Evolving standards of care and new challenges in the management of HER2-positive breast cancer.

The management of human epidermal growth factor receptor (HER2)-positive breast cancer (BC) has rapidly evolved over the last 20 years. Major advances have led to US Food and Drug Administration approval of 7 HER2-targeted therapies for the treatment of early-stage and/or advanced-stage disease. Although oncologic outcomes continue to improve, most patients with advanced HER2-positive BC ultimately die of their disease because of primary or acquired resistance to therapy, and patients with HER2-positive early BC who have residual invasive disease after preoperative systemic therapy are at a higher risk of distant recurrence and death. The concept of treatment de-escalation and escalation is increasingly important to optimally tailor therapy for patients with HER2-positive BC and is a major focus of the current review. Research efforts in this regard are discussed as well as updates regarding the evolving standard of care in the (neo)adjuvant and metastatic settings, including the use of novel combination therapies. The authors also briefly discuss ongoing challenges in the management of HER2-positive BC (eg, intrinsic vs acquired drug resistance, the identification of predictive biomarkers, the integration of imaging techniques to guide clinical practice), and the treatment of HER2-positive brain metastases. Research aimed at superseding these challenges will be imperative to ensure continued progress in the management of HER2-positive BC going forward.

Disseminated cryptococcosis with gastrointestinal involvement and false-negative cryptococcal antigen testing due to postzone phenomenon: a case report and review of the literature.

BACKGROUND: Cryptococcosis is an increasingly common infection given the growing immunocompromised population worldwide. Cryptococcal antigen (CrAg) testing demonstrates excellent sensitivity and specificity and is the mainstay of diagnosis. However, there may be rare instances in which false-negative CrAg results can delay diagnosis and early treatment, which are critical to ensure positive outcomes. CASE PRESENTATION: A 31-year-old man living with HIV/AIDS who was not taking antiretroviral therapy was hospitalized with fever, diarrhea, and headaches. CD4 count on presentation was 71 cells/uL, and HIV viral load was 3,194,949 copies/mL. Serum CrAg testing was initially negative, however CSF CrAg performed several days later was positive at 1:40 and blood and CSF cultures grew Cryptococcus neoformans. Colonoscopy revealed mucosal papules throughout the sigmoid colon, and tissue biopsy showed yeast within the lamina propria consistent with GI cryptococcosis. Given the high burden of disease, the original serum CrAg specimen was serially diluted and subsequently found to be positive at 1:2,560, confirming the postzone phenomenon. CONCLUSION: Cryptococcosis has a wide array of presentations including intraluminal GI disease, as seen in this patient. While serum CrAg testing displays excellent test characteristics, it is important for clinicians to be aware of the rare instances in which false-negative results may occur in the presence of excess antigen, as in this case.

Phase 2 study evaluating the combination of sorafenib and temsirolimus in the treatment of radioactive iodine-refractory thyroid cancer.

BACKGROUND: Patients with recurrent and/or metastatic, radioactive iodine-refractory thyroid carcinoma have limited treatment options. Sorafenib, an oral kinase inhibitor, is approved by the US Food and Drug Administration for the treatment of radioactive iodine-refractory thyroid carcinoma, although it demonstrated low response rates (12.2%) as a single agent in the first-line setting. The objective of the current study was to determine whether adding the mammalian target of rapamycin inhibitor temsirolimus to sorafenib could improve on these results. METHODS: In this single-institution, phase 2 study, 36 patients with metastatic, radioactive iodine-refractory thyroid carcinoma of follicular origin received treatment with the combination of oral sorafenib (200 mg twice daily) and intravenous temsirolimus (25 mg weekly). The receipt of prior systemic treatment with cytotoxic chemotherapy and targeted therapy, including sorafenib, was permitted. The primary endpoint was the radiographic response rate. RESULTS: The best response was a partial response in 8 patients (22%), stable disease in 21 (58%), and progressive disease in 1 (3%). Six patients were not evaluable for a response. Patients who had received any prior systemic treatment had a response rate of 10% compared with 38% of those who had not received prior systemic treatment. One of 2 patients with anaplastic thyroid cancer had an objective response. The progression-free survival rate at 1 year was 30.5%. The most common grade 3 and 4 toxicities associated with sorafenib and temsirolimus included hyperglycemia, fatigue, anemia, and oral mucositis. CONCLUSIONS: Sorafenib and temsirolimus appear to be an active combination in patients with radioactive iodine-refractory thyroid carcinoma, especially in patients who received no prior treatment compared with historic data from single-agent sorafenib. Activity is also observed in patients who previously received sorafenib. This regimen warrants further investigation. Cancer 2017;123:4114-4121. © 2017 American Cancer Society.

