Tumori Journal

Cytology smears can be effectively used for EGFR mutation testing in the qualification of NSCLC patients for EGFR tyrosine kinase inhibitor therapy. However, tissue specimens are preferred for EGFR mutation analysis. The aim of this study was to estimate the effectiveness of the real-time PCR method for EGFR testing in histology and cytology materials obtained simultaneously from NSCLC patients.

Fourteen adenocarcinoma patients with EGFR–mutation-positive primary tumor tissues were included in the study. Corresponding cytological smears of metastatic lymph nodes obtained by EBUS-TBNA were examined. EGFR Mutation Analysis Kit (EntroGen, USA) and real-time PCR (m2000rt system, Abbott, USA) were used for EGFR mutation analysis in both types of material.

In primary tumor tissues, 12 deletions in exon 19 and 2 substitutions in exon 21 (L858R mutation) of the EGFR gene were found. Except for 1 deletion in exon 19, the same EGFR gene mutations were detected in all corresponding cytology samples. The percentage of tumor cells, DNA concentration, percentage of mutated DNA as well as ΔCt values were similar in cytology slides and histology material. In both types of materials, no significant correlations were found between the percentage of tumor cells and the percentage of mutated DNA nor between the DNA concentration and the percentage of mutated DNA.

We demonstrated the high effectiveness of a sensitive real-time PCR method in EGFR gene mutation detection in cytology smears.

Delayed chemotherapy-induced nausea and vomiting (CINV) continues to be a problem in patients undergoing a hematopoietic cell transplant (HCT) despite progress in antiemetic prophylaxis. This study investigated the clinical course of nausea and vomiting (NV) and retching over the 5 days following an autologous HCT in a transplant setting.

This longitudinal observational study was an exploratory analysis of data from a trial that assessed the efficacy of aroma in preventing NV related to dimethyl sulfoxide in 69 autologous HCT patients undergoing highly emetogenic chemotherapy (HEC; n = 56) or moderately emetogenic chemotherapy (MEC; n = 13).

Nausea started to increase on the second day after reinfusion, with a peak between 72 and 96 hours, and decreased on the fifth day. The pattern for vomiting was similar, while retching episodes remained unchanged after the third day following transplant. Nausea and emesis were observed in 73% (n = 41) and 64% (n = 36) of HEC patients, respectively, and in 85% (n = 11) and 62% (n = 8) of MEC patients, respectively.

Uncontrolled delayed CINV is still a challenge for autologous HCT patients. Nausea, vomiting and retching are 3 different symptoms that should be assessed and managed separately in routine clinical practice.

Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of hematologic malignancies frequently presenting at advanced stage of diagnosis.

We report a case of PTCL with an uncommon and aggressive onset with disseminated intravascular coagulation (DIC).

Laboratory findings revealed an aberrant expression of β subunit of human chorionic gonadotropin (β-HCG). Other than for determination of pregnancy, β-HCG is regularly found as a tumor marker in germ cell tumors with trophoblastic differentiation and its aberrant expression has been reported in the literature in other neoplastic conditions only in the context of case reports.

In hematologic malignancies, β-HCG expression has been described only in sporadic cases. Awareness of this feature could avoid diagnostic delay in such an aggressive disease.

Fibro-osseous lesions of the skull and facial bones are benign tumors, but they can be mistaken for malignant tumors due to their clinically aggressive behavior. Cemento-ossifying fibroma (COF) is a benign fibro-osseous lesion characterized by slow growth and fibrous and calcified tissue content. COFs are locally destructive lesions causing deformities in the bones. The recurrence risk is high if they are not completely removed.

In this case report we describe a giant COF mimicking chondrosarcoma in the oral cavity of a 55-year-old woman causing significant facial deformity and feeding problems.

Giant COF occurs rarely in the jaws and given that this lesion has similar imaging and clinical features to several other tumors, the diagnosis is always a challenge for clinicians, radiologists and pathologists.

Neurofibromatosis type 2 (NF2) is a dominantly inherited genetic condition that clinically manifests through the appearance of multiple meningiomas, ependymomas and bilateral vestibular schwannomas (acoustic neuromas) which lead to progressive hearing loss. Neovascularization is necessary for tumor growth and is driven by tumor-produced angiogenic factors such as vascular endothelial growth factor (VEGF). Bevacizumab is a humanized monoclonal antibody that neutralizes the activity of VEGF. Recent data have shown that VEGF is produced by schwannoma tumor cells. Bevacizumab treatment in patients with NF2 who were considered poor candidates for surgery and radiation therapy was found to result in clinically meaningful hearing improvement and tumor volume reduction in previous studies.

