The Variation of Cell Type Distribution in Lung Cancer: A Study of 10,910 Cases at a Medical Center in Taiwan between 1970 and 1993

The rise in the incidence of lung cancer has been associatedwith shifts in histologic distribution. A study was conductedto investigate changes in the cell type distribution in lungcancer in relation to age, sex, and smoking history, based ona retrospective analysis of 10,910 proven cases of lung cancerat the Veterans General Hospital-Taipei during the period from1970 to 1993. The diagnosis in each case was substantiated byhistologic samples from the original tumor site in the lung.Detailed smoking histories were obtaind by personal interviewat the time of the first admission. Adenocarcinoma (38.3%) wasthe most common type of lung cancer, followed by squamous cellcarcinoma (37.1%) and small cell carcinoma (12.2%). Over thestudy period, the incidence of squamous cell carcinoma decreasedfrom 46.4% to 36.2% in men (P < 0.005), adenocarcinoma increasedfrom 30% to 36% in men (P = 0.001) and 50.7% to 64.8% in women(P = 0.008), and small cell carcinoma increased from 7% to 14%in men but showed no significant change in women. Adenocarcinomaexhibited a marked increase in both men and women, and surpassedsquamous cell carcinoma as the most frequent type of lung cancer.Lung cancer among younger men, and among non-smoking older menand women, was more often adenocarcinoma. Small cell carcinomashowed a significant increase among males, differing from thetrend for squamous cell carcinoma in men, though both are stronglyassociated with smoking. These findings suggest factors otherthen cigarette smoking could influence the development and distributionof lung cancer.     

Childhood cancer survival in Switzerland (1976–2013): Time‐trends and predictors

Population‐based studies on childhood cancer survival are key to monitor progress against cancer and to detect potential differences between regions and other subgroups in the population. We investigated time trends and factors associated with childhood cancer survival on a national level in Switzerland, from 1976 to 2013. We extracted data from the population‐based Swiss Childhood Cancer Registry of 5,776 children (age 0–14 years) diagnosed with cancer from 1985 to 2014 in Switzerland. We calculated age‐adjusted 5‐year survival, defined the annual reduction in risk of death (ARR), and explored associations of survival with clinical and demographic factors. Overall, 5‐year survival improved significantly, from 64% in 1976–1983 to 88% in 2004–2013. ARR over the whole period was 4% for all diagnostic groups, greatest for Hodgkin lymphomas (8%), ependymomas (6%), Burkitt's lymphomas (6%) and germ cell tumours (6%). Children treated in hospitals without specialised paediatric cancer centre for leukaemia (HR 12.9), lymphoma (HR 5.0) and neuroblastoma (HR 3.7) were at higher risk of death. In French‐speaking Switzerland, risk of death was lower for lymphoma (HR 0.6), CNS tumours (HR 0.7) and neuroblastoma (HR 0.5). Children with migration background had a higher risk of death from all tumours except bone tumours. Childhood cancer survival significantly improved from 1976 to 2013, but there is room for further improvement. Survival rates varied by type of clinical treatment, language region and nationality. All paediatric cancer patients should be referred to a specialised paediatric cancer centre. Further research is needed to intervene and completely eliminate inequalities in survival.     

Computed tomography (CT) evaluation of breast cancer patients with osteolytic bone metastases undergoing palliative radiotherapy—a feasibility study

Twenty-five patients with osteolytic metastases had computed tomography (CT) scans before and 3 months after palliative radiotherapy. The median % density change following single 8 Gy, 20 Gy/5#, 30 Gy/10# were: 128 (range 98–255), 141 (79–342), and 145 (65–235), respectively. It is feasible to evaluate remineralization of osteolytic lesions with palliative radiotherapy.     

控烟是预防肺癌的主要措施——记太原市肺癌病例对照流行病学调查

背景 与目的:山西省太原市空气污染常较为严重.了解各种类型肺癌的危险因素,以采取有效的预防措施.方法:2005年3月—2007年9月,山西省太原市396例肺癌新发病例和465名健康对照者纳入本研究.利用太原市肿瘤医院病理学检查确诊的肺癌病例,配以人群为基础、随机选择的对照,进行病例对照询问调查和环境监测.分析时注意排除...     

