D-CRSE: Diminishing chemotherapy-related side effects through patient education, a mixed-methods pilot study.

OBJECTIVES: Patient education materials regarding self-management of chemotherapy-related side effects are limited, which may result in patients using disreputable sources. We created a brochure that educates patients on common side effects, tools to address problems themselves, and guidance on when to contact their oncologist or seek emergency care. This mixed-methods study conducted at Penn State Cancer Institute evaluates the feasibility of using an educational brochure to improve patient outcomes through education. METHODS: Chemotherapy naïve patients with breast or gastrointestinal (GI) cancer were enrolled in a single-arm clinical trial from December 2021 to 2022. Participants received the educational brochure and were asked to provide their initial impressions. They completed The Emotional Thermometer Scale (ETS) and the Memorial Symptom Assessment Scale (MSAS) to measure changes in patient symptoms and mental health throughout their chemotherapy course at 0, 6, and 12-week intervals. The drop-out rate was recorded as a measure of study feasibility. RESULTS: The study participants were split between the following cancer types: 77.8% breast and 22.2% GI cancer. A significant decrease in overall mean ETS score was observed between baseline and week 6 (p = 0.001) and 12 (p = 0.0004), respectively. Moreover, the mean MSAS psychological symptoms decreased significantly at week 12 compared to baseline (p = 0.005), while no change was observed in physical symptoms (p = 0.101). Of the 40 participants who completed baseline surveys, 37 had at least one additional visit for a drop-out rate of 7.5%. CONCLUSION: This mixed-methods pilot study was successful in demonstrating the feasibility of distributing a standardized educational brochure as an intervention for chemotherapy patients. While participants' emotional scores and psychological symptoms decreased over time, physical symptoms did not, which aligns with side effect progression from cumulative chemotherapy burden.

Thoracic splenosis: an important consideration in oncology patients.

SummarySplenosis is the implantation of ectopic splenic tissue after splenic injury or splenectomy. Signs and symptoms of splenosis vary based on anatomic location; however, it remains asymptomatic in many cases. On radiographic imaging, splenosis often appears as a soft tissue mass and can be diagnosed using heat-damaged red blood cell scintigraphy, a non-invasive imaging modality. Radiographic findings of splenosis on imaging may be suspicious for metastatic disease in patients with known solid organ tumours. It is important to have a high degree of suspicion for splenosis with known history of splenic trauma or splenectomy in order to avoid invasive procedures and guide appropriate management.

Addressing metastatic individuals everyday: Rationale and design of the nurse AMIE for Amazon Echo Show trial among metastatic breast cancer patients.

Background: Metastatic Breast Cancer (MBC) patients often feel their symptom-related needs are unmet, despite visiting their doctors up to once a week. Novel approaches are needed to address symptoms without requiring additional appointments. Technology based symptom management approaches to address symptoms have not been well tested. Methods: Nurse AMIE (Addressing Metastatic Individuals Everyday) is a technology based supportive care platform that provides guideline-concordant symptom management interventions in response to patient reported symptoms. We have previously successfully implemented a tablet version of Nurse AMIE. However, some eligible patients chose not to participate because they were overwhelmed by the technology. To address this barrier, we translated the Nurse AMIE platform to the Amazon Echo Show, which allowed for voice-based interactions. Forty-two MBC patients were randomized 1:1 to receive the Nurse AMIE for Echo Show immediately for six months, or to receive the same intervention for three months, after a three month delay. The primary outcome was change in physical distress over three months, and secondary outcomes included feasibility, acceptability, patient reported outcomes and usability. Conclusions: Results from the Nurse AMIE for Echo Show trial will identify the feasibility, acceptability, and preliminary effects of the Nurse AMIE for Echo Show on patient reported outcomes. Untested novel technologies, particularly voice-based artificial intelligence devices may an effective and scalable vehicle through which we can deliver supportive care interventions. Clinicaltrialsgov identifier: NCT04673019.

Group-led creative writing and behavioural health in cancer: a randomised clinical trial.

