bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncommon Breast Malignancies: Presentation Pattern, Prognostic Issue and Treatment Outcome in an Italian Single Institution Experience
Authors: Maria Regina Bareggi Claudia , Consonni Dario , Galassi Barbara , Gambini Donatella , Locatelli Elisa , Visintin Roberto , Runza Letterio , Giroda Massimo , Sfondrini Maria Silvia , Onida Francesco , Tomirotti Maurizio
Published: February 2018

Aims and background

Often neglected by large clinical trials, patients with uncommon breast malignancies have been rarely analyzed in large series.

Patients and methods

Of 2,052 patients diagnosed with breast cancer and followed in our Institution from January 1985 to December 2009, we retrospectively collected data on those with uncommon histotypes, with the aim of investigating their presentation characteristics and treatment outcome.

Results

Rare histotypes were identified in 146 patients (7.1% of our total breast cancer population), being classified as follows: tubular carcinoma in 75 (51.4%), mucinous carcinoma in 36 (24.7%), medullary carcinoma in 25 (17.1%) and papillary carcinoma in 10 patients (6.8%). Whereas age at diagnosis was not significantly different among the diverse diagnostic groups, patients with medullary and papillary subtypes had a higher rate of lymph node involvement, similar to that of invasive ductal carcinoma. Early stage diagnosis was frequent, except for medullary carcinoma. Overall, in comparison with our invasive ductal carcinoma patients, those with rare histotypes showed a significantly lower risk of recurrence, with a hazard ratio of 0.28 (95% CI, 0.12–0.62; P = 0.002).

Conclusions

According to our analysis, patients with uncommon breast malignancies are often diagnosed at an early stage, resulting in a good prognosis with standard treatment.
Plasma Osteopontin Level as a Diagnostic Marker of Hepatocellular Carcinoma in Patients with Radiological Evidence of Focal Hepatic Lesions
Authors: Khalil Ashraf , Elgedawy Jamalat , Faramawi Mohammed F , Elfert Ashraf , Salama Ibrahim , Abbass Ahmed , Elsaid Hala , Elsebaai Hatem
Published: February 2018

Aims

Hepatocellular carcinoma is one of the most aggressive malignant tumors and has limited treatment options. Needle-guided biopsies have been utilized as a tool to diagnose malignant focal hepatic lesions. These techniques are discouraged because of their complications. Nowadays, alpha fetoprotein is the most widely used tumor marker for screening and diagnosis of hepatocellular carcinoma. Nevertheless, this marker has limitations. The diagnostic role of plasma osteopontin as an adjuvant or alternative marker to alpha fetoprotein to detect hepatocellular carcinoma in Egyptian patients with focal hepatic lesions was evaluated in this study.

Subject and methods

Eighty participants were recruited from the Egyptian National Liver Institute and were self-assigned to three groups, namely, focal hepatic lesions (n = 40), liver cirrhosis (n = 20), and controls (n = 20). Participants' plasma osteopontin and serum alpha fetoprotein levels were determined and were compared across the three groups.

Results

The discriminatory ability of plasma osteopontin for hepatocellular carcinoma was lower than that of alpha fetoprotein. Osteopontin and alpha fetoprotein were not correlated with each other. Neither the gender nor the age of the patients showed a significant association with plasma osteopontin level.

Conclusion

Measuring plasma osteopontin level alone has no advantage over serum alpha fetoprotein in patients with focal hepatic lesions due to chronic liver disease.
Sentinel Lymph Node Biopsy in Breast Cancer: Review on Various Methodological Approaches
Authors: Zengel Baha , Yararbas Ulkem , Sirinocak Ahmet , Ozkok Guliz , Denecli Ali Galip , Postaci Hakan , Uslu Adam
Published: February 2018

Aims and background

Sentinel lymph node biopsy has been accepted as a standard procedure for early stage breast cancer. In this retrospective analysis, the results obtained with different methodological approaches using radiocolloid with or without blue dye were examined.

Methods

A total of 158 sentinel lymph node biopsies were performed in 152 patients. Group A (85 patients) underwent lymphatic mapping using a combination of periareolar intradermal radiocolloid and subareolar blue dye injections. Group B (73 patients) underwent only periareolar intradermal radiocolloid injection. One large tin colloid and two small radiocolloids (nanocolloid of serum albumin -NC- and colloidal rhenium sulphide -CS-) were used.

Results

Successful lymphatic mapping was attained in 157 of 158 procedures (99.4%). Radiocolloids localized sentinel lymph nodes in 99.4% and blue dye in 75.3% of the cases. The number of sentinel lymph nodes removed was greater in nanocolloid and colloidal rhenium sulphide groups ( P ≤0.05). Among 60 metastatic sentinel lymph nodes, frozen section analysis using hematoxylin and eosin staining failed to detect 1 macro- and 10 micrometastasis. Radiocolloid uptake was higher in sentinel lymph nodes accumulating blue dye (1643 ± 3216 counts/10 sec vs 526 ± 1284 counts/10 sec, P <0.001). Higher count rates were obtained by using larger sized colloids (median and interquartile range: tin colloid, 2050 and 4548; nanocolloid, 835 and 1799; colloidal rhenium sulphide, 996 and 2079; P = 0.01). Only 2 extra-axillary sentinel lymph nodes were visualized using periareolar intradermal injection modality.

