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1.
Nat Commun ; 14(1): 2973, 2023 05 23.
Article in English | MEDLINE | ID: mdl-37221181

ABSTRACT

Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.


Subject(s)
Carcinoid Tumor , Neuroendocrine Tumors , Humans , B7-H1 Antigen , Lung
2.
Clin Transl Oncol ; 22(12): 2350-2356, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32488803

ABSTRACT

PURPOSE: We analysed our initial experience with SBRT in liver metastasis from colorectal cancer at our institution. MATERIALS AND METHODS: Between January/2014 and December/2017, 22 patients with 31 LMCCR were treated. Local control (LC) was assessed using the Kaplan-Meier and log-rank tests. We analysed potential prognostic factors for LC: sex, PTV size, number of LM and the radiation scheme. RESULTS: Median age: 69 years. Prior chemotherapy or local liver treatments: 81.8% and 63.6% of patients, respectively. SBRT consisted of 3 × 20 Gy (42.9%) and 3 × 15 Gy (31.4%). There were 88.5% responses (57.1% CR and 31.4% PR). Median follow-up was 30 months. LC per lesion at 12 and 24 months was 85.3% and 61.8%, respectively. Tumour volumes > 30 cc correlated with worsened 2-year-control rates (90% vs 34.5%) (p = 0.005). There was only a patient with CTC-grade 3 toxicity. CONCLUSIONS: Liver SBRT is a safe and effective treatment that achieves high local control rates. We found a significant correlation between larger LMCRC and worse local control.


Subject(s)
Colorectal Neoplasms/pathology , Liver Neoplasms/radiotherapy , Liver Neoplasms/secondary , Radiosurgery , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Liver Neoplasms/pathology , Male , Middle Aged , Prognosis , Radiosurgery/adverse effects , Radiosurgery/methods , Radiotherapy Dosage , Retrospective Studies , Sex Factors , Time Factors , Treatment Outcome , Tumor Burden
3.
Clin Transl Oncol ; 22(2): 223-235, 2020 Feb.
Article in English | MEDLINE | ID: mdl-32006340

ABSTRACT

Thyroid carcinoma is the most frequent endocrine malignancy and accounts for around 3% of global cancer incidence. Different histologies and clinical scenarios make necessary a multidisciplinary approach that includes new diagnostic methods and surgical, radiopharmaceutical and systemic therapies. This guideline updates several aspects of management of thyroid cancer.


Subject(s)
Clinical Trials as Topic/standards , Practice Guidelines as Topic/standards , Thyroid Neoplasms/therapy , Humans , Medical Oncology , Societies, Medical
4.
Clin Transl Oncol ; 22(5): 734-750, 2020 May.
Article in English | MEDLINE | ID: mdl-31385226

ABSTRACT

BACKGROUND: The optimal duration of first-line chemotherapy for patients with advanced gastric cancer is unknown. Diverse clinical trials have proposed different strategies including limited treatment, maintenance of some drugs, or treatment until progression. METHOD: The sample comprises patients from the AGAMENON multicenter registry without progression after second evaluation of response. The objective was to explore the optimal duration of first-line chemotherapy. A frailty multi-state model was conducted. RESULTS: 415 patients were divided into three strata: discontinuation of platinum and maintenance with fluoropyrimidine until progression (30%, n = 123), complete treatment withdrawal prior to progression (52%, n = 216), and full treatment until progression (18%, n = 76). The hazard of tumor progression decreased by 19% per month with the full treatment regimen. However, we found no evidence that fluoropyrimidine maintenance (hazard ratio [HR] 1.07, confidence interval [CI] 95%, 0.69-1.65) worsened progression-free survival (PFS) with respect to treatment until progression. Predictive factors for PFS were ECOG performance status, ≥ 3 metastatic sites, prior tumor response, and bone metastases. Toxicity grade 3/4 was more common in those who continued the full treatment until progression vs fluoropyrimidine maintenance (16% vs 6%). CONCLUSION: The longer duration of the full initial regimen exerted a protective effect on the patients of this registry. Platinum discontinuation followed by fluoropyrimidine maintenance yields comparable efficacy to treatment up to PD, with a lower rate of serious adverse events.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Registries , Stomach Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Clinical Decision-Making , Female , Humans , Maintenance Chemotherapy , Male , Middle Aged , Platinum/administration & dosage , Platinum/adverse effects , Progression-Free Survival , Pyrimidines/administration & dosage , Pyrimidines/adverse effects , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Survival Rate , Time Factors , Young Adult
5.
Clin Transl Oncol ; 21(9): 1231-1239, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30712234

