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1.
Vaccine X ; 13: 100261, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36654840

RESUMEN

Purpose: Despite widely disseminated guidelines, pneumococcal and influenza vaccination coverage (VC) remains insufficient in patients with cancer receiving cancer treatment. We performed an interventional study to evaluate VC in patients with cancer treated at the medical oncology departments of three North-of-France hospitals and to assess the effect of medical staff training on VC in these patients. Methods: A standardized questionnaire assessed VC in adult patients with cancer receiving anticancer treatment at three day hospitals during December 2-7, 2019. Subsequently (January 2020), we organized educational training sessions for medical staff from each hospital to discuss the current vaccination guidelines. To assess the impact of training on pneumococcal and influenza VC, we re-administered the same questionnaire in March 2020. Because there are no specific guidelines on Diphtheria-Tetanus-Pertussis (DTP) vaccination and no improvement was expected, DTP VC acted as an internal control. Results: In total, 272 patients from all three hospitals were enrolled in the "before study"; 156 patients from only two hospitals were enrolled in the "after study" as medical training and data collection at the third were impossible because of administrative reasons and COVID-19 pandemic. The predictors were age for DTP VC; treatment center for pneumococcal VC; and age, sex, and tumor histology (adenocarcinoma vs. others) for influenza VC. Neither influenza VC (42.6% vs. 55.1%, p = 0.08), nor pneumococcal VC were significantly improved post-intervention (11.8% vs. 15.4%, p = 1). There seems to be a small effect in the most fragile for influenza VC. Conclusion: As expected, VC was very low in patients with cancer, consistent with the literature. There was no impact of the intervention for pneumococcal and influenza VC.

2.
JTCVS Open ; 10: 442-453, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36004276

RESUMEN

Background: Numerous studies have shown that improving oral hygiene contributes to a reduction in the risk of postoperative complications in patients with head and neck cancer, cardiac disease, and esophageal cancer. However, the beneficial standard for oral management procedures during the perioperative period has not yet been established. Therefore, our aim was to determine whether or not their innovative oral management intervention contributed to a reduction in postoperative complications in lung cancer. Methods: We performed a retrospective analysis of medical records of patients who underwent lung cancer surgery with lobectomy and pneumonectomy at Kyorin University Hospital. Patients were divided into 2 groups: a perioperative oral management intervention group that underwent lung cancer surgery from April 2016 to March 2018 (n = 164), and a control group without oral management that underwent surgery from April 2014 to March 2016 (n = 199). In particular, our oral management procedure emphasized oral mucosa stimulation to induce saliva discharge as in gum chewing, rather than simply using teeth brushing to reduce oral microbiome. Therefore, our oral management procedure is different from traditional oral care. Results: This study demonstrated that our oral management practice was associated with a decline in the occurrence of postoperative pneumonia (odds ratio, 0.184; 95% CI, 0.042-0.571; P = .009), postoperative hospital stay duration (ß coefficient, -4.272; 95% CI, -6.390 to -2.155; P < .001) and Clavian-Dindo classification grade II or above (odds ratio, 0.503; 95% CI, 0.298-0.835; P = .009). Conclusions: We propose an innovative new strategy using their unique oral management procedure to reduce postoperative complications resulting from pulmonary resection.

3.
JTCVS Open ; 10: 370-381, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36004269

RESUMEN

Objectives: The optimal treatment for recurrent non-small cell lung cancer (NSCLC) has not been standardized. In this prospective cohort study, we evaluated post-recurrence survival (PRS) after treatment of recurrent NSCLC and identified prognostic factors after recurrence. Methods: This multicenter prospective cohort study was conducted in 14 hospitals. The inclusion criteria for this study were patients with recurrence after radical resection for NSCLC. Information about the patient characteristics at recurrence, tumor-related variables, primary surgery, and treatment for recurrence was collected. After registration, follow-up data, such as treatment and survival outcomes, were obtained every 3 months. Results: From 2010 to 2015, 505 cases were enrolled, and 495 cases were analyzed. As initial treatment for recurrence, 263 patients (53%) received chemotherapy, 46 (9%) received chemoradiotherapy, 98 (20%) had definitive radiotherapy, 14 (3%) received palliative radiotherapy, and 31 (6%) underwent surgical resection. The remaining 43 patients (9%) received supportive care. The median PRS and 5-year survival rates for all cases were 30 months and 31.9%, respectively. The median PRS according to the initial treatment was as follows: supportive care, 8 months; palliative radiotherapy, 16 months; definitive radiotherapy, 30 months; chemotherapy, 31 months; chemoradiotherapy, 35 months; and surgery, not reached. A multivariate analysis showed that the age, gender, performance status, histology presence of symptoms, duration from primary surgery to recurrence, and number of recurrent foci were independent prognostic factors for PRS. Conclusions: The PRS of patients with recurrent NSCLC was different depending on the patient's background characteristics and initial treatment for recurrence.

