Atypical Presentation of Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) in a Patient on Pembrolizumab: A Case Report.

Pembrolizumab is an immune checkpoint inhibitor that has been associated with numerous immune-mediated adverse effects. Several of these cutaneous side effects may include bullous pemphigoid, Stevens-Johnson syndrome, and drug reaction with eosinophilia and systemic symptoms (DRESS). Other case reports have reported DRESS as a rare side effect of immune checkpoint inhibitors but due to its variable presentation and similarities with other cutaneous diseases, it has proven to be a diagnostic challenge. In addition, no effective methods have been developed to monitor for such adverse skin reactions in patients on immunotherapy. Here, we report a diagnostic challenging case of pembrolizumab-induced blistering lesions that were initially treated as suspected Herpes zoster and/or bullous pemphigoid but further pathology was consistent with DRESS.

Integrating Academic and Community Cancer Care and Research through Multidisciplinary Oncology Pathways for Value-Based Care: A Review and the City of Hope Experience.

As the US transitions from volume- to value-based cancer care, many cancer centers and community groups have joined to share resources to deliver measurable, high-quality cancer care and clinical research with the associated high patient satisfaction, provider satisfaction, and practice health at optimal costs that are the hallmarks of value-based care. Multidisciplinary oncology care pathways are essential components of value-based care and their payment metrics. Oncology pathways are evidence-based, standardized but personalizable care plans to guide cancer care. Pathways have been developed and studied for the major medical, surgical, radiation, and supportive oncology disciplines to support decision-making, streamline care, and optimize outcomes. Implementing multidisciplinary oncology pathways can facilitate comprehensive care plans for each cancer patient throughout their cancer journey and across large multisite delivery systems. Outcomes from the delivered pathway-based care can then be evaluated against individual and population benchmarks. The complexity of adoption, implementation, and assessment of multidisciplinary oncology pathways, however, presents many challenges. We review the development and components of value-based cancer care and detail City of Hope's (COH) academic and community-team-based approaches for implementing multidisciplinary pathways. We also describe supportive components with available results towards enterprise-wide value-based care delivery.

Strategies to Improve Participation of Older Adults in Cancer Research.

Cancer is a disease associated with aging. As the US population ages, the number of older adults with cancer is projected to dramatically increase. Despite this, older adults remain vastly underrepresented in research that sets the standards for cancer treatments and, consequently, clinicians struggle with how to interpret data from clinical trials and apply them to older adults in practice. A combination of system, clinician, and patient barriers bar opportunities for trial participation for many older patients, and strategies are needed to address these barriers at multiple fronts, five of which are offered here. This review highlights the need to (1) broaden eligibility criteria, (2) measure relevant end points, (3) expand standard trial designs, (4) increase resources (e.g., institutional support, interdisciplinary care, and telehealth), and (5) develop targeted interventions (e.g., behavioral interventions to promote patient enrollment). Implementing these solutions requires a substantial investment in engaging and collaborating with community-based practices, where the majority of older patients with cancer receive their care. Multifaceted strategies are needed to ensure that older patients with cancer, across diverse healthcare settings, receive the highest-quality, evidence-based care.

Use of a comprehensive frailty assessment to predict morbidity in patients with multiple myeloma undergoing transplant.

Multiple myeloma (MM) is a disease of aging adults and autologous stem cell transplant (ASCT) is considered the standard of care. As the population ages a growing number of older adults will undergo ASCT and an objective approach to estimate physiologic reserve and transplant morbidity risk is warranted. Here, we evaluate assess p16INK4a (p16), a molecular aging biomarker, along with geriatric metrics to determine risk of transplant toxicity. METHODS: We prospectively evaluated 100 MM patients for frailty before and after ASCT using a Geriatric Assessment (GA) and collected T-cells for analysis of p16 using a custom nanostring codeset. RESULTS: Pre-transplant physical function was predicative of hospital length of stay (LOS). Each one-unit increase in physical function score, the average LOS decreased by 0.52 days (95% CI, -1.03-0.02); p = .04). Similarly, higher self-report of ADL/IADL (Human Activity Profile was associated with shorter LOS (0.65 less days (95% CI -1.15 to -0.15), p = .01). Patients with anxiety/depression (OR = 1.10 (95% CI 1.00-1.22), p = .056), lower handgrip strength (OR = 0.90 (95% CI 0.82-0.98), p = .02), falls (OR = 1.60 (95% CI 1.07-2.38), p = .02), or weight loss (OR = 5.65 (95% CI 1.17-25.24), p = .03) were more likely to be re-admitted. The estimated EFS at 1-year was 85% (95% CI, 75-91) with median follow-up of 15.7 months. Weight loss was a significant predictor of EFS (HR = 3.13 (95% CI 1.15-8.50), p = .03). Frailty assessment by self-reported fatigue minimally correlated with T-cell p16 expression (r = 0.28; p = .02). Age, Karnofsky Performance Status (KPS), or Hematopoietic cell transplantation-specific Co-Morbidity Index (HCT-CI) did not predict hospital LOS or readmissions. CONCLUSIONS: Our data illustrate that a GA can identify individuals with MM who are at greater risk for morbidity following ASCT.

