Coefficient of Variation in Metastatic Lymph Nodes Determined by 18F-FDG PET/CT in Patients with Advanced NSCLC: Combination with Coefficient of Variation in Primary Tumors.

Purpose The aim of the present study was to test whether the coefficient of variation (CoV) of 18F-FDG PET/CT images of metastatic lymph nodes and primary tumors may predict clinical outcome in patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods Fifty-eight NSCLC patients who had undergone 18F-FDG PET/CT at diagnosis were evaluated. SUVmax, SUVmean, CoV, MTV and TLG were determined in targeted lymph nodes and corresponding primary tumors along with Total MTV (MTVTOT) and Whole-Body TLG (TLGWB) of all malignant lesions. Univariate analysis was performed using Cox proportional hazards regression whereas the Kaplan-Meier method and log-rank tests were used for survival analysis. Results Fifty-eight metastatic lymph nodes were analyzed and average values of SUVmax, SUVmean, CoV, MTV and TLG were 11.89 ± 8.54, 4.85 ± 1.90, 0.37 ± 0.16, 46.16 ± 99.59 mL and 256.84 ± 548.27 g, respectively, whereas in primary tumors they were 11.92 ± 6.21, 5.47 ± 2.34, 0.36 ± 0.14, 48.03 ± 64.45 mL and 285.21 ± 397.95 g, respectively. At univariate analysis, overall survival (OS) was predicted by SUVmax (p = 0.0363), SUVmean (p = 0.0200) and CoV (p = 0.0139) of targeted lymph nodes as well as by CoV of primary tumors (p = 0.0173), MTVTOT (p = 0.0007), TLGWB (p = 0.0129) and stage (p = 0.0122). Using Kaplan-Meier analysis, OS was significantly better in patients with CoV of targeted lymph nodes ≤ 0.29 than those with CoV > 0.29 (p = 0.0147), meanwhile patients with CoV of primary tumors > 0.38 had a better prognosis compared to those with CoV ≤ 0.38 (p = 0.0137). Finally, we combined the CoV values of targeted lymph nodes and primary tumors in all possible arrangements and a statistically significant difference was found among the four survival curves (p = 0.0133). In particular, patients with CoV of targeted lymph nodes ≤ 0.29 and CoV of primary tumors > 0.38 had the best prognosis. Conclusions The CoV of targeted lymph nodes combined with the CoV of primary tumors can predict prognosis of NSCLC patients.

Heterogeneity of Glycolytic Phenotype Determined by 18F-FDG PET/CT Using Coefficient of Variation in Patients with Advanced Non-Small Cell Lung Cancer.

We investigated the role of Coefficient of Variation (CoV), a first-order texture parameter derived from 18F-FDG PET/CT, in the prognosis of Non-Small Cell Lung Cancer (NSCLC) patients. Eighty-four patients with advanced NSCLC who underwent 18F-FDG PET/CT before therapy were retrospectively studied. SUVmax, SUVmean, CoV, total Metabolic Tumor Volume (MTVTOT) and whole-body Total Lesion Glycolysis (TLGWB) were determined by an automated contouring program (SUV threshold at 2.5). We analyzed 194 lesions: primary tumors (n = 84), regional (n = 48) and non-regional (n = 17) lymph nodes and metastases in liver (n = 9), bone (n = 23) and other sites (n = 13); average CoVs were 0.36 ± 0.13, 0.36 ± 0.14, 0.42 ± 0.18, 0.30 ± 0.14, 0.37 ± 0.17, 0.34 ± 0.13, respectively. No significant differences were found between the CoV values among the different lesion categories. Survival analysis included age, gender, histology, stage, MTVTOT, TLGWB and imaging parameters derived from primary tumors. At univariate analysis, CoV (p = 0.0184), MTVTOT (p = 0.0050), TLGWB (p = 0.0108) and stage (p = 0.0041) predicted Overall Survival (OS). At multivariate analysis, age, CoV, MTVTOT and stage were retained in the model (p = 0.0001). Patients with CoV > 0.38 had significantly better OS than those with CoV ≤ 0.38 (p = 0.0143). Patients with MTVTOT ≤ 89.5 mL had higher OS than those with MTVTOT > 89.5 mL (p = 0.0063). Combining CoV and MTVTOT, patients with CoV ≤ 0.38 and MTVTOT > 89.5 mL had the worst prognosis. CoV, by reflecting the heterogeneity of glycolytic phenotype, can predict clinical outcomes in NSCLC patients.

