A Rare Case of Invasive Central Nervous System Aspergillus niger in a Previously Immunocompetent Patient After Corticosteroid Treatment for COVID-19.

Aspergillus is a ubiquitous saprophyte found in air, soil, and organic matter. Humans inhale the spore form of the fungus, but manifestations of the disease are typically predominantly seen in immunocompromised patients. Invasive central nervous system (CNS) aspergillosis is even more uncommon, and epidemiological data is sparse, particularly in immunocompetent patients. We report the case of a 67-year-old previously immunocompetent female with no known comorbidities who was treated with corticosteroids for COVID-19 one month prior to admission for altered mental status (AMS). Subsequent imaging and biopsy demonstrated invasive CNS Aspergillus niger. Though a rare cause of AMS in immunocompetent patients, this report draws attention to the detrimental immunosuppressive effects of corticosteroid therapy in COVID-19.

Overcoming Barriers to Tobacco Cessation and Lung Cancer Screening among Racial and Ethnic Minority Groups and Underserved Patients in Academic Centers and Community Network Sites: The City of Hope Experience.

BACKGROUND: Tobacco control is important for cancer patient health, but delivering effective low-dose CT (LDCT) screening and tobacco cessation is more difficult in underserved and patients from racial and ethnic minority groups. At City of Hope (COH), we have developed strategies to overcome barriers to the delivery of LDCT and tobacco cessation. METHODS: We performed a needs assessment. New tobacco control program services were implemented focusing on patients from racial and ethnic minority groups. Innovations included Whole Person Care with motivational counseling, placing clinician and nurse champions at points of care, training module and leadership newsletters, and a patient-centric personalized medicine Personalized Pathways to Success (PPS) program. RESULTS: Emphasis on patients from racial and ethnic minority groups was implemented by training cessation personnel and lung cancer control champions. LDCT increased. Tobacco use assessment increased and abstinence was 27.2%. The PPS pilot program achieved 47% engagement in cessation, with self-reported abstinence at 3 months of 38%, with both results slightly higher in patients from racial and ethnic minority groups than in Caucasian patients. CONCLUSIONS: Tobacco cessation barrier-focused innovations can result in increased lung cancer screening and tobacco cessation reach and effectiveness, especially among patients from racial and ethnic minority groups. The PPS program is promising as a personalized medicine patient-centric approach to cessation and lung cancer screening.

A Systems Biology Approach for Addressing Cisplatin Resistance in Non-Small Cell Lung Cancer.

Translational research in medicine, defined as the transfer of knowledge and discovery from the basic sciences to the clinic, is typically achieved through interactions between members across scientific disciplines to overcome the traditional silos within the community. Thus, translational medicine underscores 'Team Medicine', the partnership between basic science researchers and clinicians focused on addressing a specific goal in medicine. Here, we highlight this concept from a City of Hope perspective. Using cisplatin resistance in non-small cell lung cancer (NSCLC) as a paradigm, we describe how basic research scientists, clinical research scientists, and medical oncologists, in true 'Team Science' spirit, addressed cisplatin resistance in NSCLC and identified a previously approved compound that is able to alleviate cisplatin resistance in NSCLC. Furthermore, we discuss how a 'Team Medicine' approach can help to elucidate the mechanisms of innate and acquired resistance in NSCLC and develop alternative strategies to overcome drug resistance.

Increasing clinician participation in tobacco cessation by an implementation science-based tobacco cessation champion program.