Making the most of hypomethylating agents in myelodysplastic syndrome.

PURPOSE OF REVIEW: Hypomethylating agents (HMA) are the preferred therapy for patients with higher risk myelodysplastic syndromes (MDS) and an alternative therapeutic strategy for older patients with acute myeloid leukemia. These agents have improved both survival and quality of life, but results overall remain poor. The purpose of this review is to highlight recent developments in clinical research with HMA in MDS/acute myeloid leukemia over the last year. RECENT FINDINGS: Combination of HMA with B-cell lymphoma-2 inhibitors, hedgehog inhibitors, and a variety of other agents are underway, as are further studies with reformulated HMA that have more favorable pharmacokinetics (including oral bioavailability). HMA may also be promising in maintenance therapy after allogeneic transplantation. Generally speaking, testing new agents in randomized studies after 'HMA failure,' however, may be suboptimal for assessing efficacy. SUMMARY: No clear 'winner' as a combination partner with HMA or novel formulation of HMA has yet emerged. We concur with growing trends to test novel agents early in the drug development timeline, including the frontline treatment setting in combination with HMA, to bring new agents to Food and Drug Administration approval more quickly. HMA are standard in name only, clinical research should be the standard of care.

CD30 and CD30-Targeted Therapies in Hodgkin Lymphoma and Other B cell Lymphomas.

Evolution of cancer therapeutics has resulted in the development of agents with varying mechanisms of selective target inhibition. One such therapeutic approach is utilizing antibody-drug conjugates (ADCs), the combination of a cytotoxic agent linked with a monoclonal antibody, to achieve localization of the target and internalization of the cytotoxic agent in order to maximize efficacy with fewer toxicities. This review focuses on CD30 as a therapeutic target and the development and clinical activity of the ADC brentuximab vedotin in Hodgkin lymphoma (HL) and other B cell lymphomas.

Impact of transcutaneous neuromuscular electrical stimulation on dysphagia in patients with head and neck cancer treated with definitive chemoradiation.

BACKGROUND: The purpose of this study was to investigate the role of transcutaneous neuromuscular electrical stimulation (TNMES) therapy in maintaining swallowing function during chemoradiation for locally advanced head and neck cancer. METHODS: We retrospectively compared 43 consecutive patients with locally advanced head and neck cancer treated with TNMES (treatment group) to 55 control patients. Validated swallowing scale scores were assigned. RESULTS: All patients' swallowing scores declined post-chemoradiotherapy. A difference in mean decline in scores for the control group versus the treatment group using the Functional Oral Intake Scale (FOIS) was seen, favoring TNMES intervention (23% vs 7%; p = .015). Age, race, >10 pack-years smoking, diabetes, stage, nodal disease, accelerated fractionation, weight loss, dietary modification, no TNMES, and radiotherapy dose were all significant for poorer scores on the swallowing scales. CONCLUSION: TNMES should be considered an adjunct to dysphagia reduction and possible prevention in patients with locally advanced head and neck cancer. Further studies should be conducted to define the benefit of TNMES intervention.

Tumor volume change with stereotactic body radiotherapy (SBRT) for early-stage lung cancer: evaluating the potential for adaptive SBRT.

