Induction Strategy for Locally Advanced Thymoma

Surgery remains cornerstone for the management of thymoma. Complete surgical resection (R0), is recognized as the constant and significant factor for prognosis. However, in locally advanced (Masaoka-Koga stages III-IVa) thymomas, achieving R0 resection remains challenging due to local-regional invasion of the disease. Induction treatment, with the aim of reducing bulky tumor mass, offers new strategy to facilitate totally surgical resection. Herein, we reviewed recent progress and provided a comprehensive overview of induction strategy in locally advance thymoma.

Adult T cell- leukemia/lymphoma associated with HTLV-1 presenting as giant mass of the face

A 30-year-old Arabic woman of low socio-economic status, without medical history of HIV infection, presented to our department for neglected giant mass of the face evolving for 2 years. She was treated for long time with herbal traditional treatments, which explains the delay of consultation. Physical examination revealed a bulky tumor, of reddish-brown color, occupying the entire face below the franc, more lateralised on the left side. The right eye had restricted movement, while the left eye was fixed (Panel A,B). CT scan showed a nasal cavity tumour with orbital and maxillary sinus invasion, without intra cranial extension or distant metastasis. Laboratory testing was positive for HTLV I/II and she was negative for HIV. Surgical biopsy with histo-pathological study established the diagnosis of HTLV-1 associated adult lymphoma/leukaemia, with strong CD4 and CD25 antibody staining. She received chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) regimen, but she died after two cycles.

Case report of giant retroperitoneal liposarcoma in a young woman

Retroperitoneal liposarcoma is a rare malignant mesenchymal tumor with an annual incidence of approximately 2.5 cases per 100,000 inhabitants. It does not present specific symptoms, so its early diagnosis is difficult and in most cases it is performed when it has a large size. A 45-year-old patient with a history of increased abdominal perimeter and local discomfort was admitted in our center. After performing an abdominopelvic CT, she was diagnosed of a large, bulky tumor of lipomatous origin that significantly displaced the intestinal loops and the rest of neighboring organs. In view of the clinical suspicion of a liposarcoma, the patient underwent a resection of the lesion located in the retroperitoneum. The histopathological study determined a well differentiated retroperitoneal liposarcoma. The well-differentiated liposarcoma located in the lower limbs and the retroperitoneal space. Its age of presentation is between the fourth and sixth decade of life without finding differences between men and women. Its treatment is surgical and involves the resection of the tumor mass with non-affected surgical margins. Retroperitoneal liposarcoma is a malignant tumor whose treatment is fundamentally surgical. These tumors tend to be resistant to radiotherapy and / or chemotherapy. Among the most important prognostic factors related to survival is surgery with non-affected margins.

4SCAR19 Chimeric Antigen Receptor-Modified T Cells As a Breakthrough Therapy for Highly Chemotherapy-Resistant Late-Stage B Cell Lymphoma Patients with Bulky Tumor Mass

Background: Chemo-resistant, advanced B cell lymphomas with bulky tumor are difficult to treat and often fatal. Recent studies have shown that CD19 chimeric antigen receptor-engineered T (CAR-T) cells can effectively treat B-cell malignancies. However, CAR-T therapy-associated adverse systemic responses including fever, tachycardia, profound hypotension, and respiratory distress, can be life-threatening. The toxicities of CAR-T infusion are directly correlated with tumor burden, disease sites and other complications during treatment. Therefore, highly individualized CAR-T therapy regimen is key to the success of such innovative treatment. Patients and Methods: In this phase I/II multi-center CAR-T therapy trial, we have evaluated 13 patients (pts) with chemo-resistant B cell lymphomas, including 12 advanced diffuse large B cell lymphomas (DLBCL) and 1 Burkitt's lymphoma, average age 37 (range 9-61), stage IIIA/IVB. Twelve of them had bulky tumor and met the criteria of high-risk by the second-line age-adjusted international prognostic index (sAAIPI) and were associated with the following co-morbidities: Aspergillus invasive fungal infection (IFI) pneumonia (2), drug-induced liver injury (2), pleural pericardial cavity effusion (2), hepatitis B (2), diabetes mellitus (1), gastrointestinal hemorrhage (1), deep venous thrombosis (1), and lung tumor argon-helium cryoablation surgery (1). Autologous T cells were apheresis collected and lentivirally transduced with a 4th generation, apoptosis-inducible, safety-engineered CAR: CD19- scFv/CD28/CD137/CD27/CD3ζ-iCasp9 (4SCAR19). All pts received conditioning regimen of cyclophosphamide 250 mg/m2/d x3d, and fludarabine 30 mg/m2/d x3d, followed by 1 to 3 infusions of CAR-T cells in a dose range of 0.45- 4.59 x106 cells/kg per infusion. Results: The lentiviral 4SCAR19 transduction efficiencies were in the range of 5-100%. Patient response did not always correlate with CAR gene transfer efficiencies, but instead, correlated better with the condition of the T cells. Eight pts have achieved complete tumor regression (CR) for 3 to 10 months, with stable CAR DNA copies of 0.1-0.4% in the blood. Three pts achieved dramatic tumor reduction but died from various causes including: intracranial hemorrhage due to low platelet count, pre-existing ureteral obstruction/acute renal failure and cardiopulmonary complications, with or without severe cytokine release syndrome (CRS) at day 29, 28 and 66 after CAR-T infusion, respectively. Two pts died from progressive diseases. Treatment toxicities included CRS with fever over 39o C (9/13), massive hemorrhage of the alimentary tract (1/13) and severe myelo-suppression (3/13), which were correlated with increased plasma cytokines including IL-6 and IFN-γ. The 120 day disease-free survival (DFS) rate is 53% (CI, 36-69%), and the 10 month overall survival probability is 55% (CI, 39-74%). Conclusion and discussion: While 4SCAR19 T cells can relieve severe disease symptoms and obtain dramatic tumor control even in late-stage, highly chemo-resistant, bulky tumor-bearing pts, our studies suggest that in order to obtain favorable and durable clinical outcomes in the late-stage pts, the optimal timing for CAR-T engagement, a highly individualized chemo-regimen, and better clinical management for CRS and pre-existing health conditions are critical. While long-term follow-up and better understanding of the tumor genotype and immunobiology are needed, our study indicates that a highly experienced clinical management team is key to the success of CAR-T therapy for advanced B cell lymphomas. Disclosures Dong: America Yuva Biomed: Consultancy. Kuo:America Yuva Biomed: Employment. Liu:America Yuva Biomed: Employment.

