Exploring Regorafenib Responsiveness and Uncovering Molecular Mechanisms in Recurrent Glioblastoma Tumors through Longitudinal In Vitro Sampling.

Glioblastoma, a deadly brain tumor, shows limited response to standard therapies like temozolomide (TMZ). Recent findings from the REGOMA trial underscore a significant survival improvement offered by Regorafenib (REGO) in recurrent glioblastoma. Our study aimed to propose a 3D ex vivo drug response precision medicine approach to investigate recurrent glioblastoma sensitivity to REGO and elucidate the underlying molecular mechanisms involved in tumor resistance or responsiveness to treatment. Three-dimensional glioblastoma organoids (GB-EXPs) obtained from 18 patients' resected recurrent glioblastoma tumors were treated with TMZ and REGO. Drug responses were evaluated using NAD(P)H FLIM, stratifying tumors as responders (Resp) or non-responders (NRs). Whole-exome sequencing was performed on 16 tissue samples, and whole-transcriptome analysis on 13 GB-EXPs treated and untreated. We found 35% (n = 9) and 77% (n = 20) of tumors responded to TMZ and REGO, respectively, with no instances of TMZ-Resp being REGO-NRs. Exome analysis revealed a unique mutational profile in REGO-Resp tumors compared to NR tumors. Transcriptome analysis identified distinct expression patterns in Resp and NR tumors, impacting Rho GTPase and NOTCH signaling, known to be involved in drug response. In conclusion, recurrent glioblastoma tumors were more responsive to REGO compared to TMZ treatment. Importantly, our approach enables a comprehensive longitudinal exploration of the molecular changes induced by treatment, unveiling promising biomarkers indicative of drug response.

O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET as a potential selection tool for second surgery in glioblastoma patients.

BACKGROUND: Treatment-related changes still represent a diagnostic challenge in the management of patients with suspect of recurrent glioblastoma. The specificity of conventional MRI in detecting recurrence remains limited. Brain PET imaging provides information on tumor metabolism and can contribute to improving the diagnostic accuracy of cerebral neoplasms. We performed a retrospective analysis to evaluate the clinical value of O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET in the diagnosis of glioblastoma recurrence. METHODS: A retrospective analysis on patients considered suitable for salvage surgery for recurrence glioblastoma was performed. 18F-FET-PET was performed to investigate gadolinium enhancement suspected for recurrence. Static and kinetic 18F-FET parameters were analyzed and related to O-6-methylguanine-DNA methyltransferase (MGMT) status. RESULTS: Forty-two of the 51 patients who underwent 18F-FET-PET were re-operated. In each case, neuropathological diagnosis of tumor recurrence was confirmed. pMGMT hypermethylation was detected in 21 patients. Mean tumor-to-brain ratios (TBR) max was 3.87 (range 2.6-6.0). Static and kinetic 18F-FET parameters were similar according to MGMT status. CONCLUSIONS: 18FET-PET can be a reliable tool to improve the selection of patients suitable for salvage surgery for glioblastoma recurrence.

Innovative Approach to Isolate and Characterize Glioblastoma Circulating Tumor Cells and Correlation with Tumor Mutational Status.

Circulating tumor cells (CTCs) are one of the most important causes of tumor recurrence and distant metastases. Glioblastoma (GBM) has been considered restricted to the brain for many years. Nevertheless, in the past years, several pieces of evidence indicate that hematogenous dissemination is a reality, and this is also in the caseof GBM. Our aim was to optimize CTCs' detection in GBM and define the genetic background of single CTCs compared to the primary GBM tumor and its recurrence to demonstrate that CTCs are indeed derived from the parental tumor. We collected blood samples from a recurrent IDH wt GBM patient. We genotyped the parental recurrent tumor tissue and the respective primary GBM tissue. CTCs were analyzed using the DEPArray system. CTCs Copy Number Alterations (CNAs) and sequencing analyses were performed to compare CTCs' genetic background with the same patient's primary and recurrent GBM tissues. We identified 210 common mutations in the primary and recurrent tumors. Among these, three somatic high-frequency mutations (in PRKCB, TBX1, and COG5 genes) were selected to investigate their presence in CTCs. Almost all sorted CTCs (9/13) had at least one of the mutations tested. The presence of TERT promoter mutations was also investigated and C228T variation was found in parental tumors and CTCs (C228T heterozygous and homozygous, respectively). We were able to isolate and genotype CTCs from a patient with GBM. We found common mutations but also exclusive molecular characteristics.

