Summary Background Elderly patients are often under-represented in clinical trials of metastatic colorectal cancer. We aimed to assess the efficacy and safety of bevacizumab plus capecitabine ...compared with capecitabine alone in elderly patients with metastatic colorectal cancer. Methods For this open-label, randomised phase 3 trial, patients aged 70 years and older with previously untreated, unresectable, metastatic colorectal cancer, who were not deemed to be candidates for oxaliplatin-based or irinotecan-based chemotherapy regimens, were randomly assigned in a 1:1 ratio via an interactive voice-response system, stratified by performance status and geographical region. Treatment consisted of capecitabine (1000 mg/m2 orally twice a day on days 1–14) alone or with bevacizumab (7·5 mg/kg intravenously on day 1), given every 3 weeks until disease progression, unacceptable toxic effects, or withdrawal of consent. Efficacy analyses were based on the intention-to-treat population. The primary endpoint was progression-free survival. The trial is registered with ClinicalTrials.gov , number NCT00484939. Findings From July 9, 2007, to Dec 14, 2010, 280 patients with a median age of 76 years (range 70–87) were recruited from 40 sites across ten countries. Patients were randomly assigned to receive either bevacizumab plus capecitabine (n=140) or capecitabine only (n=140). Progression-free survival was significantly longer with bevacizumab and capecitabine than with capecitabine alone (median 9·1 months 95% CI 7·3–11·4 vs 5·1 months 4·2–6·3; hazard ratio 0·53 0·41–0·69; p<0·0001). Treatment-related adverse events of grade 3 or worse occurred in 53 (40%) patients in the combination group and 30 (22%) in the capecitabine group, and treatment-related serious adverse events in 19 (14%) and 11 (8%) patients. The most common grade 3 or worse adverse events of special interest for bevacizumab or chemotherapy were hand-foot syndrome (21 16% vs nine 7%), diarrhoea (nine 7% vs nine 7%), and venous thromboembolic events (11 8% vs six 4%). Treatment-related deaths occurred in five patients in the combination group and four in the capecitabine group. The most common any-grade adverse event of special interest for bevacizumab was haemorrhage (34 25% vs nine 7%). Interpretation The combination of bevacizumab and capecitabine is an effective and well-tolerated regimen for elderly patients with metastatic colorectal cancer. Funding F Hoffmann-La Roche.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The dynamic contrast-enhanced MR imaging plays a crucial role in evaluating the effectiveness of neoadjuvant chemotherapy (NAC) even since its early stage through the prediction of the final ...pathological complete response (pCR). In this study, we proposed a transfer learning approach to predict if a patient achieved pCR (pCR) or did not (non-pCR) by exploiting, separately or in combination, pre-treatment and early-treatment exams from I-SPY1 TRIAL public database. First, low-level features, i.e., related to local structure of the image, were automatically extracted by a pre-trained convolutional neural network (CNN) overcoming manual feature extraction. Next, an optimal set of most stable features was detected and then used to design an SVM classifier. A first subset of patients, called fine-tuning dataset (30 pCR; 78 non-pCR), was used to perform the optimal choice of features. A second subset not involved in the feature selection process was employed as an independent test (7 pCR; 19 non-pCR) to validate the model. By combining the optimal features extracted from both pre-treatment and early-treatment exams with some clinical features, i.e., ER, PgR, HER2 and molecular subtype, an accuracy of 91.4% and 92.3%, and an AUC value of 0.93 and 0.90, were returned on the fine-tuning dataset and the independent test, respectively. Overall, the low-level CNN features have an important role in the early evaluation of the NAC efficacy by predicting pCR. The proposed model represents a first effort towards the development of a clinical support tool for an early prediction of pCR to NAC.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In breast cancer patients, an accurate detection of the axillary lymph node metastasis status is essential for reducing distant metastasis occurrence probabilities. In case of patients resulted ...negative at both clinical and instrumental examination, the nodal status is commonly evaluated performing the sentinel lymph-node biopsy, that is a time-consuming and expensive intraoperative procedure for the sentinel lymph-node (SLN) status assessment. The aim of this study was to predict the nodal status of 142 clinically negative breast cancer patients by means of both clinical and radiomic features extracted from primary breast tumor ultrasound images acquired at diagnosis. First, different regions of interest (ROIs) were segmented and a radiomic analysis was performed on each ROI. Then, clinical and radiomic features were evaluated separately developing two different machine learning models based on an SVM classifier. Finally, their predictive power was estimated jointly implementing a soft voting technique. The experimental results showed that the model obtained by combining clinical and radiomic features provided the best performances, achieving an AUC value of 88.6%, an accuracy of 82.1%, a sensitivity of 100% and a specificity of 78.2%. The proposed model represents a promising non-invasive procedure for the SLN status prediction in clinically negative patients.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In cancer patients, malnutrition is associated with treatment toxicity, complications, reduced physical functioning, and decreased survival. The Prevalence of Malnutrition in Oncology (PreMiO) study ...identified malnutrition or its risk among cancer patients making their first medical oncology visit. Innovatively, oncologists, not nutritionists, evaluated the nutritional status of the patients in this study.