ABSTRACT

PURPOSE: In this paper we study the quality of life (QoL) of elderly breast cancer patients receiving endocrine treatment (ET). More QoL data on elderly patients treated with ET are needed. Our aims are to study QoL in early-stage breast cancer patients throughout the treatment period and compare the QoL of ET groups. METHODS: 148 patients > 65 years who began ET with either tamoxifen or aromatase inhibitor (AI) completed the EORTC QLQ-C30 and QLQ-BR23 and the Interview for Deterioration in Daily Living Activities in Dementia (IDDD) questionnaires three times over 3 years of ET. Linear mixed-effect models were used to evaluate longitudinal QoL changes. ET group comparisons were conducted after 3 years of treatment via ANCOVA adjusted by basal QoL. RESULTS: QoL scores were high (> 80/100 points) in most QoL areas, with moderate limitations (> 30) in sexual functioning and enjoyment and in future perspective. After 3 years of ET, four QoL areas improved (< 6 points) compared to baseline and 3-month assessments. Hot flushes worsened (8 points) at the 3-month assessment but by 3 years had recovered. AI patients showed more hot flushes, pain and diarrhea and less sexual enjoyment than tamoxifen patients after 3 years of ET (differences 3-12 points). CONCLUSIONS: Results indicate that elderly early-stage breast cancer patients adapted well to their disease and ET treatment over the 3 years. Few QoL differences were observed between ET groups.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Quality of Life , Tamoxifen/therapeutic use , Aged , Female , Follow-Up Studies , Humans , Prognosis , Prospective Studies , Surveys and Questionnaires
6.
Clin. transl. oncol. (Print) ; 21(1): 55-63, ene. 2019. tab, graf
Article in English | IBECS | ID: ibc-183344

ABSTRACT

NENs are a heterogeneous family of tumors of challenging diagnosis and clinical management. Their incidence and prevalence continue to rise across all sites, stages and grades. Although improved diagnostic techniques have led to earlier detection and stage migration, the improved prognosis documented over time for advanced gastrointestinal and pancreatic neuroendocrine tumors also reflect improvements in therapy. The aim of this guideline is to update practical recommendations for the diagnosis and treatment of gastroenteropancreatic and lung NENs. Diagnostic procedures, histological classification and therapeutic options are briefly discussed, including surgery, liver-directed therapy, peptide receptor radionuclide therapy, and systemic hormonal, cytotoxic or targeted therapy, and treatment algorithms are provided


No disponible


Subject(s)
Humans , Gastrointestinal Neoplasms/therapy , Pancreatic Neoplasms/therapy , Bronchial Neoplasms/therapy , Neuroendocrine Tumors/therapy , Gastrointestinal Neoplasms/diagnosis , Pancreatic Neoplasms/diagnosis , Bronchial Neoplasms/diagnosis , Neuroendocrine Tumors/diagnosis , Practice Patterns, Physicians'
7.
Clin Transl Oncol ; 21(1): 55-63, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30535553

ABSTRACT

NENs are a heterogeneous family of tumors of challenging diagnosis and clinical management. Their incidence and prevalence continue to rise across all sites, stages and grades. Although improved diagnostic techniques have led to earlier detection and stage migration, the improved prognosis documented over time for advanced gastrointestinal and pancreatic neuroendocrine tumors also reflect improvements in therapy. The aim of this guideline is to update practical recommendations for the diagnosis and treatment of gastroenteropancreatic and lung NENs. Diagnostic procedures, histological classification and therapeutic options are briefly discussed, including surgery, liver-directed therapy, peptide receptor radionuclide therapy, and systemic hormonal, cytotoxic or targeted therapy, and treatment algorithms are provided.


