Cycles Of Systemic Chemotherapy Research Articles

Rare recurrence pattern after complete response to chemotherapy in a patient with rectal cancer: a case report

BackgroundColorectal cancer (CRC) often metastasizes to the liver, lungs, lymph nodes, and peritoneum but rarely to the bladder, small intestine, and skin. We here report the rare metastasis of anal cancer in the left bladder wall, followed by metastases to the small intestine and skin, after abdominoperineal resection and left lateral lymph node dissection with chemotherapy in a patient with clinician Stage IVa disease.Case presentationA 66-year-old man presented with 1-month history of bloody stool and anal pain and diagnosed with clinical Stage IVa anal cancer with lymph node and liver metastases (cT3, N3 [#263L], M1a [H1]). Systemic chemotherapy led to clinical complete response (CR) for the liver metastasis and clinical near-CR for the primary tumor. Robot-assisted laparoscopic perineal rectal resection and left-sided lymph node dissection were performed. Computed tomography during 18-month postoperative follow-up identified a mass in the left bladder wall, which was biopsied with transurethral resection, was confirmed as recurrent anal cancer by histopathologic evaluation. After two cycles of systemic chemotherapy, partial resection of the small intestine was performed due to bowel obstruction not responding to conservative therapy. The histopathologic evaluation revealed lymphogenous invasion of the muscularis mucosa and subserosa of all sections. Ten months after the first surgery for bowel obstruction and two months before another surgery for obstruction of the small intestine, skin nodules extending from the lower abdomen to the thighs were observed. The histopathologic evaluation of the skin biopsy specimen collected at the time of surgery for small bowel obstructions led to the diagnosis of skin metastasis of anal cancer. Although panitumumab was administered after surgery, the patient died seven months after the diagnosis of skin metastasis.ConclusionsThis case illustrates the rare presentation of clinical Stage IVa anal cancer metastasizing to the bladder wall, small intestine, and skin several years after CR to chemotherapy.

Neo-adjuvant PIPAC and Systemic Chemotherapy in Management of Synchronous Peritoneal Metastasis From Gastric Cancer

Introduction: Polycystic Ovarian Disorder (PCOD) is a prevalent endocrine illness in women of reproductive age. It has hormonal abnormalities, irregular menstrual cycles and tiny ovarian cysts. Lifestyle and food affect PCOD development and maintenance, coupled with Peritoneal metastasis from gastric cancer remains a major problem. The aim of our study is a retrospective analysis in two different groups with used PIPAC as neo-adjuvant management of synchronous peritoneal metastasis. Group A: 42 patients received as neo-adjuvant treatment 2 cycles of PIPAC (Doxorubicin 3 mgr/m2, cisplatin 10 mgr/m2) and 6 cycles of neo-adjuvant systemic chemotherapy with FLOT and we performed CRS+HIPEC (with cisplatin 80 mgr/m2, mitomycin 35 mgr/m2) for 90 min and 6 cycles of adjuvant systemic chemotherapy with FLOT. Group B: 26 patients received 4 cycles of neo-adjuvant systemic chemotherapy with FLOT, we performed CRS+HIPEC as Group A and 4 cycles of systemic chemotherapy with FLOT. For patients of Group A, the Median survival time is 46months.Group B patients had a median OS of 36 months. For patients of Group A, the Median Disease Time (DFS) was 37 months. Group B patients had a median DFS of 30 months. For each degree increase in the PCI pre score and for the same treatment group, the PCI posr score increases by 0.573 degrees. Group 2, for the same PCIpre score, have a 163% higher PCI posr score. On patients with singet ring cell adenocarcinoma there is a statistical significance difference in OS for PIPAC group. Patients of group A had a median OS of 26 months. For patients of group B, the median OS was 14 months. Morbidity and mortality in both groups are 53,4% and 4,7% for Group A and 44,5% and 5,5% for Group B respectively. The neo-adjuvant PIPAC with systemic chemotherapy might be a promising approach for patients with peritoneal metastasis from gastric cancer. PIPAC is a safe and well tolerated procedure.

Central nervous system involvement at initial diagnosis of extranodal NK/T-cell lymphoma: a retrospective study of a consecutive 12-year case series.