Type 2 Deiodinase Thr92Ala Polymorphism and Aging Are Associated with a Decreased Pituitary Sensitivity to Thyroid Hormone.

Background: The DIO2 Thr92Ala polymorphism (rs225014), which occurs in about 15-30% of Caucasian people, determines a less efficient type 2 deiodinase (D2) enzyme. The aim of this study was to determine the impact of DIO2 Thr92Ala polymorphism on the serum thyrotropin (TSH) levels in thyroidectomized patients with hypothyroidism and to evaluate whether TSH levels and aging could be related, at pituitary level, to D2 activity. Methods: This prospective study was performed on 145 thyroid cancer patients, treated with total thyroidectomy, and undergoing radioiodine treatment after 3 weeks of levothyroxine (LT4) withdrawal. A mouse model has been used to determine D2 protein and mRNA levels in pituitary during aging. Results: Genetic analysis identified DIO2 Thr92Ala polymorphism in 56% of participants: 64/145 (44%) patients were homozygous wild type (WT) (Thr/Thr), 64 (44%) heterozygous (Thr/Ala), and 17 (12%) homozygous mutant (Ala/Ala). A significant negative relationship was observed between aging and the rise in serum TSH levels during LT4 withdrawal. However, this negative correlation found in WT was reduced in heterozygous and lost in mutant homozygous patients (Thr/Thr r = -0.45, p = 0.0002, 95% confidence interval [CI] -0.63 to -0.23; Ala/Thr r = -0.39, p = 0.0012, CI -0.60 to -0.67; and Ala/Ala r = -0.30, p = 0.2347; CI -0.70 to 0.20). Accordingly, when we compared the TSH measured in each patient to its theoretical value predicted from age, the TSH did not reach its putative target in 47% of WT patients, in 70% of Ala/Thr, and 76% of Ala/Ala carrying patients (p = 0.0036). This difference was lost in individuals older than 60 years, suggesting a decline of D2 associated with aging. The hypothesis that the pituitary D2 decreases with age was confirmed by the evidence that D2 mRNA and protein levels were lower in pituitary from old versus young mice. Conclusion: An age-related decline in TSH production in response to hypothyroidism was correlated with decreased D2 levels in pituitary. The presence of DIO2 homozygous Ala/Ala polymorphism was associated with a reduced level of TSH secretion in response to hypothyroidism, indicating a decreased pituitary sensitivity to serum thyroxine variation (Institutional Research Ethics board approval number no. 433/21).

The unusual first sign of presentation of renal cell carcinoma: a rare case report.

Background: Renal cell carcinoma (RCC) usually is characterized by a slow pattern of growth, although with an unpredictable evolution and metastatic potential, favored by its extensive vascularity and related high angioinvasive profile. The most common sites of metastases from kidney cancer are lung, lymph nodes, bone and liver; whereas orbital metastases are very uncommon. In more than 25% of cases, orbital metastases are the first manifestation of a primary tumor of unknown origin. The clinical features of orbital metastases from kidney cancer are non-specific and could divert attention from the real problem. Case Description: In this article, we describe the case of a 72-year-old male patient reporting a painful mass on the right orbit, with exophthalmos and ptosis, as the first and unique signs of a previously undetected advanced RCC. Due to the clinical conditions, the patient underwent palliative radiation therapy delivered to the orbital lesion with the scope to relieve pain; subsequently started systemic therapy with pazopanib at the dose of 800 mg daily. Unfortunately, he did not achieve any benefit from systemic therapy, his conditions progressively worsened, and he finally passed away after four months of treatment due to rapid disease progression. Conclusions: Despite its rarity, differential diagnosis of an orbital lesion should always consider the possibility of metastasis from RCC, performing an appropriate radiological evaluation.

New Therapeutic Strategies in the Treatment of Stomal Recurrence After Total Laryngectomy: Role of Immunotherapy.

