Enfortumab-vedotin use for urothelial carcinoma in two patients on hemodialysis.

Enfortumab vedotin (EV) is a novel treatment option for patients with advanced/metastatic urothelial carcinoma who have progressed after chemotherapy and immunotherapy. Two patients at two different New England tertiary cancer care centers were treated with EV while concurrently receiving hemodialysis (HD), where a complete response to EV in both patients was noted. The use of EV in patients requiring HD is extrapolated from the available pharmacokinetic and pharmacodynamic literature on monoclonal antibodies in patients requiring HD. There is a paucity of data for the use of antibody-drug conjugates like EV in patients needing dialysis.

FGFR inhibitors in urothelial cancer: Contextualizing THOR within the new treatment landscape.

As frontline treatment of advanced urothelial cancer (UC) evolves, optimal sequencing of subsequent therapies remains unclear. The phase 3 THOR trial compared the efficacy of erdafitinib to chemotherapy or immunotherapy in FGFR3/2-altered advanced UC. THOR offers valuable data informing sequencing strategies, reinforcing the need for molecular testing in UC.

Telehealth through the pandemic at a safety net hospital: observations and next steps for cancer care delivery.

The COVID-19 pandemic revolutionized cancer care delivery leading to rapid adoption of digital technology for telehealth in the United States. In this study, we describe telehealth utilization trends across the three largest waves of the pandemic at a safety net academic center. We also provide a perspective on lessons learnt and our vision for cancer care delivery using digital technology in the near future. The integration of interpreter services within the video platform and its integration within the electronic medical record system is crucial for safety net institutes that service a diverse patient population. Pay-parity for telehealth, especially ongoing support for audio-only visits, will be critical in overcoming health disparities for patients without access to smartphone technology. Use of telehealth in clinical trials, widespread adoption of hospital at home programs, electronic consults for rapid access, and structured telehealth slots in clinic templates will be crucial in making cancer care more equitable and efficient.

Effect of Preirradiation Fluoride Treatment on the Physical Properties of Dentin.

Objective: To determine the effects of preirradiation fluoride treatments on the Knoop hardness of dentin. Materials and Methods: Human posterior teeth mounted into acrylic resin molds were polished with silicon carbide (SiC) abrasives and 3-micron diamond paste. The Knoop hardness of dentin was measured with a Leco hardness instrument. The teeth were divided into groups of ten teeth per group as follows: no treatment (control), treatment with silver diamine fluoride (SDF), MI varnish (MI), and cavity shield (CS). The teeth were exposed to 2 Gy of daily radiation for six weeks using an X-Rad 320ix biological irradiator. Hardness was measured weekly, before, during, and after irradiation. The teeth were stored in artificial saliva at 37oC between radiation treatments. Results: In preirradiation dentin, a Knoop hardness value of 58.8 (14.1) KHN was obtained. Treatment with SDF significantly increased KHN before irradiation. Immediately after radiation treatment, hardness was significantly reduced in all experimental groups. Postirradiation fluoride treatments increased the hardness of dentin to varying degrees. Conclusions: Preirradiation fluoride treatment does not provide protection from decreases in the hardness of dentin. Treatment of teeth with fluoride formulations after radiation progressively restores the hardness of dentin to different degrees.

Coordination and optimization of FDG PET/CT and COVID-19 vaccination; Lessons learned in the early stages of mass vaccination.

As the world embarks on mass vaccination for COVID-19, we are beginning to encounter unintended dilemmas in imaging oncology patients; particularly with regards to FDG PET/CT. In some cases, vaccine-related lymphadenopathy and FDG uptake on PET/CT can mimic cancer and lead to confounding imaging results. These cases where findings overlap with cancer pose a significant dilemma for diagnostic purposes, follow-up, and management leading to possible treatment delays, unnecessary repeat imaging and sampling, and patient anxiety. These cases can largely be avoided by optimal coordination between vaccination and planned imaging as well as preemptive selection of vaccine administration site. This coordination hinges on patient, oncologist, and radiologists' awareness of this issue and collaboration. Through close communication and patient education, we believe this will eliminate significant challenges for our oncology patients as we strive to end this pandemic.

