P14.48 Extracerebral relapses of primary CNS lymphoma (PCNSL): a LOC network retrospective study

BACKGROUND Classically PCNSL remain confined within the CNS throughout their evolution for reasons still unknown (> 80% cerebral relapses). The aim of this study was to describe the characteristics and outcomes of the rare extracerebral relapses of PCNSL. MATERIAL AND METHODS This is a multicenter, retrospective study. We included all immunocompetent patients newly diagnosed with diffuse large B-cell PCNSL registered in the national LOC network database since 2010 and followed prospectively, who presented an extracerebral relapse, pure (extracerebral only site) or associated with concomitant CNS relapse (mixed). All had body scan and/or TEP -CT at diagnosis work up. RESULTS Of the 1968 PCNSL included in the database, 29 (1.5%) patients presented a systemic relapse [median age 71 years, median KPS 70% at relapse], either pure (n=19) or mixed (n=10), with a histological confirmation in 19 cases (66%). The median delay between initial diagnosis and systemic relapse was 15 months [2–49 months], with 5 very early relapses (<8 months) and 10 late relapses (>21 months). 27 patients had symptoms, 21 related to the location of relapse and 6 with only general symptoms. The localization was thoracic (n=11), abdominal/pelvic (n=14), head/neck (n=6) and limbs (n=9). We found visceral (n=24, 83%), including testis in 5 (28%) men and breast in 3 (27%) women, lymph node (n=12, 41%) and peripheral nervous system (PNS) (n=8, 28%; 4 plexus and 4 extradural roots) involvement. 27 patients were treated with chemotherapy, either with only systemic target (n=8) (R-CHOP alone) or mixed systemic and CNS target (n=19) (R-CHOP-MTX, R-ICE, GEMOX, RDHAC) and consolidated by high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) in 4 cases [median age 55 years, median KPS 80%], with 34% of complete response. After systemic relapse, median progression-free survival was 8 months and overall survival (OS) was 9 months, 15 months for pure systemic and 4.5 months for mixed relapses. KPS>70%, pure systemic relapses and complete response were significantly associated with higher OS in univariate analysis. CONCLUSION Extracerebral PCNSL relapses are very rare, mainly extranodal and involve a large spectrum of anatomical sites, the most frequent being testis, breast and PNS. Prognosis was worse in case of mixed relapse than in pure systemic relapse that was similar to non PCNSL lymphomas. Very early relapses raise the question of misdiagnosed occult extracerebral lymphoma at diagnostic work up that should include systematically a FDG PET-CT. More studies are needed to refine their treatment and to specify the role of HCT-ASCT. Paired tumor tissues at diagnosis (CNS)/relapse (extracerebral) analysis would provide a better understanding of underlying molecular mechanisms.

High-dose methotrexate is effective for prevention of isolated CNS relapse in diffuse large B cell lymphoma

The role of central nervous system (CNS) prophylaxis with high-dose methotrexate (HDMTX) in DLBCL is controversial. In this retrospective study, we evaluated the efficacy of prophylactic HDMTX on isolated CNS relapse, concomitant CNS and systemic relapse, systemic relapse, and survival outcomes in 226 patients with newly diagnosed DLBCL and high-risk CNS International Prognostic Index (CNS-IPI) score treated with RCHOP. The three-year risk of isolated CNS relapse was significantly lower in patients who received HDMTX, at 3.1% compared to 14.6% (P = 0.032) in those who did not. However, neither concomitant CNS-systemic relapse rates, systemic relapse rates, nor three-year PFS and OS were significantly different between treatment groups in multivariable analysis. Among propensity score-matched patients (N = 102), HDMTX was also associated with significantly lower isolated CNS relapse rates (HR 0.06, 95% CI 0.004–0.946, P = 0.046). HDMTX was well tolerated with manageable toxicities when given at a dose of 3 g/m2 by day 3 of RCHOP chemotherapy. Using propensity score matching and multivariable regression to yield treatment groups with well-balanced covariates, we showed that prophylactic HDMTX improved isolated CNS relapse rates but did not decrease concomitant CNS-systemic relapse rates, systemic relapse rates, or improve survival outcomes.

Isolated CNS Relapse in Acute Lymphoblastic Leukemia (ALL): An Experience from a Tertiary Care Center

Aims and Objectives In this study the various parameters of acute lymphoblastic leukemia (ALL), including the clinical features, peripheral blood and bone marrow (BM) findings, immunophenotypic and cytogenetic details in ALL cases who had isolated relapse involving the central nervous system (CNS), were studied. Patients/Materials and Methods Duration of the study is from 2015 to 2019 in which 5 ALL cases were presented to this tertiary care center. The presenting symptoms varied from headache, fever, and distension of abdomen. These cases were either on therapy or post completion of chemotherapy. The diagnosis of CNS relapse followed after the examination of cerebrospinal fluid (CSF). Patients also underwent BM examination to rule out systemic relapse. Results Age of patients ranged from 7 months to 42 years. There were three female patients. Two patients had isolated CNS relapse 3.5 years after completing therapy and succumbed to their illness. Two patients had t(9;22) while one patient had t(1;14) cytogenetic abnormality at diagnosis. One patient was diagnosed as T-ALL. Treatment offered was German Multicentre ALL protocol for induction along with 10 cycles of maintenance. Conclusion The most common hematolymphoid malignancy in children namely ALL accounts for 75% of childhood leukemias. Complete remission rates reach up to 70 to 80%. CNS involvement is known to occur in these cases. CNS relapse may occur alone or with systemic relapse. Advances in therapeutic protocols along with CNS prophylaxis have drastically brought down the rates of CNS relapse. It is essential to maintain a high degree of suspicion so that these cases of isolated CNS relapse can be identified at the earliest and definitive therapy can be offered.

