Advanced uterine papillary serous cancer: Could there be a role for newer targeted therapeutic approaches or immune checkpoint inhibitors?

BACKGROUND: Although now available in oncology clinics, comprehensive germline mutation testing is being performed only in a minority of patients with advanced uterine papillary serous cancer (UPSC). Some of these patients might harbor various targetable mutations, either heritable or acquired.Data sources: We conducted a retrospective cohort study involving all consecutive patients with UPSC treated at our institution from 2009-2019. Data on epidemiology, with an accent on personal and family history of cancer, clinical presentation, disease stage, employed treatment modalities and cancer-specific survival (CSS) was sought. FINDINGS: Thirteen patients were seventy years of age or younger (≤70) while 15 were older than seventy (>70), and the two arbitrary patient cohorts were well-balanced for the TNM stage. Four UPSC patients >70 had a personal history of metachronous breast cancer. We also identified five cases of breast cancer, two cases of colon cancer, and one of each ovarian and uterine cancer in the first-degree relatives of UPSC patients >70. More than 90% of patients had surgical excision/debulking, and nearly half of the patients in each group received systemic chemotherapy. The most common chemotherapy regimen was carboplatin-paclitaxel every three weeks. Compared to patients ≤70, the UPSC patients >70 were less likely to undergo postoperative radiation therapy (6% vs 61.5%; p = 0.001) and had a worse CSS (21.8 vs. 27.4 months; HR 0.61, p = 0.03). CONCLUSIONS: Personal and family history in a cohort of older UPSC patients identified an excess of second primary cancers, and these patients displayed a shorter CSS. Comprehensive germline and tumor mutation analysis might identify optimal candidates for various targeted agents and immune checkpoint inhibitors, and ultimately improve survival. This may represent an unmet need in the UPSC patients, and further studies are needed to confirm the significance of our findings.

Management and clinical outcomes in uterine malignant mixed Müllerian tumor: Lessons from a single-institution series.

Malignant mixed Müllerian tumor remains an important contributor to morbidity and mortality in women with uterine cancer. Surgery is the primary treatment modality, followed by chemotherapy and/or radiation for advanced disease or high-risk patients. Clinico-epidemiologic characteristics and outcomes in older versus younger women with Malignant mixed Müllerian tumor may differ. We analyzed and now report on 15 consecutive patients with uterine Malignant mixed Müllerian tumor treated at our institution from 2000 to 2018. The mean age at diagnosis was 65 years; 60% (9/15) patients were overweight/obese. Forty-six percent (7/15) had hypercholesterolemia, an association not previously linked with Malignant mixed Müllerian tumor in the literature. All patients but one had surgical excision of the tumor. A third of patients received adjuvant radiation therapy. A majority of patients received chemotherapy; the preferred regimen was carboplatin-paclitaxel. The patients older than 70 had a tendency towards a more advanced disease stage at diagnosis and a significantly shorter cancer-specific survival than their younger counterparts (6 months vs. 102 months (hazard ratio 1.32, p = 0.02)). Our study's conclusions are restricted due to its relatively small size, retrospective design, and some variation in the chemotherapy doses administered in individual patients. Larger studies are needed to confirm the significance of our findings.

Impact of therapeutic modalities on disease-specific survival in older adults with glioblastoma: A single-institution retrospective cohort study.

The standard first-line therapy for glioblastoma consists of maximal surgical resection, followed by concurrent chemoradiotherapy. Optimal management for older glioblastoma patients is unknown as they have not been extensively studied in clinical trials. We report data from a series of 156 consecutive glioblastoma patients treated at our institution from 2007 to 2017. Compared to glioblastoma patients aged 70 or less, the patients older than 70 were less likely to undergo surgical resection (34% vs. 64%; p = 0.0003), be treated with adjuvant chemotherapy (37% vs. 59%; p = 0.01) or radiation therapy (36% vs. 56%; p = 0.03). Disease-specific survival was significantly shorter in this age group (4.7 vs. 15.3 months; p = 0.002). Nonetheless, when older patients did undergo surgery or chemotherapy, the proportional improvement in cancer-specific survival was similar to the one recorded in younger patients, which is concordant with the findings of other published reports. A multidisciplinary input from neurosurgeons, medical and radiation oncologists, oncology pharmacists and geriatricians remain paramount for the optimal management of glioblastoma in patients older than 70.

Clinico-epidemiologic characteristics and patterns of care in Kaposi's sarcoma: Data from a single-institution series.

