bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiphase-computed tomography-based target volume definition in conventional fractionated radiotherapy of lung tumors: Dosimetric and reliable comparison with the technique using addition of generic margins
Authors: Wang Zheng , Lu Xueguan , Zhou Gang , Yan Liming , Zhang Liyuan , Zhu Yaqun , Tian Ye
Published: February 2018

Aims and background

The aim of the present study was to compare radiotherapeutic plans based on internal target volume determined by between multiphase computed tomography and addition of a generic margin in lung tumors and to evaluate the reliability of ITV determined by multiphase computed tomography during conventional fractionated radiotherapy.

Methods and study design

The radiotherapeutic plans based on internal target volume determined by between multiphase computed tomography and addition of a generic margin in 10 patients with lung tumors were applied. The difference of two planning target volumes (PTV) and irradiated dose and volume of normal lung tissue were compared. Weekly new targets were delineated on repeated computed tomography scans, and weekly dose coverage of clinical target volume under two different treatment plans was evaluated.

Results

For all patients, PTV3CT volume based on multiphase computed tomography was significantly smaller than that of PTVcon based on addition of a generic margin (t = 6.831, P <0.001). The volume receiving more than 20 Gy in Plan3CT and Plancon was 16.7 ± 5.2% and 20.0 ± 5.2% (t = 7.565, P <0.001), the volume receiving more than 5 Gy was 36.6 ± 7.2% and 42.7 ± 6.4% (t = 7.459, P <0.001), and mean lung dose was 1037.5 ± 275.0 cGy and 1246.8 ± 271.0 cGy (t = 8.078, P <0.001), respectively. Both Plan3CT and Planconprovided a satisfactory clinical target volume coverage weekly during conventional fractionated radiotherapy for 6–7 weeks, and the ratio of the volume receiving the prescription dose was 1.03 ± 0.02 and 1.04 ± 0.02, respectively.

Conclusions

The radiotherapeutic plan based on internal target volume determined by multiphase computed tomography can ensure weekly target coverage during conventional fractionated radiotherapy in lung tumors, and it is better than the plan based on the addition of generic internal target volume, which can effectively reduce normal lung tissue irradiation.
Defining the role of palliative radiotherapy in bone metastasis from primary liver cancer: An analysis of survival and treatment efficacy
Authors: Habermehl Daniel , Haase Kristina , Rieken Stefan , Debus Jürgen , Combs Stephanie E
Published: February 2018

Aims and background

Primary liver cancer is the fourth leading cause of cancer-related death worldwide and is still associated with a poor prognosis. Hepatocellular carcinoma and cholangiocarcinoma are known to cause bone metastasis resulting in pain, neurologic impairment and risk of fracture. Palliative radiotherapy is the treatment of choice in symptomatic bone lesions and is usually performed as percutaneous fractionated radiotherapy.

Methods and study design

From June 1987 to December 2009, 41 patients (median age, 64 years) with bone metastasis received radiotherapy in our department. The analyzed patients were treated for 67 sites of bone lesions. We analyzed the applied fractionation schedules and the preferred sites of metastasis and symptoms, evaluated the therapeutic outcome in terms of symptomatic improvement, and described the prognosis of these patients.

Results

Main indication for palliative radiotherapy was pain in 94% of all cases. Most frequent radiation protocols were 10 × 3 Gy (20 patients) and 20 × 2 Gy (19 patients). Median applied overall dose was 39 Gy (range, 4–48 Gy) and median single dose was 2.5 Gy (range, 1.8–4 Gy). The median duration of the radiotherapeutic treatment was 15 days (range, 2–24 days) and in 12 cases treatment was discontinuated. The overall response rate to palliative radiotherapy in bone metastasis was 77%. Median overall survival in both cholangiocarcinoma and hepatocellular carcinoma patients was 4.2 months after initiation of radiotherapy (range, 0.2–38.9).

Conclusions

Considering the poor prognosis of patients with bone metastasis in hepatocellular carcinoma and cholangiocarcinoma, with a poor median survival of 3.7–5.0 months according to our study and existing literature, shorter radiotherapy schedules or even single-fraction irradiation can be considered.
Relationship between expression of vascular endothelial growth factor and intratumoral hemorrhage in human pituitary adenomas
Authors: Kim Young Jin , Kim Choong Hyun , Cheong Jin Hwan , Kim Jae Min
Published: February 2018

Aims and background

Although pituitary adenoma is a primary brain tumor that occasionally accompanies intratumoral hemorrhage, there are little reports about the molecular mechanism of intratumoral bleeding in pituitary adenoma. Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis and vascular permeability of various brain tumors. The authors studied the relationship between intratumoral hemorrhage and the expression of VEGF in human pituitary adenomas.