Uncommon Metastasis of Ovarian Dysgerminoma: A Case Report and Review of the Literature

Ovarian malignant germ cell tumors (OMGCT) represent less than 10% of all ovarian tumors. Dysgerminoma is the most common malignant primitive germ cell tumor in young women, known for its curability and low propensity to invade and metastasize when diagnosed early. Herein, we report an unusual type of ovarian dysgerminoma (OD) metastasis with a brief review of the literature, lacking similar reported cases. To our knowledge, although there are several case reports of dysgerminoma metastases with variable anatomic location and presentation, vaginal metastasis has not been previously described. The local or systemic relapse together with local and distant metastasis is considered as an independent predictor of poor survival in patients with OD. In light of the absence of mutations status, our patient successfully responded to therapy. Currently, the patient remains in clinical remission. A specific follow-up plan is ongoing knowing that ovarian dysgerminomas tend to recur most often in the first 2–3 years after treatment.

Primary Mucosal Melanoma Presenting with a Unilateral Nasal Obstruction of the Left Inferior Turbinate

We report the case of a primitive nasal melanoma in an 82-year-old patient, showing how this rare malignancy, with non-specific signs and symptoms, can represent a challenging diagnosis for the physician. A 82-year-old Caucasian patient presented for unilateral nasal obstruction and occasional epistaxis. Computerized tomography (CT) and magnetic resonance imaging (MRI) of the facial massif revealed turbinate hypertrophy and a polypoid phlogistic tissue isointense in T1 with an intermediate signal in T2 and Short-TI Inversion Recovery (STIR)-T2, occupying the middle meatus and the anterior upper and lower left meatus with partial obliteration of the ostium and the infundibulum of the maxillary sinus. The Positron emission tomography (PET) exam was negative for metastases. Conservatory surgery in the left anterior video rhinoscopy was performed, allowing a radical 4-cm tumor excision. Histology reported epithelioid cell melanoma, PanK−, CD45−, and PanMelanoma+. Adjuvant radiotherapy was suggested, even considering a complete resection as the result of surgery. No local or systemic relapse was noticed at the 2-month follow-up visit. Although mucosal melanoma is a rare and aggressive malignancy characterized by a poor prognosis, early diagnosis allows a more conservative approach, with little surgical difficulty and no aesthetic effect. Our case raises awareness of the importance of early intervention even in those cases where the clinic symptoms and diagnostic images show uncertain severity.

P03.28 Structural characteristics in tumor and lymph nodes as predictors of 3-year metastasis-free survival in surgically treated NSCLC

BackgroundSurgery is the treatment of choice for early and for some locally advanced non-small cell lung cancer (NSCLC). Ipsilateral hilar and mediastinal lymph nodes are generally removed at the time of tumor resection and assessed for tumor infiltration. However, in particular in the context of immunotherapy, there is now increased awareness about the physiological role of lymph nodes in cancer. It may be possible to assess immune response by examining the cellular composition of locoregional lymph nodes. We aimed to assess structural characteristics in tumor tissue and affected and unaffected lymph nodes in patients with and without 3-year metastasis-free survival.Materials and methodsInternal hospital databases were screened for NSCLC patients fulfilling inclusion criteria. Data on patients age, sex, surgery type, (neo)adjuvant therapy, tumor characteristics and time and location of relapse was extracted. FFPE tissue blocks of primary tumor, affected and unaffected lymph nodes were collected. Hematoxylin and eosin stainings were obtained and tissues were analyzed (e.g. for B-cell proliferation and macrophage infiltration) in collaboration with an experienced pathologist.ResultsA total of 754 NSCLC patients were screened for inclusion criteria. Of these, 71 patients remained in remission for at least 3 years after surgery, and 80 patients had local or systemic relapse within 3 years after surgery. Structural characteristics in tumor and lymph node immune populations differed between patients with and without 3-year metastasis-free survival.ConclusionStructural characteristics differ between patients with and without relapse. Our findings show that structural markers in tumor and lymph nodes should be taken into account when assessing patient prognosis and relapse risk.Disclosure InformationL. Sellmer: None. J. Kovacs: None. J. Neumann: None. R. Kiefl: None. D. Kauffmann-Guerrero: None. C. Schneider: None. A. Tufman: None.

4-1BB is a target for immunotherapy in patients with undifferentiated pleomorphic sarcoma

Systemic relapse, after treatment of a localised primary tumour with neo-adjuvant radiotherapy and surgery, is the major cause of disease related mortality in patients with sarcoma. As with other cancers, many sarcoma patients derive no benefit from anti-PD-1 treatment. Combining radiotherapy and immunotherapy is under investigation as a means to improve response rates and control metastatic disease. Here, we use a retrospective cohort of sarcoma patients, treated with neoadjuvant radiotherapy, and TCGA data to explore patient stratification for immunotherapy and therapeutic targets of relevance to sarcoma. We show a group of patients with immune-hot undifferentiated pleomorphic sarcoma as one of the highest-ranking candidates for emerging 4-1BB targeting agents. A binary hot/cold classification method indicates 4-1BB-high hot sarcomas share many characteristics with immunotherapy responsive cancers of other pathologies. Hot tumours in sarcoma are however substantially less prevalent. Patient stratification, of intense interest for immunotherapies, is therefore even more important in sarcoma.