Surgical management of skull base meningiomas and vestibular schwannomas.

PURPOSE OF REVIEW: The aim of this study is to discuss surgical management of meningiomas and schwannomas of skull base. RECENT FINDINGS: Meningiomas and schwannomas are typically benign neoplasm with a good prognosis after surgery. Patients should be treated individually related to several features: size and localization of tumor and its proximity with deep critical neurovascular structures, neurological status, age and comorbidity. Also, the widespread use of neuroimaging and the progressive and constant aging of the populations inevitably result in the increase of detection rate of incidental (asymptomatic) neoplasm.Nowadays, there are still controversies about the correct management strategy. SUMMARY: Surgery represents the gold standard treatment, with the objective of gross total resection; however, it is not always feasible due to localization, encasement of neuro-vascular structure, invasion of cranial nerve and brain parenchyma. Stereotactic radiosurgery and radiation therapy are important to achieve a satisfactory functional outcome and tumor control in case of residue or recurrence. A multidisciplinary approach is pivotal.

Metabolic-imaging of human glioblastoma live tumors: A new precision-medicine approach to predict tumor treatment response early.

Background: Glioblastoma (GB) is the most severe form of brain cancer, with a 12-15 month median survival. Surgical resection, temozolomide (TMZ) treatment, and radiotherapy remain the primary therapeutic options for GB, and no new therapies have been introduced in recent years. This therapeutic standstill is primarily due to preclinical approaches that do not fully respect the complexity of GB cell biology and fail to test efficiently anti-cancer treatments. Therefore, better treatment screening approaches are needed. In this study, we have developed a novel functional precision medicine approach to test the response to anticancer treatments in organoids derived from the resected tumors of glioblastoma patients. Methods: GB organoids were grown for a short period of time to prevent any genetic and morphological evolution and divergence from the tumor of origin. We chose metabolic imaging by NAD(P)H fluorescence lifetime imaging microscopy (FLIM) to predict early and non-invasively ex-vivo anti-cancer treatment responses of GB organoids. TMZ was used as the benchmark drug to validate the approach. Whole-transcriptome and whole-exome analyses were performed to characterize tumor cases stratification. Results: Our functional precision medicine approach was completed within one week after surgery and two groups of TMZ Responder and Non-Responder tumors were identified. FLIM-based metabolic tumor stratification was well reflected at the molecular level, confirming the validity of our approach, highlighting also new target genes associated with TMZ treatment and identifying a new 17-gene molecular signature associated with survival. The number of MGMT gene promoter methylated tumors was higher in the responsive group, as expected, however, some non-methylated tumor cases turned out to be nevertheless responsive to TMZ, suggesting that our procedure could be synergistic with the classical MGMT methylation biomarker. Conclusions: For the first time, FLIM-based metabolic imaging was used on live glioblastoma organoids. Unlike other approaches, ex-vivo patient-tailored drug response is performed at an early stage of tumor culturing with no animal involvement and with minimal tampering with the original tumor cytoarchitecture. This functional precision medicine approach can be exploited in a range of clinical and laboratory settings to improve the clinical management of GB patients and implemented on other cancers as well.

Single-Cell Molecular Characterization to Partition the Human Glioblastoma Tumor Microenvironment Genetic Background.