Conclusions

Radiocolloids were more successful than blue dye in sentinel lymph node detection. More sentinel lymph nodes were harvested with small colloids, but different sized radiocolloids were similarly successful. Sentinel lymph nodes having higher radiocolloid uptake tended to accumulate blue dye more frequently. Sentinel lymph nodes manifested higher count rates when a larger colloid was used. Frozen section was very successful in detecting macrometastatic disease in sentinel lymph nodes, but the technique failed in most of the micrometastates.
Once-Weekly Stereotactic Radiotherapy for Patients with Oligometastases: Compliance and Preliminary Efficacy
Authors: Corvò Renzo , Lamanna Giorgio , Vagge Stefano , Belgioia Liliana , Bosetti Davide , Aloi Deborah , Timon Giorgia , Bacigalupo Almalina
Published: February 2018

Aims and background

This retrospective analysis reports the outcomes obtained with an original once-weekly stereotactic radiotherapy fractionation given to patients affected by evolving oligometastases from different solid malignancies.

Methods

From 2009 to 2011, patients with symptomatic and/or evolving oligometastases were submitted to a median 5-fraction cycle of stereotactic radiotherapy of one fraction per week in order to exploit a radiobiological rationale designed to increase the therapeutic index. Individual fractionation was mainly planned according to patient performance status, oligometastasis size and site, and record of previous irradiation in the same site.

Results

Thirty-six patients in stage IV UICC-TNM affected by oligometastases were treated with image-guided intensity-modulated stereotactic tomotherapy with a single weekly radiation. Median age was 70 years (range, 34–89). The median weekly single dose, number of fractions and overall total radiation dose were 7 Gy, 5 fractions and 35 Gy, respectively. Thirty-five (97%) patients completed the treatment schedule. No patient suffered mild or severe radiation-related side effects. Twenty-one (87%) of 24 patients with local pain had complete symptomatic response within 30 days following the end of radiotherapy. Local control assessed at imaging after stereotactic radiotherapy was evidenced in 30 (83%) patients. Median time to response after the end of radiotherapy was 40 days.

Conclusions

The original radiotherapy regimen delivering only a single stereotactic dose per week seems to be highly feasible with an interesting high efficacy rate in patients with oligometastases from different solid tumors. Overall, the once-weekly treatment was very compliant in an advanced cancer stage especially for elderly and frail patients.
Predictive Factors for Child-Pugh Score Elevation in Hepatocellular Carcinoma Patients Treated with Conformal Radiation Therapy: Dose-Volume Histogram Analysis
Authors: Yu Jeong Il , Park Hee Chul , Lim Do Hoon , Park Woo Yoon
Published: February 2018

Aims and background

We designed the study to identify the clinical and dose-volumetric parameters associated with the risk of Child-Pugh score elevation in hepatocellular carcinoma patients treated with conformal radiation therapy.

Methods and study design

All 161 hepatocellular carcinoma patients in the study underwent 4D-computed tomography simulation, and a dose-volume histogram was generated after radiotherapy planning. Patients who had an elevated Child-Pugh (e-CP) score of 2 or more without progressive disease within 3 months were defined as e-CP positive.

Results

Twenty-six of 142 patients without progressive disease were e-CP positive. Pretreatment Child-Pugh class, further treatment within 30 days of radiotherapy, lymph node metastasis, mean liver dose, V20 Gy, V25 Gy, and V30 Gy were significantly correlated with e-CP positivity. The e-CP developed in 13 of 106 patients (12.3%) with V30 Gy of ≤28.1% and in 13 of 36 patients (36.1%) with V30 Gy >28.1% ( P = 0.001).

Conclusions

Our data demonstrate that mean liver dose, V10 Gy, V20 Gy, V25 Gy, and V30 Gy are independent dose-volumetric predictors for e-CP positivity in hepatocellular carcinoma patients treated with conformal radiation therapy. V30 Gy should be limited to less than 28.1% to minimize the risk of e-CP.
Suspecting Malignancy in Endometrial Polyps: Value of Hysteroscopy
Authors: Daniele Alberto , Ferrero Annamaria , Maggiorotto Furio , Perrini Gaetano , Volpi Eugenio , Sismondi Piero
Published: February 2018

Aims and background

Hysteroscopic polypectomy is the gold standard to treat endometrial polyps and obtain specimens for histological evaluation. There is continuing debate as to when to offer hysteroscopic polypectomy, especially in asymptomatic women with incidental lesions. The aims of this study were to assess the accuracy of hysteroscopy and Vabra sampling in diagnosing atypical hyperplasia and cancer growing on the surface of endometrial polyps and to investigate the association between atypical endometrial polyps and some potential clinical risk factors.

Methods and study design

This was a retrospective study. We assessed 1039 hysteroscopies and we identified 345 women with endometrial polyps. All patients with endometrial polyps underwent hysteroscopic polypectomy. Data about age, menopausal status, abnormal uterine bleeding (AUB), hormone replacement therapy and tamoxifen use were collected. Hysteroscopic, histological and clinical data were analyzed.

Results

The incidence of endometrial hyperplasia or cancer growing on the surface of endometrial polyps was significantly low (1.7%). Hysteroscopy correctly excluded (negative predictive value: 100%) and accurately predicted (positive predictive value: 85.7%) preneoplastic or neoplastic lesions growing within the epithelial layer of endometrial polyps. Vabra sampling was inadequate for the histological diagnosis in 38.5% of cases. Age over 60 years and postmenopausal AUB were associated with an 8.3-fold ( P = 0.022) and 8.8-fold ( P = 0.020) increased risk, respectively, of preneoplastic and neoplastic lesions growing on the surface of endometrial polyps.