Patients with central nervous system (CNS) involvement at initial diagnosis of extranodal NK/T-cell lymphoma (ENKTL) are exceedingly rare, and the clinicopathologic features of CNS involvement have not been well characterized. In this study, we reviewed 662 patients with ENKTL from August 2008 to September 2019. Their clinical and pathological features, treatments, and survival outcomes were analyzed. The median follow-up time was 72months. Nine of 662 (1.4%) patients were diagnosed with CNS involvement. Among them, the median age was 37years, and seven patients were male. All patients had positive EBV-DNA, and three patients were asymptomatic at the time of diagnosis with CNS involvement. Common extranodal involved sites included bone, paranasal sinuses, breast, kidney, adrenal gland, and bone marrow. All patients were positive for cytoplasmic CD3ε, cytotoxic granule proteins, and EBER and negative for CD20. All patients received intrathecal chemotherapy and at least one cycle of systemic chemotherapy. Seven patients had died and two were still alive by the last follow-up. The median overall survival (OS) in patients with CNS involvement at initial diagnosis of ENKTL was 9months, and the 1-year OS was 44.4%. Five patients achieved a complete response after asparaginase-based chemotherapy; two were still alive, one died of systemic progression, one died of ENKTL-associated hemophagocytic syndrome, and one died of treatment-related infections. In conclusion, CNS involvement at initial diagnosis of ENKTL is extremely rare with poor prognosis. There is no standard treatment, and asparaginase-based chemotherapy combined with intrathecal chemotherapy might yield good efficacy.

Bilateral optic disc edema as the presenting sign of brain metastasis

To report a rare case of bilateral optic disc edema as a presentation of brain metastasis. Case report. A 51-year-old healthy woman presented with complaints of headache, diplopia, and distortion of peripheral vision for the past one month. Examination of both the eyes showed massive optic disc edema, multiple radial hemorrhages, hard exudates at the disc margin, and absent venous pulsation. Magnetic resonance imaging (MRI and MRA) showed leptomeningeal enhancement with raised intracranial pressure: a sign of metastasis. She had undergone mastectomy and had received eight cycles of systemic chemotherapy and radiation for breast carcinoma two years ago. She was urgently referred to an oncologist for further management. This case highlights the importance of neuroimaging in patients presenting with bilateral disc edema and prior history of breast carcinoma to rule out metastasis.

Primary small cell neuroendocrine carcinoma of the petrous apex: a report of an atypical case

Introduction: The head and neck region is a very uncommon location for small cell neuroendocrine carcinomas (SCNEC), which are notoriously aggressive and have a terrible prognosis. We describe the second case of a poorly differentiated SCNEC involving the petrous apex of the temporal bone in the literature and discuss its therapy. Case Summary: A 42-year-old white male smoker, without personal or familial significant history, presented with right-sided otalgia. A transnasal endoscopic biopsy of the right apical petrous bone was performed and the histopathological analysis was consistent with poorly differentiated SCNEC. The patient received 4 cycles of systemic chemotherapy followed by 30 radiotherapy sessions. Brain magnetic resonance imaging, positron emission tomography scan, and whole-body computed tomography scan images confirmed the absence of metastatic focus. Discussion: The literature lacks enough documentation of treatment regimens for head and neck SCNECs. The biggest difficulty in our management is that few studies advise combining radiotherapy and chemotherapy without surgery.

LATE CHOROIDAL NEOVASCULAR COMPLICATIONS IN A PATIENT TREATED FOR RETINOBLASTOMA. A CASE REPORT.

Case report of choroidal neovascularization (CNV) detection in patient who was treated for bilateral retinoblastoma in early childhood. Patient at 1.5 years of age treated for endophytic retinoblastoma stage 4 (according to the Reese-Ellsworth classification) bilaterally, with a positive mutation in the Rb1 gene. After undergoing bilateral retinal laser treatment and 6 cycles of systemic chemotherapy, the tumor remained inactive without other complications. At the age of 14, the boy developed visual impairment in his left eye with metamorphosis. Based on a local finding and other auxiliary examinations, he was diagnosed with CNV in the macular area at the interface of the tumor scar and the healthy retina of the left eye. After three applications of anti-VEGF (antibodies blocking vascular endothelial growth factor) substance intravitreally (bevacizumab 1.2 mg), there was a reduction in CNV and also an improvement in visual function.

A Model for Nano-Scale Spherical Surface Coverage and Protein Corona Formation By Amyloidogenic Peptides