Neurocysticercosis of the third ventricle: illustrative case.

BACKGROUND: Neurocysticercosis is a parasitic infection of the central nervous system. Cysts located in the ventricles, intraventricular neurocysticercosis (IVNCC), can cause symptoms of increased intracranial pressure and, if untreated, can be fatal. Neuroendoscopic removal of IVNCC is recommended as the first-line treatment. OBSERVATIONS: The authors present the case of a healthy 30-year-old male originally from Mexico who presented with headaches and vomiting. He was found to have a cyst in the third ventricle on imaging, consistent with IVNCC. The authors successfully performed neuroendoscopic surgery with removal of the cyst en bloc. LESSONS: A multidisciplinary team of neurosurgery and infectious disease specialists is recommended for successful management of patients with IVNCC. These patients typically require neuroendoscopic surgical removal for definitive treatment. In this case, the authors show surgery resulted in an effective cure without the need for antiparasitic medication and excellent long-term outcomes.

When Patients Make Unexpected Medical Choices.

Background: In the United States, about 500,000 patients are receiving maintenance dialysis for end-stage renal disease. The decision to discontinue dialysis and receive hospice care tends to be more difficult than to withhold or forego dialysis. Observations: Supporting patient autonomy is an important health care priority that is recognized by most clinicians. However, some health care professionals are conflicted when patient autonomy varies from their treatment recommendations. This paper describes the case of a patient on kidney dialysis who chose to discontinue a potentially life-prolonging treatment. Conclusions: Respecting a patient's autonomy to make informed decisions about their end-of-life care is a fundamental ethical and legal principle. Medical opinion should not and cannot overrule the wishes of a competent patient who refuses treatment.

Prototheca Infection: A Descriptive Study.

Prototheca is a microalgae known to cause infections in humans, with protothecosis most commonly presenting as olecranon bursitis or localized soft tissue infection. Disseminated disease can be seen in immunocompromised patients. In this retrospective single-institution case series, we describe our experience with 7 patients with Prototheca infections.

The Effect of Aromatherapy in the Management of Cancer-Related Pain at the End of Life: A Pilot Study.

BACKGROUND: The use of clinical aromatherapy for managing pain has been studied in surgical patients and in women during childbirth. However, there are limited data on the use of aromatherapy for alleviating cancer-related pain, particularly at the end of life. OBJECTIVES: This pilot study identifies the pre- and postimplementation effects of aromatherapy on pain level, pain perception, and the use of oral morphine equivalent among patients with cancer at the end of life. METHODS: A survey was conducted to assess participant pain levels preimplementation of aromatherapy. Participants were then asked to rate their pain and describe how they felt 15 minutes postimplementation of aromatherapy. A chart review comparing oral morphine equivalent use pre- and postimplementation of aromatherapy was also performed. FINDINGS: Postimplementation of aromatherapy, mean pain scores and 24-hour oral morphine equivalent use decreased. Participants also described an improved pain experience and found aromatherapy to be soothing.

Advance Care Planning and Goals-of-Care Decisions Among Veterans With Malignancy.

