Clinical Outcomes Among Immunotherapy-Treated Patients With Primary Cardiac Soft Tissue Sarcomas: A Multicenter Retrospective Study.

Background: Primary cardiac soft tissue sarcomas (CSTS) affect young adults, with dismal outcomes. Objectives: The aim of this study was to investigate the clinical outcomes of patients with CSTS receiving immune checkpoint inhibitors (ICIs). Methods: A retrospective, multi-institutional cohort study was conducted among patients with CSTS between 2015 and 2022. The patients were treated with ICI-based regimens. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates were determined according to Response Evaluation Criteria in Solid Tumors version 1.1. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events version 5.0. Results: Among 24 patients with CSTS, 17 (70.8%) were White, and 13 (54.2%) were male. Eight patients (33.3%) had angiosarcoma. At the time of ICI treatment, 18 patients (75.0%) had metastatic CSTS, and 4 (16.7%) had locally advanced disease. ICIs were administered as the first-line therapy in 6 patients (25.0%) and as the second-line therapy or beyond in 18 patients (75.0%). For the 18 patients with available response data, objective response rate was 11.1% (n = 2 of 18). The median PFS and median OS in advanced and metastatic CSTS (n = 22) were 5.7 months (95% CI: 2.8-13.3 months) and 14.9 months (95% CI: 5.7-23.7 months), respectively. The median PFS and OS were significantly shorter in patients with cardiac angiosarcomas than in those with nonangiosarcoma CSTS: median PFS was 1.7 vs 11 months, respectively (P < 0.0001), and median OS was 3.0 vs 24.0 months, respectively (P = 0.008). Any grade treatment-related adverse events occurred exclusively in the 15 patients with nonangiosarcoma CSTS (n = 7 [46.7%]), of which 6 (40.0%) were grade ≥3. Conclusions: Although ICIs demonstrate modest activity in CSTS, durable benefit was observed in a subset of patients with nonangiosarcoma, albeit with higher toxicity.

Clinical outcomes and safety of immune checkpoint inhibitors in patients with solid tumors and paraneoplastic syndromes.

BACKGROUND: Patients with paraneoplastic syndromes (PNS) are excluded from clinical trials involving immune checkpoint inhibitors (ICIs) due to safety concerns. Moreover, real-world data on efficacy and safety is scarce. METHODS: In this retrospective study, data were collected on patients with PNS and solid tumors receiving ICI between 2015 and 2022 at nine institutions. Patients were classified into: Cohort 1 (pre-existing PNS before ICI initiation), cohort 2 (PNS during ICI treatment), and cohort 3 (PNS after ICI discontinuation). Patients with metastatic non-small cell lung cancer (NSCLC) (mNSCLC) from cohort 1 were matched to patients who were PNS-free at each institution up to a 1:3 ratio for age, sex, type of ICI, use of concurrent chemotherapy, and number of lines of systemic therapy prior to ICI initiation. Kaplan-Meier method was used to assess overall survival (OS) and time-to-next treatment (TTNT). RESULTS: Among 109 patients with PNS treated with ICIs, median age at ICI initiation was 67 years (IQR: 58-74). The most represented cancer type was NSCLC (n=39, 36%). In cohort 1 (n=55), PNS exacerbations occurred in 16 (29%) patients with median time to exacerbation after ICI of 1.1 months (IQR: 0.7-3.3). Exacerbation or de novo PNS prompted temporary/permanent interruption of ICIs in 14 (13%) patients. For cohort 2 (n=16), median time between ICI initiation and de novo PNS was 1.2 months (IQR: 0.4-3.5). Treatment-related adverse events (trAEs) occurred in 43 (39%) patients. Grade ≥3 trAEs occurred in 18 (17%) patients. PNS-directed immunosuppressive therapy was required in 55 (50%) patients. We matched 18 patients with mNSCLC and PNS (cohort 1) to 40 without PNS, treated with ICIs. There was no significant difference in OS or TTNT between patients with mNSCLC with and without PNS, although a trend was seen towards worse outcomes in patients with PNS. TrAEs occurred in 6/18 (33%) and 14/40 (35%), respectively. Grade ≥3 trAEs occurred in 4 (22%) patients with PNS and 7 (18%) patients without PNS. CONCLUSIONS: Exacerbations of pre-existing PNS occurred in 29% of patients treated with ICIs and both exacerbations and de novo PNS occur early in the ICI course. TrAE from ICIs were similar between patients with and without PNS. Our data suggest that pre-existing PNS should not preclude consideration of ICI therapy although patients may not derive the same clinical benefit compared with patients without PNS.