The conformation of three amyloidogenic peptides; amyloid beta 1–40 (Aβ1−40), alpha synuclein (α-syn), and beta-2-microglobulin (β2m) are closely associated with the process of causing neurodegenerative diseases. Use of a peptide adsorbed gold nano-particle system allowed us to investigate the interactive segment of each peptide responsible for peptide-peptide networking, which is crucial to initiate the formation of an oligomer and leads to fibrillogenesis. The adsorption orientationof theamyloidogenic peptides onthe nano-goldcolloid spherical surface wasexplainedbysimulatinghowmuchareaofthemetalsurfacewascoveredbythepeptides,i.e.,coverageratio,Θ. The empirically extracted Θ was explained by the summation of the 1st layer and the 2nd layer with a spikingout orientation of the prolate. Of note, the involvement of the 2nd layer was peptide type dependent. The nanosize dependence of Θ was linearly correlated with available spacing between adjacent peptides, Sd, which were approximated as prolates, For Aβ1−40 and α-syn, the 2nd layer was more included as Sd increased. In contrast, β2m was found to gyrate over the gold surface as Sd increased, creating a partially positive (δ+) region and repelling the extra β2m from the surface. Thus, as Sd decreased, it prohibited the gyration of β2m resulting in less δ+ region, and more β2m monomers were adsorbed with δ+ segment as the 2nd layer than the case where β2m gyrates more under relatively larger Sd. Based on the trend found in an experimentally extracted Θ as a function of Sd, optimized charge distribution of Aβ1−40 and α-syn were concluded to be negative partial charge (δ−) region that was covered by the positive partial charge (δ+) region. However, β2m may have a relatively large and/or distributed δ+ region with a small portion of δ− at the one end of a prolate. The characterization made in this work confirmed current understandings on the formation of the protein corona over nano-particles.

P-OGC15 Impact of postoperative systemic treatment on survival for oesophageal adenocarcinoma after preoperative chemotherapy and oesophagectomy

Abstract Background Perioperative chemotherapy is widely used in the treatment of oesophageal cancer with substantial survival benefit over surgery alone. However, the postoperative part of these regimens is given in less than half of cases, reflecting uncertainty about its benefit. This study estimates the effect of postoperative chemotherapy after surgery for oesophageal cancer using a large population-based dataset and modern statistical methods. Methods Patients with oesophageal adenocarcinoma diagnosed between 2012 and 2018 and underwent preoperative chemotherapy followed by surgery, were identified from a national level audit in England and Wales (National Oesophagogastric Cancer Audit). Postoperative therapy was defined as the receipt of at least one cycle of systemic chemotherapy within 90 days of surgery. The comparative effectiveness of postoperative chemotherapy compared to observation was estimated using inverse propensity treatment weighting (IPTW). Results The study included 2,814 patients, in whom postoperative therapy was given to 1,054 (37.5%). Patients who received postoperative therapy were younger, with a lower ASA grade and were less likely to have surgical complications of any type, including anastomotic leak (all p < 0.001). Tumour characteristics were similar in both groups. Weighted median survival times for patients having no treatment or postoperative chemotherapy were 45.4 months and 57.5 months respectively. There was a life expectancy difference at five years of 2.9 months in favour of postoperative chemotherapy (95%CI 1.1–4.8 months, p < 0.001) with a Hazard Ratio of 0.80 (95%CI 0.70-0.91, p < 0.001). Conclusions Among patients with oesophageal adenocarcinoma treated with preoperative chemotherapy and surgery, improved overall survival was observed in those patients who received postoperative chemotherapy. Minimising surgical complications and improving patient fitness could increase the use of postoperative chemotherapy, leading to better outcomes for patients with oesophageal adenocarcinoma.

Ibrutinib Monotherapy as Bridge-to-Transplant for Relapsed/Refractory Primary Oculo-Cerebral Lymphoma.

Introduction. Primary central nervous system lymphoma is an uncommon form of extranodal non-Hodgkin’s lymphoma, with increasing incidence, a relatively aggressive course and a poor 5-year survival. Because of its localization, the therapeutic compounds used in this disease must be able to pass through the blood-brain barrier. Chemotherapy regimens based on high-dose methotrexate are currently the standard of care for all patients who can tolerate such drugs. Autologous stem cell transplantation is indicated for malignant lymphomas in the relapsed/refractory setting. Methods. Three patients, with a median age of 60 years, range 53–64, were diagnosed with primary CNS lymphoma, and treated with ibrutinib monotherapy in the Department of Hematology, Ion Chiricuta Clinical Cancer Center, Cluj-Napoca, Romania, between September 2018 and November 2020 All the patients were relapsed–refractory following high-dose methotrexate chemotherapy. We present our experience using ibrutinib monotherapy-based treatment as a bridge-to-transplant option on a single-center case series and a review of the literature in this field. Results. Two of the patients were given ibrutinib as a second line therapy, both achieving complete remission and being eligible for an autologous stem cell transplantation. The third patient achieved a short remission using six cycles of systemic chemotherapy, but was started on ibrutinib monotherapy, with limited results. Conclusion. Our data is limited, and these results should be confirmed by multicentric clinical trials and should be regarded as a single-center case series, with all its limitations. Still, it brings forward a new therapeutic option for this rare subtype of malignant lymphomas, which if left untreated has a dismal prognosis.