OBJECTIVE: The aim of this study was to investigate the incidence of stoma recurrence and the therapeutic strategy outcomes in relation to survival that have been adopted over the past few decades using a monoclonal antibody, specifically nivolumab. METHODS: This study included a total of 487 patients diagnosed with laryngeal carcinoma undergoing either a laryngectomy or salvage surgery after conservative interventions at the ENT Unit of Federico II University in Naples, Italy, between 2011 and 2021. Following a minimum 2.5-year follow-up and a maximum 21-year follow-up, the results revealed that only 38 patients suffered a stomal recurrence. RESULTS: Despite various adopted treatment strategies, the literature reports lower patient survival rates. Following a total laryngectomy, stomal recurrence represents a therapeutic management challenge due to a poor prognosis for nearly every treated case. According to the literature, in fact, despite a low incidence (ie, 0.8-31.3%), the overall mortality rate increases from 77% to 100% after three years. Nevertheless, introducing immunotherapy into cancer treatment has resulted in an observable revolution in the treatment of different types of cancers over the years. CONCLUSION: In light of recorded data on survival following the use of the nivolumab, the case presented in this study allows a new perspective of successfully treating recurrences of squamous carcinoma of the head and neck.

Impact of a cardio-oncology unit on prevention of cardiovascular events in cancer patients.

AIMS: As the world population grows older, the co-existence of cancer and cardiovascular comorbidities becomes more common, complicating management of these patients. Here, we describe the impact of a large Cardio-Oncology unit in Southern Italy, characterizing different types of patients and discussing challenges in therapeutic management of cardiovascular complications. METHODS AND RESULTS: We enrolled 231 consecutive patients referred to our Cardio-Oncology unit from January 2015 to February 2020. Three different types were identified, according to their chemotherapeutic statuses at first visit. Type 1 included patients naïve for oncological treatments, Type 2 patients already being treated with oncological treatments, and Type 3 patients who had already completed cancer treatments. Type 2 patients presented the highest incidence of cardiovascular events (46.2% vs. 12.3% in Type 1 and 17.9% in Type 3) and withdrawals from oncological treatments (5.1% vs. none in Type 1) during the observation period. Type 2 patients presented significantly worse 48 month-survival (32.1% vs. 16.7% in Type 1 and 17.9% in Type 3), and this was more evident when in the three groups we focused on patients with uncontrolled cardiovascular risk factors or overt cardiovascular disease at the first cardiologic assessment. Nevertheless, these patients showed the greatest benefit from our cardiovascular assessments, as witnessed by a small, but significant improvement in ejection fraction during follow-up (Type 2b: from 50 [20; 67] to 55 [35; 65]; P = 0.04). CONCLUSIONS: Patients who start oncological protocols without an accurate baseline cardiovascular evaluation are at major risk of developing cardiac complications due to antineoplastic treatments.

Impact of COVID-19 pandemic on 2-[18F]FDG PET/CT imaging work-flow in a single medical institution: comparison among the three Italian waves.

PURPOSE: To compare the impact of COVID-19 pandemic on 2-[18F]FDG PET/CT imaging work-flow during the three waves in a medical institution of southern of Italy. METHODS: We retrospectively reviewed the numbers and results of 2-[18F]FDG PET/CT studies acquired during the following three periods of the COVID-19 waves: 1) February 3-April 30, 2020; 2) October 15, 2020-January 15, 2021; and 3) January 18-April 16, 2021. RESULTS: A total of 861 PET/CT studies in 725 patients (388 men, mean age 64 ± 4 years) was acquired during the three waves of COVID-19 pandemic. The majority (94%) was performed for diagnosis/staging (n = 300) or follow-up (n = 512) of neoplastic diseases. The remaining 49 studies (6%) were acquired for non-oncological patients. The distribution of number and type of clinical indications for PET/CT studies in the three waves were comparable (p = 0.06). Conversely, the occurrence of patients positive for COVID-19 infection progressively increased (p < 0.0001) from the first to third wave; in particular, patients with COVID-19 had active infection before PET/CT study as confirmed by molecular oro/nasopharyngeal swab. CONCLUSION: Despite the restrictive medical measures for the emergency, the number of 2-[18F]FDG PET/CT studies was unchanged during the three waves guaranteeing the diagnostic performance of PET/CT imaging for oncological patients.

