Secondary orbital exenteration for conjunctival melanoma: A study of 25 cases.

INTRODUCTION: The treatment of conjunctival melanoma is most often conservative, but exenteration is sometimes necessary in order to achieve local control of the disease. It can be performed as a primary procedure in cases of locally advanced disease or as a secondary procedure after one or more recurrences. No benefit to secondary exenteration on patient survival has been demonstrated to date for conjunctival melanoma, and it is generally considered a palliative procedure. PATIENTS AND METHODS: Single-center retrospective study performed in the ocular oncology department of the Institut Curie (Paris, France). We included all patients who underwent secondary orbital exenteration for conjunctival melanoma between January 2008 and January 2016. RESULTS: Twenty-five patients underwent secondary exenteration for conjunctival melanoma. The maximum number of local recurrences prior to exenteration was six. Metastases occurred in 11 patients after exenteration and were more common when there was a greater tumor thickness on histology, if the tumor had not been treated initially in an ocular oncology center, or if there had been a greater number of local recurrences before the secondary exenteration was performed. Seventy-five percent of patients developed metastases when the exenteration was performed after 5 or 6 local recurrences. CONCLUSION: This study suggests that early secondary exenteration (i.e. after a number of local recurrences less than or equal to 4) may reduce the occurrence of metastases (and therefore improve patient survival) in conjunctival melanoma. Thus, secondary exenteration might be a curative surgery in some patients with recurrent disease.

Basal cell carcinomas of the eyelid: Results of an initial surgical management.

PURPOSE: Our objective was to assess the results of surgical management of palpebral basal cell carcinomas (BCC) followed by a second line treatment discussed during a Multidisciplinary Team Meeting (MTM). MATERIALS AND METHODS: This retrospective single-centred study includes all surgically-treated basal cell carcinomas of the eyelids between January 2005 and January 2015. After initial surgery, the cases were systematically discussed during a multidisciplinary team meeting in order to assess the need for additional treatment. Data relative to the patient, tumor and management were pulled from the medical record. RESULTS: A total of 171 patients were included, with a mean age of 74 years. Among the patients, 151 underwent pentagonal resection of the tumor, and 20 patients had a superficial excision. After surgical management, 120 patients (70.2%) were considered to have sufficient free margins. The other 51 patients (29.8%) had insufficient margins due to remaining tumor cells (38 patients) or free margins less than 1mm. Among these 51 patients with insufficient margins, 19 received a second surgical treatment, 17 patients received adjuvant radiotherapy, and 15 were followed closely with an intensive biannual follow-up program. No patients were lost to follow-up. With a mean follow-up of 42 months (min. 6 months-max. 128 months), 7 out of 171 patients (4.1%) developed a local recurrence. The mean time between surgical management and recurrence was 24 months. The recurrence rate was higher for the group of patients with a recurrent tumor (11.6%) than for the group of patients referred for initial management (2.8%). Incomplete resection was also associated with a higher recurrence rate (3 recurrences out of 51 patients). DISCUSSION: The management of basal cell carcinomas of the eyelid is first and foremost surgical with the goal of complete resection confirmed by histopathological analysis. The histological analyses (Mohs micrographic surgery, frozen section technic, paraffin fixation) and recommended sizes of the margins can vary in the literature, with recurrence rates from 1.8% to 9.5%. CONCLUSION: In our experience, multidisciplinary management of BCC of the eyelid, including initial macroscopic surgery, histopathological analysis stating the histological type and size of the margins, along with additional treatment discussed in a MTM, allows for a recurrence rate of 4.1%.

Ibrutinib monotherapy for relapse or refractory primary CNS lymphoma and primary vitreoretinal lymphoma: Final analysis of the phase II 'proof-of-concept' iLOC study by the Lymphoma study association (LYSA) and the French oculo-cerebral lymphoma (LOC) network.

BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal centre B-cell subtype, with unmet medical needs. This study aimed to evaluate the efficacy and toxicity of ibrutinib in DLBCL-PCNSL PATIENTS AND METHODS: This prospective, multicentre, phase II study involved patients with relapse or refractory(R/R) DLBCL-PCNSL or primary vitreoretinal lymphoma. The treatment consisted of ibrutinib (560 mg/day) until disease progression or unacceptable toxicity occurred. The primary outcome was the disease control (DC) rate after two months of treatment (P0 < 10%; P1 > 30%). RESULTS: Fifty-two patients were recruited. Forty-four patients were evaluable for response. After 2 months of treatment, the DC was 70% in evaluable patients and 62% in the intent-to-treat analysis, including 10 complete responses (19%), 17 partial responses (33%) and 5 stable diseases (10%). With a median follow-up of 25.7 months (range, 0.7-30.5), the median progression-free and overall survivals were 4.8 months (95% confidence interval [CI]; 2.8-12.7) and 19.2 months (95% CI; 7.2-NR), respectively. Thirteen patients received ibrutinib for more than 12 months. Two patients experienced pulmonary aspergillosis with a favourable (n = 1) or fatal outcome (n = 1). Ibrutinib was detectable in the cerebrospinal fluid (CSF). The clinical response to ibrutinib seemed independent of the gene mutations in the BCR pathway. CONCLUSION: Ibrutinib showed clinical activity in the brain, the CSF and the intraocular compartment and was tolerated in R/R PCNSL. The addition of ibrutinib to standard methotrexate-base induction chemotherapy will be further evaluated in the first-line treatment. CLINICAL TRIAL NUMBER: NCT02542514.

Lenalidomide in combination with intravenous rituximab (REVRI) in relapsed/refractory primary CNS lymphoma or primary intraocular lymphoma: a multicenter prospective 'proof of concept' phase II study of the French Oculo-Cerebral lymphoma (LOC) Network and the Lymphoma Study Association (LYSA)†.

BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal center B-cell (non-GCB) subtype. This study aimed to determine the efficacy of rituximab plus lenalidomide (R2) in DLBCL-PCNSL. PATIENTS AND METHODS: Patients with refractory/relapsed (R/R) DLBCL-PCNSL or primary vitreoretinal lymphoma (PVRL) were included in this prospective phase II study. The induction treatment consisted of eight 28-day cycles of R2 (rituximab 375/m2 i.v. D1; lenalidomide 20 mg/day, D1-21 for cycle 1; and 25 mg/day, D1-21 for the subsequent cycles); in responding patients, the induction treatment was followed by a maintenance phase comprising 12 28-day cycles of lenalidomide alone (10 mg/day, D1-21). The primary end point was the overall response rate (ORR) at the end of induction (P0 = 10%; P1 = 30%). RESULTS: Fifty patients were included. Forty-five patients (PCNSL, N = 34; PVRL, N = 11) were assessable for response. The ORR at the end of induction was 35.6% (95% CI 21.9-51.2) in assessable patients and 32.0% (95% CI 21.9-51.2) in the intent-to-treat analysis, including 13 complete responses (CR)/unconfirmed CR (uCR; 29%) and 3 partial responses (PR; 7%). The best responses were 18 CR/uCR (40%) and 12 PR (27%) during the induction phase. The maintenance phase was started and completed by 18 and 5 patients, respectively. With a median follow-up of 19.2 months (range 1.5-31), the median progression-free survival (PFS) and overall survival (OS) were 7.8 months (95% CI 3.9-11.3) and 17.7 months (95% CI 12.9 to not reached), respectively. No unexpected toxicity was observed. The peripheral baseline CD4/CD8 ratio impacted PFS [median PFS = 9.5 months (95% CI, 8.1-14.8] for CD4/CD8 ≥ 1.6; median PFS = 2.8 months, [95% CI, 1.1-7.8) for CD4/CD8 < 1.6, P = 0.03). CONCLUSIONS: The R2 regimen showed significant activity in R/R PCNSL and PVRL patients. These results support assessments of the efficacy of R2 combined with methotrexate-based chemotherapy as a first-line treatment of PCNSL. CLINICAL TRIALS NUMBER: NCT01956695.