4.
Lancet Reg Health Eur ; 22: 100492, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36108315

RESUMEN

Background: Long-term changes in lung cancer (LC) patients are difficult to evaluate. We report results from the French KBP-2020 real-life cohort. Methods: KBP-2020 was a prospective cohort that included all patients diagnosed with LC in 2020, in nonacademic public hospital in France. Patient and tumour characteristics were described and compared with similarly designed cohorts in 2000 and 2010. Findings: In 2020, 82 centers included 8,999 patients diagnosed with LC. The proportion of women increased: 34·6% (3114/8999) compared to, 24·3% (1711/7051) and 16·0% (904/5667) in 2010 and 2000 (p<0·0001). The proportion of non-smokers was higher in 2020 (12·6%, 1129/8983) than in previous cohorts (10·9% (762/7008) in 2010; 7·2% (402/5586) in 2000, p<0·0001). In 2020, at diagnosis, 57·6% (4405/7648) of patients had a metastatic/disseminated stage non-small-cell lung cancer (NSCLC) (58·3% (3522/6046) in 2010; 42·6% (1879/4411) in 2000, p<0·0001). Compared with 2000 and 2010 data, early survival improved slightly. In 2020, 3-month mortality of NSCLC varied from 3·0% [2·2 - 3·8] for localized to 9·6% [8·1 - 11·0] for locally advanced to 29·2% [27·8 - 30·6] for metastatic and was 24·8% [22·3 - 27·3] for SCLC. Interpretation: To our knowledge KBP cohorts have been the largest, prospective, real-world cohort studies involving LC patients conducted in worldwide. The trend found in our study shows an increase in LC in women and still a large proportion of patients diagnosed at metastatic or disseminated stage. Funding: The study was promoted by the French College of General Hospital Pulmonologists with financial support of industrials laboratories.

5.
J Clin Exp Hepatol ; 12(3): 745-754, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35677519

RESUMEN

Objective: Advanced-stage hepatocellular carcinoma is a heterogeneous group with limited treatment options. TACE has been advocated recently by various study groups. The purpose of this study was to evaluate if TACE in combination with sorafenib, as well as TACE alone, was safe and efficacious in treating BCLC stage C HCC. Methods: A retrospective evaluation of the clinical data of 78 patients with BCLC stage C HCC who received either TACE-sorafenib (TS) combination therapy or TACE monotherapy as their first treatment was done. The two groups were compared in terms of radiological tumor response 1 month after the intervention. The two groups were also compared in terms of time to progression (TTP), overall survival (OS), and adverse events. Results: The disease control rate (44.9% and 25.8%, respectively, P = 0.09) was higher in the TS combination group than in the TACE monotherapy group after 1 month of treatment. The TS combination group had significantly superior TTP and OS than the TACE group (TTP was 4.6 and 3.1 months, respectively, P = 0.001), and OS was 10.1 and 7.8 months, respectively, P < 0.001). The TACE-S group had a greater cumulative survival time at 6 months, 9 months, and 1 year than the TACE group (97.9%, 51.1%, 25.7% vs. 90.4%, 51.6%, and 0%, respectively). Conclusion: TS combination therapy in advanced-stage (BCLC-C) HCC significantly improved disease control rate, TTP, and OS compared with TACE alone, without any significant increase in adverse reactions.