BACKGROUND: We designed a process to increase tobacco cessation in an academic center and its widely distributed network community sites using clinical champions to overcome referral barriers. METHODS: In 2020 a needs assessment was performed across the City of Hope Medical Center and its 32 community treatment sites. We reviewed information science strategies to choose elements for our expanded tobacco control plan, focusing on distributed leadership with tobacco cessation champions. We analyzed smoking patterns in patients with cancer before and following program implementation. We evaluated the champion experience and measured tobacco abstinence after 6 months of follow-up. RESULTS: Cancer center leadership committed to expanding tobacco control. Funding was obtained through a Cancer Center Cessation Initiative (C3I) grant. Multi-disciplinary leaders developed a comprehensive plan. Disease-focused clinics and community sites named cessation champions (a clinician and nurse) supported by certified tobacco treatment specialists. Patient, staff, clinician, and champion training/education were developed. Roles and responsibilities of the champions were defined. Implementation in pilot sites showed increased tobacco assessment from 80.8 to 96.6%, increased tobacco cessation referral by 367%, and moderate smoking abstinence in both academic (27.2%) and community sites (22.5%). 73% of champions had positive attitudes toward the program. CONCLUSION: An efficient process to expand smoking cessation in the City of Hope network was developed using implementation science strategies and cessation champions. This well-detailed implementation process may be helpful to other cancer centers, particularly those with a tertiary care cancer center and community network.

Addressing Drug Resistance in Cancer: A Team Medicine Approach.

Drug resistance remains one of the major impediments to treating cancer. Although many patients respond well initially, resistance to therapy typically ensues. Several confounding factors appear to contribute to this challenge. Here, we first discuss some of the challenges associated with drug resistance. We then discuss how a 'Team Medicine' approach, involving an interdisciplinary team of basic scientists working together with clinicians, has uncovered new therapeutic strategies. These strategies, referred to as intermittent or 'adaptive' therapy, which are based on eco-evolutionary principles, have met with remarkable success in potentially precluding or delaying the emergence of drug resistance in several cancers. Incorporating such treatment strategies into clinical protocols could potentially enhance the precision of delivering personalized medicine to patients. Furthermore, reaching out to patients in the network of hospitals affiliated with leading academic centers could help them benefit from such innovative treatment options. Finally, lowering the dose of the drug and its frequency (because of intermittent rather than continuous therapy) can also have a significant impact on lowering the toxicity and undesirable side effects of the drugs while lowering the financial burden carried by the patient and insurance providers.

Hyperprogression on immunotherapy with complete response to chemotherapy in a NSCLC patient with high PD-L1 and STK11: A case report.

RATIONALE: Patients reporting high PD-L1 expression have shown to respond well to immunotherapy; however, some patients develop hyperprogressive disease upon initiation of immune checkpoint inhibitors. We report a patient with lung cancer and 100% PD-L1 expression who developed hyperprogressive disease while treated with pembrolizumab and responded well to salvage chemotherapy with carboplatin and pemetrexed. PATIENT CONCERNS: A 66-year-old African American female with 25-pack year smoking history, diabetes mellitus type 2, essential thrombocytosis, and a history of papillary thyroid carcinoma developed relapsed lung adenocarcinoma after 13 months of no evidence of disease. DIAGNOSIS: Surveillance imagine showed subcarinal and hilar lymphadenopathy, which was confirmed as recurrent lung adenocarcinoma via bronchoscopy. In addition, a brain scan showed a 5 mm enhancing left insular lesion. PD-L1 was reported as 100% expression. Staging was reported as stage IVB TxN3M1c lung adenocarcinoma. INTERVENTIONS: One fraction of radiation with a total dose of 20 Gray was delivered to the left insular lesion. The patient initiated pembrolizumab (200 mg) every 3 weeks. She was then treated with salvage chemotherapy consisting of carboplatin (AUC 5) and pemetrexed (500 mg/m) every 3 weeks for 3 cycles. OUTCOMES: The brain lesion resolved after the radiation therapy. The patient developed hyperprogression with a large pericardial effusion and right pleural effusion after 2 treatments of pembrolizumab. Her PD-L1 expression decreased from 100% to 0% over a 10-week period. Salvage chemotherapy with carboplatin and pemetrexed resulted with 20 months of ongoing to evidence of disease. LESSONS: Immune checkpoint inhibitor-related hyperprogressive disease may respond to second-line salvage chemotherapy. Complete PD-L1 expression loss was observed after the patient's treatment and could be a marker of hyperprogressive disease or tumor immunoevasion.