Subject(s)
Bronchial Neoplasms/therapy , Gastrointestinal Neoplasms/therapy , Neuroendocrine Tumors/therapy , Pancreatic Neoplasms/therapy , Practice Guidelines as Topic/standards , Bronchial Neoplasms/diagnosis , Clinical Trials as Topic , Combined Modality Therapy , Disease Management , Gastrointestinal Neoplasms/diagnosis , Humans , Neuroendocrine Tumors/diagnosis , Pancreatic Neoplasms/diagnosis , Prognosis , Societies, Medical
8.
Eur J Cancer ; 101: 263-272, 2018 09.
Article in English | MEDLINE | ID: mdl-30054049

ABSTRACT

BACKGROUND: This multicentre, randomised, and phase II study evaluated mFOLFOX+cetuximab followed by maintenance mFOLFOX+cetuximab or single-agent cetuximab in metastatic colorectal cancer (mCRC) patients (NCT01161316). PATIENTS AND METHODS: Previously, untreated mCRC patients (wild-type KRAS) were randomised to receive cetuximab+mFOLFOX-6 (8 cycles for 2 weeks) followed by maintenance therapy: single-agent cetuximab (Arm-A) or mFOLFOX-6 + cetuximab (Arm-B) until progression. Primary endpoint was progression-free survival (PFS) at 9 months. RESULTS: One hundred ninety-three patients (median [range] age 60 [33-74] years) were randomised (2:1): 129 Arm-A versus 64 Arm-B. PFS at 9 months (95% confidence interval) showed non-inferiority between arms (Arm-A/Arm-B: 60 [52, 69]%/72 [61, 83]%, p [non-inferiority]<0.1). There were no statistically significant differences in the PFS (Arm-A/Arm-B: 9 [95% CI 7, 10] months/10 [7,13] months, hazard ratio [HR] = 1.19 [0.80, 1.79]) or overall survival (23 [19, 28] months/27 [18, 36] months, HR = 1.24 [0.85, 1.79]) between arms. The objective response rate was also similar (48 [39, 57]%/39 [27, 52]%). The safety profile was similar between arms, and all patients experienced at least one adverse event (AE) (Arm-A/Arm-B grade ≥III AEs: 70%/68%). The most common grade ≥III AEs were as follows: neutropenia (Arm-A/Arm-B: 28%/26%), rash acneiform (15%/24%) and sensory neuropathy (2%/15%) in any group. Arm-A was associated with less grade ≥III rash and sensory neuropathy and a lower rate of serious AEs (20%/27%). CONCLUSION(S): This phase II exploratory trial with a non-inferiority design suggests that maintenance therapy with single-agent cetuximab following mFOLFOX+cetuximab induction could be a valuable option compared with mFOLFOX+cetuximab treatment continuation. We await phase III trials to confirm single-agent cetuximab as maintenance therapy in mCRC patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cetuximab/therapeutic use , Colorectal Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cetuximab/administration & dosage , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Disease-Free Survival , Exanthema/chemically induced , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Leucovorin/administration & dosage , Leucovorin/adverse effects , Maintenance Chemotherapy , Male , Middle Aged , Neoplasm Metastasis , Neutropenia/chemically induced , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Proto-Oncogene Proteins p21(ras)/genetics
9.
Gastric Cancer ; 21(1): 96-105, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28393278

ABSTRACT

BACKGROUND: Although anthracycline-based triplets are one of the most widely used schedules to treat advanced gastric cancer (AGC), the benefit of including epirubicin in these therapeutic combinations remains unknown. This study aims to evaluate both the efficacy and tolerance of triplets with epirubicin vs. doublets with platinum-fluoropyrimidine in a national AGC registry. METHODS: Patients with AGC treated with polychemotherapy without trastuzumab at 28 hospitals in Spain between 2008 and 2016 were included. The effect of anthracycline-based triplets against doublets was evaluated by propensity score matching (PSM) and Cox proportional hazards (PH) regression. RESULT: A total of 1002 patients were included (doublets, n = 653; anthracycline-based triplets, n = 349). The multivariable Cox PH regression failed to detect significantly increased OS in favor of triplets with anthracyclines: HR 0.90 (95% CI, 0.78-1.05), p = 0.20035. After PSM, the sample contained 325 pairs with similar baseline characteristics. This method was also unable to reveal an increase in OS: 10.5 (95% CI, 9.7-12.3) vs. 9.9 (95% CI, 9.2-11.4) months, HR 0.91 (CI 95%, 0.76-1.083), and (log-rank test, p = 0.226). Response rates (42.1 vs. 33.1%, p = 0.12) and PFS (HR 0.95, CI 95%, 0.80-1.13, log-rank test, p = 0.873) were not significantly higher with epirubicin-based regimens. The triplets were associated with greater grade 3-4 hematological toxicity, and increased hospitalization due to toxicity by 68%. The addition of epirubicin is viable, but 23.7% discontinued treatment because of adverse effects or patient decision. CONCLUSION: Anthracyclines added to platinum-fluoropyrimidine doublets did not improve the response rate or survival outcomes in patients with AGC but entailed greater toxicity.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/drug therapy , Adult , Aged , Anthracyclines/administration & dosage , Anthracyclines/adverse effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Pyrimidines/administration & dosage , Pyrimidines/adverse effects , Registries
10.
Clin. transl. oncol. (Print) ; 19(8): 969-975, ago. 2017. tab, ilus, graf
Article in English | IBECS | ID: ibc-164675