BACKGROUND: Cancer diagnosis can adversely affect mental well-being and overall clinical outcome. We evaluated the efficacy of a group-led creative writing workshop (CWW) on mood in patients with cancer prospectively. METHODS: We conducted a single-institution phase II study. Sixty adult patients with cancer (any type or stage) were randomised 2:1 to CWW (4×CWW sessions, bimonthly over 8 weeks) versus active control (AC) (independent writing at home with the help of a book, four sessions, bimonthly over 8 weeks). The total study duration was 6 months with a follow-up of up to 3 months. PRIMARY OBJECTIVE: changes in overall mood, depression and anxiety symptoms before and after intervention in both arms. Emotional Thermometer Scale (ETS) was used to assess changes in patients' mood. Additionally, the Patient Health Questionnaire (PHQ)-9 and General Anxiety Disorder Scale (GAD)-7 were used to evaluate depression and anxiety symptoms. RESULTS: Of 50 evaluable patients (CWW 34, AC 17), 26 patients in the CWW arm attended at least one class and 19 attended at least four classes. Patients in CWW had significant immediate improvement in the overall ETS (post vs preclass scores; p<0.0001, 95% CI -4.31 to -2.47). Four of the five subscale ETS scores were significantly lower for the CWW arm: distress (p=0.0346, 95% CI -2.6 to -0.1), anxiety (p=0.0366, 95% CI -4.1 to -0.2), depression (p=0.0441, 95% CI -3.9 to -0.1) and anger (p=0.0494, 95% CI -3.3 to 0). No significant differences were seen in the AC arm. No significant differences were observed in the PHQ-9 or the GAD-7 scores. CONCLUSION: CWW had a positive effect on mood based on ETS scores, suggesting a potential therapeutic benefit among patients with cancer.

Spontaneous Hip Dislocation Complicating the Management of Malignant Peripheral Nerve Sheath Tumor Arising Within a Plexiform Neurofibroma.

Neurofibromatosis type 1 (NF1) is one of the most common inherited neurological disorders. It can cause plexiform neurofibromas, leading to diffuse enlargement of a nerve or nerves within the body. There are benign in general, however, can cause significant symptoms due to their size, including bony erosion, pain, and joint instability. Unfortunately, they also have the capacity to become malignant by internal transformation into a malignant peripheral nerve sheath tumor (MPNST). The case presented here is a 27-year-old male with NF1 that was followed for years with a pelvic girdle plexiform neurofibroma whose course was complicated by transformation to MPNST and a spontaneous hip dislocation. He underwent excision, Girdlestone procedure, chemotherapy, and radiation. Unfortunately, he subsequently developed lung metastases and is part of a clinical trial with an MDM2 inhibitor and pembrolizumab.

Postoperative chemotherapy and radiation improve survival following cardiac sarcoma resection.

OBJECTIVE: Cardiac sarcoma represents a rare and aggressive form of cancer with a paucity of data to produce outcome-driven evidence-based guidelines. Current surgical management consists of resection with postoperative therapy (chemotherapy, radiation, or both) offered on a selective, individualized basis. This study was designed to determine whether postoperative therapy was associated with improved overall survival after resection. METHODS: The National Cancer Database was used to identify patients with cardiac sarcoma between 2004 and 2015. Patient characteristics were stratified by treatment (surgical, nonsurgical, and none), and treatment was analyzed by stage. Overall survival, assessed with Kaplan-Meier methodology, was compared between patients who received postoperative therapy and those who did not following resection. Multivariable survival modeling using a Weibull model identified risk factors associated with survival while controlling for confounders. RESULTS: The study included 617 patients diagnosed with cardiac sarcoma. Only 24% (149/617) of patients were diagnosed with early-stage disease. Angiosarcoma represented 48% (298/617) of cases and was the most commonly identified histologic subtype. 60% (372/617) underwent surgical resection and 58% (216/372) of those patients were treated with postoperative therapy. Following surgery, median survival was more than doubled for patients treated with postoperative therapy (19 months vs 8 months, P = .026). However, 5-year overall survival was similar between the groups. Multivariable analysis confirmed an improvement in survival with postoperative therapy (hazard ratio, 0.68; 95% confidence interval, 0.51-0.91, P = .009). CONCLUSIONS: Postoperative therapy is associated with better median survival following resection of cardiac sarcoma. However, at 5 years, the difference in overall survival is not statistically significant.