Case report: Rare myeloid sarcoma development following renal transplantation with KRAS and DNMT3A gene mutations

BackgroundA high incidence of malignant tumors, such as post-transplant lymphoproliferative disorders (PTLD), Kaposi sarcoma, and renal cancer is common in solid organ and bone marrow transplant recipients. However, myeloid sarcoma (MS) after renal transplantation has rarely been reported and the diagnosis is challenging due to its low incidence.Case presentationHere, we report a rare case of a 49-year-old man who developed myeloid sarcoma (MS) in the transplanted kidney two years after renal transplantation. Next-generation sequencing (NGS) showed mutations of KRAS and DNMT3A genes in the MS, and no gene mutations in the bone marrow. He presented a normal karyotype of 46, XY. Following treatment with 6 cycles of systemic chemotherapy, the patient was in satisfactory condition with stable serum creatinine (sCr) levels at the 1-year follow-up. In addition, we performed a detailed review with emphasis on the clinical manifestations, and the diagnostic and therapeutic processes of another 7 patients who developed MS following renal transplantation.ConclusionsOur report illustrates the clinical utility of comprehensive genomic profiling in benefiting the diagnosis of MS, the selection of therapeutic strategy and the determination of whether MS is donor-derived.

Histological regression of gastrointestinal peritoneal metastases after systemic chemotherapy.

ObjectivesPeritoneal metastases (PM) are relatively resistant to systemic chemotherapy, and data on histological response to therapy is rare. The aim of this study was to quantify the treatment response of PM after systemic chemotherapy.MethodsRetrospective monocentric cohort study of 47 consecutive patients with PM from gastrointestinal origin undergoing surgery (cytoreduction: CRS + Hyperthermic IntraPEritoneal Chemotherapy [HIPEC] or Pressurized IntraPeritoneal Aerosol Chemotherapy [PIPAC]) after prior systemic chemotherapy from 1.2015 to 3.2019. Tumor response was assessed using the 4-scale Peritoneal Regression Grading System (PRGS) (4: vital tumor to 1: complete response).ResultsPatients had a median of 2 (range: 1–7) lines and 10 (3–39) cycles of prior systemic chemotherapy. A median of four biopsies (range: 3–8) was taken with a total of 196 analyzed specimens. Twenty-four biopsies (12%) showed no histological regression (PRGS4), while PRGS 3, two and one were diagnosed in 37 (19%), 39 (20%), and 69 (49%) specimens, respectively. A significant heterogeneity was found between peritoneal biopsies in 51% patients. PRGS correlated strongly with peritoneal spread (PCI, p<0.0001), and was improved in patients with more than nine cycles of systemic chemotherapy (p=0.04). Median survival was higher in patients with PRGS < 1.8 (Quartiles one and 2) than higher (Q3 and Q4), but the difference did not reach significance in this small cohort.ConclusionsPRGS is an objective too to describe histological response of PM of GI origin after systemic chemotherapy. This response differs significantly between patients, allowing to distinguish between chemosensitive and chemoresistant tumors.

Systemic ALK-Positive Anaplastic Large-Cell Lymphoma (ALCL): Final Analysis of an International, Individual Patient Data Study of 263 Adults