We report the case of a 40-year-old woman with sudden right-sided hearing loss. Magnetic resonance imaging (MRI) revealed multiple meningiomas and neurinomas (C2 and L5 lesions) and a right-sided acoustic neurinoma, confirming the diagnosis of NF2. Bevacizumab was given as infusion every 2 weeks at a dose of 5.0 mg/kg body weight with MRI monitoring every 6 months.

After 6 months from the start of therapy the patient reported progressive improvement of hearing response in audiometry, word recognition and face-to-face conversation. MRI evidenced reduction of the volume of the right vestibular schwannoma and the multiple meningiomas as well as attenuation of brain stem compression.

At the time of writing the patient is continuing treatment with bevacizumab without adverse events. She has good functional status and quality of life.

Human epidermal receptor (HER) family receptors are commonly overexpressed in various human tumors, and their overexpression is thought to play a critical role in tumor progression. The aim of this meta-analysis was to evaluate the prognostic significance of HER family members in epithelial ovarian cancer (EOC).

Relevant studies published between January 1, 1980, and April 24, 2013, that evaluated the associations of HER family members with overall survival (OS), progression-free survival (PFS), response to platinum-based chemotherapy, lymph node metastasis, or ascites in EOC were identified via searches of PubMed and EMBASE.

We identified 37 eligible articles that met the inclusion criteria. The results of the meta-analysis revealed that significantly poorer OS of patients with EOC was predicted by high Her-2 expression levels (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.31-2.19). Furthermore, high Her-2 expression was significantly associated with poor PFS (HR 1.88, 95% CI 1.46-2.41) and an increased risk of ascites (risk ratio 1.21, 95% CI 1.02-1.42).

High levels of expression of Her-2 are significantly related to poor survival and an increased risk of ascites in patients with EOC. Future prospective cohorts with larger samples are needed to verify the prognostic value of Her-2 expression in EOC.

To assess the contribution of radiation oncologists in Italy in current management of breakthrough pain (BtP).

In 2012, the Palliative and Supportive Care Study Group of the Italian Association of Radiation Oncology (AIRO) proposed a survey. All Italian radiation oncologists were individually invited to complete an online questionnaire regarding their management of BtP in patients undergoing radiotherapy treatment.

A total of 303 Italian radiation oncologists (of 330 who had access to the Web site) completed the questionnaire over an 8-month period. Some important differences were shown in pain intensity assessment by validated measurement scales, as well as in setting and prescribing analgesic therapy to prevent procedural pain. These differences were also reviewed and discussed related to international guidelines and data available from the literature.

Compared to other medical professionals, the involvement of radiation oncologists in cancer pain management remains marginal, at least in Italy. More than 70% of radiation oncologists directly optimized the analgesic therapy during the treatment course and more than 50% implemented specific treatment for BtP. However, the ability of the radiation oncologist to manage BtP could be improved. In order to increase the consciousness of systematic symptom measurement and to spread the knowledge of the best type of analgesic drugs to be used, training events promoted by national associations, such as AIRO, and a collaborative multidisciplinary approach of the management of cancer pain will be promoted.

To evaluate clinical results in elderly and frail patients with bladder cancer treated with curative conformal irradiation alone.

The records of ambulatory frail elderly patients, age >80 years, Charlson Comorbidity Index (CCI) >5, with invasive bladder cancer, were retrospectively analyzed. The patients were irradiated with curative intent. Acute and late toxicities were evaluated.

A total of 27 ambulatory patients were treated. Median age was 84.5 years and a median CCI of 6.5 was recorded. Median delivered radiation dose was 64 Gy. All patients completed the planned treatment. Grade 1-2 gastrointestinal (GI) and genitourinary (GU) toxicities were observed in 55.5% of patients (15/27). At the last follow-up, no late G3+ toxicities have been observed, with G1-2 toxicities reported in 11.1% of patients (3/27). Higher values of CCI were associated with higher acute GU/GI toxicities; there was a correlation between CCI and acute GU toxicity (r = 0.43, p = 0.027). The mean survival time was 23.5 months (95% confidence interval 20.9-26.1) and no median was reached. Locoregional disease-free events and metastasis-free survival showed a 2-year actuarial rate of 90% and 87%, respectively, with an actuarial 2-year overall survival of 84.5%.

