Objective To estimate the cumulative radiation exposure and lifetime attributable risk of cancer incidence associated with lung cancer screening using annual low dose computed tomography ...(CT).Design Secondary analysis of data from a lung cancer screening trial and risk-benefit analysis.Setting 10 year, non-randomised, single centre, low dose CT, lung cancer screening trial (COSMOS study) which took place in Milan, Italy in 2004-15 (enrolment in 2004-05). Secondary analysis took place in 2015-16.Participants High risk asymptomatic smokers aged 50 and older, who were current or former smokers (≥20 pack years), and had no history of cancer in the previous five years.Main outcome measures Cumulative radiation exposure from low dose CT and positron emission tomography (PET) CT scans, calculated by dosimetry software; and lifetime attributable risk of cancer incidence, calculated from the Biological Effects of Ionizing Radiation VII (BEIR VII) report.Results Over 10 years, 5203 participants (3439 men, 1764 women) underwent 42 228 low dose CT and 635 PET CT scans. The median cumulative effective dose at the 10th year of screening was 9.3 mSv for men and 13.0 mSv for women. According to participants’ age and sex, the lifetime attributable risk of lung cancer and major cancers after 10 years of CT screening ranged from 5.5 to 1.4 per 10 000 people screened, and from 8.1 to 2.6 per 10 000 people screened, respectively. In women aged 50-54, the lifetime attributable risk of lung cancer and major cancers was about fourfold and threefold higher than for men aged 65 and older, respectively. The numbers of lung cancer and major cancer cases induced by 10 years of screening in our cohort were 1.5 and 2.4, respectively, which corresponded to an additional risk of induced major cancers of 0.05% (2.4/5203). 259 lung cancers were diagnosed in 10 years of screening; one radiation induced major cancer would be expected for every 108 (259/2.4) lung cancers detected through screening.Conclusion Radiation exposure and cancer risk from low dose CT screening for lung cancer, even if non-negligible, can be considered acceptable in light of the substantial mortality reduction associated with screening.
Epidemiology of pancreatic cancer: an overview Raimondi, Sara; Maisonneuve, Patrick; Lowenfels, Albert B
Nature reviews. Gastroenterology & hepatology,
12/2009, Letnik:
6, Številka:
12
Journal Article
Recenzirano
Pancreatic cancer, although infrequent, has an exceptionally high mortality rate, making it one of the four or five most common causes of cancer mortality in developed countries. The incidence of ...pancreatic cancer varies greatly across regions, which suggests roles for lifestyle factors, such as diet, or environmental factors, such as vitamin D exposure. Smoking is the most common known risk factor, and is the cause of 20-25% of all pancreatic tumors. Alcohol does not seem to be a risk factor, unless it leads to chronic pancreatitis, which is a probable risk factor. Long-standing diabetes increases the risk of pancreatic cancer, but can also be an early manifestation of pancreatic tumors. 5-10% of patients with pancreatic cancer have an underlying germline disorder, while the remaining percentage of cancer cases is thought to be caused by somatic mutations. Some individual studies suggest that mutations in various polymorphic genes can lead to small increases in the risk of pancreatic cancer, but these findings need to be replicated. Rising prevalence of smoking in developing countries, improved diagnosis and increasing population longevity are all likely to increase the global burden of pancreatic cancer in the coming decades.