Abstract Introduction: ALK-positive ALCL comprises 0.5% of adult lymphomas. Because of disease rarity, prospective trials specifically dedicated to adult ALK-positive ALCL are lacking. In published adult studies, mainly retrospective, ALK-positive ALCLs were most often pooled with ALK-negative ALCLs and/or other PTCLs, which are distinct entities, preventing a correct assessment of specific prognostic factors and impact of different treatments for ALK-positive ALCL. A retrospective study from the DSHNHL and a population-based study from the Nordic lymphoma registries have suggested a possible benefit of etoposide use, but definitive conclusions are lacking and the role of etoposide is still a matter of debate. Moreover, the respective impact of upfront HDT-ASCT or consolidative radiotherapy (RT) is unknown. A pooled analysis of individual patient data (IPD) would provide greater statistical power to identify prognostic factors and treatment effects. Therefore, we conducted a pooled analysis of IPD from studies of first-line therapy in adult ALK-positive ALCL. Methods: Eligibility criteria were as follows: study including patients (pts) with a diagnosis of systemic ALK-positive ALCL after initial centralized pathologic review, age ≥ 18 years, HIV-negative serology, first-line treatment including at least one cycle of systemic chemotherapy, sufficient sample size (at least 10 cases of ALK-positive ALCL) and publication between 2000 and 2015. A minimum dataset was required, comprising characteristics at diagnosis (individual IPI and PIT factors), and first-line chemotherapy regimen. We assessed PFS, OS, EFS24, cumulative incidence (CI) of relapse, and the associations between patient characteristics or treatment type (etoposide, upfront HDT-ASCT and consolidative RT) and PFS or OS. These associations were analyzed by Cox survival models stratified by cohort and assessed by Log-Likelihood Ratio (LLR) tests with predictive C-index measurement. Results: IPD of 263 pts diagnosed between 1985 and 2008 were collected and pooled from six published studies: 2 from the LYSA, 1 from the DSHNHL, 1 from Japan, 1 from the IPTCLP and 1 from the Mayo Clinic. Median follow-up was 4.9 years. Median age was 34 years (18-76). Overall, 261 (99%) pts received an anthracycline-based regimen and 92 (35%) received an etoposide-based induction. Thirty-four (13%) pts underwent planned upfront HDT-ASCT, and 54 (21%) received consolidative RT. The respective CR/CRu, PR and SD/PD rates to first-line therapy were 85%, 5% and 10%. The 5-year PFS and OS rates were 69% (95% CI, 64% to 75%) and 81% (95% CI, 76% to 86%), respectively. The respective 1-, 2- and 5-year CI of relapse were 22%, 25% and 30%. For the 82 pts with a first relapse, the respective 1-, 2- and 5-year OS rates from this event were 38%, 35% and 28%, with a median OS of only 3.2 months. Pts achieving EFS24 had a 5-year OS from this time point of 95% (Fig 1). The IPI identified different risk groups; 5-year PFS was 80% for IPI 0 to 1, 63% for IPI 2, 54% for IPI 3, and 40% for IPI 4 to 5 (p Pts who received an etoposide-based induction chemotherapy had significantly improved 5-year PFS (83% vs 62%, p=0.001) and OS (93% vs 74%, p=0.001, Fig 3), independent of IPI, age and cohort. Etoposide did not increase significantly the response rate at the end of treatment, but significantly decreased the 5-y CI of relapse (17% vs 37%, p=0.001). Finally, CHOEP (n=38), compared to CHOP (n=98), significantly improved 5-year PFS (89% vs 57%, p=0.017) and OS (97% vs 69%, p=0.049, Fig 4). In stratified Cox models, there was no independent impact of upfront HDT-ASCT or consolidative RT on PFS or OS. Conclusion: To our knowledge, this is the largest analysis of patients with ALK-positive ALCL. IPI, CD3 positivity and anemia are strong independent predictors of outcome. Etoposide use in induction is associated with important improvement of PFS and OS independent of IPI and age, whereas upfront HDT-ASCT and consolidative RT have no independent impact. Download : Download high-res image (99KB) Download : Download full-size image Disclosures Suzuki: Novartis: Honoraria; MSD: Honoraria; Kyowa-Hakko Kirin: Honoraria; Celgene: Honoraria; Takeda Pharmaceuticals: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Chugai Pharmaceutical: Honoraria; MundiPharma: Consultancy; Shionogi: Honoraria; Jazz Pharmaceuticals: Consultancy; Mochida Pharmaceutical: Honoraria; Meiji Seika Pharma: Honoraria; Bristol-Myers Squibb: Honoraria; Ohtsuka: Honoraria; Sawai Pharmaceutical: Honoraria; Gilead Sciences: Consultancy. Tilly: Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Immunogen: Honoraria; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria. Savage: Roche: Research Funding.

OCT Imaging of Schlemm’s Canal Invasion in a Retinoblastoma Patient

A 3-year-old boy with unilateral retinoblastoma Group D was seen after 3 cycles of systemic chemotherapy given elsewhere. Slit-lamp examination revealed anterior-chamber seeding (Fig A). Anterior-segment OCT distinguished tumor-free (Fig B) from invaded (Fig C) Schlemm’s canal (arrows), which was confirmed after enucleation on histopathology (Figs B’and C’). Adjuvant chemotherapy to prevent metastasis is planned. This ongoing case illustrates that OCT can accurately delineate retinoblastoma extent in the anterior segment in vivo (Magnified version of Fig A-C is available online at www.aaojournal.org).

Seminoma Retroperitoneal Relapse 23 Years After Surgery.