Stereotactic Body Radiotherapy for Palliation of Hematuria Arising From Urothelial Carcinoma of the Kidney in Unfavorable Surgical Candidates.

INTRODUCTION: Hematuria can be a distressing and debilitating complication of urothelial carcinoma (UC) of the kidney for patients who are not candidates for surgery or ureteroscopic ablation. We retrospectively assessed the efficacy, tolerability, and safety of stereotactic body radiotherapy (SBRT) for controlling gross hematuria in this patient population. MATERIALS AND METHODS: Institutional Review Board (IRB)-approved review of the records, laboratory values, pathology, and imaging of 8 consecutive patients treated with SBRT over a 5-year period for uncontrolled gross hematuria caused by UC of the renal pelvis or calyces. RESULTS: Therapy was delivered in 3 to 5 treatments over 1 to weeks. Individual treatments lasted an average of 17.2 minutes. No patient experienced treatment-related pain, vomiting, or diarrhea. All enjoyed cessation of bleeding within a week of completing therapy. Hematuria recurred in 2 patients in 4 and 22 months. Of the patients who have not re-bled, 3 expired of metastatic disease or co-morbidities, and 3 remain alive up to 6 years posttreatment. Of patients who have survived longer than a year, creatinine has changed by -0.05 to +0.35, and estimated glomerular filtration rate has fallen by an average of 22%. No patient has required dialysis. CONCLUSIONS: SBRT appears to be an effective and well-tolerated means of palliating gross hematuria secondary to UC of the renal pelvis or calyces in patients who are unfavorable candidates for nephrectomy or ureteroscopic ablation. Treatment was associated with a moderate decline in renal function.

Heart transplantation in India-looking back as we celebrate 25 years of the transplant law.

India's heart transplantation programme is the number one programme in South Asia with an average heart transplantation rate of 0.2 per million population (pmp) versus the global average of 1.06 pmp (2016-2018). The deceased donation rate was 0.67 pmp in India in 2018. The law which made it possible has completed 25 years. In the first 5 years, after the law was passed, less than 50 hearts had been transplanted. The foundation for the deceased donation programme was laid through the creation of an 'Organ Sharing Network' in the year 2000 by Multi Organ Harvesting Aid Network (MOHAN) Foundation, a non-governmental organisation in Chennai. The role of the Health Department of Tamil Nadu in streamlining the deceased donation process in 2008-2009 changed the course of the programme. The heart transplantation programme evolved due to a handful of committed hospitals from the private sector. The challenge was in the identification and certification of brain death, and this continues to be the main reason for the low donation rate. The referral government hospitals, which usually receive traumatic head injuries that result in brain death, seldom possess the infrastructure or financial autonomy to start a transplant programme. Hence, expensive transplants like heart and liver have catered to the needs of the economically affordable class mostly. To improve the donation rate will require innovative thinking by taking steps such as strengthening the national programme and creating cross-subsidy formulas in organ sharing so that the less affordable too have access to such surgeries. To showcase the success of the programme, it is also imperative to start a heart transplant outcome registry to study the short- and long-term outcomes.

Elotuzumab-based maintenance therapy following autologous stem cell transplant in multiple myeloma deepens post-transplant responses.

