Lenvatinib is a multi-kinase inhibitor approved for patients with radioactive iodine (RAI)–resistant differentiated thyroid cancer (DTC). Before the drug approval from the Italian National Regulatory ...Agency, a compassionate use programme has been run in Italy. This retrospective study aimed to analyse data from the first series of patients treated with lenvatinib in Italy.
The primary aim was to assess the response rate (RR) and progression-free survival (PFS). Secondary end-points include overall survival (OS) and toxicity data.
From November 2014 to September 2016, 94 patients were treated in 16 Italian sites. Seventeen percent of patients had one or more comorbidities, hypertension being the most common (60%). Ninety-eight percent of patients were treated by surgery, followed by RAI in 98% of cases. Sixty-four percent of patients received a previous systemic treatment. Lenvatinib was started at 24 mg in 64 subjects. Partial response and stable disease were observed in 36% and in 41% of subjects, respectively; progression was recorded in 14% of patients. Drug-related side-effects were common; the most common were fatigue (13.6%) and hypertension (11.6%). Overall, median PFS and OS were 10.8 months (95% confidence interval CI, 7.7–12.6) and 23.8 months (95% CI, 19.7–25.0) respectively.
Lenvatinib is active and safe in unselected, RAI-refractory, progressive DTC patients in real-life setting. RR and PFS seem to be less favourable than those observed in the SELECT trial, likely due to a negative selection that included heavily pretreated patients or with poor performance status.
•Patients with metastatic differentiated thyroid cancer (DTC) have poor survival rate.•Lenvatinib improved clinical outcomes in patient with metastatic radioactive iodine-refractory DTC.•Lenvatinib is active and safe, even in a real-life patient population.•Older patients show survival benefit from lenvatinib, without safety concern.
Pheochromocytoma and paraganglioma (PPGL) have currently only limited treatment options available for patients in the metastatic phase (mPPGL) in either post-surgery or inoperable settings. However, ...these rare tumors overexpress somatostatin receptors and can thus be treated with peptide receptor radionuclide therapy (PRRT). We present data about our 10-year experience treating 46 consecutive mPPGL patients with 90Y-DOTATOC or 177Lu-DOTATATE.
All patients (20 men and 26 women, median age 52 years) showed positive scintigraphic imaging at 111In-octreotide or 68Ga-DOTATOC positron emission tomography/computed tomography (PET/CT). 90Y-DOTATOC was administered in 12 patients, with cumulative dosages ranging from 7.4 to 11 GBq, while 34 patients received 18.5 or 27.5GBq of 177Lu-DOTATATE. We used Southwest Oncology Group Response Evaluation Criteria in Solid Tumors criteria to evaluate treatment efficacy and Common Terminology Criteria for Adverse Events criteria to assess toxicity. The prognostic role of primary tumor site, hormone secretion, succinate dehydrogenase (SDHx) mutation, and metastatic involvement was also evaluated.
Both 90Y-DOTATOC and 177Lu-DOTATATE PRRT were well tolerated by patients without significant renal or bone marrow toxicity. The median follow-up was 73 months (range 5-146 months). The overall disease control rate (DCR) was 80% 95% confidence interval (CI) 68.9% to 91.9% with a mean five cycles of therapy. However, 177Lu-DOTATATE patients showed a longer median overall survival (mOS) than those receiving 90Y-Dotatoc and a better DCR when higher dosages were administered, even if a direct comparison was not carried out. Syndromic patients had a poorer mOS. SDHx mutations did not interfere with treatment efficacy.
PRRT is safe and effective for the treatment of patients with progressive mPPGL, especially at higher dosages. The longer mOS of 177Lu-DOTATATE-treated patients in our protocols indicates the former radiopharmaceutical as the better candidate for further clinical application.
•PPGLs are rare tumors with limited therapeutic options.•PRRT could be an optimal candidate to treat these rare tumors.•mPPGL patients treated with 90Y- or 177LU-PRRT obtained high median progression-free survival and mOS in a long follow-up.•The safety profile is consistent with previous data on PRRT.
Advanced biliary tract cancers have a poor prognosis. Gemcitabine (G) as a single agent or in combination represents an active treatment option. Systemic chemotherapy in hepatocellular carcinoma ...represents a palliative treatment. Gemcitabine in combination with Liposomal Doxorubicin (LD) may represent an active treatment option.
Clinical trials for biliary and hepatic carcinoma have been reviewed.
We obtained RC (1 pt), RP (4 pts), SD (8 pts) and seven pts had PD (RR 25% and SD 40%). Our chemotherapy regimen was Gemcitabine 1000 mg/m2 d 1 and 8, Liposomal Doxorubicin 30 mg d 1, q 28. Patients were 21 (17 M), aged 44 to 78 (median 63 yrs). Only in 8 pts we observed G 3–4 haematological toxicity, thrombocytopenia and neutropenia (7 G3, 1 G4).