Methods

VEGF expression was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) in 71 pituitary adenomas. Clinical factors to investigate were age, gender, hormonal functioning, and radiological findings of pituitary adenomas. Radiological findings which were investigated by magnetic resonance (MR) images were intratumoral hemorrhage, cystic change, tumor size, and cavernous sinus invasion. The relationship between these factors and VEGF expression was statistically analyzed.

Results

VEGF was expressed in 25 cases (35.2%). Functioning tumors, hemorrhage, cystic change, and cavernous sinus invasion were 32 (45.1%), 18 (25.4%), 12 (16.9%), and 21 (29.6%) respectively. The expression of VEGF showed a significant relationship with the intratumoral hemorrhage of the adenomas (P <0.001). However, age, gender, tumor size, hormonal functioning, cyst formation, and cavernous sinus invasion had no relationship with VEGF expression (P >0.05).

Conclusions

This study suggests that VEGF expression may be responsible for intratumoral hemorrhage of pituitary adenomas. Therefore, VEGF can be a novel target to prevent a catastrophic apoplexy in pituitary adenomas and to establish roles in angiogenesis-based therapeutics of pituitary adenomas.
The effect of 2-methoxyestradiol liposome on growth inhibition, angiogenesis and expression of VEGF and Ki67 in mice bearing H22 hepatocellular carcinoma
Authors: Du Bin , Wang Shu-yu , Shi Xiu-fang , Zhang Chao-feng , Zhang Zhen-zhong
Published: February 2018

Aims and background

2-methoxyestradiol (2-ME), an endogenous metabolite of estrogen, has very low water solubility. It is currently in phase II clinical trials as both a chemopreventive and chemotherapeutic agent and has been orally administered to cancer patients. However, the poor oral absorption of the compound is one of the major obstacles for 2-ME development. Based on the molecular features of 2-ME, liposome can be considered an attractive formulation approach. Our purpose in this study is to research the antitumor efficacy of 2-methoxyestradiol liposome (2-ME-L) in mice bearing H22 tumors.

Methods

Murine H22 hepatocarcinoma served as an ectopic solid tumor model. The effects of antitumor therapy were evaluated by testing tumor growth, measuring the tumor inhibition rates in terms of weight and volume, and staining the tissues by hematoxylin and eosin. The synergistic mechanism of 2-ME-L therapy was elucidated by detecting changes in the expression of pathognostic factors in the tumor microenvironment.

Results

2-ME-L significantly suppressed tumor growth. The morphological changes in the tumors indicated that the tumors in the treatment groups were effectively confined with little surrounding angiogenesis. Tumor cells of the treatment groups had abundant areas of necrosis with few nuclei in the mitotic phase. It was found that there was less immunohistochemical expression of vascular endothelial growth factor (VEGF), Ki67 and CD31 in the treatment groups and the efficacy of 2-ME-L was better than that of 2-ME solution (2-ME-S). This research demonstrated that 2-ME-L inhibited the growth of H22 tumors in a concentration-dependent manner and was more effective than 2-ME-S.

Conclusions

2-ME-L can suppress the growth of H22 solid tumors and has antiproliferative, proapoptotic and antiangiogenic activity. 2-ME-L could be of potential use in the treatment of hepatocellular carcinoma.
Breast change perception in women after smoking cessation. A pilot study
Authors: De Marco Cinzia , Invernizzi Giovanni , Miceli Rosalba , Mariani Luigi , Villarini Anna , Munarini Elena , Mazza Roberto , Boffi Roberto
Published: February 2018

Aims and background

There are several barriers to smoking cessation that are unique to women. Compared to men, women report lower levels of motivation to quit and greater perceived difficulty with cessation. However, recent studies might favor commitment by women to quit through higher risk perception related e.g. to the development of premature facial wrinkling or the decrease in mammographic density due to cigarette smoking.

Methods

A pilot study to evaluate the perception of breast change after cessation and its possible motivational effect on maintenance was carried out. We interviewed 25 premenopausal women who had quit ≥1 year before. We obtained information from the women and discussed changes in breast size and fullness. The two groups of women with and without breast change were statistically compared using the non-parametric Mann-Whitney test (continuous variables) and the Fisher test (categorical variables).