Stage I seminoma is the most frequent tumour in young men. It has a very good prognosis thanks to the use of a multidisciplinary therapeutic approach including surgery, radiotherapy and systemic chemotherapy. Late (after 2 years) and very late (after 5 years) relapses are uncommon, but not impossible, even if standardized follow-up for testicular tumours lasts up to 5 years after the diagnosis. We report a case of a 67-year-old Caucasian man with metachronous bilateral testicular seminoma who developed a retroperitoneal relapse of testicular seminoma 23 years after the first orchiectomy. Based on histological confirmation of testicular relapse, the patient underwent four cycles of systemic chemotherapy with bleomycin, etoposide and cisplatin (PEB), with no adverse reactions. He subsequently achieved complete radiological response at restaging computed tomography imaging, confirmed by the absence of glucose metabolism on positron emission tomography. In conclusion, this case report suggests the importance of longer standardized follow-up for patients treated for testicular tumours in order to detect earlier recurrence, which can be successfully treated.

Ovary and Uterus, Rare Sites of Metastases from Breast Cancer: A Case Series

Bones, lungs, and liver are frequent sites of metastases of breast cancer. However, female genital tract (ovaries, uterus, etc.) metastases of breast cancer often present a challenge for diagnosis. The distinction between primary and metastasis may be difficult. Immunostaining has a pivotal role in determining the distinction of breast cancer metastases to ovaries and uterus and primary ovarian and uterine cancer. We herein report rare cases of ovarian and uterine metastases in women who have prior carcinoma of the breast and the role of immunohistochemistry in diagnosing these cases. Case 1 highlights a 42-year-old with breast cancer, stage IV who presented with a breast mass and nipple retraction and an enlarging abdominal mass, probably an ovarian new growth, probably malignant by transvaginal sonography. Exploratory laparotomy, peritoneal fluid cytology, total abdominal hysterectomy with bilateral salpingo-oophorectomy, random peritoneal biopsy, bilateral lymph node dissection were done revealing metastatic ovarian cancer probably invasive lobular carcinoma of breast origin. Case 2 reports 42 years old diagnosed with hormone receptor-positive breast cancer stage IV, received 4 cycles of systemic chemotherapy and 20 cycles of radiation therapy of mediastinal mass. On Tamoxifen as a maintenance drug hence ovarian ablation was recommended. Total abdominal hysterectomy with bilateral salpingo-oophorectomy, intraabdominal omentectomy were done with the histopathologic result of metastatic carcinoma with mixed lobular and ductal features probably breast in origin on bilateral ovaries. Case 3 is a 38 y/o with 8 month-history of breast mass with associated pain, diagnosed with invasive ductal carcinoma, right stage IIIB (T4N0M0) after modified radical mastectomy of the right breast. On follow-up, abdominopelvic CT scan done showed multiple intraabdominal and retroperitoneal and pelvic lymphadenopathies probably metastasis. Exploratory laparotomy, drainage of ascitic fluid, infrasonic omentectomy, bilateral salpingo-oophorectomy, peritoneal biopsy were done with histopathologic findings of metastatic poorly differentiated carcinoma, probably ductal carcinoma, bilateral ovaries.

Safety and feasibility of initiating a hepatic artery infusion pump chemotherapy program for unresectable colorectal liver metastases: A multicenter, retrospective cohort study.

Hepatic artery infusion pump (HAIP) chemotherapy is a specialized therapy for patients with unresectable colorectal liver metastases (uCRLM). Its effectiveness was demonstrated from a high volume center, with uncertainty regarding the feasibility and safety at other centers. Therefore, we sought to assess the safety and feasibility of HAIP for the management of uCRLM at other centers. We conducted a multicenter retrospective cohort study of patients with uCRLM treated with HAIP from January 2003 to December 2017 at six North American centers initiating the HAIP program. Outcomes included the safety and feasibility of HAIP chemotherapy. We identified 154 patients with HAIP insertion and the median age of 54 (48-61) years. The burden of disease was >10 intra-hepatic metastatic foci in 59 (38.3%) patients. Patients received at least one cycle of systemic chemotherapy before HAIP insertion. Major complications occurred in 7 (4.6%) patients during their hospitalization and 13 (8.4%) patients developed biliary sclerosis during follow-up. A total of 148 patients (96.1%) received at least one-dose of HAIP chemotherapy with a median of 5 (4-7) cycles. 78 patients (56.5%) had a complete or partial response and 12 (7.8%) received a curative liver resection. HAIP programs can be safely and effectively initiated in previously inexperienced centers with good response.

