Clear cell urethral adenocarcinoma – a case report of an exceptional response to immunotherapy in a metastatic rare tumour

2021 ◽  
pp. 205141582110226
Author(s):  
Darren Cowzer ◽  
Karen Mulligan ◽  
Kate Glennon ◽  
Nicholas Hegarty ◽  
Tom Walsh ◽  
...  
Keyword(s):  
Clear Cell ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Complete Response ◽  
Clear Cell Adenocarcinoma ◽  
Level Of Evidence ◽  
Rare Tumour ◽  
Primary Surgery ◽  
First Case ◽  
Line Setting

Primary clear cell adenocarcinoma of the urethra is extremely rare. Given the rarity of these tumours there is no high-level evidence available to guide treatments. Localized disease is typically treated with primary surgery or concurrent chemo-radiotherapy. In the advanced disease setting treatment options are limited and decisions are based on evidence in disease subtypes where similarities exist. Immuno-oncology and the use of checkpoint inhibitors, particularly for metastatic disease has transformed clinical practice over the past few years and patient outcomes continue to improve as a result of their introduction. Here we report the first case, to our knowledge, of a patient with advanced primary clear cell adenocarcinoma of the urethra who had a dramatic and almost complete response to anti-PD-1 therapy in the fourth line setting. Level of evidence: 4

scholarly journals Significant Benefit of Everolimus In a Patient With Urothelial Bladder Cancer Harboring A Rare M1043I Mutation of PIK3CA

2021 ◽  
Author(s):  
Shouhua Pan ◽  
Si Li ◽  
Mingzhe Xiao ◽  
Dongsheng Chen ◽  
Junlong Li
Keyword(s):  
Bladder Cancer ◽  
Treatment Options ◽  
Complete Response ◽  
Significant Benefit ◽  
Urothelial Bladder Cancer ◽  
Multiple Tumor ◽  
First Line Therapy ◽  
First Case ◽  
Potential Biomarker ◽  
Urothelial Bladder

Abstract Urothelial bladder cancer (UBC) is a common malignancy with significant mortality worldwide. However, treatment options of UBC were mainly chemotherapy and immunotherapy since few targeted agents had shown efficacy in UBC. In recent studies, everolimus has showed antitumor activity in patients harboring aberrations in PI3K/Akt/mTOR pathway in multiple tumor types. Here we report a patient with metastatic UBC harboring a rare M1043I mutation of PIK3CA detected by DNA based next-generation sequencing. The patient received everolimus as first-line therapy after palliative transurethral resection. Within one months, the residual lymph node metastases achieved complete response and no more ostealgia was reported. To our knowledge, this is the first case reporting a significant benefit from everolimus in PIK3CA mutant UBC, suggesting the rare M1043I mutation variant may be a potential biomarker of sensitivity to everolimus. Further mechanism insights and clinical studies are needed to clarify the effectiveness of everolimus in patients with PIK3CA M1043I mutation.

scholarly journals Checking the Checkpoint Inhibitors: A Case of Autoimmune Diabetes After PD-1 Inhibition in a Patient with HIV

2020 ◽  
Vol 4 (12) ◽  
Author(s):  
Michael S Hughes ◽  
Massimo Pietropaolo ◽  
Madhuri M Vasudevan ◽  
Marco Marcelli ◽  
Ha Nguyen
Keyword(s):  
Highly Active Antiretroviral Therapy ◽  
Checkpoint Inhibitors ◽  
Autoimmune Diabetes ◽  
Complete Response ◽  
Acid Decarboxylase ◽  
Genetic Profile ◽  
Highly Active ◽  
First Case ◽  
Primary Driver ◽  
High Index Of Suspicion

