (39·1%) patients as intermediate risk, and 1089 (19·2%) as high risk. 36 (0·6%) patients were excluded due to non-calculable geriatric risk index. Compared with standard-risk patients, high-risk patients had significantly higher COVID-19 severity (adjusted OR 7·24; 95% CI 6·20-8·45). 920 (16·2%) of 5671 patients died within 30 days of a COVID-19 diagnosis, including 161 (6·8%) of 2365 standard-risk patients, 409 (18·5%) of 2217 intermediate-risk patients, and 350 (32·1%) of 1089 high-risk patients. High-risk patients had higher adjusted odds of 30-day mortality (adjusted OR 10·7; 95% CI 8·54-13·5) than standard-risk patients. INTERPRETATION: The CCC19 geriatric risk index was strongly associated with COVID-19 severity and 30-day mortality. Our CCC19 geriatric risk index, based on readily available clinical factors, might provide clinicians with an easy-to-use risk stratification method to identify older adults most at risk for severe COVID-19 as well as mortality. FUNDING: US National Institutes of Health National Cancer Institute Cancer Center.

Carbonic anhydrase IX and pathological features as predictors of outcome in patients with metastatic clear-cell renal cell carcinoma receiving vascular endothelial growth factor-targeted therapy.

OBJECTIVE: To investigate the utility of tumour carbonic anhydrase IX (CAIX) expression and histological features for predicting the outcome in patients with metastatic clear-cell renal cell carcinoma (mRCC) treated with vascular endothelial growth factor (VEGF)-targeted therapy. PATIENTS AND METHODS: We identified 118 patients with mRCC initiating first-line VEGF-targeted therapy, including 94 with clinical and histological data, and available tissue. The primary endpoint was to detect an interaction between sorafenib vs sunitinib treatment and CAIX status on tumour shrinkage. Other treatment outcomes were also assessed. RESULTS: There was heterogeneity in tumour responsiveness to sunitinib or sorafenib according to CAIX status; the mean shrinkage was -17% vs -25% for sunitinib-treated patients with high vs low tumour CAIX expression, compared to -13% vs +9% for sorafenib-treated patients (P interaction, 0.05). A higher tumour clear-cell component was independently associated with greater tumour shrinkage (P= 0.02), response (P= 0.02) and treatment duration (P= 0.02). CONCLUSIONS: Although CAIX expression had no prognostic value in patients with clear-cell mRCC treated with VEGF-targeted therapy, it might be a predictive biomarker for response to sorafenib treatment. Patients with a higher clear-cell component in their tumours are likely to have a superior clinical benefit from VEGF-targeted therapy.

Angiogenesis inhibitor therapies for metastatic renal cell carcinoma: effectiveness, safety and treatment patterns in clinical practice-based on medical chart review.

OBJECTIVE: To assess the effectiveness, safety, and treatment patterns of anti-angiogenic agents in metastatic renal cell carcinoma (mRCC) in tertiary clinical practice settings. PATIENTS AND METHODS: We retrospectively reviewed the medical records in two tertiary oncology centres in the USA for all patients treated while off clinical trials from April 2003 to June 2008 who met the entry criteria and received one or more prescriptions for sunitinib or sorafenib, or one or more intravenous administrations of bevacizumab (off-label) as first-line anti-angiogenic treatment. The objective response rate (ORR) reviewed by independent physicians, adverse events (AEs), and treatment modifications were assessed. RESULTS: Among 144 patients receiving sunitinib (57), sorafenib (62) and bevacizumab (25), the median treatment duration was 10.5, 8.1 and 7.9 months, and the ORR was 37%, 9% and 13%, respectively. The ORR was lower for patients with metastases to bone, brain, lungs or lymph nodes. Common AEs (all grades) for sunitinib were fatigue (53%), diarrhoea (37%); for sorafenib, diarrhoea (50%), fatigue (40%); for bevacizumab, fatigue (40%), nausea (24%). In all, 34 (60%), 51 (82%) and 20 (80%) patients receiving sunitinib, sorafenib and bevacizumab, respectively, discontinued treatment; 10 (18%), 11 (18%) and four (16%) discontinued due to AEs; 21%, 40% and 12% had a dose interruption, and 30%, 35% and 0% had a dose reduction. CONCLUSIONS: Currently available anti-angiogenic agents had considerable effectiveness in clinical practice. However, the response rates appeared to be low in certain subgroups, but sample sizes were small. Patients had significant rates of AEs, many of which led to treatment modifications. The findings from this retrospective study suggest that there is a need for better-tolerated therapies for mRCC.