Combination of Lenvatinib and Pembrolizumab as Salvage Treatment for Paucicellular Variant of Anaplastic Thyroid Cancer: A Case Report.

Anaplastic thyroid cancer (ATC) is a rare but aggressive thyroid cancer, responsible for about 50% of all thyroid cancer-related deaths. During the last two decades, the development of a multimodal personalized approach resulted in an increased survival. Here, we present an unusual case of a 54-year old woman with a paucicellular metastatic ATC, a rare variant of ATC, who was treated with a combination of surgery, radiation therapy and cytotoxic chemotherapy. More than two years later, when the disease was rapidly growing, a combination of lenvatinib and pembrolizumab induced a partial tumor response of lung metastasis that persisted over 18 months. Paucicellular ATC may initially show a less aggressive behavior compared to other histological ATC variants. However, over the time, its clinical course can rapidly progress like common ATC. The combination of lenvatinib and pembrolizumab was effective as a salvage therapy for a long period of time.

Long-Term Outcomes in Uveal Melanoma After Ruthenium-106 Brachytherapy.

Uveal melanoma is the most common primary intraocular malignancy. The aim of this retrospective study was to report the results after ruthenium-106 (Ru-106) plaque brachytherapy for uveal melanoma in terms of tumor control, visual acuity, radiation-related complications, tumor recurrence, metastases, and patients' survival rate during 4 years' follow-up. A total of 355 eyes from 355 patients have been treated with Ru-106 plaque brachytherapy for uveal melanoma between February 2011 and March 2020. Five patients were lost to follow-up, and then 350 eyes of 350 patients (mean age 58 ± 11 years) were enrolled in this retrospective study. All patients underwent a complete ophthalmic examination including echography and spectral domain-optical coherence tomography. The mean follow-up was 4 years (3 months to 9 years). After treatment, the mean tumor thickness was reduced to 1.75 ± 0.21 mm. Radiation complications were found in 63% of patients: 38% showed radiation maculopathy, 11% had optic neuropathy, and 14% developed cataracts. Cancer-free survival was 99%, 97%, and 85%, respectively, at 5, 7, and 9 years. Ru-106 plaque brachytherapy represents a reliable treatment of uveal melanoma. This technique is valid and safe with a low rate of ocular complications during a long-term follow-up.

Brain Metastases Unresponsive to Immunotherapy Detected by 18F-FDG-PET/CT in a Patient with Melanoma.

Recently, newer therapies such as immunotherapy have been increasingly used in the treatment of several tumors, including advanced melanoma. In particular, several studies showed that the combination of ipilimumab, an anti-Cytotoxic T-lymphocyte Associated Protein 4 (CTLA-4) monoclonal antibody and nivolumab, an anti-Programmed Death 1 (PD-1) monoclonal antibody, leads to improved survival in patients with metastatic melanoma. Despite that, immunotherapeutic agents may not reach therapeutic concentration in the brain due to the blood-brain barrier. We report the case of a 50-year-old man with advanced melanoma who underwent whole-body 18F-FDG-PET/CT before and after treatment with immunotherapy showing resistant brain metastases confirmed by subsequent MRI of the brain. Moreover, 18F-FDG-PET/CT was able to detect an immune-related adverse event such as enterocolitis that contributed to the worsening of patient conditions. This case shows how a whole-body methodology such as 18F-FDG-PET/CT can be useful in identifying melanoma cancer patients unresponsive to immunotherapy that may benefit from traditional palliative therapy in the effort to improve their quality of life.

Total metabolic tumor volume by 18F-FDG PET/CT for the prediction of outcome in patients with non-small cell lung cancer.