Abstract Immune checkpoint inhibitor–associated diabetes mellitus (ICI-DM) is a known immune-related adverse event (irAE) following treatment with programmed cell death protein 1 (PD-1), with a reported 0.9% incidence. We hereby present the first case, to our knowledge, of ICI-DM following ICI use in a human immunodeficiency virus (HIV) patient. In this case, a 48-year-old man with HIV stable on highly active antiretroviral therapy (HAART) was diagnosed with Hodgkin lymphoma and initiated treatment with the PD-1 inhibitor nivolumab. His lymphoma achieved complete response after 5 months. However, at month 8, he reported sudden polydipsia and polyuria. Labs revealed a glucose level of 764 mg/dL and glycated hemoglobin A1c (HbA1c) of 7.1%. Low C-peptide and elevated glutamic acid decarboxylase 65 (GAD65) antibody levels confirmed autoimmune DM, and he was started on insulin. Major histocompatibility complex class II genetic analysis revealed homozygous HLA DRB1*03-DQA1*0501-DQB1*02 (DR3-DQ2), which is a known primary driver of genetic susceptibility to type 1 DM. Autoimmune DM has been reported as an ICI-associated irAE. However, patients with immunocompromising conditions such as HIV are usually excluded from ICI trials. Therefore, little is known about such irAEs in this population. In this case, risk of ICI-DM as an irAE was likely increased by several factors including family history, a high-risk genetic profile, islet-related immunologic abnormalities, active lymphoma, and HIV infection with a possible immune reconstitution event. Clinicians should maintain a high index of suspicion for development of irAEs associated with ICI, particularly as use of these therapies broadens. Thorough investigation for presence of higher-risk features should be conducted and may warrant inclusion of pre-therapy genetic and/or autoantibody screening.

New Treatment Options in Advanced Squamous Cell Lung Cancer

2019 ◽  
pp. e198-e206 ◽  
Author(s):  
Paul K. Paik ◽  
Rathi Narayana Pillai ◽  
Christopher S. Lathan ◽  
Sylvia A. Velasco ◽  
Vassiliki Papadimitrakopoulou
Keyword(s):  
Squamous Cell ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Substantial Improvement ◽  
Lung Cancers ◽  
The Past ◽  
New Treatment ◽  
Line Setting ◽  
Rapid Shift

The past few years have witnessed a rapid shift in the treatments for patients with squamous cell lung cancers (SQCLCs) after the U.S. Food and Drug Administration approval of a number of immune checkpoint inhibitors as second-line therapies for patients with non–small cell lung cancers. These series of approvals marked the first substantial improvement in overall survival for patients with SQCLC in over a decade. Further gains have been made more recently with the incorporation of immune checkpoint inhibition in the first-line setting, either as monotherapy or in combination with chemotherapy. These advances have, however, exposed existing deficiencies in the management of this disease. Despite a deeper understanding of the genomic alterations that characterize SQCLCs and years of trial work targeting these alterations, personalized therapies remain out of hand. Future studies will continue to focus on identifying targeted approaches to expand the treatment options for our patients.

scholarly journals Complete Response to PD-1 Inhibition in an Adolescent With Relapsed Clear Cell Adenocarcinoma of the Cervix Predicted by Neoepitope Burden and APOBEC Signature

2020 ◽  
pp. 1321-1332
Author(s):  
Anya Levinson ◽  
Alex G. Lee ◽  
Henry J. Martell ◽  
Marcus R. Breese ◽  
Charles Zaloudek ◽  
...  
Keyword(s):  
Clear Cell ◽  
Complete Response ◽  
Clear Cell Adenocarcinoma

scholarly journals Primary Fallopian Tube Clear Cell Adenocarcinoma in Pregnancy: Case Presentation and Review of the Literature

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Mohammed Malak ◽  
Stephanie Klam
Keyword(s):  
Fallopian Tube ◽  
Pelvic Pain ◽  
Clear Cell ◽  
Clear Cell Adenocarcinoma ◽  
Fallopian Tube Cancer ◽  
First Case ◽  
Cancer In Pregnancy ◽  
Cell Variant ◽  
Clear Cell Variant ◽  
In Pregnancy

Primary fallopian tube cancer in pregnancy is rare and is even more so for the clear cell variant. Our case is the third case of primary fallopian tube cancer in pregnancy and the first case of clear cell adenocarcinoma of the fallopian tube in pregnancy. The patient presented with increasing pelvic pain starting in the second trimester. Serial ultrasound evaluations were performed and revealed a rapidly growing complex adnexal mass adjacent to the uterus. Her pregnancy was further complicated by spontaneous preterm labor and she delivered prematurely per vaginam at 31 weeks. She underwent an urgent laparotomy in the immediate postpartum period for acute aggravation of her right pelvic pain and fever. The diagnosis of tubal clear cell adenocarcinoma was subsequently made on histopathology examination.