Conclusions

Diagnostic hysteroscopy is a good tool to predict malignancy of the epithelial layer of endometrial polyps. Age over 60 years and AUB are associated with an increased risk of malignant polyps. Few suspicious endometrial polyps should undergo surgical resection.
Proton Beam Radiotherapy: Report of the First Patient Treated at the Centro NAzionale di Adroterapia Oncologica (CNAO)
Authors: Orecchia Roberto , Srivastava Anurita , Fiore Maria Rosaria , Vitolo Viviana , Fossati Piero , Vischioni Barbara , Iannalfi Alberto , Tuan Jeffrey , Ciocca Mario , Molinelli Silvia , Mirandola Alfredo , Vilches Gloria , Mairani Andrea , Tagaste Barbara , Baroni Guido , Rossi Sandro , Krengli Marco
Published: February 2018

Proton beam radiotherapy, an innovative treatment modality, allows delivery of high radiation doses to the target while sparing surrounding healthy structures. The Centro Nazionale di Adroterapia Oncologica (CNAO), equipped with a synchrotron and capable of using both protons and ions, initiated its clinical activity in September 2011. The first treatment of a skull base tumor with protons is reported here.

The case of a 26-year-old man with an intracranial low-grade chondrosarcoma of the right petroclival junction is discussed with emphasis on technical and clinical details. Two previous surgical interventions had achieved partial removal of the tumor and the patient was treated with protons for residual disease. The prescribed dose was 70 GyE in 35 fractions of 2 GyE. Treatment was completed with minimal acute toxicity consisting of grade 1 alopecia and nausea. Nine months after treatment the disease is locally controlled. Use of high-energy protons at CNAO is a safe and effective means of treating a tumor located near critical normal structures.
Malignant Transformation of Abdominal Wall Endometriosis: Case Report and Literature Review
Authors: Vinchant Marie , Poncelet Christophe , Ziol Marianne , Vons Corinne , Bricou Alexandre
Published: February 2018

In recent years we have seen an increase in the frequency of cesarean sections. We present a case report of an endometrioid adenocarcinoma arising from abdominal wall endometriosis in a patient with a history of cesarean sections and describe its diagnostic and therapeutic management.
Adenoid Cystic Carcinoma of the Nasopharynx: A Case Report and a Discussion about Prognostic Factors and the Role of Local Treatments
Authors: Elkholti Youssef , Cosmidis Alain , Ardiet Jean Michel , Laffay Lisa , De Bari Berardino
Published: February 2018

Adenoid cystic carcinoma (ACC) is a rare epithelioid malignancy. It occurs most frequently in the salivary glands, while its localization in the nasopharynx is rare and few cases have been reported in the literature. We report the case of a 32-year-old woman presenting with ACC of the nasopharynx who was treated with surgery and adjuvant intensity-modulated radiation therapy (IMRT, total dose: 68 Gy) and concomitant chemotherapy (cisplatin 100 mg/m2 on the first and 21st days of IMRT). During irradiation, the patient developed G1 dermatitis and G2 mucositis (RTOG). Clinical and instrumental reevaluation 17 months after the end of radiotherapy did not show any signs of relapse, and she did not show any sign of local mild-severe toxicity. Adjuvant radiotherapy after standard complete surgical resection seems to be effective and well tolerated and should be strongly considered in the multidisciplinary approach to this infrequent carcinoma.
Estimates of cancer burden in Piedmont and Aosta Valley
Authors: Rosso Stefano , Sacchetto Lidia , Giacomin Adriano , Foschi Roberto , De Angelis Roberta , Rossi Silvia , Zanetti Roberto
Published: February 2018

Aims and background

Cancer registration in Piedmont currently covers the city of Turin and the province of Biella, together representing 24% of the regional population. The objective of this paper is to provide estimates of the incidence and mortality rates and prevalence proportions for cancer of the lung, breast, cervix, prostate, colon-rectum and stomach and melanoma of the skin for 2012 and the time trends up to 2015 for the Piedmont and Aosta Valley regions.

Methods

The estimates were obtained by applying the MIAMOD method, a statistical back-calculation approach to derive incidence and prevalence figures starting from mortality and relative survival data. Published data from the Italian cancer registries were modeled in order to estimate the regional cancer survival. The MIAMOD estimates were also compared with those obtained by applying a method based on the mortality-incidence and prevalence-incidence ratios.

Results

The most frequently diagnosed cancers in absolute terms were prostate, colorectal, breast and lung cancer with about 5,000, 4,700, 3,300, and 2,900 new cases, respectively, in 2012. Incidence rates were rising for melanoma in both sexes and lung cancer in women, while they diminished for cervical and stomach cancer. For prostate cancer and male lung cancer the rates initially increased but were estimated to decrease in the most recent period. Colorectal cancer also increased up to the 1990s but was estimated to reach a plateau in the final years of estimation. Prevalence increased for all the considered cancers with the exception of cervical cancer. Mortality was declining for all considered cancers with the exception of lung cancer in women.