Changing socioeconomic inequalities in cancer incidence and mortality: Cohort study with 54 million person‐years follow‐up 1981–2011

Cancer is increasingly responsible for the mortality gap between high and low socioeconomic position groups in high‐income countries. This study investigates which cancers are contributing more to socioeconomic gaps in mortality and how this changes over time.New Zealand census data from 1981, 1986, 1991, 1996, 2001 and 2006, were linked to three to five years of subsequent mortality and cancer registrations, resulting in 54 and 42 million years of follow‐up cancer incidence and mortality, respectively. Age‐ and ethnicity‐standardised cancer mortality rates and the slope index of inequality (SII) by income were calculated.The contribution of cancer to absolute inequalities (SII) in mortality increased from 16 to 27% for men and from 12 to 31% for women from 1981–84 to 2006–11, peaking in 1991–94 for men and in 1996–99 for women and then levelling off, parallel to peaks in lung cancer inequalities. Lung cancer was the largest driver of cancer inequality trends (49% of the cancer mortality gap in 1981–84 to 33% in 2006–11 for men and 32 to 33% for women) followed by colorectal cancer in men (2 to 11%) and breast cancer in women (declining from 44 to 13%). Women in the lowest income quintile experienced no decline in cancer mortality.The contribution of cancer to income inequalities in all‐cause mortality has expanded in this high‐income country. Action to address socioeconomic inequalities should prioritise equitable tobacco control, obesity control and improved access to cancer screening, early diagnosis and high quality treatment for those with the lowest incomes.     

Inv(16) may be one of the only ‘favorable’ factors in acute myeloid leukemia: A report on 19 cases with prolonged follow-up

We report our experience of treatment of acute myeloid leukemia (AML) with inv(16). Nineteen of 531 (3.6%) cases of newly diagnosed AML karyotyped over a 12 year period had inv(16)(p13q22) and none had t(16;16) or del 16q. Morphologically, all patients had M_4eo. All patients were treated with conventional anthracycline—Ara-C chemotherapy, followed by moderate or more intensive consolidation chemotherapy. All patients received central nervous system (CNS) prophylaxis with intrathecal methotrexate and Ara-C, and cranial irradiation.

Eighteen patients (95%) achieved complete remission (CR). Three had a bone marrow relapse, one had a CNS relapse and 14 patients remained in first CR, 11 of them with a followup greater than 44 months. Disease-free survival was 74% after 10 months, and actuarial survival 88% after 4 years, and 62% after 6 years. No other AML subgroup, in our experience, had a long-term survival approaching that of AML with inv(16) (although similar favorable outcome may be anticipated in acute promyelocytic leukemia treated by a combination of retinoic acid and chemotherapy).     

The cigarette burden (measured by the number of pack-years smoked) negatively impacts the response rate to platinum-based chemotherapy in lung cancer patients