Racial disparities in staging, treatment, and mortality in non-small cell lung cancer.

Background: Black race is associated with advanced stage at diagnosis and increased mortality in non-small cell lung cancer (NSCLC). Most studies focus on race alone, without accounting for social determinants of health (SDOH). We explored the hypothesis that racial disparities in stage at diagnosis and outcomes are associated with SDOH and influence treatment decisions by patients and providers. Methods: Patients with NSCLC newly diagnosed at Indiana University Simon Comprehensive Cancer Center (IUSCCC) from January 1, 2000 to May 31, 2015 were studied. Multivariable regression analyses were conducted to examine the impact of SDOH (race, gender, insurance status, and marital status) on diagnosis stage, time to treatment, receipt of and reasons for not receiving guideline concordant treatment, and 5-year overall survival (OS) based on Kaplan-Meier curves. Results: A total of 3,349 subjects were included in the study, 12.2% of Black race. Those diagnosed with advanced-stage NSCLC had a significantly higher odds of being male, uninsured, and Black. Five-year OS was lower in those of Black race, male, single, uninsured, Medicare/Medicaid insurance, and advanced stage. Adjusted for multiple variables, individuals with Medicare, Medicare/Medicaid, uninsured, widowed, and advanced stage at diagnosis, were associated with significantly lower OS time. Black, single, widowed, and uninsured individuals were less likely to receive stage appropriate treatment for advanced disease. Those uninsured [odds ratio (OR): 3.876, P<0.001], Medicaid insurance (OR: 3.039, P=0.0017), and of Black race (OR: 1.779, P=0.0377) were less likely to receive curative-intent surgery for early-stage NSCLC because it was not a recommended treatment. Conclusions: We found racial, gender, and socioeconomic disparities in NSCLC diagnosis stage, receipt of stage-appropriate treatment, and reasons for guideline discordance in receipt of curative intent surgery for early-stage NSCLC. While insurance type and marital status were associated with worse OS, race alone was not. This suggests racial differences in outcomes may not be associated with race alone, but rather worse SDOH disproportionately affecting Black individuals. Efforts to understand advanced diagnosis and reasons for failure to receive stage-appropriate treatment by vulnerable populations is needed to ensure equitable NSCLC care.

Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium.

PURPOSE: Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. METHODS: This retrospective study included PWH treated with anti-PD-1- or anti-PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). RESULTS: Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti-PD-1/anti-PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was -0.06 months (95% CI, -5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, -4.02 to 8.48; P = .48) for OS. CONCLUSION: Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.

Impact of acceptance and commitment therapy on physical and psychological symptoms in advanced gastrointestinal cancer patients and caregivers: Secondary results of a pilot randomized trial.

Patients with advanced gastrointestinal cancer often experience high symptom burden, which is associated with heightened distress in both patients and their family caregivers. Few interventions have been tested to jointly address patient and caregiver symptoms in advanced gastrointestinal cancer. In a randomized pilot trial, telephone-based, dyadic acceptance and commitment therapy (ACT) was found to be feasible in this population. The present secondary analyses examined the impact of this intervention on patient and caregiver physical and psychological symptoms. Patients and caregivers (N = 40 dyads) were recruited from clinics in Indianapolis, Indiana and randomized to either six weeks of telephone-based ACT or education/support, an attention control condition. Outcomes were assessed at baseline and at 2 weeks and 3 months post-intervention. Study group differences in outcomes were not statistically significant. However, when examining within-group change, only ACT patients experienced moderate reductions in pain severity and interference at 2 weeks post-intervention (effect size [ES]=-0.47; -0.51) as well as moderate reductions in depressive symptoms at 2 weeks (ES=-0.42) and 3 months (ES=-0.41) post-intervention. ACT caregivers experienced moderate reductions in sleep disturbance (ES=-0.56; -0.49) and cognitive concerns (ES=-0.61; -0.85) across follow-ups. Additionally, caregivers in both conditions experienced moderate reductions in fatigue (ES=-0.38 to -0.70) and anxiety (ES=-0.40 to -0.49) across follow-ups. Findings suggest that ACT may improve certain symptoms in dyads coping with advanced gastrointestinal cancer and warrant replication in a larger trial.