Conclusions

Monitoring indicators of the cancer burden is crucial for setting priorities among possible health system activities in a limited-resource setting. Piedmont has long invested in organized, population-based screening programs: these will have to be extended and accompanied by greater efforts in primary prevention.
Estimates of cancer burden in Veneto
Authors: Tognazzo Sandro , De Angelis Roberta , Ciampichini Roberta , Gatta Gemma
Published: February 2018

Aims and background

In Veneto a regional cancer registry has been operating since 1987 which provides incidence and survival data for the region. It currently covers 48% of the regional population. The aim of this paper is to provide estimates of the incidence, mortality and prevalence of the major cancers for the whole Veneto region in the period 1970—2015.

Methods

The estimates were obtained by applying the MIAMOD method, a statistical back-calculation approach to derive incidence and prevalence figures starting from mortality and relative survival data. Survival was modeled on the basis of published data from the Italian cancer registries.

Results

In 2012 the most frequent cancer sites were colon-rectum, prostate and breast with 4,677, 3,760 and 3,729 new diagnosed cases, respectively. The incidence rates were estimated to increase constantly for female lung cancer, prostate cancer, colorectal cancer and melanoma, while they were decreasing for cervical cancer and stomach cancer. For male lung cancer and female breast cancer the rates increased, reaching a peak, and then decreased. In the last years of the period of analysis, mortality declined for all cancers: the highest number of deaths (2,390 in both sexes) was estimated for lung cancer in 2012. Prevalence was increasing for all the considered cancer sites with the exception of lung cancer in men, for which the prevalence was estimated to increase until 2007 and then stabilize. By contrast, the cervical cancer decreased during the whole period. In 2012 breast cancer had the highest prevalence, with about 52,000 cases.

Conclusion

This paper provides a description of the burden of the major cancers in Veneto until 2015. The estimates highlight the continuing reduction of cancer mortality. This decline can be related to the improvement of clinical treatments and to multidisciplinary treatment approaches. In order for this positive trend to continue, implementation and reinforcement of the screening programs is needed, especially for breast and colorectal cancer.
Estimates of cancer burden in Tuscany
Authors: Ventura Leonardo , Miccinesi Guido , Buzzoni Carlotta , Crocetti Emanuele , Paci Eugenio , Foschi Roberto , Rossi Silvia
Published: February 2018

Aims and background

The Tuscan cancer registry has been operating since 1985, providing cancer incidence and survival data in Tuscany; it covers about 33% of the regional population. The purpose of this paper is to provide incidence, prevalence and mortality estimates for the major cancers in the whole Tuscany region for the period 1970—2015.

Methods

The estimated figures were obtained by applying the MIAMOD method. Starting from mortality and survival data, incidence and prevalence were derived using a statistical back-calculation approach. Survival was modeled on the basis of published data from the Italian cancer registries.

Results

According to the estimates, the most frequent cancer sites were colon-rectum in both genders, prostate in men and breast in women, with 4,188, 3,082 and 3,092 new diagnoses, respectively, in 2012. The incidence rates were steadily increasing for lung cancer in women and melanoma in both sexes, while they were decreasing for uterine cervix cancer in women, lung cancer in men and stomach cancer in both sexes. For colorectal cancer a small reduction in incidence was estimated for both sexes in recent years. The incidence rates for prostate cancer, after a steep increase and subsequent stabilization, were estimated to increase slightly in the last years. The breast cancer incidence was estimated to stabilize in the last 10 years. The mortality trends were decreasing for all considered cancers except female lung cancer. Prevalence increased for most of the studied cancers except stomach cancer in both sexes, lung cancer in men and cervix cancer in women. The highest prevalence was estimated for breast cancer, with over 42,000 cases in 2012.

Conclusion

This paper provides an updated description of the cancer burden in Tuscany until 2015. These trends will have a significant impact on the regional health services and it is therefore important to enhance both primary prevention, for reducing the cancer incidence, and oncological surveillance, for evaluating the care and assistance of cancer patients.
Estimates of cancer burden in Umbria
Authors: Stracci Fabrizio , Petrucci Maria Saba , Ciampichini Roberta , Tavilla Andrea , Foschi Roberto
Published: February 2018

Aims and background

Model-based estimates and projections of epidemiological indicators related to cancer are important tools to support public health policies and planning. The aim of the present study is to produce projections of cancer incidence, mortality and prevalence for the Umbria region (900,000 inhabitants) in central Italy.

Methods

The estimations were obtained by applying the MIAMOD method, a statistical back-calculation approach to derive incidence and prevalence figures starting from mortality and relative survival data. Published data from the Italian cancer registries were modeled in order to estimate regional cancer survival. Estimated incidence rates were validated with observed incidence rates obtained from the Umbria regional cancer registry.

Results

The most frequent cancer sites estimated were colon-rectum, prostate and breast in women, with 970, 615 and 729 new diagnoses, respectively, in 2012. The incidence rates were increasing for female lung cancer, male colorectal cancer, and melanoma. By contrast, the rates have been declining for cervix and stomach cancer. For lung cancer and prostate cancer in men and colorectal cancer in women the rates increased, reaching a peak in different periods, and then decreased. The incidence rates of breast cancer rose, reaching a plateau in the mid 2010s. Favorable mortality trends were predicted for all cancers except skin melanoma and lung cancer in women. The prevalence of cancer was increasing with the only exception of cervical cancer in women and lung cancer in men in the most recent estimation period.