OBJECTIVES: To quantify gross tumor volume (GTV) change during stereotactic body radiotherapy (SBRT) and on first follow-up, as well as to evaluate for any predictive prognostic risk factors related to GTV decrease. An attempt was also made to identify the potential timing for adaptive SBRT. METHODS: Twenty-five tumors in 24 consecutive patients were treated with SBRT to total dose of 50 Gy in 5 fractions. Median age was 72.5 years. Tumor stage was T1, 68%; T2, 20%; and other, 12%. The GTVs of on the 5 cone-beam computed tomographies (CBCT1-5) obtained before each fraction and the first follow-up CT (CTPOST) were analyzed. RESULTS: Median time from diagnosis to initiation of radiotherapy was 64 days. GTV on CBCT1 was the baseline for comparison. GTV decreased by a mean of 7% on CBCT2 (P=0.148), 11% on CBCT3 (P=0.364), 19% on CBCT4 (P=0.0021), and 32% on CBCT5 (P=0.0004). Univariate analyses of GTV shrinkage was significantly associated with "time from CBCT5 to CTPOST" (P=0.027) and "T-stage" (P=0.002). In multivariate analyses, "T-stage" remained significant with T1 tumors showing greater GTV shrinkage than T2 tumors. CONCLUSIONS: Significant decrease in GTV volume based on daily CBCT was demonstrated during SBRT treatment. Adaptive SBRT has the potential to minimize integral dose to the surrounding normal tissues without compromising GTV coverage.

A rare presentation of hepatitis a infection with extrahepatic manifestations.

Hepatitis A has a variety of associated extrahepatic manifestations that clinicians should be aware of for early diagnosis and treatment. We report a unique case of hepatitis A presenting with multiple extrahepatic manifestations not previously described in a single patient. A 34-year-old male presented with sudden onset of left sided facial pain, swelling, and skin rash, with diffuse body pains and muscle weakness, and was found to be positive for hepatitis A immunoglobulin M (IgM). He was initially started on antibiotics for concerns of bacterial parotitis but did not show any improvement. A punch biopsy of his mandibular rash and swelling was done which showed lymphohistiocytic infiltration with a few eosinophils. A trial of prednisone resulted in improvement of his symptoms. Clinicians should be aware to look for hepatitis A infection in a patient with atypical clinical picture causing a widespread systemic inflammatory response. Treatment with prednisone may result in resolution.

Bisphosphonate-related osteonecrosis of the jaw mimicking bone metastasis.

Osteonecrosis of the jaw is usually a potential complication of bisphosphonate therapy. In a cancer patient, this disease entity can be misdiagnosed as a metastatic lesion. Our aim is to make clinicians aware of bisphosphonate associated osteonecrosis of the jaw to prevent misdiagnosis and initiate proper treatment at the earliest. We present the case of a breast cancer patient with multiple bony metastases and a jaw lesion presumed to be metastases. After no response to palliative radiation, repeat radiological imaging studies revealed osteonecrosis of the jaw. Correlating a patient's clinical information with findings on diagnostic imaging studies, such as SPECT bone and CT scans, can help identify this potential complication of bisphosphonate treatment. Early diagnosis helps minimize unnecessary biopsies and allows for the proper treatment to be instituted.

The normal variant (18)F FDG uptake in the lower thoracic spinal cord segments in cancer patients without CNS malignancy.

Focal increased lower thoracic spinal cord (18)F FDG uptake is not infrequently observed as a normal physiological finding and may be confused for spinal cord metastases. This study was conducted to evaluate a possible correlation between the lower thoracic (T11-T12) spinal uptake and lower limb movements/ambulatory status of the patients as a surrogate. The primary endpoint was to identify the possible cause(s) of the normal variant focal increased thoracic spinal cord (T11-T12) (18)F FDG activity and correlate it with the lower limb movements/ambulatory status of the patients. This was a retrospective analysis of PET-CT scans of 200 patients with solid and hematological malignancies. The focal relatively increased (18)F FDG activity in the lower thoracic spinal cord correlated strongly with the (18)F FDG intensity of the liver, bowel, C3-C5 cervical cord activity, weight of the patient and injected dose of (18)F FDG. With regard to the primary endpoint, no significant correlation was found between the ambulatory status of patients in any of the groups and thoracic spine SUVmax. This could be further assessed by performing dual studies in the same patient with and without moderate to excessive leg motion. Identifying this variant focal increased (18)F FDG activity can minimize errors of misdiagnosis and unnecessary further investigation.