Diagnostic Yield of Endobronchial Ultrasound-Guided Mediastinal Lymph Node Transbronchial Forceps Biopsies (EBUS-TBFB).

OBJECTIVE: The diagnostic accuracy and yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is not well established in lymphoma and other mediastinal-related diseases. The objective of this study was to examine the yield of a combined technique of EBUS-TBNA and endobronchial ultrasound-guided transbronchial forceps biopsies (EBUS-TBFB) compared with each modality alone in lymphoma and other mediastinal-related diseases. METHODS: This was a retrospective review of cases of mediastinal lymphadenopathy of unknown etiology accessed using TBNA and TBFB. The McNemar test was used to compare the diagnostic yield of TBNA, TBFB, and the combined technique. RESULTS: The combined approach yielded a definitive diagnosis in 31/35 cases (88.6%). In 9/10 cases (90%), Hodgkin's and non-Hodgkin's lymphomas were diagnosed and subtyped without further need for invasive testing. All of the granulomatous inflammation cases were confirmed using the combined technique. Two cases led to adequate whole-genome sequencing of lung cancer, and one patient was diagnosed as having dedifferentiated liposarcoma despite a nondiagnostic preprocedural mediastinoscopy. There was only one procedure-related complication, a pneumomediastinum that required no further intervention. There were no significant adverse events. CONCLUSIONS: The combination of EBUS-TBFB and EBUS-TBNA is safe and provides a high yield in the diagnosis of mediastinal adenopathy of unknown etiology, especially lymphoma. Furthermore, the larger samples obtained from TBFB increased its sensitivity to detect granulomatous disease and provided specimens for clinical trials of malignancy when needle aspirates were insufficient.

Examining adherence to oral anticancer medications through a human factors engineering framework: Protocol for a scoping review.

BACKGROUND: The number of oral anticancer medications has increased over the past few decades, opening new possibilities in cancer care and improving convenience for patients and caregivers. However, adherence levels continue to be suboptimal, potentially jeopardizing therapeutic benefits. Poor adherence levels may indicate gaps in current strategies and interventions aimed at enhancing medication adherence and the extent to which they address the complex and multi-faceted medication management needs of patients and their caregivers. Beyond commonly understood barriers (e.g., forgetting to take medications), adherence interventions must address systemic barriers that may not be fully appreciated by members of the healthcare system. This scoping review aims to apply a systems framework (human factors engineering framework) to examine system elements targeted by adherence enhancing interventions. METHODS: Studies published in English, reporting adherence interventions for oral anticancer medications with adherence and/or persistence as primary outcome measures will be included in this review. We will search the following electronic databases with no limits on dates: Ovid MEDLINE, Cochrane Library, Web of Science Core Collection, Embase, CINAHL Complete, PsycInfo, and Scopus. Two reviewers will independently screen study titles and abstracts for inclusion with a third reviewer adjudicating conflicts. Full text of included articles will be used to extract information on systemic barriers targeted by adherence interventions as well as information about intervention type, outcomes, and study characteristics. Extracted information will be synthesized to generate a summary of work system factors targeted by adherence interventions. DISCUSSION: Through application of a systems-based approach, this scoping review is expected to shed light on the complex and multifaceted nature of factors influencing adherence to oral anticancer agents. The review may also identify areas that are ripe for further research.

Malignant gastrointestinal neuroectodermal tumour arising in the extrahepatic bile ducts; a rare neoplasm in an unusual anatomic location.