Our results demonstrate safety and feasibility of curative radiation therapy in very elderly and frail patients with bladder cancer using 3D conformal radiation therapy.

This retrospective analysis evaluated the outcome of patients with spinal bone metastases of renal cell cancer after radiotherapy (RT) in terms of stability and survival, using a validated scoring system for spinal stability assessment.

The survival rates of 155 patients with bone metastases of renal cancer treated from January 2000 to January 2012 were determined. The stability of irradiated osteolytic lesions of the thoracic and lumbar spine was evaluated retrospectively using the Taneichi score and analyzed for predictive factors. The effects of therapy in terms of changes in neurological signs and tumor-related pain were recorded.

Follow-up with regular computed tomography (CT) was available for 28 patients, 14 with unstable metastases. One hundred thiry-two patients (85%) died during follow-up. RT could not improve the stability of vertebral bodies after 3 and 6 months. Consequently, none of the examined predictive factors such as age, number of bone metastases and systemic therapy showed a significant correlation with stability 6 months after RT. The median survival of all 155 patients after diagnosis of bone metastases was 12.9 months. Improvement of pain and neurological deficits occurred in 60%, and in 24% of the respective affected in all patients.

RT was unable to improve the stability of vertebral metastases, probably due to the short overall survival, which resulted in an insufficient number of patients with evaluable follow-up. RT allowed reduction of pain and neurological deficits. A short fractionation schedule may be preferred in this situation.

Cancer is a disease that has far-reaching consequences for patients and their families. The present study targets unmet caregiver needs so that better support can be provided and planned for.

The first phase of the study was to conduct a survey designed to explore basic needs (medical and nursing information, psychological support, social welfare). The survey also investigated the caregiver's personal details (age, sex, degree of kinship). The survey was distributed to caregivers coming to the day hospitals of the 4 oncology departments involved in the study.

A total of 137 relatives of cancer patients completed the survey. Among the explored needs, the most recurrent was the availability of a doctor who provides full information on the treatment choices. A further important request was for consistency between the information provided by doctors and that provided by other health-care workers, with specific reference to a patient-centered approach that can be easily and fully understood, available therapeutic options especially at home, and prognosis.

The study showed that the need for exhaustive and simple information provided by a referral physician is still an unmet need in the Internet age.

Adolescent patients with cancer need psychological support in order to face the traumatic event of cancer diagnosis and to preserve continuity with their normal lives. Creative projects or laboratories may help young patients express their thoughts and feelings.

The Youth Project developed activities dedicated to adolescents to give them a chance to vent their creative spirit and express themselves freely. In the first project, the teenagers designed their own fashion collection in all its various stages under the artistic direction of a well-known fashion designer, creating their own brand name (B.Live), and organized a fashion show.

In all, 24 patients from 15 to 20 years old took part in the project. The fashion project proved a fundamental resource in helping the young patients involved to regain a positive self-image and the feeling that they could take action, both on themselves and in their relations with others.

Facilitating the experience of beauty may enable hope to withstand the anguish caused by disease. This experience integrated the usual forms of psychological support to offer patients a form of expression and support during the course of their treatment.

This study aimed to analyze the dose distribution using different dosimetric tools in conducting pretreatment quality assurance for lung cancer stereotactic body radiation therapy (SBRT) plans with flattening filter free (FFF) beams.

Nine patients with lung cancer treated via SBRT were randomly selected, and their treatment plans were generated using the Eclipse treatment planning system (TPS) with FFF beams. For each patient, the same plan was applied to the Delta4 phantom and MatriXX by the TPS, which calculated the dose distribution. The Delta4 and MatriXX phantoms were then used to measure the actual dose distribution at the linear accelerator, and these measured doses were compared to with the calculated doses. Gamma analysis was employed in verifying the correspondence between the dose distributions. The absolute point doses were measured by a 0.016 mL Microchamber with the RW3 phantom and Thorax phantom.

The absolute point doses measured by the 0.016 mL Microchamber were within ±3% of the calculated results for the central point of the RW3 and Thorax phantoms. The Delta4 and MatriXX dose distributions agreed well with the measured and calculated doses, over 98%, based on the 3% maximum dose and 3 mm gamma criteria.