PreMiO was a prospective, observational study conducted at 22 medical oncology centers across Italy. For inclusion, adult patients (>18 years) had a solid tumor diagnosis, were treatment-naive, and had a life expectancy >3 months. Malnutrition was identified by the Mini Nutritional Assessment (MNA), appetite status with a visual analog scale (VAS), and appetite loss with a modified version of Anorexia-Cachexia Subscale (AC/S-12) of the Functional Assessment of Anorexia-Cachexia Therapy (FAACT).
Of patients enrolled (
1,952), 51% had nutritional impairment; 9% were overtly malnourished, and 43% were at risk for malnutrition. Severity of malnutrition was positively correlated with the stage of cancer. Over 40% of patients were experiencing anorexia, as reported in the VAS and FAACT questionnaire. During the prior six months, 64% of patients lost weight (1-10 kg).
Malnutrition, anorexia, and weight loss are common in cancer patients, even at their first visit to a medical oncology center.
We aimed to assess the role of computerized tomography attenuation values (Hounsfield unit-HU) for differentiating pyonephrosis from hydronephrosis and for predicting postoperative infectious ...complications in patients with obstructive uropathy. We analysed data from 122 patients who underwent nephrostomy tube or ureteral catheter placement for obstructive uropathy. A radiologist drew the region of interest for quantitative measurement of the HU values in the hydronephrotic region of the affected kidney. Descriptive statistics and logistic regression models tested the predictive value of HU determination in differentiating pyonephrosis from hydronephrosis and in predicting postoperative sepsis. A HU cut-off value of 6.3 could diagnose the presence of pyonephrosis with 71.6% sensitivity and 71.5% specificity (AUC 0.76; 95%CI: 0.66-0.85). At multivariable logistic regression analysis HU ≥ 6.3 (p ≤ 0.001) was independently associated with pyonephrosis. Patients who developed sepsis had higher HU values (p ≤ 0.001) than those without sepsis. A HU cut-off value of 7.3 could diagnose the presence of sepsis with 76.5% sensitivity and 74.3% specificity (AUC 0.79; 95%CI: 0.71-0.90). At multivariable logistic regression analysis, HU ≥ 7.3 (p ≤ 0.001) was independently associated with sepsis, after accounting for clinical and laboratory parameters. Measuring HU values of the fluid of the dilated collecting system may be useful to differentiate pyonephrosis from hydronephrosis and to predict septic complications in patients with obstructive uropathy.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract Metronomic chemotherapy (MC) refers to the close administration of a chemotherapeutic drug for a long time with no extended drug-free breaks. It was developed to overcome drug resistance, ...partly by shifting the therapeutic target from tumor cells to the tumor vasculature, with less toxicity. Because of this peculiar way of administration, MC can be viewed as a form of long-term ‘maintenance’ treatment, and can be integrated with standard and conventional chemotherapy in a “chemo-switching” strategy. Additional mechanisms are involved in its antitumor activity, such as activation of immunity, induction of tumor dormancy, chemotherapy-driven dependency of cancer cells, and the ‘4D effect’. In this paper we report the most important studies that have analyzed these processes. In fact, a number of preclinical and clinical studies in solid tumors as well as in multiple myeloma, have been reported regarding several chemotherapy drugs which have been proposed with a metronomic schedule: vinorelbine, cyclophosphamide, capecitabine, methotrexate, bevacizumab, etoposide, gemcitabine, sorafenib, everolimus and temozolomide. The results of these studies have been sometimes conflicting, highlighting the need to develop reliable tools for patient selection and stratification. However, a more precise evaluation of MC strategies with the ongoing randomized phase II/III clinical is fundamental, because of the strict correlation of this approach with translational research and target therapy. Moreover, because of the low toxicity of MC, these studies will also help to better evaluate the clinical benefit of this treatment, with a special focus on elderly and low performance status patients.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To show different approaches for sexual-sparing robot assisted radical cystectomy in women.