BACKGROUND: Glioblastoma (GB) is a devastating primary brain malignancy. The recurrence of GB is inevitable despite the standard treatment of surgery, chemotherapy, and radiation, and the median survival is limited to around 15 months. The barriers to treatment include the complex interactions among the different cellular components inhabiting the tumor microenvironment. The complex heterogeneous nature of GB cells is helped by the local inflammatory tumor microenvironment, which mostly induces tumor aggressiveness and drug resistance. METHODS: By using fluorescent multiple labeling and a DEPArray cell separator, we recovered several single cells or groups of single cells from populations of different origins from IDH-WT GB samples. From each GB sample, we collected astrocytes-like (GFAP+), microglia-like (IBA1+), stem-like cells (CD133+), and endothelial-like cells (CD105+) and performed Copy Number Aberration (CNA) analysis with a low sequencing depth. The same tumors were subjected to a bulk CNA analysis. RESULTS: The tumor partition in its single components allowed single-cell molecular subtyping which revealed new aspects of the GB altered genetic background. CONCLUSIONS: Nowadays, single-cell approaches are leading to a new understanding of GB physiology and disease. Moreover, single-cell CNAs resource will permit new insights into genome heterogeneity, mutational processes, and clonal evolution in malignant tissues.

Impact of recurrence pattern in patients undergoing a second surgery for recurrent glioblastoma.

The impact of different patterns of glioblastoma (GBM) recurrence has not yet been fully established in patients suitable for a second surgery. Through the present observational study carried out at Pisa University Hospital, we aimed to investigate how different patterns of GBM failure influence second surgery outcomes. Overall survival (OS) and post-recurrence survival (PRS) were assessed according to clinical characteristics, including pattern of recurrence, in a prospective cohort of recurrent GBM patients. Survival curves were calculated using the Kaplan-Meier method and the log-rank test was applied to evaluate the differences between curves. Patients with local recurrence had better OS than patients with non-local one, 24.1 versus 18.2 months, respectively [P = 0.015, HR = 1.856 (1.130-3.050)]. The second surgery conferred an advantage in OS respect to non-operated patients, however, this advantage was more evident in patients with local recurrence [P = 0.002 with HR 0.212 (95% CI 0.081-0.552) and P = 0.029 with HR = 0.522 (95% CI 0.291-0.936), respectively]. The recurrence pattern can influence the outcome of patients with recurrent GBM suitable for a second surgery.

Cage with anterior plating is advantageous over the stand-alone cage for segmental lordosis in the treatment of two-level cervical degenerative spondylopathy: A retrospective study.

OBJECTIVES: To compare retrospectively the clinical and radiological outcomes in cervical spinal alignment after two consecutive levels PEEK cage-assisted ACDF when performed with or without plate fixation PATIENTS AND METHODS: Seventy-eight patients underwent two consecutive levels PEEK cage-assisted ACDF without plating (56 patients) or supplemented with plating (22 patients). The average clinical follow-up was 31.40±12.98months. The authors compared clinical parameters (Neck disability index and Robinson criteria), perioperative parameters (hospital stays, complications), and radiological parameters (global lordotic curvature, segmental lordosis, segmental height). RESULTS: Demographic features, neurological presentation, preoperative sagittal alignment, postoperative complications, length of hospitalization and clinical improvement were not different between groups. At 12-months radiological follow-up, the global lordotic curvature was similar in both groups (P=0.02). However, the use of anterior plate fixation versus stand-alone cage was associated with greater segmental lordosis (-7.68±4.82° versus -0.02±8.44°, P<0.0001) and greater segmental height (39.51±3.50 versus 36.75±3.90, P=0.005). CONCLUSION: The clinical outcomes after two consecutive levels PEEK cage-assisted ACDF with and without plate fixation were similar, but the supplement of an anterior plate was advantageous for improving segmental alignment on long-term radiological follow-up.

A new quantitative method to assess disproportionately enlarged subarachnoid space (DESH) in patients with possible idiopathic normal pressure hydrocephalus: The SILVER index.