Malignant gastrointestinal neuroectodermal tumour (GNET) is a rare, aggressive neoplasm with fewer than 100 cases reported in the literature. Most cases arise in the tubular gastrointestinal tract. We reported a unique case of GNET arising in the extrahepatic bile ducts and reviewed the literature of GNETs. The patient is a female in her mid-30s who presented with painless jaundice and diarrhoea several months after cholecystectomy for biliary dyskinesia. Workup revealed a tumour arising from the peripheral 4B bile ducts involving the left hepatic duct and bifurcation. Histologic examination of the lesion showed a malignant spindled and epithelioid neoplasm which strongly expressed S100 and SOX-10. Neoplastic cells were negative for various cytokeratins and melanoma markers. FISH testing using EWSR1 break-apart probes showed rearrangement of the EWSR1 gene region. The immunohistochemical and molecular findings are consistent with a diagnosis of GNET arising in the extrahepatic bile ducts.

Acceptance and commitment therapy for patient fatigue interference and caregiver burden in advanced gastrointestinal cancer: Results of a pilot randomized trial.

BACKGROUND: Fatigue often interferes with functioning in patients with advanced cancer, resulting in increased family caregiver burden. Acceptance and commitment therapy, a promising intervention for cancer-related suffering, has rarely been applied to dyads coping with advanced cancer. AIM: To examine the feasibility, acceptability, and preliminary efficacy of acceptance and commitment therapy for patient-caregiver dyads coping with advanced gastrointestinal cancer. Primary outcomes were patient fatigue interference and caregiver burden. DESIGN: In this pilot trial, dyads were randomized to six weekly sessions of telephone-delivered acceptance and commitment therapy or education/support, an attention control. Outcomes were assessed at baseline and at 2 weeks and 3 months post-intervention. SETTING/PARTICIPANTS: Forty patients with stage III-IV gastrointestinal cancer and fatigue interference and family caregivers with burden or distress were recruited from two oncology clinics and randomized. RESULTS: The eligibility screening rate (54%) and retention rate (81% at 2 weeks post-intervention) demonstrated feasibility. At 2 weeks post-intervention, acceptance and commitment therapy participants reported high intervention helpfulness (mean = 4.25/5.00). Group differences in outcomes were not statistically significant. However, when examining within-group change, acceptance and commitment therapy patients showed moderate decline in fatigue interference at both follow-ups, whereas education/support patients did not show improvement at either follow-up. Acceptance and commitment therapy caregivers showed medium decline in burden at 2 weeks that was not sustained at 3 months, whereas education/support caregivers showed little change in burden. CONCLUSIONS: Acceptance and commitment therapy showed strong feasibility, acceptability, and promise and warrants further testing. TRIAL REGISTRATION: ClinicalTrials.gov NCT04010227. Registered 8 July 2019, https://clinicaltrials.gov/ct2/show/NCT04010227?term=catherine+mosher&draw=2&rank=1.

Acceptance and commitment therapy for fatigue interference in advanced gastrointestinal cancer and caregiver burden: protocol of a pilot randomized controlled trial.

BACKGROUND: Fatigue interference with activities, mood, and cognition is one of the most prevalent and bothersome concerns of advanced gastrointestinal (GI) cancer patients. As fatigue interferes with patient functioning, family caregivers often report feeling burdened by increasing responsibilities. Evidence-based interventions jointly addressing cancer patient fatigue interference and caregiver burden are lacking. In pilot studies, acceptance and commitment therapy (ACT) has shown promise for addressing symptom-related suffering in cancer patients. The current pilot trial seeks to test a novel, dyadic ACT intervention for both advanced GI cancer patients with moderate-to-severe fatigue interference and their family caregivers with significant caregiving burden or distress. METHODS: A minimum of 40 patient-caregiver dyads will be randomly assigned to either the ACT intervention or an education/support control condition. Dyads in both conditions attend six weekly 50-min telephone sessions. Outcomes are assessed at baseline as well as 2 weeks and 3 months post-intervention. We will evaluate the feasibility, acceptability, and preliminary efficacy of ACT for improving patient fatigue interference and caregiver burden. Secondary outcomes include patient sleep interference and patient and caregiver engagement in daily activities, psychological flexibility, and quality of life. We will also explore the effects of ACT on patient and caregiver physical and mental health service use. DISCUSSION: Findings will inform a large-scale trial of intervention efficacy. Results will also lay the groundwork for further novel applications of ACT to symptom interference with functioning and caregiver burden in advanced cancer. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04010227 . Registered 8 July 2019.

Hemophagocytic Lymphohistiocytosis in the Medical ICU: A Single-Institution Cohort Study on Acute Liver Failure and Mortality.