Case report: Adenosquamous carcinoma of the prostate with greater than 20 month response to multimodal therapy.

Adenosquamous carcinoma is an extremely rare and lethal subtype of prostate cancer affecting an estimated 0.03 per million men annually. It has been associated with prior hormone therapy for prostate adenocarcinoma. We present a case of de novo adenosquamous carcinoma of the prostate treated with a multimodal approach including surgery, androgen-deprivation therapy, chemotherapy, and radiation.

SATB1 and bladder cancer: Is there a functional link?

PURPOSE: SATB1, a global genome organizer, has been shown to play a role in the development and progression of some solid tumors, but its role in bladder cancer is undetermined. Moreover, there is conflicting data about the role of SATB1 in other tumors. This study was initiated to assess a potential role for SATB1 with the hypothesis that SATB1 acts as a tumor promoter in bladder cancer. MATERIALS AND METHODS: We evaluated SATB1 expression in bladder cancer cell lines (HTB-5, HTB-9) and compared them to a benign urothelial cell line (UROtsa). Short-hairpin RNA was used to silence SATB1 in multiple cell lines, and cell death and cell proliferation were assessed using multiple assays. RESULTS: SATB1 expression was increased significantly in all cancer cell lines compared to benign urothelial cells. SATB1 expression was knocked down by short-hairpin RNA and functional outcomes, including cell number, cell-cycle arrest, cell viability, and apoptosis after cisplatin treatment, were measured. Surprisingly, knockdown of SATB1 in 2 high-grade cancer cell lines showed opposing functional roles. Compared to the non-silencing control, HTB-5 cells, showed decreased cellular proliferation and increased sensitivity to cisplatin, whereas HTB-9 cells, showed increased cell numbers and increased resistance to cisplatin. CONCLUSION: We conclude that our results in bladder cancer are consistent with the conflicting data reported in other cancers, and that SATB1 might have different roles in cancer dependent on genetic background and stage of the cancer.

Evolving Treatment of Oligometastatic Hormone-Sensitive Prostate Cancer.

Oligometastatic disease was postulated by Hellman and Weichselbaum in 1995 to be a disease state that may reflect a time point in the malignant process that may be amenable to local therapies to allow for patients to achieve a durable response or possible cure despite having advanced disease. Aggressive metastasis-directed therapy has been used in malignancies such as renal cell carcinoma, non-small-cell lung cancer, and colorectal cancer with some evidence of long-term benefit in selected patients. Recently, it has been proposed that some men with oligometastatic hormone-sensitive prostate cancer may also benefit from metastasis-directed therapy. As with most malignancies, optimal therapy for prostate cancer relies on multimodal therapy, best highlighted by the survival benefit seen in high-volume metastatic prostate cancer with the addition of docetaxel to androgen-deprivation therapy. This is becoming increasingly evident for oligometastatic prostate cancer, with emerging data sets suggesting a possible benefit of local ablative therapies for metastatic lesions combined with androgen-deprivation therapy. However, the bulk of the data is retrospective and thus subject to bias. Ongoing clinical trials are evaluating combination therapy to help elucidate the role of each therapy separately and together to determine optimal interventions for this population. This clinical review discusses the retrospective data evaluating local therapies such as radiation and surgery in men with lymph node-positive disease, as well as limited bone metastases, and outlines ongoing, prospective clinical trials designed to further investigate the role of multimodality therapy in the outcomes of men with oligometastatic hormone-sensitive prostate cancer.

Hematospermia and Cloacogenic Transitional Cell Carcinoma: A Twist on Significance and Meaning.

A 52-year-old gentleman presented with recurrent hematospermia. Further history revealed recent onset of constipation and difficulty voiding. Rectal examination revealed a firm, polypoid mass and colonoscopy showed suspicious, ulcerated lesions of the rectal mucosa with narrowing of the rectal vault. Pathology demonstrated transitional cell carcinoma of the rectum. While transitional cell carcinoma is a common genitourinary cancer, its presence in the anus and rectum is exceedingly rare. Furthermore, hematospermia is generally not associated with malignancy. This case is a remarkable example of two pathologic processes presenting in rare form and underscores the value of a thorough investigation of hematospermia when associated with other clinical symptoms.

Smoking-induced immune deviation contributes to progression of bladder and other cancers.

We propose here that cigarette smoke (CS), in addition to its established genotoxic effects, elicits chronic albeit sub-clinical immune suppression, which is a major contributor to cancer progression. This hypothesis, presented here primarily in the context of bladder cancers (BCs), is applicable to other cancers, including those without a confirmed link to smoking.