Conclusion

The scenario found for cancer incidence and prevalence was largely influenced by screening activities, so that increasing or stable incidence rates may reflect active preventive efforts. Aging, screening, and more complex and costly treatments pose a problem of sustainability and selection of interventions to the regional oncology system. Evaluation of effectiveness of intervention and cost-benefit analyses will be important to ensure cancer control in the future.
Estimates of cancer burden in Marche
Authors: Tavilla Andrea , Vitarelli Susanna , Rossi Silvia , Foschi Roberto
Published: February 2018

Aims and background

The aim of this paper is to provide estimates of the incidence, mortality and prevalence of seven major cancers in the Marche region for the period 1970—2015.

Methods

The MIAMOD method, a statistical back-calculation approach, was applied to derive incidence and prevalence figures from mortality and relative survival data. Published data from the Italian cancer registries were used as the basis for survival modeling.

Results

Colorectal, breast and prostate cancer were the most frequent cancers in 2012, with 1,563, 1,215 and 1,191 estimated incident cases, and leading to 539, 224 and 228 deaths, respectively. Age-standardized rates were estimated to decrease for stomach and cervical cancer and to increase for skin melanoma and female lung cancer. In men, the lung cancer incidence rates reached their maximum level during the late 1980s and decreased thereafter. The colorectal cancer trend showed an initially increasing pattern, followed by a decrease in the last decade, both for men and women. The estimated incidence rates of prostate cancer presented a very steep rise in the period 1985—2002 and then remained stable at the high levels reached in 2003. The largest increases in prevalence were for breast, colorectal and prostate cancer, for which 17,098, 11,844 and 9,269 cases were estimated, respectively, in 2012.

Conclusion

This paper provides a description of the burden of the major cancers in the Marche region until 2015. The estimates were fairly consistent with previously published data by the Macerata province cancer registry. The MIAMOD method provides a picture of the impressive increase in the prevalence of breast cancer and prostate cancer over the period studied, thereby allowing to foresee an increasing demand for cancer care services as one of the major challenges for the regional health care system.
Estimates of cancer burden in Italy
Authors: Rossi Silvia , Crocetti Emanuele , Capocaccia Riccardo , Gatta Gemma ,   AIRTUM Working Group, Buzzoni C. , Giacomin A. , Zanetti R. , Bisanti L. , Tessandori R. , Crosignani P. , Vercelli M. , Mazzoleni G. , Piffer S. , Zambon P. , Serraino D. , Ferretti S. , Michiara M. , Federico M. , de Leon M. Ponz , Mangone L. , Falcini F. , Crocetti E. , La Rosa F. , Vitarelli S. , Pannozzo F. , Fusco M. , Donato A. , Traina A. , Tumino R. , Madeddu A. , Contrino M.L. , Budroni M.
Published: February 2018

Aims and background

This paper presents updated estimates of the incidence, prevalence and mortality of stomach, colorectal, lung, breast, uterine cervix and prostate cancer and skin melanoma in the Italian population. In particular, point estimates for 2012 and time trends from 1970 to 2015 will be provided.

Methods

The presented figures were obtained by summing up the regional epidemiological indicator estimates presented in the other papers of this monographic issue, which were derived by applying the MIAMOD statistical back-calculation method to cancer registries survival data and official mortality rates.

Results

Our findings indicate that breast, colon-rectum and prostate will be the cancer sites with the highest incidence rates in the forthcoming years. The incidence rates still tend to increase for breast, male colorectal cancer and female lung cancer as well as for skin melanoma. By contrast, the incidence of stomach cancer, cervical cancer and male lung cancer, by far the most common tumor sites up to the early 1990s, will continue to decrease. The mortality estimates showed a decreasing trend for all considered cancers with the only exception of lung cancer in women.

Conclusion

These results point to the need to reinforce prevention activities by developing more effective preventive measures for population groups at risk. There is also a need to support timely and continuous cancer surveillance in the Italian population through cancer registries in order to monitor the spread of the cancer risk and to evaluate the impact of prevention policies and therapeutic advances.
Hypofractionated intensity-modulated radiotherapy using simultaneous integrated boost technique with concurrent and adjuvant temozolomide for glioblastoma
Authors: Yoon Sang Min , Kim Jeong Hoon , Kim Sang Joon , Khang Shin Kwang , Shin Seong Soo , Cho Young Hyun , Jwa Eunjin , Park Jin-hong , Ahn Seung Do
Published: February 2018

Aims and background

We assessed the therapeutic efficacy of combined hypofractionated intensity-modulated radiotherapy with temozolomide in patients with primary glioblastoma.

Methods and study design

Thirty-nine patients with histologically confirmed glioblastoma were accrued. Using the simultaneous integrated boost technique, a dose of 50 Gy in 5-Gy fractions was applied to the gross tumor volume, together with 40 Gy in 4-Gy fractions and 30 Gy in 3-Gy fractions to the 1- and 2-cm margins from the gross tumor volume, respectively. Patients were also treated with concurrent temozolomide during intensity-modulated radiotherapy, followed by six cycles of adjuvant temozolomide.

Results

Median follow-up was 16.8 months (range, 4.3–54.3). Tumor progression was observed in 28 patients (71.8%), and the median time to progression was 6.8 months. Median survival was 16.8 months, and it was affected significantly by the extent of surgery. During adjuvant temozolomide treatment, 3 patients (9.7%) developed grade 3–4 hematologic or hepatic toxicity. Radiation necrosis developed in 7 patients (17.9%) and massive necrosis, requiring emergency surgery, in 1 patient (2.6%).

