Paraneoplastic neurologic syndromes (PNS) are a group of disorders characterized by an autoimmune response against the nervous system due to cross-reactivity between malignant and normal neural tissue. The most commonly associated malignancies include small cell lung cancer, ovarian cancer, breast cancer, and lymphoma. Multiple PNS have been reported including paraneoplastic cerebellar degeneration, retinopathy, sensorimotor peripheral neuropathy, encephalopathy, opsoclonus-myoclonus syndrome, and stiff-person syndrome. We report a case of a 67-year-old woman with breast cancer who presented with a history of progressive oropharyngeal dysphagia as a paraneoplastic neurologic complication. She was diagnosed with invasive ductal carcinoma, nuclear grade 3 with moderate peritumoral lymphoid infiltrate. Hormone receptors were weakly positive for estrogen receptor (ER) (H score 15), weakly positive for progesterone receptor (PR) (H score 30), and negative for human epidermal growth factor receptor 2 (HER-2/NEU). The patient underwent a localized segmental mastectomy but declined any further adjuvant treatment. Three years after being diagnosed with invasive ductal carcinoma of the breast, she developed progressive oropharyngeal dysphagia that warranted percutaneous endoscopic gastrostomy (PEG) tube placement. Testing for onconeural antibodies was positive for voltage-gated calcium channel antibody. An extensive workup was negative for any alternative etiology that would explain her neurological symptoms. The patient declined further treatment and eventually succumbed to her illness.
Neuroendocrine tumors usually originate from the neuroendocrine cells of gastrointestinal tract and their presence in the liver is mostly in the form of metastases. A primary neuroendocrine tumor in the liver concomitantly with hepatocellular carcinoma is an infrequent phenomenon. We present a 66-year-old woman with a remote history of breast cancer coming with postprandial fullness, later found to have multiple liver masses. After a thorough investigation, she was found to have a combined type of hepatocellular and primary neuroendocrine tumor of liver with pulmonary metastases. She was not a surgical candidate due to distant metastases. She was treated with chemotherapy, immunotherapy, and targeted therapies but continued to deteriorate clinically, and finally succumbed to her illness. The presence of this combined type of tumor in our patient is unique in many different ways: It is extremely rare, she did not have any risk factors for liver cancer, no genetic mutation till date could tie all these cancers (breast cancer, neuroendocrine tumor, and hepatocellular carcinoma) together, and not a lot of literatures/studies performed on this illness.
Introduction Amyloidosis is a rare disease and there are currently no FDA approved therapies for AL amyloidosis. Most of the therapeutic and disease data come from expert guidelines, consensus and retrospective review papers. There is a paucity of data specifically for relapsed/refractory AL amyloidosis (RRAL). We conducted this systematic review of clinical trials, retrospective and prospective cohort studies to evaluate patterns of relapse and therapeutic options for RRAL. Methods PubMed and Clinicaltrials.gov were searched for clinical trials, retrospective and prospective cohort studies on RRAL. Studies were selected according to PRISMA guidelines. Cross-trial comparison of included studies and meta-analysis could not be performed for a number of reasons but mainly due to a limited number of studies on one particular treatment regimen. Results From a total of 511 studies, 11 studies (n= 698 patients) met our inclusion criteria. Five were phase I/II clinical trials, five retrospective cohort studies, and one prospective cohort study. Most studies had less than 50 patients. The largest study, a retrospective cohort by Tandon et al. included 366 patients. Mean age was 61.2. Three studies reported 2 median prior lines of therapy (n= 22, 28, and 84 patients); two reported 3 median prior lines of therapy (n= 25 and 24) and 6 studies didn't specify this data. Prior treatment options included proteasome inhibitors (PI), most commonly bortezomib (n= 259), followed by melphalan (n=211), high dose melphalan and stem cell transplant (HDM/SCT [n= 207]) and IMiDs most commonly lenalidomide (n=154). Time to progression (TTP) from first-line treatment was reported in only 4 studies as 1 month, 5 months, 5 months and 34 months respectively. The study reporting a TTP of 34-months had 11 patients who received HDM/SCT as first line treatment. Three studies reported information about their criteria for initiation of subsequent treatment. Subsequent treatment was mostly a combination regimen with dexamethasone or an alkylating agent. The only agent evaluated as single agent was bortezomib in a phase I/II clinical trial by Reece et al. Therapeutic options for RRAL are PI (non-specific) based therapy (n= 145), lenalidomide (n= 105), bortezomib (n= 99), IMiD (non-specific) based therapy (n=83), melphalan based therapy (n= 33), carfilzomib (n=28), pomalidomide (n=27), ASCT (n= 25), daratumumab (n=25) and bendamustine (n=22). Efficacy: Hematologic responses were reported to be following: bortezomib + dexamethasone/melphalan (85%, n=17/20), daratumumab + dexamethasone (76%, n= 19/25), HDM/ASCT (73%, n= 8/11), single agent bortezomib (67%, n=23/34), carfilzomib ± dexamethasone (63%, n= 15/24), lenalidomide + dexamethasone (61%, n=51/84), bendamustine + dexamethasone (55%, 11/22) and pomalidomide + dexamethasone (50%, 12/24). Five of eleven studies reported organ responses which ranged from 18% to 23%. The studies which reported organ responses had evaluated the following agents: single agent bortezomib, carfilzomib ± dexamethasone, lenalidomide + dexamethasone, and bendamustine + dexamethasone. Best survival outcomes were seen with bortezomib with median overall survival (OS) 62 months. With bendamustine and dexamethasone (retrospective cohort study n=22) median OS was 31 months. With lenalidomide + dexamethasone (prospective cohort study n=24 ) median OS was 14 months. For the remaining studies, the median OS was either not reported or not reached at the time of presentation of data. Conclusion AL amyloidosis patients progressing after front line therapy show good responses with bortezomib (median overall survival of 62 months). Novel combinations using lenalidomide, pomalidomide, carfilzomib, daratumumab, and bendamustine show promising efficacy. Ongoing trials of daratumumab (AMYDARA trial) and ixazomib (TOURAMALINE-AL1) will bring further insight into therapeutic armamentarium for RRAL patients. After relapse, a salvage HDM/ASCT can be considered. Comparisons of regimen efficacy between studies are not practical because of multiple factors which include but are not limited to heterogenous nature of AL patients, small sample sizes, variable prior treatments, exposure to novel agents, observational study versus clinical trial and variable endpoints. Table Disclosures Anwer: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; In-Cyte: Speakers Bureau.
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