6.
J Clin Tuberc Other Mycobact Dis ; 29: 100341, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36466135

RESUMEN

Introduction: Acute respiratory distress syndrome (ARDS) is considered a poor prognostic factor for miliary tuberculosis (MTB), but little is known about the effectiveness of steroid pulse therapy for MTB complicated by ARDS. Patients and methods: Medical records were used to retrospectively investigate the prognosis and clinical information of 13 patients diagnosed with MTB complicated by ARDS among 68 patients diagnosed with MTB at our hospital between January 1994 and October 2016. None of the patients had multidrug resistant tuberculosis (TB). MTB was diagnosed by 1 radiologist and 2 respiratory physicians based on the observation of randomly distributed, uniformly sized diffuse bilateral nodules on chest computed tomography and the detection of mycobacterium TB from clinical specimens. ARDS was diagnosed based on the Berlin definition of ARDS. The effect of steroid pulse therapy on death within 3 months of hospitalization was examined using Cox proportional hazards models. Variables were selected by the stepwise method (variable reduction method). Results: Six of 8 patients with MTB complicated by ARDS were alive 3 months after hospitalization in the steroid pulse therapy group, whereas only 1 of 5 patients was alive in the non-steroid pulse therapy group. Analysis of factors related to the survival of patients with MTB complicated by ARDS revealed that steroid pulse therapy was the strong prognostic factor (hazard ratio = 0.136 (95 % CI: 0.023-0.815)). Conclusion: Our findings suggest that steroid pulse therapy improves the short-term prognosis of patients with MTB complicated by ARDS.

7.
Clin Transl Radiat Oncol ; 37: 57-63, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36065360

RESUMEN

Purpose: Intensity-modulated radiotherapy (IMRT) is currently used more commonly than 3-dimensional conformal radiation for definitive thoracic radiation. We examined the efficacy profiles of concurrent chemoradiotherapy (CCRT) with IMRT after durvalumab became clinically available. Methods: We reviewed the clinical records of patients with stage III non-small cell lung cancer (NSCLC) treated with CCRT and IMRT at seven centers in Japan and investigated relapse and survival from May 2018 to December 2019. The primary endpoint of this report was progression-free survival (PFS). Results: Among 107 patients enrolled in the study, 87 were sequentially administered durvalumab. From CCRT commencement, patients were followed up for a median period of 29.7 months. The median PFS at the end of the CCRT was 20.7 months. Among the 87 patients, 58 experienced disease relapses, of whom 36 (62.1 %) had distant metastases. Multivariate Cox regression analysis revealed that a favorable response to CCRT, a radiation dose ≥ 62 Gy, and stage IIIA NSCLC were associated with prolonged PFS (all P = 0.04). Multivariate logistic regression by landmark analysis revealed that mortality risk factors were durvalumab treatment duration ≤ 11.7 months, a lower maximum grade of immune-related adverse events, FEV1 < 2805 mL, and radiation dose < 62 Gy (P = 0.01, 0.01, 0.03, and 0.04, respectively). Conclusions: In patients with NSCLC receiving CCRT using IMRT, long PFS was associated with a better response to CCRT, stage IIIA NSCLC, and an increased radiation dose. The duration of durvalumab consolidation also played an essential role in the survival of patients receiving CCRT with IMRT. (250 words).

8.
EClinicalMedicine ; 31: 100663, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33554075

RESUMEN

BACKGROUND: Anatomical lung resection offers the best prospect of long-term survival in patients with non-small cell lung cancer (NSCLC). However, some patients with significant dyspnoea, impaired performance status (PS), borderline or poor pulmonary function are considered inoperable and instead referred for radiotherapy, chemotherapy or palliative care. The aims of the study were to determine whether pre-operative pulmonary physiotherapy (Prehab), by improving clinical parameters, (i) makes patients suitable for surgery who were considered inoperable on subjective criteria of dyspnoea >3 and PS >2, and objective criteria of diffusing capacity for carbon monoxide (DLCO) <50%; and (ii) thereby allows them to safely receive curative surgery with reduced morbidity and mortality. METHODS: From January 2017 to December 2018 a total of 306 patients were prospectively and sequentially assessed for Prehab and 216 patients with lung cancer studied. Their mean age (95% CI) was 71.7 ± 1.1 years, 50.5% (n = 109) were men and they received Prehab over 39.0 ± 7.0 days averaging 3.1 ± 0.6 sessions. Their dyspnoea scores, PS, level of activity, six minute walk test (6MWT) and frailty index prior to and following Prehab were determined. Following surgery the post-operative length of hospital stay (LOHS), complications and mortality at 30 days, 90 days and 1 year determined. Similar outcomes were determined for (i) high-risk patients with dyspnoea scores >3 and PS >2, and compared with low-risk patients having dyspnoea scores <2 and PS <2 (subjective criteria); and (ii) high-risk patients with DLCO <50% and compared with low-risk patients with DLCO >80% (objective criteria). FINDINGS: In the total cohort following Prehab, there was significant improvement in the dyspnoea scores <2 / ≥2 (40%/60% prior to Prehab vs. 65%/35% following Prehab, p = 0.00002), PS <2 / ≥2 (45%/55% prior to vs. 62%/38% following Prehab, p = 0.003), frailty index ≤3 / >3 (49%/51% vs 70%/30%, p = 0.0006), and 6MWT (306.6 ± 6.8 m vs 354.8 ± 52.7 m, p = 0.04). Post-operative major complication rates were 8.7%; median LOHS was 7 (IQR 6) days; hospital mortality at 30 days 1.3%, 90 days 4.7% and 1 year 16%. Using subjective criteria of dyspnoea scores >3 and PS >2, 100% of high-risk patients were considered inoperable. Following optimization with Prehab 84.2% of the high-risk patients were ready to proceed with radical treatment and 52.6% with surgery, and subsequently 42.8% of patients underwent surgery. Likewise, 78.8% of patients with DLCO <50% were considered inoperable. Following Prehab 86.5% of high-risk patients were ready to proceed with radical treatment and 59.1% with surgery, and 54.6% of high-risk patients underwent surgery. In each category there were no significant differences in complications, LOHS or mortality rates between the high-risk and low-risk patients. INTERPRETATION: Our prospective study showed that with Prehab there was clinical and statistically significant improvement in the dyspnoea scores, PS, level of activity and frailty, particularly in the high-risk group of patients. Importantly, Prehab made previously inoperable patients operable, allowing them to safely undergo curative lung resection. This strategy helps improve resection rates and may contribute to the long term survival of lung cancer patients. FUNDING: This is a Welsh Health Specialised Services Committee (WHSSC) commissioned service.