OBJECTIVE: Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are imaging parameters derived from 18F-FDG PET/CT that have been proposed for risk stratification of cancer patients. The aim of our study was to test whether these whole-body volumetric imaging parameters may predict outcome in patients with non-small cell lung cancer (NSCLC). METHODS: Sixty-five patients (45 men, 20 women; mean age ± SD, 65 ± 12 years), with histologically proven NSCLC who had undergone 18F-FDG PET/CT scan before any therapy, were included in the study. Imaging parameters including SUVmax, SUVmean, total MTV (MTVTOT) and whole-body TLG (TLGWB) were determined. Univariate and multivariate analyses of clinical and imaging variables were performed using Cox proportional hazards regression. Survival analysis was performed using Kaplan-Meier method and log-rank tests. RESULTS: A total of 298 lesions were analyzed including 65 primary tumors, 114 metastatic lymph nodes and 119 distant metastases. MTVTOT and TLGWB could be determined in 276 lesions. Mean value of MTVTOT was 81.83 ml ± 14.63 ml (SE) whereas mean value of TLGWB was 459.88 g ± 77.02 g (SE). Univariate analysis showed that, among the variables tested, primary tumor diameter (p = 0.0470), MTV of primary tumor (p = 0.0299), stage (p < 0.0001), treatment (p < 0.0001), MTVTOT (p = 0.0003) and TLGWB (p = 0.0002) predicted progression-free survival in NSCLC patients, while age (p = 0.0550), MTV of primary tumor (p = 0.0375), stage (p < 0.0001), treatment (p < 0.0001), MTVTOT (p = 0.0001) and TLGWB (p = 0.0008) predicted overall survival. At multivariate analysis age, TLGWB and stage were retained in the model for prediction of progression-free survival (p < 0.0001), while age, MTVTOT and stage were retained in the model for prediction of overall survival (p < 0.0001). Survival analysis showed that patients with TLGWB ≤ 54.7 g had a significantly prolonged progression-free survival as compared to patients with TLGWB > 54.7 g (p < 0.0001). Moreover, overall survival was significantly better in patients showing a MTVTOT ≤ 9.5 ml as compared to those having MTVTOT > 9.5 ml (p < 0.0001). Similar results were obtained in a subgroup of 43 patients with advanced disease (stages III and IV). CONCLUSIONS: Whole-body PET-based volumetric imaging parameters are able to predict outcome in NSCLC patients.

Systemic treatment of malignant gastrointestinal neuroectodermal tumour after childhood neuroblastoma: chemotherapy in malignant gastrointestinal neuroectodermal tumour.

Malignant gastrointestinal neuroectodermal tumour is an extremely rare neoplasm that arises in the wall of the small bowel, stomach or large bowel in young-aged and middle-aged adults. Histologically, it is generally characterized by monomorphic cells with clear cytoplasma, S-100 protein expression, and EWSR1 gene translocation. To the best of our knowledge, we describe for the first time, the case of a young woman with a diagnosis of metastatic gastrointestinal neuroectodermal tumour arising from ileum, who had a childhood adrenal neuroblastoma with liver, bone and lymph nodes metastasis, treated with four cycles of chemotherapy with the schedule CADO-CVP (CADO: cyclophosphamide 300 mg/m/day on days 1-5, vincristine 1,5 mg/m/day on days 1 and 5, and doxorubicin 60 mg/m/day on day 5; CVP: cisplatin 40 mg/m/day on days 1-5 and etoposide 100 mg/m/day on days 1-5) followed by right adrenal, kidney, lymph nodes and liver lesion resection, conditioning chemotherapy (melphalan-carmustine-teniposide), stem cells autologous transplantation and consecutively radiotherapy on the spine (T9 to L3) for a total of 30 Gy. For the second diagnosis of gastrointestinal neuroectodermal tumour with liver metastasis, she underwent ileal tumour resection and platinum-anthracycline based chemotherapy with initial shrinkage of liver metastasis. Unfortunately, despite the initial response and the following delivered therapies, she died for rapid progressive disease. Taking into account the late effects of past therapeutic modalities, a long-term surveillance of young child treated for neuroblastoma, is required to appreciate their overall risks of second malignancies.

A case report of limbic encephalitis in a metastatic colon cancer patient during first-line bevacizumab-combined chemotherapy.