BACKGROUND: Post-transplant maintenance provides progression-free survival benefit in multiple myeloma (MM). Here we report our institution's experience with elotuzumab-based maintenance following autologous stem cell transplant. METHODS: We retrospectively evaluated the outcomes of MM patients who were started on elotuzumab-based maintenance (elotuzumab/lenalidomide/dexamethasone, elotuzumab/bortezomib/dexamethasone, or elotuzumab/bortezomib/methylprednisolone) following transplant (N = 7). Baseline characteristics, treatment response, survival, and adverse events were reviewed. RESULTS: Median age was 68 (56-81) years at the time of transplant, and median lines of induction therapy was 2 (1-6). Three patients (42.9%) had high-risk cytogenetics and five (71.4%) had stage II or greater disease at diagnosis. At a median follow-up of 24 months (12-50), five patients (71.4%) had improvement of quality of response, with a combined CR or VGPR rate increasing from 57.1% to 100% (CR = 3, VGPR = 4). All patients were alive without relapse or progression at the time of this analysis. Grade 3-4 adverse events were observed in three (42.9%) patients. None of the patients discontinued the treatment due to intolerance. CONCLUSIONS: Our study demonstrates that elotuzumab-based maintenance may deepen response post-transplant in MM and can be safely administered even in older patients. Given its unique action and rare side effects, further studies of elotuzumab in the post-transplant setting are warranted.

Axillary Access TAVR: Entrapment of a Transcatheter Aortic Valve in the Innominate Artery With Aortic Dissection.

Non-femoral transcatheter aortic valve replacement (TAVR) is indicated when peripheral vascular disease is diagnosed. We describe the "double-stick" technique via the axillary artery. During the procedure, the pigtail coiled around the TAVR system. While retracting the TAVR sheath, the seam along system split dislodging the valve from the balloon. The valve was entrapped in the innominate artery, and an aortic dissection required surgery. With the double-stick technique, friction and resistance between the pigtail and delivery system must be avoided. Pre-procedural planning and early identification is paramount. Smaller and more seamless delivery systems may reduce risk for dissection and entrapment.

Drug Holiday in Metastatic Renal-Cell Carcinoma Patients Treated With Vascular Endothelial Growth Factor Receptor Inhibitors.

INTRODUCTION: Tyrosine kinase inhibitor (TKI) therapy in metastatic renal-cell carcinoma (mRCC) is noncurative and may be associated with significant toxicities. Some patients may receive treatment breaks as a result of TKI-related adverse effects or planned drug holidays. PATIENTS AND METHODS: In this retrospective study, mRCC patients who underwent drug holidays during TKI therapy at 2 different institutions were analyzed. A drug holiday was defined as a period of drug cessation for ≥ 3 months for reasons other than progressive disease. RESULTS: Of the 112 patients, the median duration of the first drug holiday for the overall cohort was 16.8 months (95% confidence interval, 12.5-26.4), and 40 patients (36%) remain on the first drug holiday. Overall, patients received a median of 2 lines of treatment. Complete response before the initial drug holiday (n = 14) was associated with a longer surveillance period (P = .0004). The observed median survival of this cohort was 71.7 months (range, 1.3 to 93+ months). CONCLUSION: Some selected mRCC patients with a favorable response to TKIs may be eligible for drug holidays. The cohort evaluated in this retrospective study represents a highly selected group of patients with indolent disease biology.

Antiplatelet antibodies in oxaliplatin-induced immune thrombocytopenia.

Drug-induced immune thrombocytopenia may be potentially fatal; here we report the development of severe thrombocytopenia with strong oxaliplatin-dependent antiplatelet antibodies.

Angiogenesis and the tumor microenvironment: vascular endothelial growth factor and beyond.

Our understanding of the dynamic tumor microenvironment (TME) has improved exponentially over the last few decades. In addition to traditional cytotoxic agents, anti-cancer strategies now include numerous molecular-targeted drugs that modulate distinct elements of the TME. Angiogenesis is an underlying promoter of tumor growth, invasion, and metastases. From traditional and emerging angiogenic cytokines and their receptors to novel immune checkpoint inhibitors, regulation of the tumor microenvironment is potentially key in countering tumor progression. In this article, an overview of the architecture of the TME and the orchestration of angiogenesis within the TME is provided. Additionally, traditional and novel angiogenic targets of current interest within the TME are reviewed.