Results

Median age was 41 years (range, 30–49 years). Median carbon monoxide (CO) before quitting was 18 ppm and median pack years (PY) was 22.5; both parameters characterize a category of mild smokers. Sixteen women (64%) reported breast changes 6 months after quitting smoking. This outcome was paralleled by only moderate effects on weight or body mass index (BMI) increase after quitting. Notably, of the 16 women with breast change, only 3 (19%) with a normal baseline BMI showed a BMI increase to >25.

Conclusions

Within the limitations of the small size of a pilot study, these results indicate that premenopausal women experience subjective perception of change in breast size after smoking cessation, which may not be totally explained by weight gain. Further studies are needed to understand the effect, if any, of such perception on the motivation to quit smoking.
Hemolytic uremic syndrome induced by infusion of oxaliplatin: A case report
Authors: Racca Patrizia , Spadi Rosella , Fora Gianluca , Fanchini Laura , Ritorto Giuliana , Ferrari Laura , Pinta Francesco , Lista Patrizia , Ciuffreda Libero
Published: February 2018

Introduction

Oxaliplatin is a third-generation platinum compound with proven antitumor activity in the treatment of colorectal cancer. The occurrence of life-threating hemolitic uremic syndrome has been observed after oxaliplatin therapy. The kind of tumor and treatment modalities seem to influence the onset of hemolitic uremic syndrome.

Methods

The clinical course of the case is reviewed and compared with reports of other similar cases in the literature.

Results

We describe the development of hemolitic uremic syndrome as a result of prolonged oxaliplatin treatment of a colon cancer patient.

Conclusions

Although this rare event requires the concurrence of other unknown factors, it should be considered in a decision-making setting.
Delays in the Diagnosis and Treatment of Non-Small-Cell Lung Cancer
Authors: Sulu Ebru , Tasolar Oktay , Takir Huriye Berk , Tuncer Leyla Yagci , Karakurt Zuhal , Yilmaz Adnan
Published: February 2018

Aims

To investigate patterns of delays among patients with non-small-cell lung cancer and to identify reasons for the delays.

Methods

This prospective study included 101 patients with non-small-cell lung carcinoma. Clinical files of the patients were analyzed and a questionnaire was created to obtain data. Several time intervals and delays were determined for each patient. The reasons for the delays were also evaluated.

Results

The mean time was 59.9 days for the application interval, 40.3 days for the referral interval, 16.4 days for the diagnostic interval, and 24.7 days for the treatment interval. The application interval was longer than 30 days (patient's delay) in 48 patients (48.5%). There was a doctor delay in 54 (53.5%) patients, a referral delay in 47 (46.5%) patients, a diagnostic delay in 37 (36.6%) patients, and a treatment delay in 57 (56.4%) patients. The mean total time was 119.6 days. Sixty-two patients (62.6%) had a total delay. The most common reason for patient's delay was neglect of symptoms by patients. A low index of suspicion for lung cancer was the most common cause for referral delay. The low performance of diagnostic tests was the frequent reason for diagnostic delay.

Conclusions

Patient's and doctor's delays were a common problem among patients with non-small-cell lung cancer. The rate of doctor's delay was higher than that of patient's delay. Several efforts such as education of the physicians and people about lung cancer should be made to reduce these delays.
Increased Mean Corpuscular Volume of Erythrocytes during Capecitabine Treatment: A Simple Surrogate Marker for Clinical Response
Authors: Arslan Cagatay , Aksoy Sercan , Dizdar Omer , Kurt Mevlut , Guler Nilufer , Ozisik Yavuz , Gullu Ibrahim , Altundag Kadri
Published: February 2018

Aims and Background

Capecitabine, as all fluoropyrimidines, interferes with vitamin metabolism and may thus have an impact on hematopoiesis. It is metabolized to its active form 5-fluoruracil by the enzyme thymidine phosphorylase, which exists in higher concentrations in tumor tissue and liver than in normal tissues. In the study, we investigated the changes in mean corpuscular volume (MCV) of red blood cells and the possible correlation of these changes with the clinical outcome of capecitabine treatment in women with metastatic breast cancer.

Methods and Study Design

Data from 75 metastatic breast cancer patients were analyzed retrospectively. Capecitabine was used at a dose of 2500 mg/m2 daily for 14 days of every 3-week period. Mean corpuscular volume of red blood cells and other parameters of complete blood count were recorded at the beginning of the treatment, in the ninth week, and periodically thereafter.