OBJECTIVES: Preoperative diagnosis of idiopathic normal-pressure hydrocephalus (iNPH) remains challenging. Recently, the presence of disproportionally enlarged subarachnoid spaces and hydrocephalus (DESH) on diagnostic images has been linked to clinical improvement after ventriculoperitoneal (VP) shunt placement. In this study we describe a new quantitative method to assess DESH on CT scans and to evaluate its prognostic value. PATIENTS AND METHODS: A multiplanar reconstruction software was used to retrospectively evaluate prospectively collected radiological data (CT scans) of 26 controls and 29 consecutive patients that underwent VP shunt placement for possible iNPH. The ratio between the areas of the sylvian fissure and the subarachnoid space at the vertex was calculated (SILVER index). The diagnostic accuracy of the SILVER index and the estimate of the best cut-point were assessed using ROC analysis. RESULTS: The mean value of the SILVER index was 11.52±14.27 in the study group and 1.68±0.98 in the control group (p-value<0.0001). The area under the ROC curve for the SILVER index was 0.903 (95% CI 0.813-0.994). A cut-off value for the SILVER index of 3.75 was extrapolated with a sensitivity and specificity of 0.828 and 0.962 respectively. CONCLUSIONS: The SILVER index is a reliable tool to easily quantify DESH on CT scans of patients with suspected iNPH. Its high sensitivity and specificity should encourage further investigations in order to confirm its clinical utility.

Aneurysm rebleeding after placement of external ventricular drainage: a systematic review and meta-analysis.

BACKGROUND: The association between external ventricular drainage (EVD) and aneurysm rerupture is still a controversial issue. We performed a systematic review and meta-analysis of published series reporting data of EVD placement in aneurysmal subarachnoid hemorrhage (SAH) with the aim to evaluate the relationship between ventricular drainage and aneurysm rebleeding. METHOD: PRISMA/MOOSE guidelines were followed. The Newcastle-Ottawa Scale was used to assess the quality of the studies. We conducted a comprehensive literature search of three databases (PubMed, Ovid MEDLINE, and Ovid EMBASE) on series reporting patients with EVD placement and aneurysmal SAH. The reported studies were analyzed with a primary aim to calculate the strength of the association (odds ratio) between rebleeding and EVD placement in patients with SAH. RESULTS: Our systematic review included 16 articles with a total of 6804 patients with SAH of which 595 (8.7%) had aneurysmal rebleeding. Ventricular drainage was inserted in 19% of patients. Rebleeding occurred in 18.8% (95% CI = 16.4-20.6%) of patients requiring EVD and in 6.4% (95% CI = 5.8-7.1%) of patients who did not require EVD (OR = 3.92, p < 0.0001). The mean time between EVD placement and rebleeding was 1 h (range, 0-8 h). The maximal aneurysm diameter of patients with rerupture was larger when compared with patients without rerupture (9.9 mm vs. 7.5 mm; p < 0.04). High Fisher grades (III-IV) were present in 75% of patients with rerupture and in 60% of patients without aneurysmal rerupture (p < 0.0001). CONCLUSIONS: Our study conclusively defined an association between EVD and rebleeding. However, the effective role of EVD in aneurysm rebleeding is insufficiently investigated in the literature. Other significant factors of rebleeding are usually observed in patients requiring ventricular drainage. According to our findings, a causal relationship between EVD and aneurysm rebleeding could be a plausible hypothesis, at least in certain cases.