Role of nuclear medicine imaging in recognizing different causes of osteonecrosis of the jaw.

The incidence of osteonecrosis of the jaw (ONJ) among patients with cancer and metastatic bone disease being treated with bisphosphonates is as high as 10%, which dictates that an understanding of the risk factors, preventative measures, means of early diagnosis, and treatment is critical. Despite ONJ occurring in the clinical setting of intravenous bisphosphonates, there are other causes associated with higher risk of ONJ, such as multiple dental extractions. Overall, it is important for imaging health care professionals to recognize, describe, and understand ONJ to help minimize biopsies and allow proper treatment to begin as soon as possible.

Interfraction accumulation of seroma during accelerated partial breast irradiation: preliminary results of a prospective study.

PURPOSE: To quantify and characterize the process of seroma accumulation during accelerated partial breast irradiation using multicatheter balloon brachytherapy. MATERIALS AND METHODS: Twenty-two patients were treated using the Contura Multilumen brachytherapy catheter to a dose of 34Gy in 10 fractions over 5 treatment days. Serial aspirations of the vacuum port of the catheter were performed at the time of CT simulation and before each treatment. Volume and characteristics of fluid drawn were recorded. Univariate analysis was performed to evaluate various factors predictive of seroma formation. RESULTS: Median patient age was 59.5 years, body mass index was 31, and volume of surgical specimen was 62.4cm(3). Median time from breast conservation surgery to placement of Contura catheter was 18.5 days. Pericatheter seroma, typically scant with a median volume of 0.75mL, was noted in 91% of patients at CT simulation. A total of 203 aspirations were performed with a median-aspirated seroma volume of 4.05mL. There was no significant correlation between the volume of seroma and histology (invasive vs. in situ), quadrant of location, body mass index, reexcision or reoperation, days from breast conservation surgery to balloon placement, or the volume of specimen removed. Radiation treatment factors, including balloon volume, balloon to skin distance, and planning target volume evaluation, also did not correlate with aspirated seroma. CONCLUSIONS: Interfraction seroma accumulation has a variable pattern of development with no discernible predictors of occurrence. Routine pretreatment aspirations via vacuum port may potentially improve dosimetric reproducibility for a minority of patients.

Impact of interfraction seroma collection on breast brachytherapy dosimetry - a mathematical model.

PURPOSE: Balloon brachytherapy is a widely accepted modality for delivery of accelerated partial breast irradiation (APBI). Our hypothesis was that inter-fraction seroma collection around the balloon surface would have an adverse effect on dosimetry of the target. MATERIAL AND METHODS: This is a dosimetric re-planning study using two volumetric models (30 cc and 45 cc) in a Contura(®) multi-lumen balloon (MLB) catheter. In a previously treated patient, two customized baseline plans were generated using multiple channels of the Contura(®) catheter prescribed to the Planning Target Volume Evaluation (PTV_Eval). Symmetric expansions of 1.0 mm (0-9 mm) increments around the balloon surface were performed to simulate a "Virtual Seroma" (VS) accumulation for both balloon volumes and plans were obtained for each expansion using Eclipse Brachyvision™. An analysis of these plans was then performed to evaluate the effect of seroma accumulation on dosimetric parameters of V100 and V90. RESULTS: 20 plans were generated and analyzed (10 plans for each balloon volume), representing VS of 6.0-66.0 cc. There was a commensurate decrease in the dose delivered to the PTV_Eval V100 and V90 (as defined by the original treatment plan) with increasing VS accumulation leading to a sub-optimal coverage of the PTV_Eval. For 30 cc MLB catheter, V100 decreased by 1.4% and V90 decreased by 0.9% for every 1 cc of VS. For 45cc MLB catheter, V100 decreased by 1.3% and V90 decreased by 1.15% for every 1.0 cc accumulation of VS. CONCLUSIONS: Balloon catheter-tissue adherence ensures daily dose delivery to the planned PTV_Eval. Accumulation of seroma, hematoma or air between HDR fractions can significantly impact PTV_Eval dosimetry. Vacuum-port aspiration prior to delivery of each fraction, if available, should be considered to minimize the risk of geographic under dosing.