Small Cell Lung Cancer from Traditional to Innovative Therapeutics: Building a Comprehensive Network to Optimize Clinical and Translational Research.

Small cell lung cancer (SCLC) is an aggressive, complex disease with a distinct biology that contributes to its poor prognosis. Management of SCLC is still widely limited to chemotherapy and radiation therapy, and research recruitment still poses a considerable challenge. Here, we review the current standard of care for SCLC and advances made in utilizing immunotherapy. We also highlight research in the development of targeted therapies and emphasize the importance of a team-based approach to make clinical advances. Building an integrative network between an academic site and community practice sites optimizes biomarker and drug target discovery for managing and treating a difficult disease like SCLC.

The Community Oncology and Academic Medical Center Alliance in the Age of Precision Medicine: Cancer Genetics and Genomics Considerations.

Recent public policy, governmental regulatory and economic trends have motivated the establishment and deepening of community health and academic medical center alliances. Accordingly, community oncology practices now deliver a significant portion of their oncology care in association with academic cancer centers. In the age of precision medicine, this alliance has acquired critical importance; novel advances in nucleic acid sequencing, the generation and analysis of immense data sets, the changing clinical landscape of hereditary cancer predisposition and ongoing discovery of novel, targeted therapies challenge community-based oncologists to deliver molecularly-informed health care. The active engagement of community oncology practices with academic partners helps with meeting these challenges; community/academic alliances result in improved cancer patient care and provider efficacy. Here, we review the community oncology and academic medical center alliance. We examine how practitioners may leverage academic center precision medicine-based cancer genetics and genomics programs to advance their patients' needs. We highlight a number of project initiatives at the City of Hope Comprehensive Cancer Center that seek to optimize community oncology and academic cancer center precision medicine interactions.

Effect of Surgical Intervention on Survival of Patients With Clinical N2 Non-Small Cell Lung Cancer: A Veterans' Affairs Central Cancer Registry (VACCR) Database Analysis.

BACKGROUND: Optimal management of locally advanced non-small cell lung cancer (NSCLC) lacks consensus. A retrospective analysis of patient data entered in the Veterans Affairs Central Cancer Registry was conducted to evaluate these issues. PATIENTS AND METHODS: Data of patients with cT1-4, cN2, and cM0 NSCLC diagnosed in the VA Health System between 1995 and 2003 were evaluated. Age, sex, race, smoking history, TNM stage, treatment, and overall survival were abstracted. Survival was compared using multivariate Cox proportional hazards regression analysis. RESULTS: Of the 7328 patients analyzed, 7218 (98.5%) were male, 6061 (82.7%) were white, and 321 (4.4%) were never smokers. The treatment received included: none, 23.8%; chemotherapy alone, 14.3%; radiation alone, 23%; and chemoradiation (sequential or concurrent), 31.4%. Only 7.5% of patients had a surgical resection, with or without multimodality therapy. The median survival (months) of these patient groups were: surgery, 19.3; chemoradiation, 13; chemotherapy alone, 9.2; radiation alone, 7.3; and no treatment, 4 (P<0.0001). African Americans had a significantly decreased risk of mortality compared with whites (hazard ratio 0.92; 95% confidence interval, 0.87-0.98). CONCLUSIONS: Inclusion of surgical resection as a treatment modality was associated with a better overall survival. Also, African Americans appeared to do better than whites. These hypothesis-generating findings should be useful in the ongoing pursuit of better treatment strategies for locally advanced NSCLC.

Cetuximab Rechallenge and Monotherapy in Patients with Squamous Cell Carcinoma of the Head and Neck.

Smokers with squamous cell carcinoma of the head and neck (SCCHN) have a particularly poor prognosis when compared with human papillomavirus-positive SCCHN. Here, we present case reports of two smokers with SCCHN treated with cetuximab-based therapy, highlighting the potential benefit of cetuximab before definitive chemoradiotherapy in patients with poor performance status as well as cetuximab rechallenge after progression. We conclude that cetuximab demonstrated notable effectiveness in two patients at high risk for poor prognosis, yielding a durable response in one and retaining activity on rechallenge in the other.