9.
Urol Case Rep ; 31: 101156, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32322507

RESUMEN

Prostate cancer is the second most frequent among men. Bones and lymph nodes are the most common sites of metastases in advanced prostate cancer. Oral cavity metastases are rare. We report a case of 65-year-old man with a prostate adenocarcinoma revealed by gingival metastasis. We analyze through this observation the clinical, morphological and therapeutic characteristics of this neoplasia.

10.
Prostate Int ; 8(1): 27-33, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32257975

RESUMEN

BACKGROUND: Several studies have reported the efficacy of cabazitaxel in cancer therapy; however, investigations of its safety are few. The aim of this study was to retrospectively analyze the efficacy and safety of cabazitaxel based on treatment outcome data. METHODS: A questionnaire form on the use of cabazitaxel was mailed to hospitals associated with the Shinshu University. Responses were received from 11 institutions regarding 55 cases. RESULTS: Patients received a median of 4 courses of cabazitaxel treatment. Decreases in prostrate-specific antigen (PSA) were observed in 61.5% of cases with declines of 30%, 50%, and 90% in 36.5%, 23.0%, and 7.6% of cases, respectively. PSA progression-free survival was 5.0 months, and overall survival after the start of cabazitaxel was 13.0 months. Forty-five patients received postcabazitaxel treatment; 17 showed decreased PSA. Safety assessment indicated that white blood cell and neutrophil counts were significantly higher in the second than in the first course of treatment and Grade 3 to 4 leukopenia and neutropenia significantly decreased. Twenty-four subjects were aged ≥75 years; 79% of them had their doses reduced at the first administration. The mean dose was 20 mg/m2. However, there was no significant difference in the PSA progression-free survival between the ≥75-year-old and <75-year-old groups. Patients in the ≥75-year-old group, particularly those whose doses were not reduced, experienced several Grade 3 to 4 adverse effects. Ten patients discontinued treatment owing to adverse effects and systemic worsening. CONCLUSIONS: To use cabazitaxel effectively, starting administration as early as possible before disease progression is important, and even if Grade 3 to 4 leukopenia and neutropenia are observed during the first course, it is important to carefully maintain the dose. Even when treating elderly patients, reducing the dose does not reduce therapeutic efficacy. However, because this cohort experienced several ≥ Grade 3 adverse effects, a great deal of caution is required.