PURPOSE: To evaluate the impact of the cigarette burden (CB) on the response rate to platinum-based chemotherapy (CT) in patients with lung cancer (LC). METHODS: Retrospective study of patients with LC treated by CT from 2000 to 2005, in a tertiary referral center in Brazil. The CB was measured by the number of pack-years smoked (PY). To evaluate the response (by RECIST), it was necessary to accomplish two cycles of CT. The relevant variables were studied by univariate and multivariate statistical techniques. RESULTS: Two hundred and eighty-five patients (203 men) were studied (mean age=60.6+/-10.1 years, mean PY=58.3+/-35.4). 62.8% were current smokers, 26.7% were former smokers, and 10.5% were non-smokers. 63.2% had non-small-cell lung cancer (NSCLC), and 36.8% had small-cell lung cancer (SCLC). The treatment intent was palliative in 63.9% and curative in 36.1%. All 285 patients received platinum-based CT (etoposide/cisplatin in 68.8% and etoposide/carboplatin in 31.2%). Of these, 155 patients (54.4%) received RT (median dose=50.0 Gy; range=45.0-80.0). The 94 patients (33.0%) who responded to treatment had a mean PY of 38.7+/-27.1, and the 191 patients (67.0%) who did not respond had a mean PY of 67.8+/-35.1, p<0.001. In the multivariate analysis, the main independent negative predictor was CB>or=40 PY (adjusted OR=10.42; 95% CI=5.13-21.28). The others independent negative predictors were: CT (no. of cycles=2-4) (adjusted OR=4.86; 95% CI=2.44-9.68), treatment regimen with CT alone (adjusted OR=3.38; 95% CI=1.67-6.84), and NSCLC histology (adjusted OR=2.75; 95% CI=1.12-6.76). CONCLUSION: Patients with CB>or=40 PY have a worse response to platinum-based CT compared to those who have a CB<40 PY.     

Evaluation of the Simplified Comorbidity Score (Colinet) as a prognostic indicator for patients with lung cancer: A cancer registry study

Introduction

A Simplified Comorbidity Score (SCS) provided additional prognostic information to the established factors in patients with non-small cell lung cancer lung cancer. We undertook this analysis to test the prognostic value of the SCS in a population-based study.

Patients and methods

Retrospective survey of all Victorians diagnosed with lung cancer in January–June 2003, identified from the Victorian Cancer Registry.

Results

There were 921 patients, with data available for 841 (91.3%). Median age was 72 years (range 30–94) and 63.1% were male. A tissue diagnosis was made for 89.9%, of which 86.6% were non-small cell (NSCLC), and 13.4% small cell carcinoma (SCLC). Comorbidities on which the SCS is based were distributed: cardiovascular 54.6%; respiratory 38.9%; neoplastic 19.9%; renal 4.6%; diabetes 11.7%; alcoholism 5.5%; and tobacco 83.1%.In patients with NSCLC, higher SCS score (>9) was associated with increasing stage, ECOG performance status, male sex, increasing age, tobacco consumption and not receiving treatment. Using Cox regression, survival was analysed by SCS score after adjusting for the effect of age, sex, cell type (NSCLC, SCLC, no histology), ECOG performance status and stage for all patients and then restricted to NSCLC. As a continuous or dichotomous (≤ or >9) variable, SCS was not a significant prognostic factor for all patients or when restricted to NSCLC.

Conclusion

In this retrospective analysis of population based registry patients, SCS did not provide additional prognostic information in patients with lung cancer. ECOG performance status may be a substitute for the effect of comorbidity.     

Synchronous cancer of squamous cell carcinoma of the lung and lymphocytic leukemia (B-cell type): a case report.

The patient was an 82-year-old male who consulted us over a lymph node enlargement in the right side of his neck. The WBC was 23,700/microliters (lymphocytes 80%), and a diagnosis of chronic lymphocytic leukemia (CLL) was given based on the findings of a bone marrow puncture and lymph node biopsy. During the observation period, abnormal shadows accompanied by cavitation appeared in the right lower lung field, and CT-guided percutaneous biopsy findings indicated a squamous cell carcinoma of the lung. No metastatic lesions were noted. No aggressive surgical or internal treatments were performed in consideration of the patient's age. The patient was admitted again and died of respiratory failure due to lung carcinoma. Reports of CLL and other malignant tumors arising in one patient are rare in Japan, and those of their occurring concurrently are even rarer. In the present report, a case of synchronous cancer of squamous cell carcinoma of the lung and CLL is described, together with a review of the literature.     

EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII)

Mutations in the epidermal growth factor receptor (EGFR) gene are commonly observed in non-small-cell lung cancer (NSCLC), particularly in tumors of adenocarcinoma (ADC) histology (NSCLC/ADC). Robust data exist regarding the prevalence of EGFR mutations in Western and Asian patients with NSCLC/ADC, yet there is a lack of data for patients of other ethnicities. This review collated available data with the aim of creating a complete, global picture of EGFR mutation frequency in patients with NSCLC/ADC by ethnicity. Worldwide literature reporting EGFR mutation frequency in patients with NSCLC/ADC was reviewed, to create a map of the world populated with EGFR mutation frequency by country (a ‘global EGFR mutMap’). A total of 151 worldwide studies (n=33162 patients with NSCLC/ADC, of which 9749 patients had EGFR mutation-positive NSCLC/ADC) were included. There was substantial variation in EGFR mutation frequency between studies, even when grouped by geographic region or individual country. As expected, the Asia-Pacific NSCLC/ADC subgroup had the highest EGFR mutation frequency (47% [5958/12819; 87 studies; range 20%-76%]) and the lowest EGFR mutation frequency occurred in the Oceania NSCLC/ADC subgroup (12% [69/570; 4 studies; range 7%-36%]); however, comparisons between regions were limited due to the varying sizes of the patient populations studied. In all regional (geographic) subgroups where data were available, EGFR mutation frequency in NSCLC/ADC was higher in women compared with men, and in never-compared with ever-smokers. This review provides the foundation for a global map of EGFR mutation frequency in patients with NSCLC/ADC. The substantial lack of data from several large geographic regions of the world, notably Africa, the Middle East, Central Asia, and Central and South America, highlights a potential lack of routine mutation testing and the need for further investigations in these regions.     

Secular trends in the incidence,mortality, and survival rate of gastric cancer in a general Japanese population: the Hisayama study

To examine secular trends in the incidence and mortality of gastric cancer in a Japanese community, Hisayama, we established three study-cohorts of Hisayama residents aged ≥40 years in 1961 (1637 subjects), 1974 (2054), and 1988 (2602). Each cohort was followed up for ten years. The age-standardized mortality from gastric cancer significantly decreased from 2.4 per 1000 person-years in the first cohort to 0.8 in the third cohort for men, and from 1.0 to 0.2, respectively, for women (p < 0.01 for trend in both sexes). The five-year survival rate after gastric cancer significantly improved from the first (32.6%) to the third cohort (73.0%, p < 0.01) for men and from 43.2% to 72.3% (p < 0.05), respectively, for women. The age-standardized incidence of cancer in men was not different among the cohorts (4.3 per 1000 person-years in the first, 5.0 in the second, and 4.9 in the third cohort), while it decreased significantly in women (2.0, 1.8, and 1.2, respectively, p < 0.01 for trend). In conclusion, our findings suggest that in a Japanese population, the mortality from gastric cancer declined during the past 40 years, due mainly to the improvement of survival in both sexes and a decrease in the incidence for women.     

Childhood cancer survival in Finland (1953–2010): A nation‐wide population‐based study

Population based survival studies are critical in monitoring changes in anticancer therapy, evaluating effectiveness of new treatments as well as identifying possibilities for further improvement. The previous report on cancer survival in Finland covered patients diagnosed in 1953–1995. Data on survival in the European and Nordic pediatric populations have been published with follow‐up ending in 2002. We describe population‐based survival of childhood cancer patients (n = 8270, age 0–14 years) in Finland overall and by disease category with follow‐up extending from 1953 to 2010 and focusing on the modern treatment era. Data were collected from the Finnish Cancer Registry. Age‐standardised observed survival proportions (rates) were calculated using the actuarial (or life‐table) method. Trends in observed survival rates were studied over six diagnostic periods: 1953–1960, 1961–1970, 1971–1980, 1981–1990, 1991–2000 and 2001–2010. The overall 5‐year survival reached 82.1% (95% CI 80.0–84.2) in the most recent period. In most diagnostic categories, the biggest leap in survival was seen between 1961–1970 and 1981–1990, after which slight improvements occurred between 1981–1990 and 1991–2000, with no significant increase thereafter. In analyses by diagnostic group, positive trends in survival over the last three decades were seen for leukemia (p = 0.000), non‐Hodgkin's lymphoma (p = 0.002) and CNS tumours (p = 0.02). Although survival of childhood cancer patients overall has significantly improved from 1953 to 2000, improvement thereafter has been marginal. Future treatment efforts should be directed at bone tumours, soft‐tissue sarcoma, neuroblastoma and malignant brain tumours as well as high‐risk leukemia.     