ABSTRACT

Background. The objective of the study is to determine the correlations among the variables of dose and the sphincter function (SF) in patients with locally advanced rectal cancer treated with preoperative capecitabine/radiotherapy followed by low anterior resection (LAR) + TME. Methods. We retrospectively reviewed 92 consecutive patients with LARC treated at our center with LAR from 2006 and more than 2 years free from disease. We re-contoured the anal sphincters (AS) of patients with the help of the radiologist. SF was assessed with the Wexner scale (0-20 points, being punctuation inversely proportional to annal sphincter functionality). All questionnaires were filled out between January 2010 and December 2012. Dosimetric parameters that have been studied include V20, V30, V40, V50, mean dose (Dmean), minimum dose (Dmin), D90 (dose received by 90% of the sphincter) and D98. Statistical analysis. The correlations among the variables of dose and SF were studied by the Spearman correlation coefficient. Differences in SF relating to maximum doses to the sphincter were assessed by the Mann-Whitney test. Results. Mean Wexner score was 5.5 points higher in those patients with V20 > 0 compared to those for which V20 = 0 (p = 0.008). In a multivariate regression model, results suggest that the effect of V20 on poor anal sphincter control is independent of the effect of distance, with an adjusted OR of 3.42. Conclusions. In order to improve the SF in rectal cancer treated with preoperative radiotherapy/capecitabine followed by conservative surgery, the maximum radiation dose to the AS should be limited, when possible, to <20 Gy (AU)


No disponible


Subject(s)
Humans , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Fecal Incontinence/complications , Anal Canal/radiation effects , Chemoradiotherapy/methods , Capecitabine/therapeutic use , Quality of Life , Rectal Neoplasms/complications , Rectal Neoplasms/surgery , Fecal Incontinence/radiotherapy , Anal Canal/pathology , Retrospective Studies , Multivariate Analysis
11.
Br J Cancer ; 116(12): 1526-1535, 2017 Jun 06.
Article in English | MEDLINE | ID: mdl-28463962

ABSTRACT

BACKGROUND: To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy. METHODS: Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination. RESULTS: The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5-6.6), 9.4 (95% CI, 8.5-10.6), and 14 months (95% CI, 11.8-16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3-8.1), 12.7 (95% CI, 11.3-14.3), and 18.3 months (95% CI, 14.6-24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591-0.631) and 0.673 (95% CI, 0.636-0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351). CONCLUSIONS: We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Neoplasms/secondary , Esophageal Neoplasms/drug therapy , Esophagogastric Junction , Nomograms , Stomach Neoplasms/drug therapy , Adenocarcinoma/chemistry , Adenocarcinoma/secondary , Adult , Aged , Aged, 80 and over , Ascites/etiology , Esophageal Neoplasms/chemistry , Esophageal Neoplasms/pathology , Health Status , Humans , Lymphocyte Count , Middle Aged , Neoplasm Grading , Neutrophils , Receptor, ErbB-2/analysis , Stomach Neoplasms/chemistry , Stomach Neoplasms/pathology , Survival Rate , Trastuzumab/administration & dosage , Tumor Burden , White People , Young Adult
12.
Clin Transl Oncol ; 19(8): 969-975, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28194687