Paragangliomas (PGLs) are neuroendocrine tum-ors that arise embryologically from the neural crest. Sympathetic PGLs can be located in the thoracic-abdominal region while parasympathetic PGLs are ...mainly situated in the head and neck region. Most PGLs are sporadic, but in 30% of cases they are hereditary (associated with mutations of SDHB, SDHC, SDHD, SDHAF2, SDHA, TMEM, MAX, and VHL); they can be classified into 4 different paraganglioma syndromes: PGL1, PGL2, PGL3, and PGL4. Surgery is the treatment of choice for both sympathetic and parasympathetic PGLs. Other types of treatment include medical agents (such as gemcitabine, cisplatin, or sunitinib) and radiotherapy (external-beam radiotherapy or stereotactic surgery). Surgery and radiotherapy, however, can cause important side effects such as vascular complications and peripheral nerve damage (hypoglossal, recurrent laryngeal, glossopharyngeal, and vagus). Another possible treatment option is the use of peptide receptor radionuclide therapy (PRRT), including PRRT with 177Lu-DOTATATE. We studied 4 patients with hereditary nonmetastatic paraganglioma syndrome type 1 (PGL1), with progressive disease, in whom surgical excision was not possible. They were treated with 177Lu-DOTATATE (3-5 cycles) and all had a partial response (PR) or a stable disease (SD) to the treatment. In conclusion, a good alternative treatment when surgical or radiation therapy are contraindicated could be radiometabolic therapy with 177Lu-DOTATATE.
Abstract
Background: There are several options for cancer reduction in women with a BRCA 1-2 mutation, including prophylactic surgery, chemo-prevention and close surveillance. Each of these measures ...offers varying levels of effectiveness with prophylactic mastectomy (PM) and oophorectomy (PO) providing the greatest risk reduction for the development of breast and ovarian cancer. The uptake of preventive procedures, however, differs according to country, not only in relation to access to care, but also cultural preferences. Here we present data on the experience of the Hereditary Cancer Center at the Istituto Oncologico Veneto, which is one of the few centers in Northern Italy to offer not only genetic testing, but also long-term follow-up to healthy carriers of the BRCA 1-2 genes. Methods: 106 healthy women were identified within a cohort of BRCA positive individuals followed since 2008. Upon learning of their BRCA mutation carrier status, they all agreed to enroll in a long-term protocol of close-surveillance. All women were also informed about risk-reducing surgery such as PO and PM. Results: The age in this sample ranged between 20 and 77 years with a median of 41.5. The average follow-up time was 4.3 +/-2.4 years. We observed that PO was more commonly accepted (41% 44/106) than PM (11% 12/106). The mean age at the time of PO was 47.3. In the PM group, half of the women decided to undergo such procedure only after being diagnosed with breast cancer. The mean age at the time of PM in the healthy subjects was 41.8 years.
Over the follow-up period, 9.4% of the patients (10/106) developed BRCA related malignancies, of which 9 breast and 1 ovarian cancer. Of the 9 breast events, 2 were diagnosed at stage 0, 2 at stage I, 3 at stage II, and 2 at stage III. All cancer cells were aggressive (grade 3). Of the 2 stage III breast tumors, 1 was diagnosed on the very 1st breast MRI screening, and the other after an interval of 3 years due to the patient being pregnant and then breastfeeding. The 3 cases of stage II breast cancer, despite being 1 cm or less in size, already had node involvement. Both stage III breast tumors were triple negative in BRCA 1 carriers. The other breast cancers were ER+ and none was Her2+. Of the ER+ breast events 4 occurred in BRCA2 and 2 in BRCA1 carriers. Except for the 2 Stage 0 tumors, which arose in women who had a previous oophorectomy, all the other breast malignancies developed in carriers who still had their ovaries and were premenopausal. The one serous ovarian cancer was diagnosed at Stage II in a 77 years-old BRCA1+ woman.
Conclusions: In this sample of healthy northern Italian women carriers of BRCA mutations, close to 10% developed a tumor within 5 years of follow-up with an aggressive cell phenotype. The more accepted method of risk-reduction in this group of women was PO as compared to PM. A protocol of close-surveillance allows for an early stage diagnosis in about half of the women who develop a breast tumor.
Citation Format: Rastelli A, Azzolin F, Tognazzo S, Alducci E, Zovato S. Uptake of risk reducing measures in healthy BRCA 1-2 mutation carriers from Northern Italy: Outcomes of 9 years of close-surveillance. Experience of the hereditary cancer clinic in the region of Veneto, Italy abstract. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-10-07.
Von Hippel-Lindau disease is a rare autosomal dominant inherited disorder that predisposes the occurrence of cysts and various types of cancers such as hemangioblastoma, pheochromocytoma, renal cell ...carcinoma and more rarely pancreatic tumors. In this review, we analyze the characteristics and management of pancreatic lesions, in particular cysts and neuroendocrine tumors, in Von Hippel-Lindau disease.
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