BACKGROUND: There is a limited knowledge base about factors affecting advance directives and code status decisions among veterans with malignancy. In addition, few studies have focused on the benefit of palliative care (PC) in goals-of-care discussions among veterans with cancer. OBJECTIVES: This study examined advance care planning and goals-of-care decisions among veterans with malignancy. METHODS: Demographic and clinical data were obtained using retrospective chart analysis. Patient characteristics were analyzed using univariate descriptive statistics. To compare patients with and without a do-not-resuscitate (DNR) decision, chi-square test was performed. FINDINGS: More than half of the patients in the study were referred to PC within one year of their cancer diagnosis. Most had documented metastatic disease at the time of their PC referral. Veterans with prostate cancer were more likely to elect full code status. In this study, White veterans were more likely to choose a DNR order than African American veterans.

The Meaning of Words and Why They Matter During End-of-Life Conversations.

Effective communication during end-of-life is crucial for health care delivery, but misinterpretation can influence how the quality of the care is rendered and perceived.

Inguinoscrotal herniation of the bladder: A rare case of obstructive uropathy.

Inguinoscrotal herniation of the bladder is a rare presentation of inguinal hernia that can result in significant complications if untreated. We describe a case of an elderly male with a delayed presentation of bladder herniation resulting in severe acute kidney injury requiring urgent placement of nephrostomy tubes. Ultimately surgery is required for definitive management.

Thromboembolic Disease in COVID-19.

Coronavirus disease 2019 (COVID-19) was initially recognized in late December 2019 and has quickly spread globally with over 114 million reported cases worldwide at the time of this publication. For the majority of patients infected with COVID-19, the clinical manifestations are absent or mild. In more advanced cases, severe respiratory dysfunction is the leading cause of morbidity and mortality. However, increasingly, there have been reports of increased thrombotic complications including pulmonary embolism and deep vein thrombosis seen in these patients. We present herein a series of cases of concomitant COVID-19 pneumonia and venous thromboembolism. These cases highlight the importance of clinical and radiologic vigilance to ensure this often clinically silent complication is not missed.

Successful encorafenib desensitization in a patient with recurrent metastatic melanoma.

Type I hypersensitivity reactions (HSR) to dabrafenib are rare but have been previously described. We present a case where a 72-year-old woman with recurrent, metastatic BRAF-mutated melanoma developed a type I HSR to dabrafenib. We, therefore, developed a desensitization protocol with encorafenib, a similar class agent, to allow the patient to continue with treatment. Patients with a history of HSR to dabrafenib may be considered for encorafenib desensitization when other therapeutic options are limited.

Orbital apex syndrome due to invasive aspergillosis in an immunocompetent patient.

Infection is a rare cause of orbital apex syndrome (OAS) and most commonly occurs in immunocompromised hosts. We report a case of OAS in an elderly immunocompetent female due to invasive aspergillosis and Staphylococcus aureus co-infection. The patient required both surgical debridement and prolonged courses of antibiotic and antifungal therapy. Invasive fungal disease must be considered in cases of OAS, even in patients without classic risk factors.

Group III phospholipase A2 downregulation attenuated survival and metastasis in ovarian cancer and promotes chemo-sensitization.

BACKGROUND: Aberrant lipogenicity and deregulated autophagy are common in most advanced human cancer and therapeutic strategies to exploit these pathways are currently under consideration. Group III Phospholipase A2 (sPLA2-III/PLA2G3), an atypical secretory PLA2, is recognized as a regulator of lipid metabolism associated with oncogenesis. Though recent studies reveal that high PLA2G3 expression significantly correlates with poor prognosis in several cancers, however, role of PLA2G3 in ovarian cancer (OC) pathogenesis is still undetermined. METHODS: CRISPR-Cas9 and shRNA mediated knockout and knockdown of PLA2G3 in OC cells were used to evaluate lipid droplet (LD) biogenesis by confocal and Transmission electron microscopy analysis, and the cell viability and sensitization of the cells to platinum-mediated cytotoxicity by MTT assay. Regulation of primary ciliation by PLA2G3 downregulation both genetically and by metabolic inhibitor PFK-158 induced autophagy was assessed by immunofluorescence-based confocal analysis and immunoblot. Transient transfection with GFP-RFP-LC3B and confocal analysis was used to assess the autophagic flux in OC cells. PLA2G3 knockout OVCAR5 xenograft in combination with carboplatin on tumor growth and metastasis was assessed in vivo. Efficacy of PFK158 alone and with platinum drugs was determined in patient-derived primary ascites cultures expressing PLA2G3 by MTT assay and immunoblot analysis. RESULTS: Downregulation of PLA2G3 in OVCAR8 and 5 cells inhibited LD biogenesis, decreased growth and sensitized cells to platinum drug mediated cytotoxicity in vitro and in in vivo OVCAR5 xenograft. PLA2G3 knockdown in HeyA8MDR-resistant cells showed sensitivity to carboplatin treatment. We found that both PFK158 inhibitor-mediated and genetic downregulation of PLA2G3 resulted in increased number of percent ciliated cells and inhibited cancer progression. Mechanistically, we found that PFK158-induced autophagy targeted PLA2G3 to restore primary cilia in OC cells. Of clinical relevance, PFK158 also induces percent ciliated cells in human-derived primary ascites cells and reduces cell viability with sensitization to chemotherapy. CONCLUSIONS: Taken together, our study for the first time emphasizes the role of PLA2G3 in regulating the OC metastasis. This study further suggests the therapeutic potential of targeting phospholipases and/or restoration of PC for future OC treatment and the critical role of PLA2G3 in regulating ciliary function by coordinating interface between lipogenesis and metastasis.