Conclusions

The regimen of hypofractionated intensity-modulated radiotherapy with temozolomide showed a relatively good outcome in patients with glioblastoma. Further studies are required to define the optimal fraction size for glioblastoma using this highly sophisticated radiation technique.
Expression of cell metabolism-related genes in different molecular subtypes of triple-negative breast cancer
Authors: Jeon Hyae Min , Kim Do Hee , Jung Woo-Hee , Koo Ja Seung
Published: February 2018

Aims and background

We evaluated the difference in and significance of cancer cell metabolism by molecular subtyping of triple-negative breast carcinoma.

Methods

Tissue microarrays from 122 surgical specimens of triple-negative breast carcinoma patients and immunohistochemical staining for CK5/6, epidermal growth factor receptor, claudin 3, claudin 4, claudin 7, E-cadherin, androgen receptor, and gamma-glutamyltransferase 1 were used to classify triple-negative breast carcinoma as follows: basal-like type, molecular apocrine type, claudin low type, mixed type and null type. In addition, immunohistochemical staining for metabolism-related proteins such as c-myc, insulin-like growth factor (g)-1, hypoxia-inducible factor 1–1α, glucose transporter 1, carbonic anhydrase IX antibody, macrophage migration inhibitory factor, and pyruvate dehydrogenase kinase 1 was used to compare the differences according to molecular subtype and clinicopathological factors.

Results

The basal-like type showed the highest proportion of high glucose transporter 1 expression (P = 0.049) and carbonic anhydrase IX antibody expression (P = 0.008). Hypoxia-inducible factor 1–1α expression was associated with lymph node metastasis (P = 0.001) and central fibrotic zone (P = 0.012), and high glucose transporter 1 expression was related to high histologic grade (P = 0.007), cytokeratin 5/6 positivity (P = 0.002), and central fibrotic zone (P = 0.017). Finally, carbonic anhydrase IX antibody was associated with cytokeratin 5/6 positivity (P = 0.001) and central fibrotic zone (P = 0.048).

Conclusions

Our study revealed the different characteristics of cancer cell metabolism according to the molecular subtypes of triple-negative breast carcinoma. Among them, basal-like type was the most glycolytic and acid-resistant phenotype.
A School-Based Peer-Led Smoking Prevention Intervention with Extracurricular Activities: The LILT-LdP Cluster Randomized Controlled Trial Design and Study Population
Authors: Bosi Sandra , Gorini Giuseppe , Tamelli Marco , Monti Claudia , Storani Simone , Carreras Giulia , Martini Andrea , Allara Elias , Angelini Paola , Faggiano Fabrizio
Published: February 2018

Aims and background

Few school programs are effective in preventing adolescents' tobacco smoking initiation. The “Lega contro i Tumori - Luoghi di Prevenzione” is a cluster randomized controlled trial designed to evaluate a school-based peer-led smoking prevention intervention with extracurricular activities for students aged 14–15 years. This paper presents the study design and the baseline characteristics of the study population.

Methods and study design

Twenty secondary schools located in the Reggio Emilia province took part in the study. Five schools were excluded because they already participated in smoking prevention interventions. The schools were randomized to control or intervention arms. The study population consisted of students attending the first grade. Components of the intervention included 1) the out-of-school “Smoking Prevention Tour” (SPT) at the “Luoghi di Prevenzione” Center, a 4-hour (4 sessions) extracurricular activity; 2) the “Smoke-free Schools” intervention, combining a life–skills-based peer-led intervention at school, an in-depth lesson on one of the SPT sessions, and enforcement surveillance of the school antismoking policy. Tobacco use was studied through a questionnaire administered before and 6 months after the intervention.

Results

Eleven high schools and 9 vocational secondary schools took part in the study for a total of 2,476 out of 3,050 eligible students (81.2%). The proportions of respondents in high schools and vocational secondary schools were 90.9% and 64.5%, respectively (P <0.001). Intervention and control arms showed a different distribution of gender and school type, whereas no difference was observed in any tobacco-use characteristic.

Conclusions

This study is one of the few Italian trials to evaluate the effectiveness of a school-based program for preventing smoking initiation.
Antismoking Centers in Milan's Communal Pharmacies: Analysis of the 2010–2011 Campaign
Authors: Munarini Elena , Marabelli Chiara , Marmotti Aldo , Gardiner Anna , Invernizzi Giovanni , Mazza Roberto , De Marco Cinzia , Pozzi Paolo , Boffi Roberto
Published: February 2018

Aims and background

According to recent assessments from the Italian Istituto Superiore della Sanità, information and assistance to smokers are still far from satisfactory. We evaluated the impact of a new smoking cessation service located in pharmacies. Smokers' individual characteristics were also considered.

Material and Methods

A 1-year pilot study was carried out from October 2010 to September 2011. Five pharmacies in Milan were selected. A psychologist with experience in smoking cessation was present in each pharmacy one afternoon per week, and pharmacists were trained by a team from the Antismoking Center of the Fondazione IRCCS Istituto Nazionale dei Tumori. Each pharmacy was equipped with informative material, carbon monoxide analyzers, and motivational and nicotine dependence questionnaires, in addition to a clinical briefcase. Counseling sessions were also arranged upon request.