Benefits of Surgical Treatment of Stage IV Breast Cancer for Patients With Known Hormone Receptor and HER2 Status.

BACKGROUND: For the 6% of breast cancer patients with a diagnosis of stage IV disease, systemic therapy is the cornerstone of treatment, with an unclear role for surgery. Limited evidence exists to delineate treatment methods with regard to hormone receptor and human epidermal growth factor receptor 2 (HER2) status. METHODS: The National Cancer Database was used to identify 12,838 stage IV breast cancer patients with known hormone receptor and HER2 status from 2010 to 2015. Chi square tests examined subgroup differences between the treatment methods received. Using the Kaplan-Meier method, 5-year overall survival (OS) was assessed. Multivariate Cox proportional hazard models examined factors associated with survival. RESULTS: A survival advantage was noted for patients who received either systemic therapy and surgery (ST + Surg: hazard ratio [HR] 0.723; 95% confidence interval [CI] 0.671-0.779) or systemic therapy, surgery, and radiation (Trimodality: HR 0.640; 95% CI 0.591-0.694) (both p < 0.0001) compared with systemic therapy alone (ST). The HER2+ patients who received Trimodality or ST + Surg had a better 5-year OS rate than those who received ST (Trimodality [48%], ST + Surg [41%], ST [29%]; p < 0.0001). The sequence of chemotherapy in relation to surgery is significant, with the greatest survival advantage noted for recipients of neoadjuvant chemotherapy (NAC) compared with patients who had adjuvant chemotherapy when they had positive hormone receptor and HER2 status (HER2 + NAC: HR 0.477; estrogen receptor-positive [ER+] NAC: HR 0.453; progesterone receptor-positive [PR+] NAC: HR 0.448; all p < 0.0001). CONCLUSIONS: Surgery in addition to ST has a survival benefit for stage IV breast cancer patients with known hormone receptor and HER2 status and should be considered after NAC for patients with ER+, PR+, or HER2+ disease.

Prognostic Value of DNA Damage Response Genomic Alterations in Relapsed/Advanced Urothelial Cancer.

BACKGROUND: DNA damage response (DDR) genomic alterations may play an important role in clinical outcomes of patients with urothelial cancer (UC). However, data on the prognostic role of DDR gene alterations in patients with advanced UC remain unclear. MATERIALS AND METHODS: We retrospectively collected data of three independent patient cohorts with relapsed or advanced UC including 81 and 91 patients from four institutions who underwent FoundationOne genomic sequencing as well as 129 patients selected from The Cancer Genome Atlas bladder cohort. Fisher's exact test was used to determine differences of mutation frequency among the three cohorts. Logistic regression analysis was performed to calculate odds ratio (OR) and 95% confidence interval (CI). Overall survival (OS) was measured from time of initial diagnosis and Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% CI. RESULTS: DDR genomic alterations were present in 76.5% (62/81), 40.7% (37/91), and 51.2% (66/129) of the three cohorts. ATM alterations consistently correlated with significantly shorter OS, whereas other DDR alterations (excluding ATM) were associated with better prognosis. In 152 patients treated with platinum pooled from the three cohorts, the prognostic value of alterations in ATM as compared with other predefined DDR genes was substantially different (ATM: adjusted HR [HR], 2.03; 95% CI, 1.03-4; p = .04; other DDR: adjusted HR, 0.49; 95% CI, 0.31-0.8; p = .003). CONCLUSIONS: Genomic alterations in ATM and other DDR genes may have opposite prognostic value in relapsed and/or advanced UC. ATM may have a complex role in UC progression. IMPLICATIONS FOR PRACTICE: Somatic mutations of DNA damage response (DDR) genes are frequently found in urothelial cancer and appear to play an important role in tumorigenesis, progression, treatment response, and outcomes. In a set of DDR genes, ATM alterations were associated with worse survival, while other alterations were associated with better survival in advanced urothelial cancer. The results of this study suggest a complex role of ATM in tumor progression and call for further studies to determine the underlying mechanisms and biomarker clinical utility.