Objective(s) We evaluated a large series of patients undergoing robotic lobectomy for the treatment of early-stage non–small cell lung cancer (NSCLC) to assess long-term oncologic efficacy. Methods A ...multi-institutional retrospective review of patients undergoing robotic lobectomy for NSCLC was performed. Robotic lobectomy was performed in a manner consistent with the Cancer and Leukemia Group B (CALGB) consensus video-assisted thoracic surgery (VATS) lobectomy technique using a robotic surgical system. Perioperative outcomes and long-term follow-up were recorded prospectively, and survival was calculated from the date of surgery to last follow-up. Results From November 2002 through May 2010, a total of 325 consecutive patients underwent robotic lobectomy for early-stage NSCLC at 3 institutions. The median age of patients was 66 years (range, 30-87 years), and 37% (120) were female. The majority were in clinical stage I (IA, 247; IB, 63). Conversion rate to thoracotomy was 8% (27/325). Overall morbidity rate was 25.2% (82/325), and major complication rate was 3.7% (12/325). There was 1 in-hospital death (0.3%), and the median length of stay was 5 days (range, 2-28 days). Pathologic stage distribution was 54% (176) IA, 22% (72) IB, 13% (41) IIA, 5% (15) IIB, and 6% (21) IIIA. With a median follow-up of 27 months, overall 5-year survival was 80% (95% confidence intervals CI = 73-88), and by pathologic stage, 91% (CI = 83-99) for stage IA, 88% (CI = 77-98) for stage IB, and 49% (CI = 24-74) for all patients with stage II disease. Overall 3-year survival for patients with stage IIIA disease was 43% (CI = 16-69). Conclusions Robotic lobectomy for early-stage NSCLC can be performed with low morbidity and mortality. Long-term stage-specific survival is acceptable and consistent with prior results for VATS and thoracotomy.
Objectives We investigated the feasibility and safety of four-arm robotic lung lobectomy in patients with lung cancer and described the robotic lobectomy technique with mediastinal lymph node ...dissection. Methods Over 21 months, 54 patients underwent robotic lobectomy for early-stage lung cancer at our institute. We used a da Vinci Robotic System (Intuitive Surgical, Inc, Mountain View, Calif) with three ports plus one utility incision to isolate hilum elements and perform vascular and bronchial resection using standard endoscopic staplers. Standard mediastinal lymph node dissection was performed subsequently. Surgical outcomes were compared with those in 54 patients who underwent open surgery over the same period and were matched to the robotic group using propensity scores for a series of preoperative variables. Results Conversion to open surgery was necessary in 7 (13%) cases. Postoperative complications (11/54, 20%, in each group) and median number of lymph nodes removed (17.5 robotic vs 17 open) were similar in the 2 groups. Median robotic operating time decreased by 43 minutes ( P = .02) from first tertile (18 patients) to the second-plus-third tertile (36 patients). Median postoperative hospitalization was significantly shorter after robotic (excluding first tertile) than after open operations (4.5 days vs 6 days; P = .002). Conclusions Robotic lobectomy with lymph node dissection is practicable, safe, and associated with shorter postoperative hospitalization than open surgery. From the number of lymph nodes removed it also appears oncologically acceptable for early lung cancer. Benefits in terms of postoperative pain, respiratory function, and quality of life still require evaluation. We expect that technologic developments will further simplify the robotic procedure.
Summary Background Intraoperative radiotherapy with electrons allows the substitution of conventional postoperative whole breast irradiation with one session of radiotherapy with the same equivalent ...dose during surgery. However, its ability to control for recurrence of local disease required confirmation in a randomised controlled trial. Methods This study was done at the European Institute of Oncology (Milan, Italy). Women aged 48–75 years with early breast cancer, a maximum tumour diameter of up to 2·5 cm, and suitable for breast-conserving surgery were randomly assigned in a 1:1 ratio (using a random permuted block design, stratified for clinical tumour size <1·0 cm vs 1·0–1·4 cm vs ≥1·5 cm) to receive either whole-breast external radiotherapy or intraoperative radiotherapy with electrons. Study coordinators, clinicians, and patients were aware of the assignment. Patients in the intraoperative radiotherapy group received one dose of 21 Gy to the tumour bed during surgery. Those in the external radiotherapy group received 50 Gy in 25 fractions of 2 Gy, followed by a boost of 10 Gy in five fractions. This was an equivalence trial; the prespecified equivalence margin was local recurrence of 7·5% in the intraoperative radiotherapy group. The primary endpoint was