11.
J Clin Exp Hepatol ; 10(6): 563-573, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33311893

RESUMEN

BACKGROUND: Radiofrequency ablation (RFA) is a standard treatment for small inoperable hepatocellular carcinoma (HCC). Studies on mid- and long-term outcome of RFA as first-line therapy for HCC from India are limited. METHODS: We evaluated consecutive HCC patients who underwent RFA as primary treatment modality at our institute between July 2009 and April 2016. The median follow-up period was 26 months, range 1-84 months. We evaluated post-RFA tumor response, disease-free survival (DFS), overall survival (OS), and local tumor progression (LTP). Prognostic factors were also analyzed. RESULTS: In 147 patients (male:female = 121:26; mean age, 59.2 years), 209 RFA sessions were done for 228 lesions (mean size of 21.5 ± 8.3 mm, range 10-50 mm). Primary success rate was 94.2%. The estimated cumulative proportion survival at 1, 3, and 5 years was 90.2%, 63.8%, and 60.2%, respectively. The cumulative incidence of LTP estimated at 1, 3, and 5 years was 13.1%, 19.7%, and 20.1%, respectively. The mean estimate of LTP-free survival was 53.6 months (95% confidence interval: 0.49-0.58) which is 58.2 months in <3 cm lesions and 20.4 months in >3 cm lesions (P < 0.01). There was no significant difference in LTP rates between lesions in perivascular versus nonperivascular location (P = 0.71) and surface versus parenchymal lesions (P = 0.66). The mean DFS was 30.3 months (95% CI: 25.6-35.0). For OS, age and Child-Turcotte-Pugh class B were significant factors while for LTP, tumor size >3 cm was significant. Higher baseline alpha-fetoprotein level and LTP were poor predictors for DFS. Complication rate per RFA session was 7/209 (3.3%). CONCLUSIONS: RFA is a safe and effective curative modality for first-line treatment of HCC < 3 cm.

12.
World Neurosurg X ; 3: 100022, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31225516

RESUMEN

BACKGROUND: Despite the most recent surgical aids and tools, surgical removal of infiltrating brain tumors remains a challenge. Unclear margins, edematous areas, and infiltrative behavior are the main causes for failing gross total removals. Also, excessive resection of peri-tumoral tissue often carries risks of damaging the nearby functioning cortical and subcortical structures with an unacceptable decrease in patient's quality of life and postoperative functional status, and the risk of making patients not eligible to adjuvant treatments. Awake surgery and intraoperative magnetic resonance imaging (ioMRI) are among the most effective aids in preventing damage to functional brain while maximizing the extent of resection. METHODS: We present our series of 46 patients operated on at Southmead Hospital (North Bristol NHS Trust) in between July 2014 and February 2017 using ioMRI plus or minus awake surgery. Setting, patient features, indications, type and size of tumors, surgical times, extent of resection, morbidity, and survival are analyzed and discussed. RESULTS: Overall, ioMRI check led to a +43% resections in Group 1 and +58% in Group 2. In grade 2 tumors, GTR was 46% in Group 1 and 55% in Group 2 (41% in control group). In grade 3 tumors, GTR was 57% in Group 1 and 66% in Group 2 (30% in control group). In Grade 4 tumors, GTR was 63% in Group 1, 66% in Group 2 (36% in control group). In terms of theatre occupation, the use of ioMRI added 1/2 operative session; the addition of awake surgery implied the use of another 1/2 operative session. Morbidity did not differ among the groups, with low incidence of permanent post-operative deficits (<5%). Group 2 OS was statistically longer when compared to the control group. CONCLUSIONS: Using ioMRI together with awake surgery is demanding for the anesthetic team, staff nurses, and for the patient. Nevertheless, low morbidity, greater total resections rates, and longer survival suggest its use is effective in making more approachable gliomas of all grades that we would consider "complex" due to their intrinsic features or locations.

13.
Contemp Clin Trials Commun ; 8: 55-61, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29696197

RESUMEN

INTRODUCTION: The combination of a fluoropyrimidine [5-fluorouracil (5-FU), capecitabine, or S-1] with a platinum analog (cisplatin or oxaliplatin) is the most widely accepted first-line chemotherapy regimen for metastatic or recurrent advanced gastric cancer (AGC), based on the results of clinical trials. However, there is little evidence to guide chemotherapy for elderly patients with AGC because of under-representation of this age group in clinical trials. Thus, the aim of this study is to determine the optimal chemotherapy regimen for elderly patients with AGC by comparing the efficacies and safeties of combination therapy versus monotherapy as first-line chemotherapy. METHODS: This study is a randomized, controlled, multicenter, phase III trial. A total of 246 elderly patients (≥70 years old) with metastatic or recurrent AGC who have not received previous palliative chemotherapy will be randomly allocated to a combination therapy group or a monotherapy group. Patients randomized to the combination therapy group will receive fluoropyrimidine plus platinum combination chemotherapy (capecitabine/cisplatin, S-1/cisplatin, capecitabine/oxaliplatin, or 5-FU/oxaliplatin), and those randomized to the monotherapy group will receive fluoropyrimidine monotherapy (capecitabine, S-1, or 5-FU). The primary outcome is the overall survival of patients in each treatment group. The secondary outcomes include progression-free survival, response rate, quality of life, and safety. DISCUSSION: We are conducting this pragmatic trial to determine whether elderly patients with AGC will obtain the same benefit from chemotherapy as younger patients. We expect that this study will help guide decision-making for the optimal treatment of elderly patients with AGC.