Radical cystectomy (RC) is a mainstay treatment for localized muscle invasive bladder cancer and high-risk ...non muscle invasive bladder cancer not responding to adequate endovesical therapy.1 In women traditionally RC is performed with hystero-adnexectomy and resection of the anterior vaginal wall, but this technique often brings sexual disorders. With time, vaginal sparing techniques have been developed to improve functional outcomes in women motivated to preserve their sexual function.2-4 The indications for vaginal-sparing RC are absence of tumor in bladder neck or urethra and no sign of infiltration of anterior vaginal wall and parametria at preoperative staging.
Procedure steps as follows. Step 1: Bilateral adnexectomy and ureteral isolation until their distal portion. Step 2: Vesico-vaginal dissection. Step 3: Bilateral pelvic and common iliac node dissection. Step 4: Ureteral clamping and section. Step5: Posterolateral bladder pedicle dissection. Step 6: Anterior dissection of the bladder towards the urethra. In women, this should be achieved without injuring the Santorini plexus and innervation of the clitoris. Step 7: Bladder neck identification and urethral dissection. Cystectomy is completed. Step 8: En bloc hystero-adnexectomy with anterior vaginal wall preservation; the vaginal pedicles are spared too. Step 9: Specimen extraction from the vagina and vaginal suture.It is also possible to perform a fully sexual-sparing robotic RC by following the vesico-vaginal plan without dissecting the vaginal dome and leaving internal genitalia intact. This technique is typically carried out in case of young women with no pathological uterine and ovarian findings.Vesico-vaginal plan can also be developed after opening the vaginal dome. This approach gives the possibility to subsequently dissect the cervix, to identify and spare the vaginal pedicles and to perform an “en bloc” radical cystectomy, with preservation of the anterior vaginal wall.In case of neobladder, diversion is carried out intracorporeally following the principles of the Saint Augustin neobladder.5
Robot assisted anterior pelvectomy with anterior vaginal wall preservation is a feasible and mini-invasive technique. For a satisfying functional result, it is crucial to preserve the vaginal neurovascular pedicles. This sexual-sparing approach must be carried out after a correct patient selection: women motivated to preserve their sexual function and ideally in the neobladder setting, when a posterior support for the urinary diversion is needed. Absence of tumor in bladder neck and urethra at magnetic resonance imaging could help patient selection.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Dasatinib (BMS-354825, Sprycel®) is an oral, multitargeted inhibitor of receptor tyrosine kinases (RTKs), including BCR-ABL fusion protein, stem cell factor receptor (c-KIT), platelet-derived growth ...factor receptor (PDGFR), and Src family kinases (SFKs). Several early- and late-phase clinical trials for chronic myelogeneous leukaemia (CML) have demonstrated the direct inhibition of BCR-ABL fusion protein and SFKs, which led to dasatinib approval by the Food and Drug Administration (FDA) and the European Union for the treatment of imatinib-resistant or -intolerant CML, and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Phase III dose-optimization study was performed to compare different regimens, stating that dasatinib 100 mg once daily is now the recommended schedule for patients with chronic CML, and 140 mg once daily for patients with accelerated phase or myeloid or lymphoid blast phase CML, and for patients with Ph+ ALL until progression. Because of the myriad of critical roles of SFKs in biological processes, SFKs inhibition could induce numerous biological responses. Ongoing clinical trials evaluate dasatinib in the treatment of several solid tumours, including gastrointestinal stromal tumours (GIST), prostate cancer, malignant pleural mesothelioma, sarcomas, NSCLC, colorectal cancer, glioblastoma and other haematologic malignancies as multiple myeloma. Ongoing pre-clinical studies assess the therapeutic potential of dasatinib in other solid tumours, including melanoma, head and neck cancer, breast cancer and ovarian cancer. Dasatinib is generally well tolerated. Myelosuppression is the common adverse event which is, however, reversible by dose reduction, discontinuation, or interruption. Thrombocytopenia is more significant than neutropenia and associated to gastrointestinal bleeding and CNS haemorrhage. The most common non-haematologic adverse events include gastrointestinal symptoms (diarrhoea, nausea, vomiting, abdominal pain and anorexia), headache, peripheral edema, and pleural effusion. In respect of these encouraging studies investigating dasatinib in the treatment of patients with GIST, prostate cancer, multiple myeloma and sarcomas, ongoing phase III clinical trials warrant the drug evaluation as recommended agent for the treatment of these diseases, also in association with chemotherapy or other targeted therapies.