In the late 20th to early 21st century, most new Kaposi's sarcoma cases were associated with HIV coinfection and low CD4 T-cell counts. After introduction of effective antiretroviral therapy, the clinical and epidemiologic characteristics of Kaposi's sarcoma may have changed. We analyzed and now report on 27 consecutive Kaposi's sarcoma patients treated at our institution from 2007 to 2017. Most patients were HIV-positive Caucasian men on antiretroviral therapy; the average CD4 T-cell count was above the AIDS-defining level of 200 cells/mm3. Seven patients had Kaposi's sarcoma with mucosal involvement, and 20 had skin-only Kaposi's sarcoma. Mucosal Kaposi's sarcoma patients had a mean CD4 T-cell count of 83 cells/mm3 as opposed to 381 cells/mm3 for patients with skin-only involvement (p = 0.005). Survival was significantly compromised in both groups but even more so in Kaposi's sarcoma patients with mucosal involvement (306 vs. 609 days). Along with other reports, our findings suggest that Kaposi's sarcoma may develop in HIV patients in the modern era despite well-controlled HIV disease. This is significant since Kaposi's sarcoma remains an important contributor to morbidity and mortality in HIV-infected patients.

Cystic acne due to imatinib therapy for chronic myelocytic leukemia.

Imatinib mesylate is a tyrosine kinase inhibitor used in the treatment of several malignancies. Its use, however, is associated with a number of toxic effects including adverse cutaneous reactions. Herein, we present a case of facial cystic acne in a patient receiving imatinib therapy for chronic myelocytic leukemia. This side effect resolved with cessation of therapy. To the best of our knowledge, this clinical entity has never been previously reported in the medical literature.

Stevens-Johnson syndrome manifesting late in the course of pembrolizumab therapy.

Pembrolizumab is a humanized antibody that targets programmed cell death receptor-1. This agent is approved for use in the treatment of several malignancies. While pruritus and papulo-erythematous rash are not uncommon with its use, severe reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis are very rare. We present herein a case of Stevens-Johnson syndrome occurring in a patient who had previously tolerated pembrolizumab without significant side effects for seven months. Prompt recognition of Stevens-Johnson syndrome/toxic epidermal necrolysis and discontinuation of the offending agent are paramount to ensure a favorable outcome.

Severe warm-antibody autoimmune hemolytic anemia due to multicentric Castleman disease: Responding to rituximab.

Castleman disease is a rare B-cell lymphoproliferative disorder characterized by lymph node enlargement with or without constitutional signs. Herein, we describe a unique patient with multicentric Castleman disease and retroviral infection who presented with a sudden onset of constitutional signs and was found to have severe warm-antibody autoimmune hemolytic anemia. Rituximab monotherapy yielded an excellent clinical response. We aim to inform the medical community of this rare paraneoplastic phenomenon in patients with Castleman disease and its effective management. Prompt recognition of this entity may help avoid costly diagnostic workups, excessive blood transfusions, and lengthy hospital stays.

Polymyalgia rheumatica due to pembrolizumab therapy.

Pembrolizumab is a humanized anti-programmed cell death 1 antibody used for the therapy of several malignancies. While autoimmune adverse events are not uncommon with this agent, they are typically mild and self-limiting. Severe autoimmunity is rare but can be life-threatening. Herein, we describe a unique case of severe proximal muscle weakness and joint pain shortly after beginning therapy with pembrolizumab. Work-up revealed elevated pro-inflammatory markers leading to the diagnosis of polymyalgia rheumatica. Steroids allowed for resolution of the joint pain. We call for awareness of this rare autoimmune toxicity with pembrolizumab.

Successful re-introduction of alectinib after inducing interstitial lung disease in a patient with lung cancer.

Alectinib is a member of the family of anaplastic lymphoma kinase inhibitors. This agent is effective in the treatment of advanced anaplastic lymphoma kinase-positive non-small cell lung cancer and has excellent blood-brain barrier penetrability. It is generally well tolerated; however, significant toxicities such as interstitial lung disease have been reported. We present herein an instance of interstitial lung disease four weeks into alectinib treatment. Alectinib was held, and the patient showed clinical and radiographic improvement of her interstitial lung disease. Alectinib was then resumed at half dosage without further complications. Prompt recognition of adverse reactions to this targeted agent is paramount. Cessation of therapy may be needed on a case-to-case basis. However, as our case highlights, safe re-introduction of alectinib can be accomplished in some cases.

EGFR inhibitor-induced cut-like skin lesions of the fingers.

Cetuximab and osimertinib are epidermal growth factor receptors (EGFRs) inhibitors used in the treatment of several malignancies. These agents have been associated with several skin lesions, the most common being papulopustular acneiform rash involving the face, neck, chest and back. Herein, we describe a unique toxic effect of these agents involving the fingertips and lateral aspects of fingers in a small patient series. The lesions presented approximately 4 weeks into treatment were cut-like and caused local discomfort/pain. Application of a colloidal solution allowed for partial resolution of these lesions in one patient, while discontinuation of the drug led to the disappearance of the lesions in another. Thus, we call for awareness of this unique skin toxicity with the use of EGFR inhibitors in patients with cancer.