Comparing the role of different treatment modalities in locoregionally advanced olfactory neuroblastoma: The 20-year clinical experience of a single institution.

BACKGROUND: The clinical value of different treatment modalities, especially systemic chemotherapy (CT) in patients with locoregionally advanced olfactory neuroblastoma (LA ONB) remains unclear. METHODS: Patients with LA ONB from 2000 to 2020 at our center were collected retrospectively. The entire cohort was divided into combined systemic and local therapy (CSLT) versus local therapy (LT) groups (grouping method 1), and the same cohort was divided into neoadjuvant chemotherapy (NAC) versus non-NAC groups (grouping method 2). CSLT group included patients treated with CT + LT. LT group included patients treated with surgery (SG), radiotherapy (RT), concurrent chemoradiotherapy (CCRT), or any combination of the above methods. LT group was further divided into mono-modality local therapy (MOLT) group and multi-modality local therapy (MULT) group. MOLT group included patients treated with RT alone or SG alone. MULT group included patients treated with SG + RT/CCRT, or CCRT alone. NAC group included patients treated with NAC + LT ± adjuvant chemotherapy (ADC). Non-NAC group included patients who received LT ± ADC. RESULTS: A total of 111 patients with LA ONB were included. The median follow-up was 80.2 months (range, 2.1-254.9). The 5- and 10-year OS rates were 70.2% and 61.3%, respectively. In univariate analysis, patients treated with NAC (n = 43) had significantly better overall survival (OS) compared with those without NAC (n = 68) (p = 0.041). Patients in MULT group (n = 45) had significantly improved OS (p = 0.004) and PFS (p = 0.003) compared with those in MOLT group (n = 15). Multivariate analysis identified NAC and CSLT (n = 51) were independent prognostic factors for superior OS (p = 0.020, p = 0.046). CONCLUSIONS: Our study suggested that CSLT, especially a combination of NAC and LT, improved the survival of patients with LA ONB. Multiple treatment modalities yielded better PFS and OS compared to single-modality treatment.

Clinical outcomes, Kadish-INSICA staging and therapeutic targeting of somatostatin receptor 2 in olfactory neuroblastoma.

INTRODUCTION: Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy. METHODS: We conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT](177Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763). RESULTS: Dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n = 278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD). CONCLUSIONS: This study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease.

Pulmonary nocardiosis mimicking small cell lung cancer in ectopic ACTH syndrome associated with transformation of olfactory neuroblastoma: a case report.

BACKGROUND: Pulmonary nocardiosis frequently develops as an opportunistic infection in cell-mediated immunosuppressive patients, and sometimes requires differentiation from pulmonary malignancy. Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a neoplastic disorder which leads to impaired cell-mediated immunity, and is commonly associated with small cell lung cancer (SCLC). Because pulmonary infection and causative malignancy can appear as pulmonary lesions with EAS, differentiation of these diseases remains a critical issue for physicians. CASE PRESENTATION: A 52-year-old woman with progressive lower limb paralysis and general fatigue was referred to us. She had been diagnosed with olfactory neuroblastoma (ONB) and treated with surgery and radiation therapy 10 years before the referral and had required stereotactic radiosurgery and chemotherapy 4 years later for a relapse of the ONB. On referral, she presented with Cushing's syndrome with elevated cortisol and ACTH levels. Potassium supplement improved her symptoms; however, a month later, she was urgently hospitalized due to acute pleuritic chest pain on inspiration. Chest computed tomography revealed left lower lobular consolidations and a contralateral nodule in the right middle lobe. The clinical history and laboratory work-up suggested that her Cushing's syndrome had most likely arisen from EAS. Additionally, the lungs were suspected as the ACTH source due to high levels of progastrin-releasing peptide and progressive pulmonary consolidation with a contralateral nodule, suggesting SCLC. However, histological examination from bronchoscopy revealed no evidence of malignancy, and Nocardia cyriacigeorgica was isolated from bronchoalveolar lavage fluid. Sulfamethoxazole/trimethoprim improved her pulmonary lesions. Somatostatin receptor scintigraphy revealed strong tracer uptake in the ONB lesions, indicating that the origin of the EAS was the olfactory tumor. However, histological examination of ONB specimens resected 10 years earlier showed no intracytoplasmic immunopositivity for ACTH. CONCLUSIONS: We highlight a rare case of pulmonary nocardiosis, which was associated with EAS mimicking SCLC, and was related to ONB transformation. Nocardiosis has to be considered even though anamnestic, clinical, and radiological aspects suggest the presence of metastasis. Additionally, physicians should carefully monitor patients with ONB for the development of Cushing's symptoms because the tumor can transform into an ACTH-producing form, even after long-term follow-up.