RATIONALE: Paraneoplastic limbic encephalitis (PLE) is one of the most common causes of neurologic paraneoplastic syndromes, with unclear pathogenesis. While several reports published in the last decades showed the occurrence of PLE in a variety of cancers, only a few cases have been associated with colon cancer. PATIENT CONCERNS: In February 2017, a 54-year-old man with clinical history of radically resected colon cancer started first line chemotherapy with FOLFOXIRI plus bevacizumab, after radiological diagnosis of multiple liver and bone metastases. During the third cycle of treatment, the patient developed psychomotor agitation and hallucinations followed by severe consciousness level reduction and cognitive impairment. DIAGNOSES: Magnetic resonance imaging showed hyperintense signals in both hippocampal areas, insula and right cingulate gyrus on fluid attenuated inversion recovery, diffusion weighted imaging, and T2-weighted images, highly suggestive of limbic encephalitis. Other causes (brain metastases, toxicity of chemotherapeutic agents, and infections) were excluded. INTERVENTIONS: Empirical immunosuppressive treatment (high-dose immunoglobulins and corticosteroids) was administered and chemotherapy was resumed. OUTCOMES: A slowly progressive improvement in neurological condition has been observed, even though radiological signs of limbic encephalitis are still evident. LESSONS: The present case highlights the complex diagnostic process of PLE, and the lack of a standard treatment. Moreover, the absence of correlation between PLE and tumor progression or tumor burden, and the opportunity of treating underlying neoplasm is discussed.

Preventing Venous Thromboembolism in Ambulatory Cancer Patients: The ONKOTEV Study.

BACKGROUND: The efficacy of risk model scores to predict venous thromboembolism (VTE) in ambulatory cancer patients is under investigation, aiming to stratify on an individual risk basis the subset of the cancer population that could mostly benefit from primary thromboprophylaxis. MATERIALS AND METHODS: We prospectively assessed 843 patients with active cancers, collecting clinical and laboratory data. We screened all the patients with a duplex ultrasound (B-mode imaging and Doppler waveform analysis) of the upper and lower limbs to evaluate the right incidence of VTE (both asymptomatic and symptomatic). The efficacy of the existing Khorana risk model in preventing VTE was also explored in our population. Several risk factors associated with VTE were analyzed, leading to the construction of a risk model. The Fine and Gray model was used to account for death as a competing risk in the derivation of the new model. RESULTS: The risk factors significantly associated with VTE at univariate analysis and further confirmed in the multivariate analysis, after bootstrap validation, were the presence of metastatic disease, the compression of vascular/lymphatic structures by tumor, a history of previous VTE, and a Khorana score >2. Time-dependent receiving operating characteristic (ROC) curve analysis showed a significant improvement in the area under the curve of the new score over the Khorana model at 3 months (71.9% vs. 57.9%, p = .001), 6 months (75.4% vs. 58.6%, p < .001), and 12 months (69.8% vs. 58.3%, p = .014). CONCLUSION: ONKOTEV score steps into history of cancer-related-VTE as a promising tool to drive the decision about primary prophylaxis in cancer outpatients. The validation represents the goal of the prospective ONKOTEV-2 study, endorsed and approved by the European Organization for Research and Treatment of Cancer Young Investigators Program. The Oncologist 2017;22:601-608 IMPLICATIONS FOR PRACTICE: Preventing venous thromboembolism in cancer outpatients with a risk model score will drive physicians' decision of starting thromboprophylaxis in high-risk patients.

Basaloid squamous cell carcinoma: a rare tumor at the esophagogastric junction and an unexpected durable complete response to FOLFOX-4.

BACKGROUND: Basaloid squamous cell carcinoma (BSCC) is a high-grade variant of squamous cell carcinoma usually localized in the aerodigestive tract, with a poor prognosis. Surgical resection is generally recommended, even if no standard treatment has been established yet. CASE REPORT: Here, we report the case history of a patient diagnosed with BSCC at the esophagogastric junction who was successfully treated with chemotherapy alone, leading to a durable complete response. CONCLUSIONS: The presented case illustrates the diagnostic challenges associated with BSCC of the esophagus and reports an unexpected chemosensitivity of this histotype to the combination of a platinum salt plus 5-fluorouracil, which could represent an optimal treatment strategy in unfit patients.

FOLFIRI in patients with locally advanced or metastatic pancreatic or biliary tract carcinoma: a monoinstitutional experience.