Esophageal Cancer: A Case Study of a Rare Metastatic Esophageal Squamous Cell Carcinoma.

The expected pattern of spread in metastatic esophageal squamous cell carcinoma involves the upper torso and thorax. This article presents an unusual instance of an isolated osseous metastasis of esophageal squamous cell carcinoma to the distal bone of the left ankle and describes the contributions of advanced practice nursing assessment and clinical judgment to improve patient outcomes. This case study also highlights comprehensive cancer care by an interprofessional palliative care team.

End-of-Life Care: Use of Antineoplastic Therapy and Nonessential Medications in Veteran Patients Receiving Palliative Care.

BACKGROUND: The use of antineoplastic therapy and nonessential medications at the end of life can lead to poorer quality of life for patients, decreased satisfaction with care among caregivers, financial toxicity, increased use of the emergency department, and hospitalization. OBJECTIVES: This study evaluated the incidence of antineoplastic therapy administration and use of nonessential medications at 30 and 14 days prior to death among patients with metastatic lung, prostate, colon, or pancreatic cancer who were also receiving palliative care. METHODS: Using retrospective chart review, this study evaluated patients admitted to a U.S. Department of Veterans Affairs healthcare system during a two-year period. Variables assessed included use of antineoplastic therapy and nonessential medications, emergency department visits, hospitalizations, palliative care accessibility, and hospice referrals. FINDINGS: All patients in the study (N = 57) received palliative care. Sixteen percent of patients in this study received antineoplastic therapy, 14% received nonessential medications, and 40% were hospitalized or visited the emergency department within 30 days of death.

Long-term quality of life in older patients with HPV-related oropharyngeal cancer.

BACKGROUND: We explored if age affects quality of life (QOL) in survivors of locally advanced human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC). METHODS: In a cross-sectional survey of 185 patients, at least 12 months from radiation, we evaluated generic (EuroQOL-5D questionnaire [EQ-5D]) and head and neck specific (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35-questions [EORTC-QLQ-H&N35]) QOL questionnaires and compared differences between younger (<65) and older (≥65) patients. RESULTS: The median age was 57.0 years (range 25-77 years), and 31 patients (16.8%) were ≥65 years old. There was no significant difference in EQ-5D global QOL scores by age (P = .53). Patients ≥65 years reported more immobility (P < .01), problems with social eating (P < .0001), and coughing (P < .01). Patients ≥65 years were not more likely to ever require a gastrostomy (P = .24) but were more likely to remain gastrostomy-dependent at the time of the survey (P = .02). CONCLUSION: Despite similar generic QOL, older survivors may have more mobility problems and issues with social eating compared with younger survivors deserving of further evaluation.

Integrating Palliative Care in COPD Treatment.

After receiving palliative care, patients with chronic obstructive pulmonary disease showed a decrease in the average number of emergency department visits for exacerbations.