An evaluation of serum microelement concentrations in lung cancer and matched non-cancer patients to determine the risk of developing lung cancer: a preliminary study.

In a case-control study to determine the risk of developing lung cancer, the serum levels of vitamins A and E, carotene and selenium were determined in 31 patients, newly diagnosed as having lung cancer, and in matched controls, the said controls being selected from outpatients with no cancer. A significant, inverse association was found between serum vitamins A and E and lung cancer. The relative risk for the low vs high tertiles were, respectively, 5.94 for serum vitamin A and 8.44 for serum vitamin E. Taking histological cancer subtype into account, no relation was revealed between the microelements and squamous cell carcinoma of the lung. The relative risk for lung cancer was 6.50, however, when three, or all four, microelement levels were in the lowest tertile, compared with there being fewer than three in the lowest tertile. Even when three microelements, excluding vitamin E which had the most significant inverse association with lung cancer, were considered, the relative risk was 7.50 when any two or all three were in the lowest tertile, compared with there being just one microelement or none at all in the lowest tertile. A combined effect of vitamins A and E, carotene and selenium on the development of lung cancer has, therefore, been suggested. Further studies will thus be necessary to elucidate the cumulative effect of the serum micronutrients and trace elements, as well as the effect of single elements, on the development of lung cancer.     

Feasibility of the use of the Active Breathing Co ordinator™ (ABC) in patients receiving radical radiotherapy for non-small cell lung cancer (NSCLC)

Introduction

One method to overcome the problem of lung tumour movement in patients treated with radiotherapy is to restrict tumour motion with an active breathing control (ABC) device. This study evaluated the feasibility of using ABC in patients receiving radical radiotherapy for non-small cell lung cancer.

Methods

Eighteen patients, median (range) age of 66 (44-82) years, consented to the study. A training session was conducted to establish the patient’s breath hold level and breath hold time. Three planning scans were acquired using the ABC device. Reproducibility of breath hold was assessed by comparing lung volumes measured from the planning scans and the volume recorded by ABC. Patients were treated with a 3-field coplanar beam arrangement and treatment time (patient on and off the bed) and number of breath holds recorded. The tolerability of the device was assessed by weekly questionnaire. Quality assurance was performed on the two ABC devices used.

Results

17/18 patients completed 32 fractions of radiotherapy using ABC. All patients tolerated a maximum breath hold time >15 s. The mean (SD) patient training time was 13.8 (4.8) min and no patient found the ABC very uncomfortable. Six to thirteen breath holds of 10-14 s were required per session. The mean treatment time was 15.8 min (5.8 min). The breath hold volumes were reproducible during treatment and also between the two ABC devices.

Conclusion

The use of ABC in patients receiving radical radiotherapy for NSCLC is feasible. It was not possible to predict a patient’s ability to hold breath. A minimum tolerated breath hold time of 15 s is recommended prior to commencing treatment.     

Time trends in the prevalence of HPV in oropharyngeal squamous cell carcinomas in northern Spain (1990–2009)