Metastasis of Ewing Sarcoma to the Pancreas: Case Report and Literature Review.

Ewing sarcoma (ES) is a highly aggressive malignant bone cancer. ES is part of the Ewing sarcoma family of tumors (ESFT), which express characteristic t(11;22) translocation as well as higher levels of CD99. Given that metastasis and tumor burden are significant prognostic factors in patient's response to treatment, prompt diagnosis is needed to effectively treat ESFT patients. However, the challenges in classifying and characterizing ESFT complicate effective management and treatment of ES. In this report, we present a rare case of ES metastasis to the pancreas. Upon review of the literature, we found 39 cases of ESFT involving the pancreas, but only 3 were metastatic to the pancreas while the remaining cases of ESFT primarily originated from the pancreas. Given the rarity of such metastasis, the positive outcome in our patient's case may explain the importance of prompt diagnosis in order to initiate appropriate treatment.

ATM/RB1 mutations predict shorter overall survival in urothelial cancer.

BACKGROUND: Mutations of DNA repair genes, e.g. ATM/RB1, are frequently found in urothelial cancer (UC) and have been associated with better response to cisplatin-based chemotherapy. Further external validation of the prognostic value of ATM/RB1 mutations in UC can inform clinical decision making and trial designs. RESULTS: In the discovery dataset, ATM/RB1 mutations were present in 24% of patients and were associated with shorter OS (adjusted HR 2.67, 95% CI, 1.45-4.92, p = 0.002). There was a higher mutation load in patients carrying ATM/RB1 mutations (median mutation load: 6.7 versus 5.5 per Mb, p = 0.072). In the validation dataset, ATM/RB1 mutations were present in 22.2% of patients and were non-significantly associated with shorter OS (adjusted HR 1.87, 95% CI, 0.97-3.59, p = 0.06) and higher mutation load (median mutation load: 8.1 versus 7.2 per Mb, p = 0.126). MATERIALS AND METHODS: Exome sequencing data of 130 bladder UC patients from The Cancer Genome Atlas (TCGA) dataset were analyzed as a discovery cohort to determine the prognostic value of ATM/RB1 mutations. Results were validated in an independent cohort of 81 advanced UC patients. Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% confidence interval (CI) to compare overall survival (OS). CONCLUSIONS: ATM/RB1 mutations may be a biomarker of poor prognosis in unselected UC patients and may correlate with higher mutational load. Further studies are required to determine factors that can further stratify prognosis and evaluate predictive role of ATM/RB1 mutation status to immunotherapy and platinum-based chemotherapy.

Relationship of smoking status to genomic profile, chemotherapy response and clinical outcome in patients with advanced urothelial carcinoma.

Smoking has been linked to urothelial carcinoma (UC), but the implications on genomic profile and therapeutic response are poorly understood. To determine how smoking history impacts genomic profile and chemotherapy response, clinicopathologic data was collected for patients with metastatic UC (mUC) across 3 academic medical centers and comprehensive genomic profiling (CGP) was performed through a CLIA-certified lab. Unsupervised hierarchical clustering based on smoking status was used to categorize the frequency of genomic alterations (GAs) amongst current smokers (CS), ex-smokers (ES) and non-smokers (NS), and survival was compared in these subsets. Fisher's exact test identified significant associations between GAs and smoking status. Amongst 83 patients, 23%, 55% and 22% were CS, ES, and NS, respectively, and 95% of patients had stage IV disease. With a median follow up of 14.4 months, the median overall survival (OS) was significantly higher in NS and ES (combined) as compared to CS (51.6 vs 15.6 months; P = 0.04). Of 315 cancer-related genes and 31 genes often related to rearrangement tested, heatmaps show some variations amongst the subsets. GAs in NSD1 were more frequent in CS as compared to other groups (P < 0.001). CS status negatively impacts OS in patients with mUC and is associated with genomic alterations that could have therapeutic implications.

Novel Immunotherapies for Hematological Malignancies.