Pertuzumab plus trastuzumab for HER2-positive metastatic urothelial cancer (mUC): Preliminary data from MyPathway.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 348-348 ◽  
Author(s):  
Alan Haruo Bryce ◽  
Razelle Kurzrock ◽  
Funda Meric-Bernstam ◽  
Herbert Hurwitz ◽  
John D. Hainsworth ◽  
...  
Keyword(s):  
Preliminary Data ◽  
Treatment Options ◽  
Complete Response ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Open Label ◽  
Molecular Alterations ◽  
Metastatic Urothelial Cancer ◽  
Duration Of Response ◽  
Line Setting

348 Background: Patients (pts) with mUC have few treatment options beyond the second-line setting. HER2 gene amplification has been reported in a minority of pts with UC, but there have been anecdotal reports of the activity of HER2-targeted agents. MyPathway is a multi-basket study evaluating the efficacy and safety of targeted therapies in non-indicated tumor types harboring relevant molecular alterations. We present preliminary data for pts with HER2-positive mUC receiving HER2-targeted treatment with pertuzumab + trastuzumab. Methods: MyPathway (NCT02091141) is an open-label, multicenter, phase IIA study. Pts in this subset analysis had refractory mUC with HER2 amplification or putative activating mutations by gene sequencing, FISH, or IHC. Pts received standard doses of pertuzumab + trastuzumab without chemotherapy until disease progression or unacceptable toxicity. The primary endpoint is investigator-assessed overall response rate (RECIST v1.1). Results: As of July 31, 2016, 12 pts with platinum-resistant HER2-positive mUC (HER2-amplified, n=9; HER2-mutated, n=3) have been enrolled. At a median follow-up of 5.4 (range 0.9–14.5) mos, 1 pt had complete response (CR, ongoing at 12.5 mos), 2 had partial responses (PR; duration of response, 3.7 and 5.5 mos), and 2 had stable disease (SD) for >4 mos (Table). Safety was consistent with the product labels. Conclusions: Preliminary results indicate that the combination of pertuzumab + trastuzumab has activity in previously treated HER2-amplified mUC, including a durable CR in a pt with peritoneal metastases. Accrual to MyPathway is ongoing. Clinical trial information: NCT02091141. [Table: see text]

Genital Tract Metastases from Renal Cell Carcinoma—A Case Report and Discussion

1985 ◽  
Vol 30 (1) ◽  
pp. 43-45 ◽  
Author(s):  
N. D. Sharma ◽  
G. B. McKelvie
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Genital Tract ◽  
World Literature ◽  
Clear Cell ◽  
Female Genital Tract ◽  
Clear Cell Adenocarcinoma ◽  
Menopausal Woman ◽  
First Case

A case of renal cell carcinoma presenting with metastases in the female genital tract is reported. Clinical and histological features distinguishing primary and secondary clear cell adenocarcinoma of the genital tract are discussed. It is emphasised that when a clear cell adenocarcinoma is found, particularly in a post-menopausal woman, metastatic renal carcinoma has to be excluded. Although so far there are 61 cases reported in the world literature from English speaking countries, we believe that this is the first case reported from the United Kingdom.

scholarly journals Laparoscopic Nephrectomy with Adrenalectomy for Synchronous Adrenal Myelolipoma and Renal Cell Carcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-3
Author(s):  
Kallappan Senthil ◽  
Manickam Ramalingam ◽  
Karpagam Janardhan ◽  
Anandan Murugesan ◽  
Mizar Ganapathy Pai
Keyword(s):  
Renal Cell Carcinoma ◽  
Case Report ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Clear Cell Adenocarcinoma ◽  
Adrenal Myelolipoma ◽  
First Case ◽  
Biopsy Report ◽  
Work Up