ABSTRACT

BACKGROUND: The objective of the study is to determine the correlations among the variables of dose and the sphincter function (SF) in patients with locally advanced rectal cancer treated with preoperative capecitabine/radiotherapy followed by low anterior resection (LAR) + TME. METHODS: We retrospectively reviewed 92 consecutive patients with LARC treated at our center with LAR from 2006 and more than 2 years free from disease. We re-contoured the anal sphincters (AS) of patients with the help of the radiologist. SF was assessed with the Wexner scale (0-20 points, being punctuation inversely proportional to annal sphincter functionality). All questionnaires were filled out between January 2010 and December 2012. Dosimetric parameters that have been studied include V 20, V 30, V 40, V 50, mean dose (D mean), minimum dose (D min), D 90 (dose received by 90% of the sphincter) and D 98. STATISTICAL ANALYSIS: The correlations among the variables of dose and SF were studied by the Spearman correlation coefficient. Differences in SF relating to maximum doses to the sphincter were assessed by the Mann-Whitney test. RESULTS: Mean Wexner score was 5.5 points higher in those patients with V 20 > 0 compared to those for which V 20 = 0 (p = 0.008). In a multivariate regression model, results suggest that the effect of V 20 on poor anal sphincter control is independent of the effect of distance, with an adjusted OR of 3.42. CONCLUSIONS: In order to improve the SF in rectal cancer treated with preoperative radiotherapy/capecitabine followed by conservative surgery, the maximum radiation dose to the AS should be limited, when possible, to <20 Gy.


Subject(s)
Adenocarcinoma/therapy , Anal Canal/pathology , Chemoradiotherapy/adverse effects , Fecal Incontinence/etiology , Rectal Neoplasms/therapy , Adenocarcinoma/secondary , Adult , Aged , Aged, 80 and over , Anal Canal/radiation effects , Fecal Incontinence/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Preoperative Care , Prognosis , Radiation Dosage , Rectal Neoplasms/pathology , Retrospective Studies , Survival Rate
14.
Ann Oncol ; 27(7): 1304-11, 2016 07.
Article in English | MEDLINE | ID: mdl-27059553

ABSTRACT

BACKGROUND: Emerging agents blocking the programmed cell death 1 (PD-1) pathway show activity in metastatic clear cell renal cell carcinoma (mRCC). The aim of this study was to evaluate the efficacy and safety of vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-tyrosine kinase inhibitor (TKI) therapy after PD-1 inhibition. PATIENTS AND METHODS: Patients with mRCC treated with anti-PD-1 antibody (aPD-1) monotherapy or in combination (with VEGFR-TKI or ipilimumab) that subsequently received VEGFR-TKI were retrospectively reviewed. The efficacy end points were objective response rate (ORR) and progression-free survival (PFS) stratified by the type of prior PD-1 regimen. Safety by the type and PD-1 exposure was also evaluated. RESULTS: Seventy patients were included. Forty-nine patients received prior therapy with immune checkpoint inhibitors (CPIs) alone and 21 had combination therapy of aPD-1 and VEGFR-TKI. Overall, ORR to VEGFR-TKI after PD-1 inhibition was 28% (19/68) and the median PFS was 6.4 months (mo) (4.3-9.5). ORR to VEGFR-TKI after aPD-1 in combination with VEGFR-TKI was lower than that in patients treated with VEGFR-TKI after CPI alone (ORR 10% versus 36%, P = 0.039). In the multivariable analysis, patients treated with prior CPI alone were more likely to achieve an objective response than those treated with aPD-1 in combination with VEGFR-TKI (OR = 5.38; 95% CI 1.12-26.0, P = 0.03). There was a trend toward numerically longer median PFS in the VEGFR-TKI after the CPI alone group, 8.4 mo (3.2-12.4) compared with 5.5 mo (2.9-8.3) for those who had VEGFR-TKI after aPD-1 in combination with VEGFR-TKI (P = 0.15). The most common adverse events (AEs) were asthenia, hypertension, and diarrhea. CONCLUSIONS: The efficacy and safety of VEGFR-TKIs after PD-1 inhibition were demonstrated in this retrospective study. The response rate was lower and the median progression-free survival was shorter in those patients who received prior PD-1 in combination with VEGFR-TKI. PD-1 exposure does not seem to significantly influence the safety of subsequent VEGFR-TKI treatment.