Clinicopathological features and survival outcomes of primary signet ring cell and mucinous adenocarcinoma of colon: retrospective analysis of VACCR database.

BACKGROUND: Signet ring cell carcinoma (SRCC) accounts for less than 1% of all colon cancers. We examined the clinicopathological features and prognosis of signet ring cell and mucinous adenocarcinoma (MCC) of colon. METHODS: A total of 206 patients diagnosed with SRCC from 1995 to 2009 were identified from the VA Central Cancer Registry (VACCR) database. Age, race, histology, grade, lymph node status, stage and type of treatment received data were collected. RESULTS: Out of 206 patients, 173 (84%) were white, 31 (15%) were black, and 2 patients were listed as unknown. Median age of diagnosis was 67 years as compared to 70 years for both mucinous cell (MCC) and non-mucinous adenocarcinoma (NMCC) of colon. Pathological T-stages were as follows: T1 =3%, T2 =5%, T3 =34%, T4 =26%, and unknown 32%. Of the total, 22.3% were located in cecum, 7.7% in appendix, 21.8% in ascending colon, 7.7% in hepatic flexure of colon, 11% in transverse colon, 2.9% in splenic flexure 4.4% in descending colon, and 15.5% in sigmoid colon. 46.5% were lymph node positive, 21% were lymph node negative, and 32.5% were unknown. SRCC were in general poorly differentiated tumors (57%), small proportion of patients included were well-differentiated tumors with focal signet ring cell pathology (10%) and in 33% grade was unknown. Among stage 3 patients, 34% patients received only surgery while 64% received surgery with adjuvant chemotherapy and 2% received chemotherapy alone. The stage specific 5-year survivals for SRCC, MCC and NMCC were--Stage I: 100%, 61%, and 41% respectively (P<0.0001); Stage II: 42%, 58% and 32% respectively (P<0.0001); Stage III: 19%, 41% and 47% respectively (P=0.0002); Stage IV: 1.5%, 7% and 31% respectively (P<0.0001). Median survival of SRCC compared to NMCC was 18.6 vs. 46 months (P<0.0001) and mucinous cell adenocarcinoma versus NMCC was 47.8 and 46 months (P=0.63) respectively. CONCLUSIONS: SRCC of colon has poor survival rates compared to other histological subtypes. SRCC presents at an earlier age, has higher tumor grade and advanced stage at diagnosis when compared to mucinous and NMCC of colon. Due to rarity of this disease further prospective multi-institute studies are required for in-depth understanding of this disease.

Association between race and survival of patients with non--small-cell lung cancer in the United States veterans affairs population.

BACKGROUND: Racial disparities in outcomes of non-small-cell lung cancer (NSCLC) patients in the United States are well documented. A retrospective analysis of patients in the Veterans Affairs Central Cancer Registry was conducted to determine whether similar disparities exist in a population with a single-payer, accessible health care system. PATIENTS AND METHODS: Demographic data of patients diagnosed with NSCLC between January 1995 and February 2009 were analyzed using Kruskal-Wallis test or the χ(2) test. Multivariate Cox proportional hazards regression analysis was used to compare survival among races. RESULTS: Of the 82,414 patients, 98% were male, 82% had a smoking history, and 81% were Caucasian. Caucasian individuals had better prognostic features compared with African-American individuals (stage I/II [24% vs. 21%]; Grade I/II [21% vs. 17%]). A larger proportion of Caucasian compared with African-American individuals received stage-appropriate treatment (surgery for stage I [48% vs. 41%; P < .001]; chemotherapy for stage IV [18% vs. 16%; P = .003]). African-American individuals had a lower risk of mortality compared with Caucasian individuals (hazard ratio, 0.94; 95% confidence interval, 0.92-0.96). CONCLUSION: Although African-American patients had a higher stage and grade of NSCLC, they had a better overall survival than Caucasian patients. In a single-payer system with accessible health care, previously described racial differences in lung cancer outcomes were not observed.