Cetuximab plus chemotherapy is a first-line treatment option in metastatic KRAS and NRAS wild-type colorectal cancer (CRC) patients. No data are currently available on continuing anti-epidermal ...growth factor receptor (EGFR) therapy beyond progression.
We did this open-label, 1:1 randomized phase II trial at 25 hospitals in Italy to evaluate the efficacy of cetuximab plus 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) as second-line treatment of KRAS exon 2 wild-type metastatic CRC patients treated in first line with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) plus cetuximab. Patients received FOLFOX plus cetuximab (arm A) or FOLFOX (arm B). Primary end point was progression-free survival (PFS). Tumour tissues were assessed by next-generation sequencing (NGS). This report is the final analysis.
Between 1 February 2010 and 28 September 2014, 153 patients were randomized (74 in arm A and 79 in arm B). Median PFS was 6.4 95% confidence interval (CI) 4.7–8.0 versus 4.5 months (95% CI 3.3–5.7); hazard ratio (HR), 0.81; 95% CI 0.58–1.12; P = 0.19, respectively. NGS was performed in 117/153 (76.5%) cases; 66/117 patients (34 in arm A and 32 in arm B) had KRAS, NRAS, BRAF and PIK3CA wild-type tumours. For these patients, PFS was longer in the FOLFOX plus cetuximab arm median 6.9 (95% CI 5.5–8.2) versus 5.3 months (95% CI 3.7–6.9); HR, 0.56 (95% CI 0.33–0.94); P = 0.025. There was a trend in better overall survival: median 23.7 (95% CI 19.4–28.0) versus 19.8 months (95% CI 14.9–24.7); HR, 0.57 (95% CI 0.32–1.02); P = 0.056.
Continuing cetuximab treatment in combination with chemotherapy is of potential therapeutic efficacy in molecularly selected patients and should be validated in randomized phase III trials.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Contrast-Enhanced Spectral Mammography (CESM) is a recently introduced mammographic method with characteristics particularly suitable for breast cancer radiomic analysis. This work aims to evaluate ...radiomic features for predicting histological outcome and two cancer molecular subtypes, namely Human Epidermal growth factor Receptor 2 (HER2)-positive and triple-negative. From 52 patients, 68 lesions were identified and confirmed on histological examination. Radiomic analysis was performed on regions of interest (ROIs) selected from both low-energy (LE) and ReCombined (RC) CESM images. Fourteen statistical features were extracted from each ROI. Expression of estrogen receptor (ER) was significantly correlated with variation coefficient and variation range calculated on both LE and RC images; progesterone receptor (PR) with skewness index calculated on LE images; and Ki67 with variation coefficient, variation range, entropy and relative smoothness indices calculated on RC images. HER2 was significantly associated with relative smoothness calculated on LE images, and grading tumor with variation coefficient, entropy and relative smoothness calculated on RC images. Encouraging results for differentiation between ER+/ER-, PR+/PR-, HER2+/HER2-, Ki67+/Ki67-, High-Grade/Low-Grade and TN/NTN were obtained. Specifically, the highest performances were obtained for discriminating HER2+/HER2- (90.87%), ER+/ER- (83.79%) and Ki67+/Ki67- (84.80%). Our results suggest an interesting role for radiomics in CESM to predict histological outcomes and particular tumors' molecular subtype.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