Results

In the first 12 months of activity, 216 persons asked for a consultation. The sample, aged 15–79 years, reported the following median values: 30 pack/years, 14 ppm CO, and a Fagerström Test of Nicotine Dependence score of 5. More than one-third of the sample (40.3%) had one pathology and 25% had more than one. In some cases (15.7%), people just wanted information about what the service offered. For those who tried to quit, smoking cessation rates were 33.3% at 3 months, 28% at 6 months, and 24.6% at 1 year. Three kinds of pharmacologic therapies were suggested to smokers: nicotine replacement therapy (75.5%), varenicline (17.5%), and bupropion (7%).

Conclusions

The results show that an accessible and free smoking cessation service is considered useful by smokers as demonstrated by the large number of requests compared with other smoking centers in Italy. Increased involvement of pharmacists in supporting smoking cessation makes this a promising initiative for the near future.
Male Breast Cancer: Clinical Features and Multimodal Treatment in a Retrospective Survey Analysis at Italian Centers
Authors: La Verde Nicla , Collovà Elena , Lonardi Sara , Generali Daniele , Moretti Anna , Atzori Francesco , Cazzaniga Marina , Saggia Chiara , Tondulli Luca , Marcon Ilaria , Gentile Anna Lisa , Rossello Rosalba , Martelli Olga , Aglione Stefania , Farina Gabriella , Cinquini Michela , Garassino Marina
Published: February 2018

Aims and background

We report a collection of data about early breast cancer in male patients from 13 Italian institutions.

Methods and study design

We obtained data from patient charts and performed statistical analysis. The primary end points were overall survival and disease-free survival.

Results

A total of 205 men with invasive breast cancer was identified, with a median age of 66 years. Pathological characteristics were heterogeneous for T stage, N stage and HER2 status. Histological subtype was predominantly ductal infiltrating carcinoma. Most of them were hormone receptor positive. Mastectomy was the most common strategy. Postsurgical treatment was not standardized. Patients with large tumors were more likely to be treated with chemotherapy. Disease recurrence was associated with an ER+ and PR+ status.

Conclusions

We identified a correlation between relapse and hormone receptor expression, as is the case in female breast cancer.
Nuclear Localization of Cancer Stem Cell Marker CD133 in Triple-Negative Breast Cancer: A Case Report
Authors: Cantile Monica , Collina Francesca , D'Aiuto Massimiliano , Rinaldo Massimo , Pirozzi Giuseppe , Borsellino Carmela , Franco Renato , Botti Gerardo , Di Bonito Maurizio
Published: February 2018

Aim and background

It has been recently demonstrated that the detection of stem cell niches in triple-negative (TN) breast cancer may provide good prognostic clues for this tumor.

Methods and study design

We investigated the subcellular expression and localization of the cancer stem cell marker CD133 in a TN breast cancer biopsy from a 42-year-old Caucasian woman with a histological diagnosis of high-grade invasive ductal breast carcinoma by immunohistochemistry, flow cytometry and quantitative real-time PCR (qRT-PCR).

Results

We describe for the first time in a TN breast cancer the nuclear mislocalization of CD133, which normally shows membrane localization and more sporadically cytoplasmic localization. We also found this aberrant expression with qRT-PCR analysis but not flow cytometry.

Conclusions

Nuclear localization of CD133 may be an indicator of poor prognosis in TN breast cancer, as it is known that surface molecules, when moving into the nucleus, can act as transcriptional regulators by interfering with molecular pathways directly connected to the proliferation and differentiation of tumor cells.
Timing of Failure in Limited Disease (Stage I-III) Small-Cell Lung Cancer Patients Treated with Chemoradiotherapy: A Retrospective Analysis
Authors: Manapov Farkhad , Klöcking Sabine , Niyazi Maximilian , Oskan Feras , Niemöller Olivier M , Belka Claus , Hildebrandt Guido , Fietkau Rainer , Klautke Gunther
Published: February 2018

Aims and background

Follow-up in limited disease (stage I-III) small cell lung cancer could be further optimized by assessment of the temporal and locational distribution of treatment failure after completion of chemoradiotherapy.

Methods and study design

Follow-up was retrospectively analyzed in 125 limited disease (stage I-III) small cell lung cancer patients with initial performance status WHO <3 who had successfully completed chemoradiotherapy. Thoracic irradiation was applied in the concurrent or sequential mode. Time from initial pathological diagnosis and treatment end to local, distant and brain recurrence was documented.

Results

One- and two-year progression-free survival rates were 50% and 27.2% in patients treated with concurrent and 45.2% and 14.2% in those treated with sequential chemoradiotherapy, respectively. Local relapse was documented in 14% patients treated with concurrent and 16% with sequential chemoradiotherapy. The distant failure rate was 43% in both subgroups. Up to the end of the follow-up period, more patients treated with concurrent chemoradiotherapy had developed brain metastases than those treated sequentially (37% vs 20%, P = 0.049). Median time (in days) to local relapse was 376 and 401 from the initial diagnosis, 200 and 309 from the end of chemotherapy, and 316 and 196 from the end of thoracic irradiation; to distant failure was 275 and 298 from the initial diagnosis, 151 and 157 from the end of chemotherapy and 180 and 84 from the end of thoracic irradiation; to brain relapse was 330 and 273 from the initial diagnosis, 123 and 151 from the end of chemotherapy and 213 and 73 from the end of thoracic irradiation in patients treated with concurrent and sequential chemoradiotherapy, respectively. There was no significant difference in the temporal distribution of treatment failure in either subgroup.