Assessment of prognostic factors after primary tumor resection in metastatic colon cancer patients: a Veteran's Affairs Central Cancer Registry (VACCR) analysis, 1995-2008.

BACKGROUND: Resection of the primary tumor in metastatic colon cancer may occur for palliation of bleeding or obstruction despite distant metastases. This study evaluates clinicopathologic features that serve as prognostic markers in those patients with stage IV colon cancer who undergo resection of their primary tumor. METHODS: Retrospective analysis of stage IV colon cancer patients who underwent surgical resection of the primary tumor from 1995 to 2008 was done via the Veteran's Affairs Central Cancer Registry. Age, Charlson co-morbidity index score, extent of metastases, sex, number of lymph nodes examined, lymph node ratio (LNR), type of surgery, use of adjuvant chemotherapy, primary tumor site, and grade were studied with respect to overall survival by using log-rank and Kaplan-Meier analysis. RESULTS: There were 2,625 patients with stage IV colon cancer who had primary tumor resection. Age at diagnosis, Charlson co-morbidity index score, lymph node ratio, and use of chemotherapy were found to be independent predictors of survival by multivariate analysis. CONCLUSION: Clinicopathologic factors such as LNR, use of chemotherapy, age, co-morbidities, site of primary colon tumor, and number of sites of metastasis are all independent predictors of overall survival in patients who undergo primary colon tumor resection in the metastatic setting.

Effect of palliative care services on the aggressiveness of end-of-life care in the Veteran's Affairs cancer population.

BACKGROUND: Cancer care near the end of life (EOL) has become more aggressive over the years. Palliative care services (PCS) may decrease this aggressive cancer care in terminally ill cancer patients. Our objective was to observe the aggressiveness of cancer care near the EOL among Veterans Affairs cancer patients before and after the institution of a PCS team. We also assessed the time taken prior to death to initiate a PCS consultation and its effect on the aggressiveness of cancer care near the EOL. METHODS: This is a retrospective chart review analysis performed at the local Veterans Affairs hospital looking at the last 100 patients in each of the years, 2002 and 2008, who died with active cancer. Only patients in 2008 had access to a PCS team. RESULTS: In the last 30 days of life, compared to 2002, patients in 2008 had a higher incidence of: chemotherapy administration, more than one hospital admission, more than 14 days of hospital stay, intensive care unit admissions, and in-hospital deaths. Patients with timely PCS consults in 2008 appeared to have a lower incidence of: chemotherapy administration, more than one emergency department visit, more than one hospital admission, more than 14-day hospital stays, intensive care unit admissions, and deaths in the hospital. Timely PCS consults were associated with earlier and more frequent hospice referral. CONCLUSIONS: Cancer care near the EOL has become more aggressive with time at one of the hospitals in the Veterans Affairs healthcare system (VAHS). Institution of a PCS service was unable to completely decrease this trend of increasing aggressiveness of cancer care near the EOL. However, timely PCS consults may help attenuate this aggressiveness.

Clinicopathologic factors associated with lymph node retrieval in resectable colon cancer: a Veterans' Affairs Central Cancer Registry (VACCR) database analysis.

BACKGROUND: A long-term determinant of survival in resectable colon cancer is the involvement of regional lymph nodes. We evaluated the clinicopathologic factors associated with lymph node retrieval. METHODS: We conducted a retrospective analysis of patients with resected stage I-III colon cancer in the Veteran's Affairs Central Cancer Registry between 1995 and 2008. One-way ANOVA compared the differences between various groups. Multivariate logistic regression analysis was performed to determine the factors associated with the harvest of 12 or more lymph nodes for pathologic examination. RESULTS: There were 19,240 patients with resectable colon cancer included in our analysis. Mean number of lymph nodes retrieved increased with later year of diagnosis, higher overall stage, higher T descriptor, age <65 years, poorer differentiation and right-sided tumors (P < 0.01 for all covariates). These aforementioned factors are also associated with an increased probability of retrieving 12 or more lymph nodes after surgical resection (P < 0.01 for all covariates). CONCLUSIONS: Later year of diagnosis, younger patients, right-sided tumors, poorer differentiation, higher T descriptor and overall stage are associated with increased number of lymph nodes retrieved. These may indicate the presence of an immunological response of tumor versus host affecting lymph node retrieval.