Outcomes after surgical resection of lower eyelid tumors and reconstruction using a nasal chondromucosal graft and an upper eyelid myocutaneous flap.

INTRODUCTION: Surgical excision of large malignant lower eyelid tumors may cause important full-thickness eyelid defects. The reconstruction of such defects must restore the physiologic function of the eyelid and also re-establish an acceptable aesthetic result. MATERIALS AND METHODS: We report the outcomes of full-thickness excision of tumors extending over half of the horizontal lid length, followed by reconstruction using a nasal chondromucosal graft (coming from the ipsilateral ala of the nose) and an upper eyelid myocutaneous flap. Histological analysis of the specimen identified the tumor type and surgical margins for each patient. RESULTS: A total of 25 patients were operated using this reconstruction technique between March 2009 and June 2015: 17 basal cell carcinomas, 3 spindle cell carcinomas and 5 conjunctival melanomas (out of which 2 were associated with lentigo maligna). Mean duration of follow-up after surgery was respectively 36, 41 and 17 months for each of these 3 tumor types. We found a single local tumor recurrence and this was a basal cell carcinoma in a xeroderma pigmentosum patient. After surgery, none of the patients had lagophthalmos or ocular surface complications. Only 4 patients had a 1mm scleral show postoperatively; 3 other patients developed a small retraction of the eyelid after adjuvant radiotherapy and a 1mm scleral show occurred. CONCLUSION: In malignant tumors, complete surgical excision with histological margins adapted to tumor type prevents local recurrence in most cases. Our repair strategy of nasal chondromucosal graft and skin-muscle flap for large inferior eyelid defects provides good functional and aesthetic results.

High-dose thiotepa-based chemotherapy with autologous stem cell support in elderly patients with primary central nervous system lymphoma: a European retrospective study.

In this retrospective multicentre study, we investigated the outcomes of elderly primary central nervous system lymphoma (PCNSL) patients (⩾65 years) who underwent high-dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT) at 11 centres between 2003 and 2016. End points included remission, progression-free survival (PFS), overall survival (OS) and treatment-related mortality. We identified 52 patients (median age 68.5 years, median Karnofsky Performance Status before HDT-ASCT 80%) who all underwent thiotepa-based HDT-ASCT. Fifteen patients (28.8%) received HDT-ASCT as first-line treatment and 37 (71.2%) received it as second or subsequent line. Remission status before HDT-ASCT was: CR 34.6%, PR 51.9%, stable disease 3.8% and progressive disease 9.6%. Following completion of HDT-ASCT, 36 patients (69.2%) achieved CR (21.2% first-line setting and 48.1% second or subsequent line setting) and 9 (17.3%) PR (5.8% first-line setting and 11.5% second or subsequent line setting). With a median follow-up of 22 months after HDT-ASCT, median PFS and OS were reached after 51.1 and 122.3 months, respectively. The 2-year PFS and OS rates were 62.0% and 70.8%, respectively. We observed two HDT-ASCT-associated deaths (3.8%). In selected elderly PCNSL patients, HDT-ASCT, using thiotepa-based conditioning regimes, is feasible and effective. Further prospective and comparative studies are warranted to further evaluate the role of HDT-ASCT in elderly PCNSL patients.

Evisceration and ocular tumors: What are the consequences?