Dual VEGF/VEGFR inhibition in advanced solid malignancies: clinical effects and pharmacodynamic biomarkers.

Our prior phase I study of the combination of vascular endothelial growth factor (VEGF) antibody, bevacizumab, and VEGF receptor (VEGFR) inhibitor, sunitinib, in advanced solid tumors identified an encouraging response evaluation. An expansion phase of this study was thus undertaken to obtain further safety data, response assessment and characterization of pharmacodynamic biomarkers in melanoma, renal, and adrenal carcinoma patients. Patients with metastatic solid tumors received sunitinib (37.5 mg/d, 4 wk on/2 wk off) and bevacizumab (5 mg/kg intravenously every 2 wk). Responses were assessed every 2 cycles. Serum levels of angiogenic molecules were measured using ELISA assays. Twenty-two patients were enrolled, including 11 melanoma, 5 renal cell carcinoma (RCC), 5 adrenal cancer, and 1 angiosarcoma. Grade 3 or higher adverse events were observed in 15 patients, including hypertension (41%), thrombocytopenia (23%), and fatigue (14%). Three RCC patients, and 1 melanoma patient developed thrombotic microangiopathy (TMA). Partial response (PR) occurred in 21% patients, including melanoma (2), adrenal (1), and renal (1) carcinomas. Overall, 6 patients demonstrated some reduction in their tumor burden. Serum VEGF and several other proangiogenic proteins declined over the first 4 wk of treatment whereas the putative VEGF-resistant protein, prokineticin-2, increased over 10-fold. Occurrence of TMA related to dual VEGF/VEGFR inhibition can result from systemic or nephron specific injury even in non-renal malignancies. While the combination of sunitinib and bevacizumab was clinically efficacious in renal cell carcinoma and melanoma, the observance of microangiopathy, even in non-RCC patients, is a significant toxicity that precludes further clinical development.

Isolated secondary CNS relapse in a case of stage I diffuse large B-cell lymphoma.

A 55-year-old woman was admitted to our hospital with a 10-day history of right arm weakness and numbness. The patient's medical history was notable for lobular carcinoma in situ of the right breast in 2008 and stage I diffuse large B-cell lymphoma of the left axilla. The patient had completed treatment with chemotherapy and radiation 2 months prior to presentation. Blood counts, metabolic panel and lumbar puncture were unremarkable. MRI of the brain revealed multiple enhancing masses. The patient was started on dexamethasone, with rapid symptom improvement. A stereotactic brain biopsy revealed CD20 diffuse large B-cell lymphoma. The patient was started on high-dose intravenous methotrexate. She has received 11 cycles and has regained near normal function of the right arm. The patient's most recent brain MRI showed near complete resolution of all previously seen abnormal foci of enhancement.

Use of a standardized code status explanation by residents among hospitalized patients.

OBJECTIVES: There is wide variability in the discussion of code status by residents among hospitalized patients. The primary objective of this study was to determine the effect of a scripted code status explanation on patient understanding of choices pertaining to code status and end-of-life care. METHODS: This was a single center, randomized trial in a teaching hospital. Patients were randomized to a control (questionnaire alone) or intervention arm (standardized explanation+ questionnaire). A composite score was generated based on patient responses to assess comprehension. RESULTS: The composite score was 5.27 in the intervention compared to 4.93 in the control arm (p=0.066). The score was lower in older patients (p<0.001), patients with multiple comorbidities (p≤0.001), KATZ score <6 (p=0.008), and those living in an assisted living/nursing home (p=0.005). There were significant differences in patient understanding of the ability to receive chest compressions, intravenous fluids, and tube feeds by code status. CONCLUSION: The scripted code status explanation did not significantly impact the composite score. Age, comorbidities, performance status, and type of residence demonstrated a significant association with patient understanding of code status choices. PRACTICE IMPLICATIONS: Standardized discussion of code status and training in communication of end-of-life care merit further research.