Subject(s)
Carcinoma, Renal Cell/drug therapy , Programmed Cell Death 1 Receptor/genetics , Protein Kinase Inhibitors/administration & dosage , Receptors, Vascular Endothelial Growth Factor/genetics , Adult , Aged , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Clinical Trials as Topic , Disease-Free Survival , Everolimus/administration & dosage , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Protein Kinase Inhibitors/adverse effects , Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors , Sirolimus , Vascular Endothelial Growth Factor A/antagonists & inhibitors
15.
Crit Rev Oncol Hematol ; 101: 193-206, 2016 May.
Article in English | MEDLINE | ID: mdl-27021395

ABSTRACT

Pancreatic neuroendocrine tumours (PanNETs) are considered a relatively unusual oncologic entity. Due to its relative good prognosis, surgery remains the goal standard therapy not only in localized disease but also in the setting of locally or metastatic disease. Most of the patients are diagnosed in metastatic scenario, where multidisciplinary approach based on surgery, chemotherapies, liver-directed and/or molecular targeted therapies are commonly used. Owing to a deeper molecular knowledge of this disease, these targeted therapies are nowadays widely implemented, being the likely discovery of predictive biomarkers that would allow its use in other settings. This review is focused on describing the different classifications, etiology, prognostic biomarkers and multidisciplinary approaches that are typically used in PanNET.


Subject(s)
Neuroendocrine Tumors , Pancreatic Neoplasms , Biomarkers, Tumor/blood , Humans , Molecular Targeted Therapy , Neoplasm Staging , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/drug therapy , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Prognosis
16.
17.
Clin. transl. oncol. (Print) ; 17(2): 139-144, feb. 2015. tab, ilus
Article in English | IBECS | ID: ibc-132884

ABSTRACT

Objective. To determine the impact of initial FDG PET/CT staging on clinical stage and the management plan in patients with locally advanced head and neck cancer (LAHNC). Materials and methods. We retrospectively reviewed the records of 72 consecutive patients (2007–2010) staged with PET/CT and conventional CT with tumours of hypopharynx/larynx (26 patients, 36 %), oral cavity (17 patients, 24 %), oropharynx (16 patients, 22 %), nasopharynx (12 patients, 17 %), and others (2 %). The impact of PET/CT on management plans was considered high when PET/CT changed the planned treatment modality or treatment intent, and intramodality changes were considered as minor changes with low impact. Results. FDG PET/CT changed the stage in 27 patients and had high impact on the management plan in 12 % of patients (detection of distant metastases in 6 patients and stage II in 2 patients). Intramodality changes were more frequent: FDG PET/CT altered the TNM stage in 18/72 (25 %) of patients, upstaging N stage in 90 % of patients with low impact. Conclusions. Initial FDG PET/CT staging not only improves stage but also affects the management plan in LAHNC patients (AU)


No disponible


Subject(s)
Humans , Male , Female , Head and Neck Neoplasms , Positron-Emission Tomography/instrumentation , Positron-Emission Tomography/methods , Positron-Emission Tomography , Neoplasm Staging/instrumentation , Neoplasm Staging/methods , Head and Neck Neoplasms/physiopathology , Head and Neck Neoplasms/radiotherapy , Positron-Emission Tomography/standards , Retrospective Studies , Hypopharynx/pathology , Hypopharynx , Hypopharyngeal Neoplasms , Mouth , Nasopharynx , Nasopharyngeal Neoplasms
18.
Clin Transl Oncol ; 17(2): 139-44, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25078571

ABSTRACT

OBJECTIVE: To determine the impact of initial FDG PET/CT staging on clinical stage and the management plan in patients with locally advanced head and neck cancer (LAHNC). MATERIALS AND METHODS: We retrospectively reviewed the records of 72 consecutive patients (2007-2010) staged with PET/CT and conventional CT with tumours of hypopharynx/larynx (26 patients, 36 %), oral cavity (17 patients, 24 %), oropharynx (16 patients, 22 %), nasopharynx (12 patients, 17 %), and others (2 %). The impact of PET/CT on management plans was considered high when PET/CT changed the planned treatment modality or treatment intent, and intramodality changes were considered as minor changes with low impact. RESULTS: FDG PET/CT changed the stage in 27 patients and had high impact on the management plan in 12 % of patients (detection of distant metastases in 6 patients and stage II in 2 patients). Intramodality changes were more frequent: FDG PET/CT altered the TNM stage in 18/72 (25 %) of patients, upstaging N stage in 90 % of patients with low impact. CONCLUSIONS: Initial FDG PET/CT staging not only improves stage but also affects the management plan in LAHNC patients.