Both measured and calculated doses for the Delta4 and MatriXX phantoms agreed well for each patient with lung cancer. The absolute point dose measurements using the 0.016 mL Microchamber exhibited excellent agreement with the TPS calculated between the RW3 and Thorax phantoms.

Dendritic cells (DCs) play a pivotal role in regulating CD8⁺ cytotoxic T-lymphocyte (CTL) responses. Currently, DC vaccines have been used in experimental animal models and clinical trials for evaluation of antitumor immunity. However, their efficacy is limited, warranting the improvement of DC-based cancer vaccines. CD40 ligand (CD40L) stimulates DC activation and maturation via CD40-CD40L interaction. We demonstrated that DCs that had phagocytized apoptotic tumor cells induced antitumor immunity.

We generated CD40L-expressing (EG7-CD40L) and the control (EG7-Null) EG7 tumor cells by transfection of EG7 tumor cells with CD40L-expressing adenoviral vector AdVCD40L and the control vector AdV_pLpA, respectively. We also generated DC vaccines (DC-EG7/CD40L and the control DC-EG7/Null) using DCs with phagocytosis of irradiated EG7-CD40L and EG7-Null tumor cells, and assessed their phenotype and immunogenicity by flow cytometry and animal studies in C57BL/6 mice.

We demonstrate that an irradiation of 9000-rad induced Annexin V-expressing cell apoptosis in most (~75%) tumor cells, and provide evidence for phagocytosis of apoptotic tumor cells by flow cytometry and confocal microscopy. The DC-EG7/CD40L cells showed higher expression of DC maturation markers (Ia^b, CD40, CD80, and CD86) and peptide/major histocompatibility complex I than the control DC-EG7/Null cells. In addition, DC-EG7/CD40L vaccine stimulates more efficient (0.97%) tumor-specific CTL responses than DC-EG7/Null cells (0.31%). Furthermore, 80% (4/5) of mice immunized with DC-EG7/CD40L vaccine become tumor-free after EG7 tumor cell challenge, whereas DC-EG7/Null vaccine only delays immunized mouse death.

Dendritic cells that have phagocytized CD40L-expressing apoptotic tumor cells appear to offer new strategies in DC cancer vaccines.

To evaluate postoperative pain (PoP) and quality of life (QoL) in patients undergoing open (O-) or laparoscopic (L-) retroperitoneal lymph node dissection (RPLND) for clinical stage I (CS I) and normal markers CS IIA nonseminomatous germ cell tumors.

Since March 2010, a prospective nonrandomized trial evaluated dynamic and rest (R) numeric pain scale (NPS) following patient-controlled analgesia and baseline (T0), 3-month (T3), and 6-month (T6) QoL status assessed by Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire and the Italian-validated Functional Assessment of Chronic Illness Therapy (FACT-T-SG) at T6. Secondary endpoints included length of hospital stay (LHS), interval to recovery (ItR), complications, and oncologic outcomes.

In March 2012, 69 (64 CS I) patients were enrolled. Five patients only chose O-RPLND. The PoP and complete QoL data are available in 41 and 56 patients, respectively. The R-NPS significantly improved in days 1-2 vs day 0 (p<0.0008). The FACT-G scores improved from baseline: the emotional well-being scale was the most relevant at T3 (+7.0, p = 0.0001) and T6 (+6.9, p = 0.0002). The FACT-TS-G indicated high satisfaction levels. Median LHS and ItR were 3 and 15 days. Six complications required an intervention. Nodal metastases were found in 14 (20.3%) patients. Following a median follow-up of 36 months, 6 (8.9%) patients relapsed (2/12 among pN+), and 8 patients (11.9%) underwent chemotherapy. All patients maintained antegrade ejaculation and are alive and disease-free.

Almost all patients chose L-RPLND, which is associated with a rapid improvement of postoperative pain; QoL scores improved up to 6 months. The L-RPLND may be considered as an alternative only when performed in highly experienced centers.

The aims of this paper are to compute the risks of dying of ischemic heart disease (IHD), lung cancer (LC), stroke, and chronic obstructive pulmonary disease (COPD) for Italian smokers by gender, age and daily number of cigarettes smoked, and to estimate the benefit of stopping smoking in terms of risk reduction.