Primary sellar neuroblastoma. A new case and review of literature.

The primary intracranial development of olfactory neuroblastomas, outside olfactory epithelium, is rare. We report a case of primary sellar neuroblastoma without any aggressive histopathological features, managed solely surgically without adjuvant therapy, with good outcomes at 3 years. Primary sellar neuroblastomas mostly occur in women in the 4th decade with a context of a non-secreting pituitary tumour. Diagnosis is made on histopathological examination (small cells, fibrillary intercellular background, strong immunoreactivity for neurons markers, negative immunoreactivity for anterior pituitary hormones). Management is based on surgery. Adjuvant treatment is not consensual, largely depends on patient's conditions and aggressive histopathological features.

Maxillary removal and reinsertion: a favorable approach for extensive anterior cranial base tumors.

OBJECTIVE: To analyze the long-term results and the complications related to an expanded series of maxillary removal and reinsertion (MRRI) with 18-year surgical experience. STUDY DESIGN: Case series with chart review of the MRRI patients in the last 18 years. SETTING: The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute. SUBJECTS AND METHODS: Seventy-eight patients who underwent MRRI from February 1990 through February 2007. The median age was 51 years (range 11-77 yrs). Sixty-two (80%) patients had malignant lesions. RESULTS: MRRI has been successfully completed in all 78 patients, with no intraoperative mortality. The most commonly encountered malignant neoplasm was squamous cell cancer (40.3%), followed by esthesioneuroblastoma (24.1%), adenoid cystic cancer (8%), and other neoplasms (27.4%). The most commonly encountered postoperative complication was diplopia, which has persisted in five (6.4%) patients in the short-term and in three (4%) patients in the long-term follow-up. Nasal asymmetry was the most common long-term complication (17.9%), followed by plate-associated problems (10.2%) and midface asymmetry (10.2%). Overall five-year survival for the patients with squamous cell carcinoma was 62 percent. CONCLUSION: MRRI is a favorable surgical technique for the treatment of anterior cranial base (ACB) tumors in adults and even in children. It improves operative morbidity by preserving both function and form of the maxillary region and gives excellent exposure to ACB.

Olfactory neuroblastoma: the 22-year experience at one comprehensive cancer center.

BACKGROUND: Olfactory neuroblastoma (ONB) is a rare tumor arising from the olfactory neuroepithelium. There is no universally accepted staging system, and treatment approaches lack uniformity. We present one institution's experience with this tumor and the results of therapy. METHODS: Thirty patients treated for ONB at The University of Texas M. D. Anderson Cancer Center between 1979 and 2002 were retrospectively reviewed. The diagnosis of ONB was histologically confirmed for each patient. RESULTS: The mean follow-up was 7.32 years. In 77% of cases, patients received treatment with surgery followed by postoperative radiation therapy. Sixteen percent received chemotherapy as part of their initial treatment. Overall 5-year and 10-year survival rates were 89% and 81%, respectively. Nine patients whose disease was initially stage C had a recurrence. The mean time for recurrence was 4.67 years. CONCLUSIONS: The M. D. Anderson Cancer Center approach to ONB is complete surgical resection, usually involving a craniofacial approach, with postoperative radiation therapy. This approach seems to be curative in early-stage disease. Late recurrence warrants long-term follow-up.

[The value of the proton magnetic resonance spectroscopy (HMRS) of white matter injury in children treated with chemo- and/or radiotherapy. Preliminary report]. / Wartosc spektroskopii protonowej rezonansu magnetycznego (HMRS) w diagnostyce zmian w istocie bialej u dzieci leczonych radio- i/lub chemoterapia. Doniesienie wstepne.