Intracranial aneurysms in patients with autosomal dominant polycystic kidney disease: prevalence, risk of rupture, and management. A systematic review.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder associated with high incidences of intracranial aneurysms. We performed a systematic review with the purpose of clarifying the prevalence, risk of rupture, and appropriate management of intracranial aneurysms in the ADPKD population. METHOD: PRISMA guidelines were followed. We conducted a comprehensive literature search of three databases (PubMed, Ovid MEDLINE, and Ovid EMBASE) on all series reporting ADPKD patients with intracranial aneurysms. RESULTS: Our systematic review included 16 articles with a total of 563 patients with ADPKD and intracranial aneurysms. The prevalence of unruptured aneurysms was 11.5% (95% CI = 10.1-13%), whereas 1.9% (95% CI = 1.3-2.6%) of aneurysms were ruptured. Hypertension was present in 79.3% of patients with ADPKD and renal impairment in 65%. The mean size of ruptured aneurysms was slightly higher than unruptured (6 mm vs. 4.4 mm). The most common locations of unruptured and ruptured aneurysms were the ICA (40.5%) and MCA (45%), respectively. Asymptomatic patients studied with four-vessel angiography experienced 25% transient complications. Overall, 74% unruptured aneurysms were surgically treated with lower complication rates compared to endovascular treatment (11% vs. 27.7%). Among conservatively treated aneurysms, 2.9% ruptured at follow-up (rupture rate 0.4%/patient-year). Finally, the growth rate was 0.4% per patient-year, and the incidence of de novo aneurysm formation was 1.4% per patient-year. CONCLUSIONS: The prevalence of unruptured intracranial aneurysms in the ADPKD population is approximately 11%. Given the non-negligible rate of procedural complications, the management of these patients must be cautious and individualised. The rupture rate appears comparable to that of the general population. On the other hand, the 1.4% rate per patient-year of de novo aneurysms is non-negligible. These findings should be considered when counselling ADPKD patients regarding the appropriate management of intracranial aneurysms.

Surgical management of acute subdural haematomas in elderly: report of a single center experience.

OBJECTIVE: To evaluate the clinical outcome of patients over 70 years old who have received surgical treatment for traumatic acute subdural haematoma (aSDH) in our Neurosurgical Department. We also disclose related surgical and medical costs. METHODS: A retrospective analysis was performed by analyzing the medical records of patients older than 70 who had undergone surgery for evacuation of traumatic aSDH between June 2011 and December 2014. Through univariate and multivariate analyses, we correlated clinical and radiological pre-operatory features with outcome at one and six months after surgery. Overall costs for each patient were recorded. RESULTS: We observed 67 patients, 36 male and 31 female, with a median age of 80.5 years old (range 71-94). The mortality rate at one month and six months after surgery was respectively 55.1% and 67.2% while functional recovery was respectively 10.4% and 13.4%. Multivariate analysis age and Glasgow Coma Score (GCS) are the most significant parameters in relation to clinical outcome. Age greater than 90, shift midline >20 mm and volume of the haematoma >200 cu cm were independent parameters to predict mortality within 10 days of surgery. CONCLUSION: Our study confirms a poor outcome for patients of 70 years and over who received surgical treatment for traumatic aSDH.

Survival outcomes following repeat surgery for recurrent glioblastoma: a single-center retrospective analysis.

The aim of the present study is to evaluate the impact of extent of resection at initial and repeat craniotomy on overall survival of patients with recurrent glioblastoma. The authors retrospectively reviewed the records of all adults patients who underwent repeat resection of recurrent glioblastoma following radiation and chemotherapy at an academic tertiary-care institution between 2011 and 2015. We evaluated the survival outcomes with regard to extent of resection considering both the initial and repeat resections. The role of possible prognostic factors that may affect survival after repeat resection, including age, preoperative performance status, tumor location and adjuvant treatment, was evaluated using Cox regression analyses. Forty-eight patients were included in this study. The overall median survival of 14 patients who had subtotal resection at recurrence after initial subtotal resection did not statistically differ from seven patients who had gross-total resection at recurrence after initial subtotal resection (18 months vs. 22 months, p = 0.583). The overall median survival of 13 patients who had gross-total resection at recurrence after initial gross-total resection was significantly increased compared with survival of 13 patients who had subtotal resection at recurrence after initial gross-total resection (47 months vs. 14 months, p = 0.009). A Cox proportional hazards model was created demonstrating that preoperative performance status at recurrence (HR 0.418, p = 0.035) and the extent of repeat resection (HR 0.513, p = 0.043) were independent predictors of survival. Gross-total resection at repeat craniotomy is associated with longer overall survival and should be performed whenever possible in patients with recurrent glioblastoma and in good performance status.