Spontaneous hemopericardium leading to cardiac tamponade in a patient with essential thrombocythemia.

Acute cardiac tamponade requires urgent diagnosis and treatment. Spontaneous hemopericardium leading to cardiac tamponade as an initial manifestation of essential thrombocythemia (ET) has never been reported in the literature. We report a case of a 72-year-old Caucasian female who presented with spontaneous hemopericardium and tamponade requiring emergent pericardiocentesis. The patient was subsequently diagnosed to have ET. ET is characterized by elevated platelet counts that can lead to thrombosis but paradoxically it can also lead to a bleeding diathesis. Physicians should be aware of this complication so that timely life-saving measures can be taken if this complication arises.

Phase II trial of thalidomide as maintenance therapy for extensive stage small cell lung cancer after response to chemotherapy.

BACKGROUND: Extensive-stage small cell lung cancer (SCLC) is a highly aggressive malignancy for which little therapeutic progress has been made over the past 20 years. SCLC is a highly angiogenic tumor and targeting angiogenesis is being investigated. The putative mechanism of action of thalidomide is through inhibition of new blood vessel formation. This trial was designed to evaluate thalidomide in ES-SCLC. PATIENTS AND METHODS: Patients who had received first-line chemotherapy without disease progression were eligible. Patients received thalidomide 200 mg daily as maintenance therapy starting 3-6 weeks after completion of chemotherapy. RESULTS: Thirty patients were enrolled. Toxicity was minimal with grade 1 neuropathy in 27% of patients and only one case of grade 3 neuropathy. Median survival from time of initiation of induction chemotherapy was 12.8 months (95% CI: 10.1-15.8 months) and 1-year survival of 51.7% (95% CI: 32.5-67.9%). Median duration on thalidomide was 79 days. CONCLUSION: Thalidomide 200mg daily is well tolerated when given as maintenance therapy for ES-SCLC after induction chemotherapy. Further evaluation of anti-angiogenic agents in SCLC is warranted.

Randomized phase II trial of different schedules of administration of rebeccamycin analogue as second line therapy in non-small cell lung cancer.

Rebeccamcyin analogue (RA) is an antitumor antibiotic that results in DNA intercalation and topoisomerase I and II inhibition. Phase I trials of the daily x 5 schedule and once every 3 week schedule have been completed. Antitumor activity was observed during the phase I trials. The purpose of this study is to primarily determine the response rate of 2 different schedules of administration of RA in patients with advanced non-small cell lung cancer (NSCLC) who had progressed on one prior chemotherapy regimen. Secondary endpoints were median and 1-year survival rates. A two-stage Simon design was employed for both arms of the study. Patients were randomly assigned to either of two RA treatment schedules of 500 mg/m(2) as a 1 hr infusion repeated every 3 weeks (Arm A) or 140 mg/m(2)/day x 5 days repeated every 3 weeks (Arm B). Forty-two patients were randomized. No confirmed objective responses were seen. Stable disease was seen in 52% of patients on arm A and 37% on arm B. Median survival and 1 year survival rates were 5.6 months and 33.3% for arm A, 9.7 months and 42.1% for arm B respectively. Cox regression model demonstrated increased risk of death in patients younger than the age of 61 and for patients treated on arm A. RA failed to demonstrate a significant response rate in this disease setting, although the proportion of patients with stable disease and 1-year survival were encouraging and similar to other published studies of approved single agents for second-line therapy of NSCLC.