Results

Mean age was 51.5 ± 10.8 and 61.3% of the patients were premenopausal. Capecitabine was administered as the median 3rd line (min-max: 1–9) treatment and a median of 6 cycles (min-max: 1–24) for metastatic breast cancer. Median ΔMCV level (post-treatment values at ninth week - baseline) was 8. ΔMCV was ≥8 in 37 patients and <8 in 38 patients. The 35 of the 37 patients with ΔMCV level ≥8 and 25 of the 38 patients with ΔMCV level <8 had clinical benefit (complete response + partial response + stable disease) from capecitabine treatment (P = 0.02). However, the difference between progression-free survival of the patients with ΔMCV levels higher than 8 and those with ΔMCV levels lower than 8 according to Kaplan-Meier survival analysis was not statistically significant (6.7 and 4.3 months, respectively, P = 0.26). Additionally, median ΔMCV level was 9.1 (min-max: −2.4 to 24.9) among patients who had clinical benefit and 5.90 (min-max: −0.8 to 12.3) among nonresponders (P = 0.016).

Conclusions

Capecitabine increases the mean corpuscular volume levels of red blood cells by a yet unidentified mechanism. Early increment of mean corpuscular volume levels is higher than 8, i.e. by the 9th week, might predict clinical benefit from the treatment.
Circulating Tumor Cells as Predictors of Prognosis in Metastatic Breast Cancer: Clinical Application outside a Clinical Trial
Authors: Consoli Francesca , Grisanti Salvatore , Amoroso Vito , Almici Camillo , Verardi Rosanna , Marini Mirella , Simoncini Edda
Published: February 2018

Aims and Background

Circulating tumor cells have a prognostic role in metastatic breast cancer. The aim of the study was to confirm the ability of circulating tumor cells, detected by the US Food and Drug Administration approved Cell Search assay, to predict the outcome of patients treated in a community general hospital.

Patients and Methods.

A prospective mono-institutional study was conducted at the Department of Medical Oncology at Spedali Civili, Brescia, Italy, from January 2009 to September 2010. A total of 93 consecutive patients with metastatic breast cancer were enrolled. Patients underwent a blood sample collection to detect circulating tumor cells at baseline and, subsequently, at the first follow-up examination (after 3-4 weeks from the beginning of a systemic therapy). A third sample was drawn at disease progression (at the beginning of a subsequent new course of therapy). The prognostic cutoff value of circulating tumor cells was fixed at 5 cells/7.5 ml of blood.

Results

At baseline, median overall survival and progression-free survival in the subgroup ≥5 circulating tumor cells/7.5 ml of blood were significantly shorter (5 months and 3 months, respectively) than in the subgroup with <5 circulating tumor cells (8 months and 7 months, respectively) (P = 0.003 and P <0.001). At the first follow-up, the subgroup with more than 5 circulating tumor cells/7.5 ml of blood had a median overall survival of 4 months versus 8 months in the subgroup with <5 circulating tumor cells (P <0.001) and a median progression-free survival of 3 months versus 7 months respectively (P <0.001). At multivariate analysis, the level of circulating tumor cells at the first follow-up and at baseline remained significant as a predictor of progression-free and overall survival. The number of metastatic sites was significantly associated with overall and progression-free survival and correlated with the number of circulating tumor cells.

Conclusions

Our study confirms the role of circulating tumor cells as predictors of prognosis in metastatic breast cancer patients treated in general clinical practice.
Targeted Inhibition of Mammalian Target of Rapamycin (mTOR) Signaling Pathway Inhibits Proliferation and Induces Apoptosis of Laryngeal Carcinoma Cells in vitro
Authors: Li Rongrui , Wang Riguang , Zhai Raosheng , Dong Zhen
Published: February 2018

Aim and Objective

Laryngeal carcinoma is one of the most aggressive cancers of the head and neck region. The survival rate of patients with laryngeal carcinoma is low due to its late metastases and resistance to chemotherapy and radiotherapy. It was reported that mTOR was involved in the growth and apoptosis of various cancer cells. The aim of this study was to detect the effects of mTOR inhibition by mTOR shRNA on the proliferation, apoptosis and invasive ability of Hep-2 human laryngeal carcinoma cells in vitro.