Subdural fluid collection and hydrocephalus following cervical schwannoma resection: hydrocephalus resolution after spinal pseudomeningocele repair: case report.

The authors report the case of a 31-year-old man who developed neck pain and headache 2 months after the uncomplicated resection of a cervical schwannoma. MR imaging revealed infratentorial subdural fluid collections and obstructive hydrocephalus associated with cervical pseudomeningocele. The clinical symptoms, subdural fluid collections, and ventricular dilation resolved after surgical correction of the pseudomeningocele. This report emphasizes that hydrocephalus may be related to disorders of cerebrospinal fluid flow dynamics induced by cervical pseudomeningocele. In these rare cases, both the hydrocephalus and the symptoms are resolved by the simple correction of the pseudomeningocele.

Anterior cervical corpectomy for cervical spondylotic myelopathy: Reconstruction with expandable cylindrical cage versus iliac crest autograft. A retrospective study.

OBJECTIVES: To compare retrospectively the clinical and radiographic outcomes between cervical reconstruction with expandable cylindrical cage (ECC) and iliac crest autograft after one- or two-level anterior cervical corpectomy for spondylotic myelopathy. PATIENTS AND METHODS: Forty-two patients underwent cervical reconstruction with either iliac crest autograft and plating (20 patients) or ECC and plating (22 patients). The average clinical and radiological follow-up period was 77.54 ± 44.28 months (range 14-155 months). The authors compared clinical parameters (Nurick Myelopathy Grade, modified Japanese Orthopedic Association (mJOA) scores), perioperative parameters (hospital stays, complications) and radiological parameters (Cobb's angles of the fused segments and C2-C7 segments, cervical subsidence, fusion rate). Fusion was assessed on flexion-extension X-ray films. RESULTS: No significant differences between the two groups were found in demographics, neurological presentation, preoperative sagittal alignment, clinical improvement and length of hospitalization. Patients of the autograft group experienced more postoperative complications, although the difference between the two treatment groups was not statistically significant (15 versus 4.5%, p=0.232). The fusion rate was 100% in both groups. The average lordotic increase of the segmental angle was significantly greater in the ECC group (p<0.05). Other radiological parameters were not significantly different in the two groups. CONCLUSION: Cervical reconstruction either with iliac crest autograft and plating or ECC and plating provides good clinical results and similar fusion rates after one- or two-level corpectomy for spondylotic myelopathy. However, the use of ECC obviates donor site complications and provides a more significant increase of lordosis in segmental angle.

Disseminated bone metastases from occult thyroid cancer effectively treated with debulking surgery and a single dosimetry-guided administration of radioiodine / Metástasis óseas diseminadas de un carcinoma de tiroides oculto tratado efectivamente con cirugía citorreductora y administración simple de radioyodo rastreado con dosimetría

In this paper we report on a successful management of multiple bone metastases from differentiated thyroid cancer. In 2007, a 75-year-old female patient, previously referred for thyroidectomy for multinodular goiter, underwent surgical removal of a lumbar mass with histological findings of metastasis from well differentiated thyroid cancer. After surgery, serum thyroglobulin (sTg) was 204.4 ng/mL. A diagnostic/dosimetric 123 I WBS was performed, following stimulation by rTSH. Serial WBSs were acquired, along with SPECT/CT and bone scan for localization of lesions. sTg raised to 3.810 ng/mL, and 123 I WBS showed thyroid remnants and numerous areas with high iodine-uptake corresponding to skeletal sites, the two largest loading on the skull, with osteolytic pattern. Calculated radiation absorbed dose for skull lesions, determined by mean of MIRD methodology, was 63.5 mGy/MBq. The patient underwent surgical removal of the two major skull lesions. Successively, 100mCi 131I was administered after stimulation by rTSH, with stimulated sTg 297 ng/mL. After 8 months, diagnostic WBS was negative both for remnants and metastases and rTSH-stimulated Tg was 0.6 ng/mL. To date, the patient has maintained sTg values <1 ng/mL during L-T4 suppressive therapy and after rTSH stimulations. In this unusual case of extensive bone cancerous involvement with high iodine avidity, a multidisci-plinary approach based on surgery and dosimetry-guided radiometabolic therapy allowed to accurately assess the patient, execute a small number of treatments and achieve a complete remission of the disease in a very short time, with no additive morbidity (AU)