14.
Cancer Biol Ther ; 16(8): 1128-35, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26047060

RESUMEN

Interdigitating dendritic cell sarcoma is an extremely rare tumor. The diagnosis is difficult and is based on clinical, pathological and immunohistochemical evaluation. Differential diagnosis includes melanoma, mesenchymal and hematological malignancies. The mainstay of treatment is surgery for limited disease and different chemotherapy combinations have been tested for advanced disease. No evidence from prospective trials is currently available. We report the case of a 59 year-old male patient who experienced axillary lymphadenopathy with initial diagnosis of large-cell lung cancer on tumor biopsy. He underwent surgical resection with radical intent. Pathological diagnosis of interdigitating dendritic cell sarcoma was obtained on surgical samples. Nine months after radical surgery, he experienced systemic recurrence of disease and underwent chemotherapy with epirubicin and ifosfamide for 4 courses. During chemotherapy, he developed brain disease progression and underwent whole-brain radiotherapy. Systemic progression was then observed and molecular characterization was performed. B-RAF evaluation resulted positive for V600E mutation and the patient was treated with Vemurafenib according to molecular findings. He thus obtained initial clinical benefit but eventually died of brain hemorrhage. In conclusion, we report a case of B-RAF mutation detected in an interdigitating dendritic cell sarcoma patient treated with targeted therapy. B-RAF pathway could have a role in pathogenesis and evolution of this rare disease and could open new perspectives of treatment.


Asunto(s)
Sarcoma de Células Dendríticas Interdigitantes/genética , Terapia Molecular Dirigida/métodos , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Sarcoma de Células Dendríticas Interdigitantes/tratamiento farmacológico , Sarcoma de Células Dendríticas Interdigitantes/cirugía , Epirrubicina/administración & dosificación , Humanos , Ifosfamida/administración & dosificación , Indoles/administración & dosificación , Indoles/efectos adversos , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Vemurafenib
15.
Cancer Biol Ther ; 15(11): 1542-51, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25482940

RESUMEN

Adverse events in platinum-based chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) are major challenges. In this study, we investigated the role of the p53 and MDM2 genes in predicting adverse events in NSCLC patients treated with platinum-based chemotherapy. Specifically, we examined the p53 p. Pro72Arg (rs1042522), MDM2 c.14 + 309T>G (rs2279744) and MDM2 c.- 461C > G (rs937282) polymorphisms using PCR-based restriction fragment length polymorphism (RFLP) in 444 NSCLC patients. We determine that MDM2 c.14 + 309T > G was significantly associated with severe hematologic and overall toxicities for advanced NSCLC patients treated with platinum-based chemotherapy, especially for patients aged 57 and younger. This was also true for patients with adenocarcinoma. Second, we determine that severe gastrointestinal toxicities in patients with heterozygous MDM2 c.-461C > G were significantly higher than in patients with the G/G genotype. Third, patients with the MDM2 c.-461C > G - c.14 + 309T > G CT haplotype show much higher toxicities than those of CG haplotype. Moreover, patients carrying the MDM2 c.-461 > G -c.14 + 309T > G CG/CT diplotype exhibited higher toxicities than those carrying CG/CG. Fourth, we found that the p53 p. Pro72Arg polymorphism interacts with both age and genotype. In addition, no significant associations were observed between the 3 SNPs and the response to first-line platinum-based chemotherapy in advanced NSCLC patients. In summary, we found that the p53 p. Pro72Arg, MDM2 c.14 + 309T > G and MDM2 c.-461C > G polymorphisms are associated with toxicity risks following platinum-based chemotherapy treatment in advanced NSCLC patients. We suggest that MDM2 c.14 + 309T > G may be used as a candidate biomarker to predict adverse events in advanced NSCLC patients who had platinum-based chemotherapy treatment.


Asunto(s)
Antineoplásicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Farmacogenética , Polimorfismo Genético , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteína p53 Supresora de Tumor/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Resultado del Tratamiento
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