PURPOSE: Evisceration can be performed for blind, painful eyes. This surgery can promote the dissemination of tumor cells within the orbit if an ocular tumor has been missed preoperatively. METHODS: We reviewed the medical records of patients who were eviscerated for blind, painful eyes between 2009 and 2014 and who were referred after the surgery to the Institut Curie or the Rothschild Foundation in Paris. We included the patients with a histological diagnosis of ocular tumor or orbital recurrence. Cytogenetic analysis was performed whenever possible. RESULTS: Four patients turned out to have an ocular tumor after evisceration (two choroidal melanomas, a rhabdoid tumor and an adenocarcinoma of the retinal pigment epithelium); two had a history of prior ocular trauma. The tumors were diagnosed either on histological analysis of the intraocular contents (2 patients) or biopsy of orbital recurrence (2 patients). Prior to evisceration, fundus examination was not performed in 3 patients. One had preoperative imaging but no intraocular tumor was suspected. At the time of this study, 3 patients had had an orbital recurrence and died. We also found 2 patients who had an evisceration despite a past history of choroidal melanoma treated with proton beam therapy. CONCLUSION: We showed that evisceration of eyes with unsuspected ocular malignancies was associated with a poor prognosis due to orbital recurrence and metastasis. The evisceration specimen should therefore always be sent for histological analysis in order to perform prompt adjuvant orbital radiotherapy if an ocular tumor is found.

[Aneurysmal bone cyst: A rare cause of orbital disease]. / Kyste anévrysmal osseux : une atteinte exceptionnelle au niveau orbitaire.

Aneurysmal bone cyst is a rare benign bone neoplasm of unknown cause. The most commonly affected anatomical sites are the vertebral column and long bones. We report two uncommon cases of primary orbital aneurysmal bone cyst presenting as an acute orbital compartment syndrome due to subperiosteal hemorrhage. Case 1 is a 45-year-old woman. Imaging studies revealed a small cystic frontal bone tumour associated with a subperiosteal hematoma. The patient achieved full visual recovery after drainage of the hematoma, with no recurrence after treatment. Case 2 is a 74-year-old woman whose visual acuity was light perception due to severe papilledema. Imaging studies of the orbit revealed a large cystic frontal bone tumor associated with a subperiosteal hematoma causing globe and optic nerve compression. Preoperative arteriography showed a moderate vascular blush. Drainage of the hematoma was performed. A local recurrence with hematoma formation occurred two years after the surgery.

Radiofrequency ablation and surgical resection of liver metastases from uveal melanoma.

BACKGROUND: The resection of liver metastasis from uveal melanoma (LMUM) remains controversial. In this study, we evaluated treatment with radiofrequency ablation (RFA) for liver metastases alone or in combination with surgical liver resection. METHODS: A total of 72 patients with LMUM were evaluated in this study. Of these, 57 patients underwent surgical resection (S) while 15 patients had RFA ± S. Clinicopathologic factors were evaluated in terms of recurrence and survival using Chi-square and log-rank tests, respectively. RESULTS: We studied 22 metastases treated by RFA. There were no statistically significant differences between the groups in terms of median age of onset, synchronous nature of the metastases, time from primary tumour treatment to liver metastasis, diameter of the largest metastasis, presence of liver miliary disease, and the type of liver resection. There was a statistically lower number of liver metastases and more bilobar metastases in the RFA group than in the S group. The median overall survival after liver surgery was 27 months in group S and 28 months in the RFA group ± S. The median disease-free survival was 10 months in group S and 7 months in the RFA group ± S. There were no statistically significant differences in the median overall survival and disease-free survival between groups. CONCLUSIONS: The results of this retrospective analysis show that RFA can be used to treat liver metastases to spare the hepatic parenchyma. RFA ± liver surgery and liver surgery alone demonstrate similar survival times.

Conservative treatment of retinoblastoma: a prospective phase II randomized trial of neoadjuvant chemotherapy followed by local treatments and chemothermotherapy.