Conclusions

In more than half of the patients who developed a distant recurrence, including brain metastases, treatment failure occurred in the first year after the initial diagnosis. Intensified follow-up can be recommended at least in the first year, because no sufficient eradication of the systemic small cell lung cancer with the applied chemoradiotherapy protocol could be achieved.
Non-small cell lung cancer in surgically treated women
Authors: Rena Ottavio , Massera Fabio , Boldorini Renzo , Papalia Esther , Turello Davide , Davoli Fabio , Baietto Guido , Roncon Alberto , Robustellini Mario , Casadio Caterina
Published: February 2018

Aim and background

To determine whether female patients operated on for non-small cell lung cancer (NSCLC) have a survival advantage compared to male patients.

Methods and study design

We analyzed data from 1,426 prospectively collected patients submitted to lung resection for NSCLC between 1999 and 2008.

Results

Two groups, including 1,014 male and 412 female patients, were compared. Female patients were significantly younger, were more frequently asymptomatic, were less likely to be smokers, had better preoperative respiratory function, had a lower frequency of COPD, and were less commonly affected by cardiovascular comorbidity than men. Adenocarcinoma was more frequently present and early pathological stage (stage IA) more frequently detected in women at diagnosis. The operative mortality was significantly lower among women (1.6% vs 4.6%) (P = 0.012), and women underwent significantly more segmentectomies and fewer pneumonectomies (P = 0.001). The disease-related 5-year survival rate was significantly higher in women (66% vs 51%) (P= 0.0008). At univariate analysis the absence of symptoms at presentation, lower pathological stage, squamous cell type, and female gender were positive factors influencing long-term survival. At multivariate analysis low pathological stage, squamous cell type and female gender were confirmed as independent positive prognostic predictors. Women had a significant survival advantage irrespective of the histological subtype at pathological stage IA, IB, IIB and IIIA disease (P <0.05).

Conclusions

Female gender was confirmed to be a particular subset amongst patients affected by NSCLC and exerted a positive effect on disease-related survival of patients submitted to surgical resection. This important effect of gender should be cautiously kept in mind in analyzing the results of current and future trials for lung cancer therapy.
Tumor refractoriness to endostatin anti-angiogenesis is associated with the recruitment of CD11b+Gr1+ myeloid cells and inflammatory cytokines
Authors: Zhang Hui , Wang Zi , Peng Qian , Liu Yan-Yang , Zhang Wei , Wu Lu , Wang Xia , Luo Feng
Published: February 2018

Aims and background

A major challenge in developing antiangiogenic therapies is tumor intrinsic refractoriness and the emergence of treatment-induced resistance. Recently, such resistance is considered to be associated with inflammatory changes in the tumor microenvironment. However, no information has been acquired about the effect of endostatin on tumor microenvironment in this field. We established two tumor models refractory to endostatin treatment and sought to determine the role of inflammatory changes in the development of tumor refractoriness to antiangiogenic therapy.

Methods

Three xenograft tumor murine models were treated with low-dose endostatin or high-dose endostatin for 10 days. The effect of endostatin on tumor growth was observed, and tumors refractory to endostatin treatment were defined. Flow cytometry were carried out to assess the presence of CD11b+Gr1+ myeloid cells in the peripheral blood and in the tumor. Inflammatory cytokine levels in peripheral blood were measured using the enzyme-linked immunosorbent assay. The expression of NF-κB, versican and hypoxia-inducible factor-1α in the tumor was evaluated using immunohistochemistry.

Results

LLC and B16F1 tumors were defined as animal models of refractoriness to endostatin treatment. CD11b+Gr1+ myeloid cells were inherently recruited into the peripheral blood and the tumor microenvironment in the LLC tumor-bearing mice, and levels of serum G-CSF and TNF-α were increased along with the progression of tumor growth. In the B16F1 tumor-bearing mice, CD11b+Gr1+ myeloid cells were acquiredly recruited by endostatin into the peripheral blood and the tumor microenvironment. Additionally, high levels of G-CSF and TNF-α in serum and high expression of NF-κB, versican and hypoxia-inducible factor-1α in tumor tissue were found in B16F1 tumor-bearing mice after endostatin administration.

Conclusions

A tumor can grow inherently or acquiredly with refractoriness to endostatin treatment in vivo. Recruitment of CD11b+Gr1+ myeloid cells and inflammatory cytokines may play an important role in the development of tumor refractoriness to endostatin anti-angiogenesis.
Rapid tumor shrinkage with lapatinib plus capecitabine in a patient with massive liver involvement
Authors: Giotta Francesco , Latorre Agnese , Cramarossa Antonio , Simone Giovanni , Florio Carlo , Oliva Stefano , Lorusso Vito
Published: February 2018

We present the case of a 58-year-old woman with breast cancer metastasizing to the liver after adjuvant chemotherapy. A liver biopsy confirmed metastatic lesions from breast cancer that were immunohistochemically positive for estrogen/progesterone receptors and HER2. After first-line treatment with trastuzumab and vinorelbine, the patient commenced therapy with capecitabine (1000 mg/m2 twice daily, days 1–14) and lapatinib (1250 mg/day). Three months after the administration of this combination therapy, the liver metastases had shrunk substantially. Lapatinib may have the potential to convert trastuzumab-refractory tumors to trastuzumab-sensitive tumors in HER2-positive breast cancer by upregulation of the cell surface expression of HER2. Further study will be needed to evaluate in the clinic the combination of lapatinib and an m-TOR inhibitor as a treatment approach in HER2 overexpressing breast cancer that shows a poor response to trastuzumab.