En este trabajo presentamos el abordaje adecuado de múltiples metástasis óseas de un cáncer diferenciado de tiroides. En 2007, una mujer de 75 años previamente remitida para tiroidectomía por bocio multinodular, se sometió a la extirpación quirúrgica de una masa lumbar con resultado histológico de metástasis de cáncer bien diferenciado de tiroides. Tras la cirugía, los niveles séricos de tiroglobulina (Tgs) fueron 204,4 ng/ml. Se realizó un rastreo de cuerpo completo diagnóstico/dosimétrico con 123 I después de la estimulación con rTSH. Se adquirieron rastreos seriados junto con SPECT/TC y gammagrafía ósea para la localización de las lesiones. Los niveles de Tgs se elevaron a 3810 ng/ml, y el rastreo de cuerpo completo con 123 I demostró captación en restos tiroideos y en numerosas localizaciones esqueléticas, las dos de mayor tamaño en la calota con un patrón osteolítico. La dosis absorbida calculada para las lesiones de calota, determinada mediante metodología MIRD, fue 63,5 mGy/MBq. Se extirparon mediante cirugía las 2 lesiones de la calota. Posteriormente, se administraron 100 mCi 131 I tras la estimulación con rTSH y unos niveles de Tgs 297 ng/ml. Después de 8 meses, el rastreo diagnóstico de cuerpo completo fue negativo tanto para los restos tiroideos como para las metástasis y la Tgs estimulada con rTSH fue 0,6 ng/ml. En la actualidad, la paciente ha mantenido valores de Tgs <1 ng/ml durante la terapia supresora con T4L y después de la estimulación con rTSH. En este caso poco habitual de extensa afectación metastásica ósea con elevada captación de radioiodo, una estrategia multidisciplinaria basada en cirugía y radioterapia metabólica según dosimetría permitió evaluar con precisión a la paciente, administrar un número pequen ̃o de tratamientos y alcanzar una remisión completa de la enfermedad en muy breve tiempo, sin originar morbilidad adicional (AU)

Disseminated bone metastases from occult thyroid cancer effectively treated with debulking surgery and a single dosimetry-guided administration of radioiodine.

In this paper we report on a successful management of multiple bone metastases from differentiated thyroid cancer. In 2007, a 75-year-old female patient, previously referred for thyroidectomy for multinodular goiter, underwent surgical removal of a lumbar mass with histological findings of metastasis from well differentiated thyroid cancer. After surgery, serum thyroglobulin (sTg) was 204.4 ng/mL. A diagnostic/dosimetric (123)I WBS was performed, following stimulation by rTSH. Serial WBSs were acquired, along with SPECT/CT and bone scan for localization of lesions. sTg raised to 3.810 ng/mL, and (123)I WBS showed thyroid remnants and numerous areas with high iodine-uptake corresponding to skeletal sites, the two largest loading on the skull, with osteolytic pattern. Calculated radiation absorbed dose for skull lesions, determined by mean of MIRD methodology, was 63.5 mGy/MBq. The patient underwent surgical removal of the two major skull lesions. Successively, 100 mCi (131)I was administered after stimulation by rTSH, with stimulated sTg 297 ng/mL. After 8 months, diagnostic WBS was negative both for remnants and metastases and rTSH-stimulated Tg was 0.6 ng/mL. To date, the patient has maintained sTg values <1 ng/mL during L-T4 suppressive therapy and after rTSH stimulations. In this unusual case of extensive bone cancerous involvement with high iodine avidity, a multidisciplinary approach based on surgery and dosimetry-guided radiometabolic therapy allowed to accurately assess the patient, execute a small number of treatments and achieve a complete remission of the disease in a very short time, with no additive morbidity.