Methods and Study Design

mTOR shRNA was designed and transfected into Hep-2 human laryngeal carcinoma cells. Untreated cells and cells treated with control vector (non-targeted shRNA) were used as control. The proliferation and apoptosis of Hep-2 cells were detected by MTT and flow cytometry. A transwell assay was used to measure the invasive ability of Hep-2. The inhibition effects on the mTOR signaling pathway by mTOR shRNA were studied using RT-PCR and Western blot.

Results

Our results showed that the mRNA and protein expression of mTOR and Akt were high in laryngeal carcinoma cells and could be inhibited by mTOR shRNA. At the same time, low expression of PTEN mRNA and protein was observed in Hep-2 cells. The expression increased when the cells were transfected with mTOR shRNA. This showed that mTOR shRNA could inhibit the proliferation and invasive ability of Hep-2 cells. It also could induce the apoptosis of Hep-2 cells in vitro.

Conclusions

The mTOR signaling pathway plays an important role in the development of laryngeal carcinoma. The mTOR shRNA we designed in this experiment effectively inhibited the mTOR signaling pathway. It inhibited the proliferation and invasive ability of the studied laryngeal carcinoma cells and induced their apoptosis in vitro. mTOR might therefore be a useful target in the therapy of laryngeal carcinoma.
Colon Perforation during Sorafenib Therapy for Advanced Hepatocelluar Carcinoma. A Case Report
Authors: Park Sang-Gon , Chung Choon-Hae , Park Chi-Young
Published: February 2018

There are no effective conventional systemic cytotoxic therapies for patients with unresectable or advanced hepatocellar carcinoma (HCC). Sorafenib, an oral multi-targeted tyrosine kinase inhibitor, was recently approved for the treatment of patients with HCC. Sorafenib is generally well tolerated and has an acceptable toxicity profile. Gastrointestinal perforation is a rare adverse event. We present a case of transverse colon perforation during sorafenib therapy for advanced HCC. A 68-year-old woman with advanced HCC was treated with sorafenib. Eight weeks later the patient presented with the sudden onset of sharp abdominal pain. Emergency surgery was performed for panperitonitis and a perforation involving the transverse colon.
Obstructive Colon Metastases from Lobular Breast Cancer: Report of a Case and Review of the Literature
Authors: Mistrangelo Massimiliano , Cassoni Paola , Mistrangelo Marinella , Castellano Isabella , Codognotto Elena , Sapino Anna , Lamanna Ginevra , Cravero Francesca , Bianco Lavinia , Fora Gianluca , Sandrucci Sergio
Published: February 2018

Introduction

Gastrointestinal metastases from breast cancer are rare. One large series reported a rate of 0.7% of gastrointestinal metastatic manifestations from breast cancer, but its true incidence could be underestimated. Here we report a case of bowel obstruction caused by sigmoid metastases from breast cancer and describe its relevance to histological origin and clinical practice.

Methods

The clinical course and histopathology of the case are reviewed and compared with reports of similar cases in the literature.

Results

An 80-year-old woman presented with bowel obstruction. Her medical history included infiltrating lobular breast cancer treated with left radical mastectomy 25 years before the current presentation; 13 years later bone metastases developed and were treated with hormone therapy. In 2003 the patient came to our emergency department because of symptoms of bowel obstruction. A computed tomography (CT) scan revealed a mass in the distal sigmoid causing the obstruction. A colostomy was performed, followed by a second operation completed with Hartmann's procedure. Histological examination revealed metastases from invasive lobular carcinoma. The patient was discharged 45 days postoperatively and died 9 months later because of disease progression.

Conclusions

Although gastrointestinal metastases from breast cancer are rare, patients with diagnosed breast cancer, particularly invasive lobular carcinoma, should be regularly followed up with endoscopy, CT, endosonography and PET-CT when abdominal symptoms are present. This could permit early diagnosis of gastrointestinal metastases and improve treatment planning.
Giant Condyloma Acuminatum of the Anorectum: Successful Radical Surgery with Anal Reconstruction
Authors: Battaglia Luigi , Vannelli Alberto , Belli Filiberto , Rampa Mario , Milione Massimo , Gasparini Patrizia , Leo Ermanno
Published: February 2018