Subject(s)
Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/secondary , Fluorodeoxyglucose F18 , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/pathology , Positron-Emission Tomography/methods , Tomography, X-Ray Computed/methods , Adult , Aged , Aged, 80 and over , Disease Management , Female , Follow-Up Studies , Humans , Male , Middle Aged , Multimodal Imaging/methods , Neoplasm Staging , Prognosis , Radiopharmaceuticals , Retrospective Studies
19.
Clin. transl. oncol. (Print) ; 16(8): 739-745, ago. 2014. tab, ilus
Article in English | IBECS | ID: ibc-126562

ABSTRACT

AIMS: Pathological response has been shown to be a predictor for survival after preoperative chemotherapy and surgical resection of colorectal cancer liver metastases. This retrospective analysis evaluated the effect on pathological response of adding bevacizumab to standard neoadjuvant chemotherapy in patients with metastatic colorectal cancer (mCRC) and liver metastases. METHODS: Patient records from two Spanish centres were retrospectively examined for this analysis. Patients were included if they had stage IV mCRC with liver metastases, were unresectable or marginally resectable tumour before chemotherapy, and had oxaliplatin- or irinotecan-based chemotherapy, with or without bevacizumab, before resection. Tumour response was evaluated using response evaluation criteria in solid tumours (RECIST). Pathological response was assessed by pathologists blinded to treatment. RESULTS: Ninety-five patients were included. Good pathological responses (PR0/PR1) were observed in 37 patients (39 %). The RECIST response rate was 51 %. Only 42 % of patients with a good pathological response had a complete or partial response according to RECIST, while 57 % of those with a poor pathological response had a complete or partial response according to RECIST. RECIST response rates were similar with and without bevacizumab, although 49 % of bevacizumab-treated patients had a good pathological response versus 27 % of those receiving chemotherapy alone (χ (2) P = 0.0302). CONCLUSION: Pathological response may be a better indicator of treatment efficacy than RECIST for patients with mCRC receiving bevacizumab in the neoadjuvant setting. Adding bevacizumab to chemotherapy has the potential to increase pathological response rates. Well-designed prospective clinical studies are required to establish the efficacy and tolerability of this approach (AU)


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Subject(s)
Humans , Male , Female , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Neoplasm Metastasis/drug therapy , Neoadjuvant Therapy/methods , Neoadjuvant Therapy , Antibodies, Monoclonal, Humanized , Antibodies, Monoclonal, Humanized/metabolism , Retrospective Studies , Colorectal Neoplasms/complications , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Liver Neoplasms/complications , Liver Neoplasms/diagnosis , Liver Neoplasms/drug therapy
20.
Crit Rev Oncol Hematol ; 92(3): 166-80, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25048167

ABSTRACT

The application of nanotechnology in oncology has increased the efficacy and efficiency of some cytotoxic agents. The paradigm in this field is nab-paclitaxel, a soluble form of paclitaxel that is linked to albumin nanoparticles. The development of nanotechnology as a delivery system for paclitaxel has provided better pharmacokinetic and pharmacodynamic characteristics, neutralizing its hydrophobicity. This procedure significantly improves the treatment of metastatic breast cancer compared to conventional paclitaxel-based therapies, including other type of cancers such as metastatic pancreatic cancer, stage IIIB-IV non-small cell lung cancer (NSCLC) and metastatic melanoma. In these last cases, significant differences were found in primary end-points for patients treated with nab-paclitaxel-based chemotherapy compared to those treated with conventional treatments. The application of nanotechnology in cancer treatment may also improve the efficacy of other known drugs, as a result of improved pharmacokinetic and pharmacodynamic profiles, similarly to paclitaxel.


Subject(s)
Albumins/therapeutic use , Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Paclitaxel/therapeutic use , Albumins/pharmacology , Animals , Antineoplastic Agents/pharmacology , Biological Transport , Biomarkers , Clinical Trials as Topic , Drug Evaluation, Preclinical , Humans , Nanomedicine , Paclitaxel/pharmacology , Treatment Outcome
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