PurposeIntraocular retinoblastoma treatments often combine chemotherapy and focal treatments. A first prospective protocol of conservative treatments in our institution showed the efficacy of the use of two courses of chemoreduction with etoposide and carboplatin, followed by chemothermotherapy using carboplatin as a single agent and diode laser. In order to decrease the possible long-term toxicity of chemotherapy due to etoposide, a randomized neoadjuvant phase II protocol was conducted using vincristine-carboplatin vs etoposide-carboplatin.Patients and methodsThe study was proposed when initial tumor characteristics did not allow front-line local treatments. Patients included in this phase II noncomparative randomized study of neoadjuvant chemotherapy received vincristin-carboplatin (new arm) vs etoposide-carboplatin (our reference arm). They were subsequently treated by local treatments and chemothermotherapy. Primary end point was the need for secondary enucleation or external beam radiotherapy (EBRT) not exceeding 40% at 2 years.ResultsA total of 65 eyes in 55 children were included in the study (May 2004 to August 2009). Of these, 32 eyes (27 children) were treated in the arm etoposide-carboplatin and 33 eyes (28 children) in the arm vincristin-carboplatin. At 2 years after treatment, 23/33 (69.7%) eyes were treated and salvaged without EBRT or enucleation in the arm vincristin-carboplatin and 26/32 (81.2%) in the arm etoposide-carboplatin.ConclusionEven if the two treatment arms could be considered as sufficiently active according to the study decision rules, neoadjuvant chemotherapy by two cycles of vincristine-carboplatin followed by chemothermotherapy appear to offer less optimal local control than the etoposide-carboplatin combination.

Treatment of retinoblastoma: The Institut Curie experience on a series of 730 patients (1995 to 2009).

INTRODUCTION: To describe the results of retinoblastoma treatment from 1995-2009 in a single institution. MATERIAL AND METHODS: Retrospective review of the charts of patients treated for retinoblastoma. Clinical characteristics at diagnosis, treatments and outcomes in terms of survival and ocular preservation are described. RESULTS: During the study period 826 children were referred for retinoblastoma and 730 were managed in our institution. Four hundred and eleven children presented with unilateral retinoblastoma and 319 with bilateral retinoblastoma. Median follow-up is of 93 months. Global survival is 98.5% of children, 10 children presented with second tumors, 11 children died (6 of tumor-related causes). Of the 411 children with unilateral retinoblastoma enucleation was needed at diagnosis for 324 (78.8%). Conservative treatments were attempted for 87 patients (21.2%) and ocular preservation obtained for 65 patients (74% of eyes). Three hundred and nineteen patients presented with bilateral retinoblastoma. Three hundred and ten could be treated conservatively for at least one eye. Initial intravenous chemotherapy was necessary for 75% of them. Ocular preservation without external beam radiation was possible for 221 patients (70%). The use of EBR decreased significantly after 2004 (9.1% of eyes vs 25.1%: P<0.001). DISCUSSION: Management and treatment of retinoblastoma are complex, adapted to the extent of the disease. Survival is good. Enucleation is still required for extensive ocular disease, especially for unilateral patients. Intravenous chemotherapy allows good tumor control and eye preservation and decrease the need of EBR. CONCLUSIONS: Retinoblastoma treatment with intravenous chemotherapy and ocular adjuvant therapies is very effective on the local tumor control and eye preservation.

Prospective study of surveillance testing for metastasis in 100 high-risk uveal melanoma patients.

Despite advances in the local treatment of UM, half of patients develop metastases typically to the liver with poor survival. Microscopic complete surgical resection (R0) of liver metastases improves survival in high selected patients. Early identification of high-risk patients might allow detection of asymptomatic metastases, and increase R0 liver surgery rate. From October 2006 to December 2009, we conducted a prospective study to detect early minimal lesions with 6-monthly liver function tests (LFTs) and liver MRI in 100 high-risk patients. High risk was defined by primary tumor clinical or genomic criteria: thickness>8mm or diameter>15 mm, or extra-scleral extension, or monosomy 3 by FISH or aCGH. With a median follow-up of 49 months, the 5-year metastasis-free survival and overall survival were 47 and 33%, respectively. Of the 60 patients who became metastatic, 50 (83%) had exclusive liver metastasis. LFTs screening had no sufficient accurary, but biannual MRI showed high predictive value to detect metastasis and select patients eligible for curative surgery: 25/50 underwent laparotomy and among them, 8/25 (32%) had a R0 surgery. Median survival after metastasis was 14 months, mean survival reached 40 months in the R0 resected population. Six-monthly liver MRI screening is recommended in patients with large tumors or genomic high risk in order to detect early patient candidates to complete resection of liver metastases.