The successful treatment of hematological malignancies remains challenging. Prognosis is often dismal given the frequency of disease relapse or treatment refractory disease. Cytotoxic and cytostatic chemotherapy remain mainstream therapeutics for most hematological malignancies. However, improved understanding of tumor immunobiology is providing appealing anti-cancer strategies targeting selected component of immune response. Since approval of rituximab for treating B cell malignancies in 1997, availability of monoclonal antibodies against tumor specific surface molecules has driven the development of the emerging field of cancer immunotherapy. This strategy of modulating the immune response is taking an increasingly prominent role in the treatment of hematological malignancies with several new antibody-based therapeutics becoming available for patients with leukemia/lymphoma. In addition, with an increasingly appreciated role for T cell immunity in cancer pathogenesis, strategies enhancing T cell activation as well as inhibiting T cell suppression mechanisms are under active development. Therapeutic vaccines to improve efficacy of antigen processing and presentation, agonists for co-stimulatory molecules, adoptive transfer of genetically-modified T cells, as well as agents that suppress negative regulatory pathways for T cell function are all under active clinical investigation. Although most of these studies are in early stages, preliminary data are very promising. Availability of additional immune-based therapeutic options for patients with hematological malignancies is anticipated in the near future.

Immunotherapy in Bladder Cancer.

With the advent of Bacille Calmette Guerin (BCG), bladder cancer was one of the earliest cancers where the concept of immunotherapy was utilized. While this is true, recent advances in the use of immunotherapy are enabling oncologists to expand the armamentarium for the treatment of bladder cancer. Unacceptable side effects and failure to produce a durable response with the use of chemotherapeutic agents in bladder cancer has led to the evaluation of more targeted and personalized approaches. Increased understanding of the underlying carcinogenesis of bladder cancer, coupled with the ability to engineer targeted agents implicated in bladder cancer associated pathways has provided new avenues for the management of this disease. Newer immunotherapeutic approaches have generated a great deal of interest in bladder cancer along with other diseases. In this article we will focus on various forms of immunotherapies that may have a therapeutic potential in bladder cancer. We will briefly review the current status of "non-targeted" immunotherapeutic agents like BCG, interferons and interleukins in bladder cancer. But the main focus of this article is to discuss the emerging role of "targeted" immunotherapeutic agents like cytotoxic T cell lymphocyte associated protein-4 blocking antibody and programmed death pathway blocking antibodies in localized or metastatic bladder cancer.

Targeted immunotherapy for non-small cell lung cancer.

Targeted therapies that deliver the expected anti-tumor effects while mitigating the adverse effects are taking the cancer world by storm. The need for such therapies in non-small cell lung cancer (NSCLC), where systemic cytotoxic chemotherapies still remain the backbone of management, is felt more than ever before. Runway success of immunotherapies such as Ipilimumab for melanoma has brought excitement among oncologists. Immune-based treatments are in various stages of evaluation for NSCLC as well. Immunotherapies using strategies of antigen based or cell based vaccines, and blocking immune checkpoints are of substantial interest. Meaningful clinical responses are yet to be reaped from these new treatment modalities.

Emerging molecular therapies for the treatment of acute lymphoblastic leukemia.

The improved molecular understanding of cancer initiation, progression, and therapeutic resistance has yielded several novel molecular events that are being targeted by emerging therapies. While the treatment of ALL is a success story in the pediatric population, achieving a sustained remission in the adult population remains an area of investigation. Nevertheless, certain therapies have significantly improved the overall survival for adult ALL patients that should continue to improve with the discovery of better molecular targets and targeted agents. Here, we discuss novel therapeutic options under clinical investigation for the treatment of Philadephia chromosome negative ALL including immunotherapy, monoclonal antibodies, and small molecules that may be used as single agent or adjuvant therapy in the management of adult ALL.

ACE inhibitor-induced angioedema.

Much has been written about hereditary angioedema (HAE) in recent literature; however, the prevalence of angiotensin-converting enzyme inhibitor-induced angioedema (ACEiIA) far exceeds that of HAE. Similarly, multiple therapies have been developed for HAE, yet no definitive therapy is available for ACEiIA. In this article, we discuss the mechanism, prevalence, pathophysiology, and management of ACEiIA, with focus on newer therapies recently approved for HAE and how they may be effective for ACEiIA.