Abstract 817: Pancreatic acinar carcinoma - a rare entity with a targetable BRAF V600E mutation

Abstract Background: Pancreatic acinar carcinomas account for less than 1% of all pancreatic cancers and are considered genetically distinct entities form other pancreatic carcinomas. The pathogenesis of this malignancy is incompletely understood, and the efficacy of cytotoxic chemotherapy is not well defined especially in unresectable or metastatic disease. Methods: We identified one patient with pancreatic acinar carcinoma who was treated at our institution and was found to have a unique targetable pathogenic mutation on tumor sequencing. Results: A 64-year-old male patient was diagnosed with localized pancreatic acinar carcinoma during workup for epigastric pain. He underwent distal pancreatectomy with final pathology consistent with stage T3N0 acinar cell carcinoma without any adenocarcinoma component. He subsequently received six months of adjuvant chemotherapy with gemcitabine plus capecitabine, derived from evidence on pancreatic adenocarcinoma due to the size of his original tumor. Seven months after completion of adjuvant therapy, he was found to have local recurrence within the surgical bed and was treated with three cycles of systemic chemotherapy with FOLFIRINOX. During a following planned surgical resection, multiple liver lesions were seen intraoperatively, and surgery was aborted. Liver lesions were biopsied and hybrid capture next-generation sequencing was performed which revealed: a BRAF V600E gain of function mutation, CDKN2A loss as well as MYCN amplification. The patient declined further chemotherapy and his treatment was switched to Encorafenib (BRAF inhibitor) plus Binimetinib (MEK inhibitor). He attained a partial response to therapy at his first restaging CT scan after 2 months of therapy (-39% per RECIST 1.1). Both mass at the surgical bed as well as liver metastases were decreased in size. He tolerated treatment very well without significant adverse events (including no clinically significant rash). Conclusions: While BRAF rearrangements as described in the literature may occur in 15-23% of patients with acinar cell carcinoma of the pancreas, BRAF activating mutations and in particular the BRAF V600E substitution has not been reported. This particular substitution is commonly present in melanoma, hairy cell leukemia, Langerhans cell histiocytosis and less frequently in lung and colon cancer. A combination of BRAF and MEK inhibition may be used in patients with tumors harboring this activating mutation with variable efficacy across different histologies. In light of the rarity of acinar cell carcinomas of the pancreas and the lack of established systemic treatment guidelines, tumor sequencing should be considered if no other therapies are available. This is the first case reported in the literature of a patient with acinar cancer of the pancreas and BRAF V600E mutation where targeted therapy has shown an early response. Citation Format: Vaia Florou, Chris Nevala-Plagemann, Sean Mulvihill, Ignacio Garrido-Laguna. Pancreatic acinar carcinoma - a rare entity with a targetable BRAF V600E mutation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 817.

Successful chemotherapy management of disseminated intravascular coagulation presenting with metastatic clear cell renal carcinoma: a case report and review of the literature

BackgroundDisseminated intravascular coagulation is a critical complication of advanced clear cell renal cell carcinoma, despite the rarity of the occurrence of disseminated intravascular coagulation in such tumors. The diagnosis of cancer-related disseminated intravascular coagulation is mostly based on clinical bleeding and laboratory test; available data suggest that treating the primary cancer also treats the disseminated intravascular coagulation. Among three reported cases of renal cell carcinoma-related disseminated intravascular coagulation in the literature, this is the first patient whose disseminated intravascular coagulation was successfully treated, in particular, with chemotherapy without any anti-disseminated intravascular coagulation therapies.Case presentationThis case is a 66-year-old Vietnamese man who presented disseminated intravascular coagulation 2 weeks after his admission for severe back pain. At admission, his initial laboratory work-up revealed only a mild thrombocytopenia with a platelet count of 93 × 109/L (normal range, 150–450 × 109/L) without clinical bleeding. His past medical history and family history were unremarkable. An open-biopsy was performed and the definitive diagnosis was bone metastatic clear cell renal cell carcinoma based on immunohistochemistry. Two weeks after admission, the diagnosis of disseminated intravascular coagulation was confirmed according to the International Society on Thrombosis and Haemostasis. Immediately, he was treated with a paclitaxel plus carboplatin regimen and disseminated intravascular coagulation completely disappeared after one cycle of systemic chemotherapy. Until recently, 11 months subsequent to the diagnosis of disseminated intravascular coagulation, he had been being undergoing maintenance therapy for metastatic clear cell renal cell carcinoma.ConclusionsFirst, an early detection of overt disseminated intravascular coagulation is essential, although disseminated intravascular coagulation in cancer presents as a chronic or even subclinical process with unique thrombocytopenia. Second, making a decision of systemic chemotherapy without delay at the time of disseminated intravascular coagulation diagnosis is the key to successful cancer-related disseminated intravascular coagulation treatment.

Effects of oral maintenance chemotherapy and predictive value of circulating EBV DNA in metastatic nasopharyngeal carcinoma.