Pancreatic and biliary tract carcinomas are very chemoresistant. After a first-line treatment with a gemcitabine-based regimen, no second-line scheme is consolidated in clinical practice. The aim of this study was to evaluate the toxicity and the activity of the FOLFIRI regimen as first-line or second-line chemotherapy in patients with pancreatic or biliary tract tumors. Fifty-four patients (30 with pancreatic tumor, nine with gallbladder tumor, and 15 with biliary tract tumor) were treated with FOLFIRI (irinotecan 180 mg/m², day 1; leucovorin 100 mg/m² intravenously, days 1 and 2; 5-fluorouracil 400 mg/m² intravenous bolus, days 1 and 2; and 600 mg/m² in 22 h intravenously, continuous infusion days 1 and 2; every 14 days). Toxicity was recorded at each cycle according to the NCI-CTC V3.0 criteria, the response rate was verified each four cycles according to the RECIST criteria, and the progression-free survival rates as well as the overall survival rates were calculated according to the Kaplan-Meier method. Overall, the toxicity was mild. Grade 3-4 neutropenia occurred in 42.6% of patients. Grade 3-4 gastrointestinal toxicity was rare. FOLFIRI as a first-line treatment produced a response rate of 25%. In the second-line group, 9/21 patients (42.9%) obtained a stable disease as best response. In the entire population, the median progression-free survival rates were 3.1 months [95% confidence interval (CI), 1.9-4.4] and 3.5 months (95% CI, 2.6-4.4), respectively, in the first-line and the second-line cohort of patients. The median overall survival rates were 14.5 months (95% CI, 7.0-22.1) and 6.2 months (95% CI, 5.4-7.0), respectively, in the first-line and the second-line cohort of patients. FOLFIRI is feasible and well tolerated in patients with pancreatic or biliary tract tumors; it has a good activity in first line and mostly in patients with pancreatic cancer.

Non-AIDS-related Kaposi's sarcoma: A single-institution experience.

AIM: To evaluate the outcomes and potential prognostic factors in patients with non-acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma (KS). METHODS: Patients with histologically proven non-AIDS-related KS treated with systemic chemotherapy were included in this retrospective analysis. In some cases, the human herpes virus 8 status was assessed by immunohistochemistry. The patients were staged according to the Mediterranean KS staging system. A multivariable model was constructed using a forward stepwise selection procedure. A P value < 0.05 was considered statistically significant, and all tests were two-sided. RESULTS: Thirty-two cases were included in this analysis. The average age at diagnosis was 70 years, with a male/female ratio of approximately 2:1. Eighty-four percent of the cases had classic KS. All patients received systemic chemotherapy containing one of the following agents: vinca alkaloid, taxane, and pegylated liposomal doxorubicin. Ten patients (31.5%) experienced a partial response, and a complete response was achieved in four patients (12.4%) and stable disease in sixteen cases (50%). Two patients (6.2%) were refractory to the systemic treatment. The median progression-free survival (PFS) was 11.7 mo, whereas the median overall survival was 28.5 mo. At multivariate analysis, the presence of nodular lesions (vs macular lesions only) was significantly related to a lower PFS (hazard ratio: 3.09; 95%CI: 1.18-8.13, P = 0.0133). CONCLUSION: Non-AIDS-related KS appears mostly limited to the skin and is well-responsive to systemic therapies. Our data show that nodular lesions may be associated with a shorter PFS in patients receiving chemotherapy.

Tumor-to-tumor metastasis: breast cancer metastatic to thymic epithelial tumor.

Tumor-to-tumor metastasis is a rare phenomenon, with around 150 cases being reported in the literature. Breast cancer is the second most commonly reported donor tumor after lung cancer, but thymic epithelial tumors have never been reported as recipient tumors. Furthermore, the thymus is rarely affected by metastases. To our knowledge, the present report is the first case of breast cancer metastatic to thymic epithelial tumor.

EMPACT syndrome associated with phenobarbital.

Intracranial malignancies can be complicated by seizure activity, and anticonvulsants such as phenytoin are usually administered to prevent this neurological kind of complication. Cranial radiation therapy is instead the treatment of choice when the tumor is unresectable. Anyway, the combination of phenytoin and cranial radiation therapy can lead to a rare and severe mucocutaneous complication called EMPACT syndrome. It is composed of "erythema (E) multiforme (M) associated with phenytoin (P) and (A) cranial radiation (C) therapy (T)." Herein, we report 2 cases of EMPACT syndrome related to the use of phenobarbital instead of phenytoin as usually described in literature.