UNLABELLED: THE AIM of this study was to estimate the value of HMRS in the diagnosis of brain lesions observed in children treated with chemo and radiotherapy and to assess the possibility to differentiate these lesions from neoplasm or recurrent disease. MATERIALS AND METHOD: We examined 6 children, aged from 7 to 15 yrs, 3 with brain tumours, 1 with esthesioneuroblastoma treated with chemo and radiotherapy and 2 patients with chemotherapy only, for other neoplasms (leukemia, Wilms tumor). Indications to perform imaging studies were routine for brain tumour patients (no clinical symptoms) and suspicion of disease recurrence in others. MR with 1.5 T scanner and additionally single voxel HMRS in PRESS sequence were performed. RESULTS: In all cases MRI showed extensive hyperintensive changes in brain tissue with significant mass effect. In 3 cases HMRS was within normal limits, in other 3 cases moderately elevated peak of choline and peak of lactate and lipids were found. In follow up examinations all lesions regressed and all patients are in good clinical condition. COMMENTS: It could be difficult to differentiate white matter injury from malignancies on MRI. HMRS in case of doubtful findings on MRI in children treated with chemo and radiotherapy, especially in those without symptoms of their disease, is a helpful method.

Estesioneuroblastoma: diagnóstico e abordagem / Esthesioneuroblastoma: diagnosis and management

Apresentamos seis casos de estesioneuroblastoma acompanhados em nosso serviço durante os últimos oito anos. A idade dos pacientes variou entre 11 e 63 anos. Näo houve predominância entre homens e mulheres (3:3) Os sintomas principais observados foram obstruçäo nasal e hiposmia. O diagnóstico conclusivo foi conseguido através do exame anatomopatológico com uso de técnica de imuno-histoquímica, para a correta diferenciaçäo com linfoma, carcinoma indiferenciado, melanoma, sarcoma e tumores de glândulas salivares menores. O estadiamento foi realizado usando-se o sistema de Kadish. Em nossa casuística, quatro pacientes foram classificados no grupo C e dois pacientes no grupo B. Metástases foram observadas em linfonodos (2), pulmäo (2), fígado (l)e osso (1). O tratamento consistiu de cirurgia e radioterapia pós-operatóna em três pacientes; radioterapia e quimioterapia após a cirurgia em dois pacientes; e somente radioterapia mais quimioterapia em um paciente, devido ao estágio avançado do tumor. Três pacientes (em dois destes sendo administrada quimioterapia) têm pelo menos quatro anos de acompanhamento sem recorrência do tumor; e outro paciente está vivo, mas com metástases em linfonodos e/ou pulmäo. Concluindo, o estesioneuroblastoma Ú um tumor maligno da linhagem epitelial que nÒo tem protocolo de tratamento bem estabelecido. A alta taxa de mortalidade sugere que procedimentos agressivos devem ser usados na abordagem terapêutica. Protocolos de quimioterapia têm sido desenvolvidos e säo promissores para o futuro tratamento destes casos

Recurrent renal salt wasting in a child treated with carboplatin and etoposide.

BACKGROUND: Nephrotoxicity of carboplatin is rare, especially in children with normal renal function. A 3-year-old boy had localized esthesioneuroblastoma and received 2 courses of carboplatin (200 mg/m2/day during a 1-hour infusion for 3 consecutive days) associated with etoposide (150 mg/m2/day after carboplatin). Because of a good tumor response, a second course was given 21 days later. Complete surgical excision and local irradiation were performed. However, the tumor recurred a few months later, and the patient subsequently died of the disease. METHODS: Renal function initially was assessed by standard baseline chemistry and technetium-panetetic acid (Tc-DTPA) clearance. Follow-up included ionic controls and tubular exploration during the episodes of hyponatremia. RESULTS: Hyponatremia occurred 4 days after completion of the first course and resolved after intravenous supplementation. It recurred 20 days after the second course despite salt and magnesium prehydration and posthydration and resolved 17 days later. No glomerular dysfunction was noticed. The association of urinary bicarbonate loss with elevated N-acetyl-beta-glucosaminidase suggested a proximal tubular damage. CONCLUSIONS: Standard doses of carboplatin may lead to recurrent renal salt wasting in children with initially normal renal function.