Hemophagocytic lymphohistiocytosis is a life-threatening hyperinflammatory disorder that is associated with high morbidity and mortality in the ICU. It has also been associated with acute liver failure. DESIGN: Retrospective observational study. SETTING: Tertiary-care medical ICU. PATIENTS: Thirty-one patients critically ill with hemophagocytic lymphohistiocytosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We performed a comprehensive review of critically ill hemophagocytic lymphohistiocytosis patients admitted to a tertiary-care medical ICU from January 2012 to December 2018. Most patients presented with constitutional symptoms and elevated liver enzymes and thrombocytopenia were common upon hospital admission. ICU admission laboratory and clinical variables were used to calculate Acute Physiology and Chronic Health Evaluation II, hemophagocytic syndrome diagnostic score, and model for end-stage liver disease. Mean age of the cohort was 48.1 years, and 45% were male. The mortality rate was 65% at 28 days and 77% at 1 year. About 28-day survivors were younger, had lower mean Acute Physiology and Chronic Health Evaluation II score (16.5 vs 23.0; p = 0.004), and higher mean hemophagocytic syndrome diagnostic score (249.1 vs 226.0; p = 0.032) compared with nonsurvivors. Survivors were less likely to receive mechanical ventilation, renal replacement therapy, or vasopressor support and were more likely to receive chemotherapy for hemophagocytic lymphohistiocytosis. In this ICU cohort, 29% were diagnosed with acute liver failure, of whom only 22% developed acute liver failure early during their hospital stay. Acute liver failure was associated with a higher model for end-stage liver disease score upon hospital admission. Available histology in those that developed acute liver failure showed massive hepatic necrosis, or histiocytic or lymphocytic infiltrates. CONCLUSIONS: Patients admitted to the ICU with hemophagocytic lymphohistiocytosis have a high mortality. Those who survived had lower Acute Physiology and Chronic Health Evaluation scores, had higher hemophagocytic syndrome diagnostic scores, are more likely to receive hemophagocytic lymphohistiocytosis specific chemotherapy, and are less likely to have organ failure. Hemophagocytic lymphohistiocytosis can be associated with acute liver failure especially when model for end-stage liver disease score is elevated upon admission.

A Case Report of an Early Response to Definitive Chemoradiation for Esophageal Carcinoma Cuniculatum.

This case report describes a 63-year-old female with a locally advanced esophageal carcinoma cuniculatum treated with definitive chemoradiation who had a rapid and early response. This case is illustrative of an aggressive behavior with rapid response and rapid recurrence. The cases of esophageal carcinoma cuniculatum as well as the closely related clinical entity of verrucous carcinoma are reviewed suggesting good clinical outcomes after definitive therapy with chemoradiation and/or surgery.

Superior vena cava syndrome in a patient with locally advanced lung cancer with good response to definitive chemoradiation: a case report.

BACKGROUND: The incidence of superior vena cava syndrome within the United States is roughly 15,000 cases per year. Superior vena cava syndrome is a potentially life-threatening medical condition; however, superior vena cava syndrome is not fatal in the majority of cases. Superior vena cava syndrome encompasses a collection of signs and symptoms resulting from obstruction of the superior vena cava, including swelling of the upper body of the head, neck, arms, and/or breast. It is also associated with cyanosis, plethora, and distended subcutaneous vessels. Lung cancer, including both non-small cell lung cancer and small cell lung cancer, is the most common extrinsic cause of superior vena cava syndrome. Intrinsic disruption of superior vena cava flow can also precipitate superior vena cava syndrome. This case report describes an unusual presentation and potential etiology of superior vena cava syndrome. CASE PRESENTATION: Our patient was a 51-year-old black woman with locally advanced, stage IIIB non-small cell lung cancer who had no clinical symptoms of superior vena cava syndrome at the time of diagnosis. However, she did have radiographic evidence of superior vena cava stenosis caused by extrinsic compression from her large right hilar primary tumor. She was treated with definitive chemoradiation, receiving 60 Gy of external beam radiation therapy given concurrently with chemotherapy. Three months after completion of radiotherapy, she developed signs of superior vena cava syndrome, including breast and supraclavicular swelling. She had a chest computed tomography scan showing over 50% reduction in the size of a right hilar mass; however, she had continued radiographic stenosis of the superior vena cava. The distribution of stenosis appeared to be inferior to the caudal extent of pretreatment tumor volume. She had no other radiographic indications for superior vena cava syndrome. CONCLUSIONS: Generally, superior vena cava syndrome is the result of extrinsic compression of the superior vena cava by tumor. Our patient's case represents the development of superior vena cava syndrome after an excellent response of tumor with near-complete tumor response. We suspect chemoradiation therapy as a potential etiology for the precipitation of the superior vena cava syndrome, which is currently not well reported in the medical literature.