Life tables by sex and smoking status were computed for each smoking-related disease based on Italian smoking data, and risk charts with 10-year probabilities of death were computed for never, current and former smokers.

Men aged 45-49 years, current smokers, have a 8, 10, 3 and 1 in 1,000 chance of dying of IHD, LC, stroke and COPD, respectively, whereas women with the same characteristics have a 2, 6, 3 and 1 in 1,000 chance, respectively, for all smokers combined, i.e., independent of the smoking intensity. The risk reduction rates from quitting smoking are remarkable: a man who quits smoking at 45-49 years can reduce the risk of dying of IHD, LC, stroke and COPD in the next 10 years by 43%, 53%, 57% and 55%, respectively; a woman by 49%, 49%, 59% and 57%, respectively.

Estimates of risk reduction by quitting smoking are useful to provide a sounder scientific basis for public health messages and clinical advice.

To update cancer mortality statistics in Italy, analyzing 1980-2010 trends, and to predict 2015 mortality rates.

World Health Organization cancer mortality and census data were extracted to calculate death rates for 30 cancer sites from 1980 to 2010. Trends were analyzed with joinpoint regression and predicted 2015 deaths rates were computed.

In 2010 in Italy, there were 175,046 cancer deaths (98,847 men and 76,199 women), with total mortality rates, respectively, of 138.22 and 82.6/100,000. The leading cause of cancer death in men was lung cancer (25,457 deaths, 36.2/100,000), whereas in women it was breast cancer (12,115 deaths, 15.38/100,000). Total cancer mortality in men has been decreasing since the late 1980s, with an estimated annual percentage change (EAPC) of −1.8 in 1994-2010. In women, total cancer mortality rates decreased throughout the study period, with an EAPC of −1.1 in 1992-2010. Trends in mortality were decreasing for most cancers in both sexes. Only pancreatic and lung cancer trends in women were unfavorable. Total numbers of predicted cancer deaths in Italy for 2015 increased to 102,647 men and 82,047 women; however, the predicted rates decreased in men (129.1/100,000), while remaining stable in women (82.6/100,000).

Mortality rates for the most common cancers in Italy showed favorable trends that are likely to continue in the near future, with the exception of lung cancer mortality in women. Maintaining these trends requires continuous and improved control of tobacco, alcohol, and nutrition/overweight. Further improvements in diagnosis and treatment may also have a significant impact on cancer mortality.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy exhibiting a strong geographic preference and a close association with Epstein-Barr virus (EBV). The aim of this study was to investigate the precise mechanism of nasopharyngeal epithelial-to-NPC tumorigenesis and to identify possible biomarkers and targets for therapy.

Proteomic analysis was performed on the immortalized nasopharyngeal epithelial cell line NP69 and the NPC cell line C666.

A comparative analysis of total lysates from the cell lines using 2-D gel electrophoresis–mass spectrometry resulted in the identification of 87 different protein spots. The different proteins were grouped into 5 main categories: (i) energy production and general metabolism, (ii) adaptation/stress tolerance, (iii) cell proliferation, (iv) cell structure and (v) epithelial-mesenchymal transition. The detection of metabolism-related proteins indicated that the NPC cells relied on aerobic glycolysis, with reduced use of the citric acid cycle. Glucose uptake and lactate secretion increased in the medium of C666 compared with NP69.

The present study revealed that glycolysis was up-regulated in the NPC cell lines compared with nasopharyngeal epithelial cells. A number of molecules involved in metabolism were identified, and further investigations will be needed to validate these potential biomarkers or targets.

Recent clinical reports of stereotactic ablative radiotherapy (SABR) in the treatment of low-risk prostate cancer have been encouraging. Our study evaluates the efficacy and safety of SABR using the CyberKnife system for treating intermediate- to very-high-risk prostate cancer.

Between May 2010 and June 2013, 31 patients (15 intermediate risk, 14 high risk, and 2 very high risk) without pelvic lymph node metastasis were enrolled retrospectively. The treatment consisted of 37.5 Gy in 5 fractions over 1-2 weeks using CyberKnife SABR. Twenty-five patients (81%) received androgen deprivation therapy (ADT). Biochemical failure was defined using the nadir + 2 criterion. Toxicity was assessed with the Common Terminology Criteria of Adverse Events (version 4).