Background/ObjectivesOral maintenance chemotherapy can effectively prolong overall survival (OS) in many types of metastatic cancer, but its role in metastatic nasopharyngeal carcinoma (mNPC) is unclear. In this study, the efficacy of oral maintenance chemotherapy in mNPC and the effectiveness of circulating tumor EBV‐DNA for screening patients were evaluated.MethodsBetween June 2016 and December 2017, 141 patients with mNPC who received platinum‐based systemic chemotherapy were included (median follow‐up time, 21 months). Patients were classified into two groups according to the administration of oral maintenance chemotherapy. Plasma samples were collected before, during, and after treatment for the measurement of circulating EBV DNA.ResultsThe 2‐year OS was higher for patients who received maintenance chemotherapy than for patients without maintenance chemotherapy (78.9% vs 62.7%, P = .016). Patients with undetectable posttreatment EBV‐DNA after 4‐6 cycles of systemic chemotherapy (n = 73) had a higher 2‐year OS than that of patients with detectable EBV‐DNA (n = 68) (82.16% vs 51.45%, P = .001). For patients with undetectable posttreatment EBV‐DNA, OS was better for those with maintenance chemotherapy than for those without (86.7% vs 73%, P = .027). For patients with detectable posttreatment EBV‐DNA, maintenance chemotherapy did not improve outcomes (49.5% vs 55.4%, P = .824). The most common acute events were hematological toxicity, and all were tolerable and curable.ConclusionsOral maintenance chemotherapy with S1 or capecitabine can improve OS in mNPC. Posttreatment EBV‐DNA was not only an independent prognosis factor for mNPC but also can screen out beneficiaries of maintenance chemotherapy.

Hepatic arterial infusion pump chemotherapy combined with systemic therapy for patients with advanced colorectal liver metastases: Outcomes in a newly established program

Presenter: Brett Walker MD | Oregon Health and Science University Background: Metastatic disease to the liver is a leading cause of morbidity and mortality in patients with colorectal cancer, with the majority of patients presenting with initially unresectable disease. Although hepatic resection offers the best chance of cure for colorectal liver metastases (CRLM), 40% of patients will develop intrahepatic recurrence not amenable to additional hepatic resection. Hepatic arterial infusion (HAI) chemotherapy with floxuridine has been demonstrated to improve survival in patients with resected CRLM and can be integrated with systemic therapy to convert patients with technically unresectable disease to a resectable status. Herein, we describe the experience of a recently established multidisciplinary hepatic arterial infusion program for the treatment of patients with advanced CRLM at an NCI Comprehensive Cancer Center. Methods: Between 2016 and 2018, n=22 consecutive patients had a HAI pump placed as part of their multidisciplinary treatment plan for advanced CRLM. All patients received systemic chemotherapy peri-operatively and concurrently with HAI. A multidisciplinary tumor board reviewed each HAI candidate before pump placement and throughout their therapy. Clinicopathologic data were collected and patient overall (OS) and progression-free (PFS) survival was assessed using the Kaplan-Meier method. Results: Over the 30-month period, 7 patients with resected CRLM and 15 patients with unresectable CRLM had an HAI pump operatively placed at a median of 6 months after diagnosis. The median age was 55 years (range: 32-67) and 59% (n=13) were women. The majority of patients had a high hepatic tumor burden (76% with >10 metastases) and received a median of 8 (range: 4-18) cycles of systemic chemotherapy, mostly commonly FOLFOX, prior to HAI pump placement (Table). Of the 12 patients with an intact primary cancer, 11 had simultaneous HAI pump placement with resection of their primary cancer. Only 1 patient experienced a major complication (Clavien-Dindo ≥ 3) within 30 days of their operation (small bowel obstruction from prior loop ileostomy procedure). 21 patients received at least one HAI cycle of floxuridine and had a median of 5 cycles (range: 1-10) before HAI therapy was discontinued or held after clearance of intrahepatic disease. In total, 32% (n=7) of patients developed pump related complications, with biliary sclerosis being the most common (n=5/21, 24%). Of the 13 patients treated to convert their initially unresectable disease, 3 patients (23%) underwent hepatic resection with curative intent after a median of 7 HAI cycles (range: 4-10) and achieved complete clearance of their hepatic disease. For all patients treated with HAI and systemic therapy, the median OS from diagnosis was 52 months (95%: IQR 43-64 months) and the median PFS from pump placement was 21 months (95%: IQR 17-31 months). Conclusion: HAI pump therapy with floxuridine can be used in combination with modern systemic chemotherapy for patients with advanced CRLM, both in the adjuvant setting and to facilitate conversion of unresectable disease in more than 20% of patients presenting with high liver disease burden. When implemented in a multidisciplinary program, HAI therapy is safe with low of peri-operative morbidity and promising outcomes in patients with limited treatment options.