Introduction. Adrenal myelolipomas are uncommon nonfunctioning tumors of the adrenal. Synchronous renal cell carcinomas with adrenal myelolipomas are very rare. We present the case report of adrenal myelolipoma with synchronous RCC managed laparoscopically.Case Report. A 60-year-old old gentleman presented with incidental right upper polar mass with right adrenal mass. Metastatic work-up was negative. Laparoscopic radical nephrectomy with adrenalectomy was done under general anesthesia. The biopsy report was right kidney clear cell adenocarcinoma (T1b) with right adrenal myelolipoma.Conclusion. This is the first case report of laparoscopic adrenalectomy with nephrectomy for ipsilateral synchronous renal cell carcinoma with adrenal myelolipoma.

A randomized, open-label, phase II study of azacitidine (AZA) in combination with durvalumab in patients (pts) with previously untreated higher-risk myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) ineligible for hematopoietic stem cell transplantation (HSCT).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS7074-TPS7074 ◽  
Author(s):  
Lewis R. Silverman ◽  
Hartmut Dohner ◽  
Herve Dombret ◽  
Ghulam J. Mufti ◽  
Richard M. Stone ◽  
...  
Keyword(s):  
Overall Survival ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Complete Response ◽  
Open Label ◽  
Hematopoietic Stem ◽  
Poor Risk ◽  
Increased Risk ◽  
Programmed Cell Death 1 ◽  
Open Label Phase

TPS7074 Background: Hypomethylating agents (HMAs) induce hematologic response in ~ 50% of higher-risk MDS pts; however, there are few treatment options for nonresponding pts at increased risk of AML progression and death. While older AML pts ineligible for HSCT have similar overall survival (OS) with AZA and chemotherapy (13.3 vs 12.2 months) (Döhner et al. Haematologica 2015;100:P566), there is an opportunity to further improve responses and OS in these pts. Blockade of the programmed cell death-1 (PD-1)/PD-ligand 1 (PD-L1) pathway with immune checkpoint inhibitors is an emerging paradigm in anticancer therapy. PD-L1 is expressed on cells from AML and MDS pts; expression is upregulated on myeloblasts following HMA therapy (Yang et al. Leukemia 2014;28:1280) and during MDS transformation to AML (Ogata et al. Leuk Res 2012;36:1229). Durvalumab (MEDI-4736), a human anti-PD-L1 monoclonal antibody, is well tolerated and induces durable responses in pts with solid tumors (Lutzky et al. JCO 2014;32:3001). This randomized, open-label, phase 2 study evaluates efficacy and safety of subcutaneous (SC) AZA ± durvalumab in pts with higher-risk MDS and older pts with AML. Methods: Eligible MDS pts ( < 20% blasts) aged ≥ 18 years, with IPSS intermediate- or high-risk MDS, and AML pts (≥ 20% blasts) aged ≥ 65 years, are randomized 1:1 to receive either AZA 75 mg/m2 SC for 7/28 days or AZA 75 mg/m2 SC for 7/28 days plus durvalumab 1500 mg IV on day 1 of 28-day cycles. Pts are stratified by cytogenetic risk: intermediate- vs poor-risk AML, and intermediate- vs poor-/very-poor-risk MDS. Primary endpoint is overall response rate per IWG 2006 criteria in MDS pts, and proportion of pts achieving complete response (CR) or CR with incomplete blood count recovery (CRi) per modified IWG 2003 criteria in AML pts. Other endpoints include safety, time to response, overall survival and PD-1/PD-L1 activity. Pts will be followed every 3 months until discontinuation. Target enrollment is 182 pts: 72 MDS pts and 110 AML pts. Enrollment began in June 2016 (ClinicalTrials.gov NCT02775903).

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