Recent studies support an important role for human papillomavirus (HPV) in oropharyngeal squamous cell carcinomas (OPSCC), although the incidence varies widely depending on the geographic location and time period studied. The aim of this study was to determine the proportion of HPV in a large cohort of OPSCC in northern Spain in the years 1990–2009. Clinical records and paraffin embedded tumor specimens of 248 consecutive patients surgically treated for OPSCC (140 tonsillar and 108 base of tongue) between 1990 and 2009 were retrieved. OPSCC cases were histomorphologically evaluated, and protein expression of p16 and p53 was analyzed by immunohistochemistry. Detection of high‐risk HPV DNA was performed by GP5+/6+‐PCR and in situ hybridization (ISH). Thirty cases (12%) were positive for p16 immunostaining, of which eight (3.2% of the total series) were found positive for HPV type 16 by genotyping of GP5+6+‐PCR products. All HPV GP5+/6+‐PCR‐positive tumors were p53‐immunonegative, seven had a basaloid morphology and seven were also positive by HPV ISH. Presence of HPV correlated inversely with tobacco and alcohol consumption (p < 0.001), but not with age of onset of OPSCC. Overall survival was better in the HPV‐positive group, although not statistically significant (p = 0.175). OPSCC patients in northern Spain demonstrated a low involvement of HPV, increasing (although not significantly, p = 0.120) from 1.8% in 1990–1999 to 6.1% of cases in 2000–2009.     

Induction of pulmonary neoplasia in the smoke-exposed ferret by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK): a model for human lung cancer

Research into dietary chemoprevention against lung carcinogenesis has been limited by the lack of appropriate animal models that closely mimic smoking-related human lung cancer. Ferrets (Mustela putorius furo) have been used to study the biologic activities of carotenoids against smoke-induced lung lesions, but this model has yet to be thoroughly established and validated. To determine the appropriateness of the ferret as a model for human lung cancer, we have performed a 6-month in vivo study in ferrets exposed to both tobacco smoke and a carcinogen (4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone, NNK) found in cigarette smoke. Results showed that six out 12 ferrets exposed to both NNK injection and cigarette smoke developed grossly identifiable lung tumors whereas none of nine ferrets from the sham treatment group developed any lung lesions. The histopathological types of these tumors (squamous cell carcinoma, adenosquamous carcinoma and adenocarcinoma) in ferret lungs are very similar to those in humans. In addition, 10 out of 12 ferrets exposed to both NNK and cigarette smoke developed preneoplastic lesions (squamous metaplasia, dysplasia, and atypical adenomatous hyperplasia) with complex growth patterns whereas the sham group did not show any of these lesions. Furthermore, the expression of proliferating cellular nuclear antigen increased markedly in both gross tumors and preneoplastic lesions in the lungs. In summary, the development of both preneoplastic lesions and gross lung tumors in ferrets provides an excellent and unique model for studying lung cancer chemoprevention with agents such as carotenoids, and for studying the molecular mechanism of carcinogenesis in the earlier stages of smoke-related lung cancer.     

Drivers of advanced stage at breast cancer diagnosis in the multicountry African breast cancer – disparities in outcomes (ABC‐DO) study

Breast cancer (BC) survival rates in sub‐Saharan Africa (SSA) are low in part due to advanced stage at diagnosis. As one component of a study of the entire journey of SSA women with BC, we aimed to identify shared and setting‐specific drivers of advanced stage BC. Women newly diagnosed in the multicountry African Breast Cancer–Disparities in Outcomes (ABC‐DO) study completed a baseline interview and their stage information was extracted from medical records. Ordinal logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for advanced stage (I, II, III, IV) in relation to individual woman‐level, referral and biological factors. A total of 1795 women were included from Nigeria, Uganda, Zambia, and the multiracial populations of Namibia and South Africa, 1091 of whom (61%) were stage III/IV. Stage was lower in women with greater BC knowledge (OR 0.77 (95% CI: 0.70, 0.85) per point on a 6 point scale). More advanced stage was associated with being black (4.00 (2.79, 5.74)), having attended <secondary education (1.75 (1.42, 2.16)), having never heard of BC (1.64 (1.31, 2.06)), an unskilled job (1.77 (1.43, 2.20)) and pregnancy in the past 3 years (30% of ≤45 year olds) (1.63 (1.15, 2.31)), and were mediated through delays to diagnosis: symptom duration of ≥ 1 year (OR 2.47 (1.93, 3.15)). These findings provide further evidence that late‐stage BC in SSA is largely attributed to modifiable factors and strategies to improve BC education and awareness in women and the health system should be intensified.