The median follow-up was 36 months (range 7-58 months). The median pretreatment prostate-­pecific antigen (PSA) was 13.5 ng/mL (range 4.5-124.0 ng/mL). The median PSA decreased to 0.09 ng/mL (range <0.04-5.38 ng/mL) and 0.12 ng/mL (range <0.04-2.63 ng/mL) at 6 months and 12 months after SABR, respectively. The 3-year biochemical relapse-free survival was 90.2% for all patients, 100% for the intermediate-risk patients, and 82% for the high- and very-high-risk patients (p = 0.186). No patient experienced ≥ grade 3 toxicity. There were 7 acute and 5 late grade 2 genitourinary toxicities and 1 acute and no late grade 2 gastrointestinal toxicity.

Our preliminary results support that CyberKnife SABR with ADT is safe and feasible in patients with intermediate- to high-risk prostate cancer. A further large-scale clinical trial with longer follow-up is warranted.

There is a paucity of data regarding the incidence, intensity, and treatment of nausea and vomiting during the intercycle periods of chemotherapy (CHT). The aims of the study were to assess the incidence and intensity of intercycle nausea and vomiting, to assess the use of rescue antiemetic medications, and to define the more uncomfortable symptom between nausea and vomiting.

In a prospective study, 108 chemotherapy-naive patients treated with highly or moderately emetogenic CHT for different primary cancers were enrolled. All patients filled out the Edmonton Symptom Assessment System tool before the first cycle of CHT (T0) and on 14-16 days thereafter for the first 3 cycles of CHT (i.e., T1, T2, T3).

Sixty-seven patients completed the study. During CHT administration, all patients received antiemetics according to international guidelines. During the intercycle periods, nausea was reported in 6.0% of patients at T0, 10.5% at T1, and 26.9% at T2 and T3, respectively. The intensity of nausea was mild for 6.0%, 21%, and 18% of patients at T1, T2, and T3, respectively; moderate for 1.5%, 3.0%, and 6.0% at T1 to T3; and severe in only 3.0% of patients at any time. Vomiting was present in 1.5% and 10.5% of patients at T2 and T3. Rescue antiemetic medication was required for 41.8% at T1, 53% at T2, and 47.8% at T3. At the end of the study, 70.1% of patients described nausea as the more uncomfortable symptom compared to vomiting.

Nausea has a higher burden of impact over vomiting and should be assessed and treated separately throughout multiple cycles of CHT.

To investigate whether positive peritoneal cytology (PPC) has an effect on expected survival in endometrial cancer and to present factors that affect PPC occurrence.

Patient chart information of 224 patients who had been treated at the Ankara Oncology Education and Research Hospital due to endometrial cancer between 1996 and 2006 were retrospectively reviewed. Factors that were likely to have an effect on peritoneal fluid cytology in all patients, such as age, histologic type, grade, myometrial invasion, cervical invasion, tumor size, and lymphatic metastasis, were analyzed.

We observed peritoneal cytology, grade, myometrial invasion, cervical stromal invasion, tumor size, and lymphatic metastasis to have a significant effect on survival. Cytology was positive in 20 of 224 patients (8.9%). Statistical analysis revealed a significant effect on PPC occurrence of myometrial invasion, cervical stromal invasion, tumor size, histologic type, and lymphatic metastasis.

Positive peritoneal cytology has a significant effect on survival in endometrial cancer. Positive peritoneal cytology occurrence is influenced by myometrial invasion, cervical stromal invasion, tumor size, histologic type, and lymphatic metastasis.

The introduction of agents targeting vascular endothelial growth factor has radically changed the approach to metastatic renal cell carcinoma (mRCC): sunitinib and pazopanib are now the standard first-line therapy in mRCC. At sunitinib failure, second-line axitinib or everolimus or sorafenib should be considered to improve the clinical outcome. No data are available for a third-line tyrosine kinase inhibitor (TKI) after 2 previous lines of therapy with TKIs. At pazopanib failure, no prospective data are available.

The TOKIO study was designed to evaluate progression-free survival, safety, and efficacy of third-line therapy with TKI in 44 patients already treated with 2 previous lines of TKIs in 10 Italian centers, and relapsed from sunitinib-axitinib (group A) or pazopanib-sorafenib (group B). Standard treatment is sorafenib in group A and sunitinib in group B, administered until disease progression or unacceptable toxicity. Secondary endpoints include the evaluation of overall survival, safety, and quality of life.