occurrence of ipsilateral breast tumour recurrences (IBTR); overall survival was a secondary outcome. The main analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT01849133. Findings 1305 patients were randomised (654 to external radiotherapy and 651 to intraoperative radiotherapy) between Nov 20, 2000, and Dec 27, 2007. After a medium follow-up of 5·8 years (IQR 4·1–7·7), 35 patients in the intraoperative radiotherapy group and four patients in the external radiotherapy group had had an IBTR (p<0·0001). The 5-year event rate for IBRT was 4·4% (95% CI 2·7–6·1) in the intraoperative radiotherapy group and 0·4% (0·0–1·0) in the external radiotherapy group (hazard ratio 9·3 95% CI 3·3–26·3). During the same period, 34 women allocated to intraoperative radiotherapy and 31 to external radiotherapy died (p=0·59). 5-year overall survival was 96·8% (95% CI 95·3–98·3) in the intraoperative radiotherapy group and 96·9% (95·5–98·3) in the external radiotherapy group. In patients with data available (n=464 for intraoperative radiotherapy; n=412 for external radiotherapy) we noted significantly fewer skin side-effects in women in the intraoperative radiotherapy group than in those in the external radiotherapy group (p=0·0002). Interpretation Although the rate of IBTR in the intraoperative radiotherapy group was within the prespecified equivalence margin, the rate was significantly greater than with external radiotherapy, and overall survival did not differ between groups. Improved selection of patients could reduce the rate of IBTR with intraoperative radiotherapy with electrons. Funding Italian Association for Cancer Research, Jacqueline Seroussi Memorial Foundation for Cancer Research, and Umberto Veronesi Foundation.
Gastroenteropancreatic (GEP) neuroendocrine carcinomas (NECs) are defined as neuroendocrine neoplasms (NENs) with a Ki-67 index >20% according to the 2010 WHO classification. Some reports suggest ...that this category is heterogeneous. We retrospectively studied a series of 136 patients affected by grade 3 GEP-NECs with the aim to clarify the prognostic role of tumor morphological differentiation, proliferation, defect in mismatch repair proteins (MMRd), CD117 expression, and site of origin. The primary endpoint was the correlation between these parameters and the overall survival (OS).
Univariate and multivariable Cox proportional hazards regression analyses were used to assess the prognostic significance of various clinical and histopathologic features.
With a median follow-up of 81 months, the median OS was 12.9 months. At multivariate analysis, morphological differentiation, Ki-67 index, MMRd, stage, and CD117 expression were independent prognostic markers in NECs. Three different prognostic categories of NECs were identified according to the degree of morphologic differentiation (well vs. poorly differentiated) and Ki-67 index (<55% vs. ≥55%). On this basis, median OS was 43.6 months in well-differentiated neoplasms with a Ki-67 index 20-55% (named type A), 24.5 months in poorly differentiated neoplasms with a Ki-67 index 20-55% (type B), and 5.3 months (p < 0.0001) in poorly differentiated neoplasms with a Ki-67 index ≥55% (type C).
The present study suggests that GEP-NECs represent a heterogeneous group of neoplasms which can be better classified in different prognostic categories using both tumor morphology and Ki-67 index.
Epidemiology and burden of pancreatic cancer Maisonneuve, Patrick
La Presse médicale (1983),
March 2019, 2019-Mar, 2019-03-00, 20190301, Letnik:
48, Številka:
3
Journal Article
Recenzirano
Pancreatic cancer, although infrequent, has a very poor prognosis, making it currently the fourth common causes of cancer mortality in most developed countries including the European Union (EU). Its ...incidence varies across regions, which suggests that lifestyle factors play an important role in its etiology, although part of the variation could be ascribed to difference in diagnostic and coding practices. Because pancreatic cancer is strongly age-dependent, increasing population longevity and ageing will lead to an increase of the global burden of pancreatic cancer. It was estimated that, by 2040, the total number of cases in the EU will increase by more than 30%. Pancreatic cancer is a multifactorial disease and many risk factors have been identified. Hereditary factors are responsible for less than 10% of the cases while tobacco smoking and excess body weight, the two most important potentially modifiable risk factors, are responsible for 10 to 30% of the cases, affording a unique opportunity for preventing one of our deadliest cancers.In this issue
Invasive lobular breast cancer (ILBC) is the second most common histologic subtype after invasive ductal breast cancer (IDBC). Despite clinical and pathologic differences, ILBC is still treated as ...IDBC. We aimed to identify genomic alterations in ILBC with potential clinical implications.