Pancreatic acinar cell carcinoma: A review on molecular profiling of patient tumors.

Pancreatic carcinomas with acinar differentiation are rare, accounting for 1%-2% of adult pancreatic tumors; they include pancreatic acinar cell carcinoma (PACC), pancreatoblastoma, and carcinomas of mixed differentiation. Patients with PACC have a prognosis better than pancreatic ductal adenocarcinomas but worse than pancreatic neuroendocrine tumors. Reports of overall survival range from 18 to 47 mo. A literature review on PACCs included comprehensive genomic profiling and whole exome sequencing on a series of more than 70 patients as well as other diagnostic studies including immunohistochemistry. Surgical resection of PACC is the preferred treatment for localized and resectable tumors. The efficacy of adjuvant treatment is unclear. Metastatic PACCs are generally not curable and treated with systemic chemotherapy. They are moderately responsive to chemotherapy with different regimens showing various degrees of response in case reports/series. Most of these regimens were developed to treat patients with pancreatic ductal adenocarcinomas or colorectal adenocarcinomas. Review of PACC's molecular profiling showed a number of gene alterations such as: SMAD4, BRAF, BRCA2, TP53, RB1, MEN1, JAK-1, BRCA-1, BRCA-2, and DNA mismatch repair abnormalities. PACCs had multiple somatic mutations with some targetable with available drugs. Therefore, molecular profiling of PACC should be an option for patients with refractory PACC.

Metastatic malignant transformation of teratoma to primitive neuroectodermal tumor (PNET): results with PNET-based chemotherapy.

BACKGROUND: Metastatic germ cell cancers are highly chemosensitive and have 80% cure rate with cisplatin-based chemotherapy. Postchemotherapy teratoma can usually be surgically resected. However, teratoma, which is pluripotent tissue, can undergo malignant transformation along mesodermal elements to primitive neuroectodermal tumor (PNET). Unlike teratoma, PNET can metastasize and render a patient unresectable and incurable. We report the results of treatment of patients with malignant transformation to PNET with cyclophosphamide+doxorubicin+vincristine (CAV) alternating with ifosfamide+etoposide (IE). METHODS: We reviewed 86 patients with histologically confirmed PNET transformed from testicular teratoma at Indiana University from 1998 to 2012. We identified 18 patients who were treated with chemotherapy comprising cyclophosphamide (1000 to 1200 mg/m), doxorubicin (50 to 75 mg/m), and vincristine (2 mg) alternating with ifosfamide (1.8 g/m) plus etoposide (100 mg/m) for 5 consecutive days. Treatment was given every 3 weeks with a maximum of 6 cycles or until progression or undue toxicity. Hematopoietic growth factors were usually incorporated. The remaining 68 patients underwent surgical resection. RESULTS: Twelve patients had unresectable disease and 6 were treated in an adjuvant setting. Median age was 29 years (range, 20 to 53 y). Nine of the 12 metastatic patients achieved objective response by RECIST criteria. Six of those were rendered with no evidence of disease (NED) with further surgery. Although 4 of the 6 patients subsequently relapsed, 1 patient remains alive and NED at 78 months. The 6 patients who received adjuvant treatment are alive with NED at 9 to 90 months with a median duration of 32.7 months. CONCLUSIONS: CAV and IE alternating chemotherapy has high objective response rate for PNET transformed from teratoma and results in occasional long-term disease-free survival when combined with subsequent resection. We recommend adjuvant CAV alternating with IE chemotherapy for patients with PNET after RPLND due to the high probability of recurrent disease and their high chemosensitivity to this regimen.