Metabolic Tumor Volume Is an Independent Prognosis Factor Predicting patient's Outcome in Hodgkin Lymphoma

Abstract 3631 Positron emission tomography with [18F]fluorodeoxyglucose (PET) performed after two cycles of chemotherapy allows to predict treatment outcome in Hodgkin lymphoma (HL) with a pretty good accuracy specifically when the SUVmax reduction (DSUVmax) of the most hypermetabolic lesion is used to interpret interim PET. However, about 15% of false negative and 30% of false positive interim PET results are observed. To investigate the prognosis impact of the metabolic tumor volume at baseline (MTV0) we compared the respective clinical usefulness and prognosis value of the MTV0 and the SUVmax reduction between baseline PET (PET0) and interim PET (PET2) performed after 2 cycles of chemotherapy (DSUVmaxPET0–2) in a retrospective single centre study. From January 2007 to January 2010, 59 consecutive patients with a first diagnosis of HL were treated in our institution. All patients received 4 to 8 cycles of chemotherapy including ABVD in 50 cases (85%) and BEACOPP in 9 cases. Radiotherapy was performed in 14 responding patients with localized disease. PET was done at baseline (PET0) and after 2cycles of chemotherapy (PET2) and therapeutic strategy was not modified according to PET2 result. All PET scans were reviewed by SK, ABR and IDC. MTV0 was measured with a semi-automatic method using various volume shapes and systematic 41% SUVmax thresholding. Based on a receiver operating characteristics approach patients with a MTV0 >225 cc were considered to have a hypermetabolic bulky disease. Interim PET were interpreted using DSUVmaxPET0–2 and patients with a DSUVmaxPET0–2 >71% were considered as good responders after 2 cycles. Progression-free survival (PFS) and freedom from treatment failure (FFTF) were analyzed according to MTV0 and DSUVmaxPET0–2.Median follow-up was 39 months (range: 6–62). Median MTV0 was 120 cc (range: 10 – 1610) and 17 patients (29%) had a MTV0 >225 cc. Patients with a MTV0 >225 cc had more frequently a bulky tumor>10 cm (41% vs 5%; p = 0.0021). MTV0 (≤ 225 vs > 225) was predictive of 3-year PFS (85% vs 42%; p = 0.001) and FFTF (88% vs 45%; p = 0.0015). Bulky tumor was also predictive of 3-year PFS (44% vs 78%, p <0.04), but of border line significance for 3-year FFTF (80% vs 53%, p = 0.09). In multivariate analysis, using the international prognosis score, DSUVmaxPET0–2, MTV0 and bulky tumor as covariates, only DSUVmaxPET0–2 and MTV0 remained independent predictors for PFS (p= 0.0005; RR=6.4, and p<0.007; RR= 4.2, for DSUVmaxPET0–2 and MTV0 respectively) and FFTF (p= 0.0002; RR= 8.2,and p= 0.01; RR= 4.4, for DSUVmaxPET0–2 and MTV0 respectively). Then, 3 prognosis groups could be identified (Figure 1): patients with either DSUVmaxPET0–2>71 and MTV0≤225 (n = 37; 63%), or DSUVmaxPET0–2<71 or MTV0>225 (n = 17; 29%), or DSUVmaxPET0–2<71 and MTV0>225 (n = 5; 8%), had a 92%, 48%, and 20% 3-year PFS (p<0.0001) and a 94%, 54% and 20% 3-year FFTF (p<0.0001) respectively. MTV0 is more relevant that tumor bulk to predict outcome of patients with Hodgkin lymphoma, and adds significant prognosis insights to interim PET response assessment. The combination of MTV0 with DSUVmaxPET0–2 allows identifying 3 subsets of HL patients with significantly different outcomes that may help clinicians to guide therapeutic strategy. Figure 1: PFS according to DSUVmaxPET0–2 and MTV0 results Figure 1:. PFS according to DSUVmaxPET0–2 and MTV0 results Solid line: patients with DSUVmaxPET0–2 >71 and MTV0 ≤225. Dashed line: patients with DSUVmaxPET0–2 <71 or MTV0 >225. Dotted line: patients with DSUVmaxPET0–2 <71 and MTV0 >225. Disclosures: No relevant conflicts of interest to declare.