From an initial 630 ILBC primary tumors, we interrogated oncogenic substitutions and insertions and deletions of 360 cancer genes and genome-wide copy number aberrations in 413 and 170 ILBC samples, respectively, and correlated those findings with clinicopathologic and outcome features.
Besides the high mutation frequency of CDH1 in 65% of tumors, alterations in one of the three key genes of the phosphatidylinositol 3-kinase pathway, PIK3CA, PTEN, and AKT1, were present in more than one-half of the cases. HER2 and HER3 were mutated in 5.1% and 3.6% of the tumors, with most of these mutations having a proven role in activating the human epidermal growth factor receptor/ERBB pathway. Mutations in FOXA1 and ESR1 copy number gains were detected in 9% and 25% of the samples. All these alterations were more frequent in ILBC than in IDBC. The histologic diversity of ILBC was associated with specific alterations, such as enrichment for HER2 mutations in the mixed, nonclassic, and ESR1 gains in the solid subtype. Survival analyses revealed that chromosome 1q and 11p gains showed independent prognostic value in ILBC and that HER2 and AKT1 mutations were associated with increased risk of early relapse.
This study demonstrates that we can now begin to individualize the treatment of ILBC, with HER2, HER3, and AKT1 mutations representing high-prevalence therapeutic targets and FOXA1 mutations and ESR1 gains deserving urgent dedicated clinical investigation, especially in the context of endocrine treatment.
Tobacco use is a serious public health concern as it causes various deleterious health problems. The aim of this study was to determine the prevalence of tobacco use and various types of tobacco used ...among a population-based sample of adults 18 years and above in Qatar (residents and expatriates). The study also attempted to assess tobacco use initiation age, tobacco dependency, and to identify factors associated with current tobacco use. This 2019 cross-sectional study was conducted among governmental employees and University students in Qatar using cluster sampling methodology. Study participants completed a self-administered, country-adapted summarized version of the Global Adult Tobacco Survey. 25.2% (n = 1741; N = 6904) of the surveyed sample reported current tobacco use. 21.5% (n = 1481) smoked tobacco (cigarettes, waterpipe, medwakh and cigar) concomitant with other forms of tobacco and only 1.0% (n = 69) were using other forms of tobacco (electronic cigarettes, smokeless tobacco and heat-not-burn tobacco products) and 2.7% (n = 191) did not mention the type of tobacco products used by them. Of the 1550 tobacco users, 42.8% were cigarette smokers, 20.9% waterpipe, 3.2% medwakh (Arabic traditional pipe) and 0.7% cigar. Moreover, 1.9% reported smokeless tobacco use (sweika), 2.0% electronic cigarette use, and 0.3% heat-not-burn tobacco use. The mean age for smoking initiation was 19.7±5.3 (Qataris 18.6±4.8 and non-Qataris 20.3±5.6). Using multivariable logistic regression, significant association was observed between tobacco use and gender, nationality, age, monthly income, living with a smoker, and self-rated health. This large population-based cross-sectional survey provides the first evidence for the prevalence of different types of tobacco use including medwakh smoking among adults (Qataris and non-Qataris) 18 years and above in Qatar. This can serve as a baseline for future research studies on the topic. Based on the review of previous and current tobacco survey findings, it is evident that the prevalence of tobacco use (current) in Qatar has declined suggesting that tobacco control measures implemented by the country have been effective in reducing tobacco consumption.
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