Buschke-Löwenstein tumor, or giant condyloma acuminatum, is a relatively uncommon lesion of the anus with aggressive local invasive behavior which may present as a large warty tumor of the genital region with expansive and destructive growth. Many sporadic reports have been published suggesting various therapeutic strategies. We report a case of Buschke-Löwenstein tumor treated with conservative surgery followed by reconstructive procedures without a loop colostomy.
Role of Radiotherapy in the Treatment of Fibrosarcoma of the Spermatic Cord: A Case Report and Review of the Literature
Authors: Balducci Mario , Di Rito Alessia , Mantini Giovanna , Manfrida Stefania , Chiesa Silvia , Frascino Vincenzo , D'Agostino Giuseppe Roberto , Valentini Vincenzo , De Bari Berardino
Published: February 2018

Background

Spermatic cord sarcomas are rare. The therapeutic approach is based only on case reports and small series. The standard treatment is radical orchiectomy with wide local resection, while the role of adjuvant therapies is not clear. We present a case of fibrosarcoma of the spermatic cord treated with surgery and adjuvant radiotherapy. A review of the literature about the role of adjuvant treatments is also discussed.

Case Report

A 59-year-old man presented a right testicular mass of about 4 × 3 cm in size. Biopsy showed a high-grade polymorphous sarcoma, consistent with a diagnosis of poorly differentiated fibromyosarcoma. He underwent a right radical inguinal orchiectomy and adjuvant radiotherapy (total dose: 5940 cGy). During treatment the patient developed a G3 skin toxicity (RTOG score) in the inguinal fold. After a follow-up of 57 months, he is alive and without evidence of local or distant recurrence. No late toxicity was noted.

Conclusion

The optimal adjuvant management of spermatic cord sarcoma is still uncertain. Looking at the literature, it seems that adjuvant radiotherapy can improve locoregional control and disease-free survival without additional late toxicity.
Cervical Cancer Screening visit as an Occasion for Counseling Female Smokers to Quit
Authors: Chellini Elisabetta , Gorini Giuseppe , Gasparrini Antonio , Grazzini Grazia , Iossa Anna , Martellucci Pietro Mario , Terrone Rosangela
Published: February 2018

Aims and Background

In the last decades in Italy, a smaller decrease in smoking among women than in men has been observed and a younger age at start in young women. Nevertheless, gender-specific strategies for smoking cessation have rarely been developed, except those for pregnant women. A study was conducted to evaluate the feasibility of carrying out an intervention of primary prevention by counseling for smoking cessation the female smokers attending cervical cancer screening programs in Florence, Italy.

Methods

All female smokers attending the services for cervical cancer prevention at the Cancer Prevention and Research Institute in Florence, Italy, between March 2004 and January 2005, who volunteered to participate in the study, received a brief motivational stage-matched counseling for smoking cessation and a face to face interview at enrollment and after 6 and 12 months. The counseling was evaluated by comparing quit rates, changes in smoking intensity, and motivation to quit at the first and second follow-up periods to the same data collected at enrollment. Multivariate logistic regression analysis was performed to estimate the influence on smoking cessation of demographic characteristics, smoking habit and attitude to quit.

Results

177 women participated in the study. After 1 year, a quit rate of 12.4% (95% CI, 7.5–17.3) was observed. Among those who never quit, there was a 39.3% reduction in the average daily cigarette consumption and a 51.9% reduction in smoking the first cigarette of the day immediately on awaking or just after breakfast.

Conclusions

The results and the opportunity to contact a large number of female smokers on the occasion of cervical cancer screening suggest the importance to evaluate the efficacy of the intervention of primary prevention in this health setting.
Lapatinib-Based Therapy in Heavily Pretreated HER2-Positive Metastatic Breast Cancer: A Single Institution Experience
Authors: Crivellari Diana , Spazzapan Simon , Lombardi Davide , Militello Loredana , Torrisi Elena , Russo Alessia E , Sorio Roberto , Talamini Renato , Miolo Gianmaria , Carli Paolo , Veronesi Andrea
Published: February 2018

Aims and Background

Lapatinib in combination with capecitabine is feasible in patients with HER2-positive metastatic breast cancer pretreated with anthracyclines, taxanes and trastuzumab, but inferior results were reported in the global lapatinib expanded access program in comparison with the phase III registration trial.

Methods and Study Design

Women with HER2-positive metastatic breast carcinoma after antracycline, taxane and trastuzumab-based regimens were treated at progression with lapatinib plus capecitabine. The outcome of these patients was evaluated. From April 2007 to August 2010, 68 patients were treated overall.

Results

Median progression-free survival was 6 months (range, 1–29), and median overall survival was 26 months (range, 1–39). Eight (12%; 95% CI, 4–25) patients experienced a complete response. Partial response was observed in 22 patients (31%; 95% CI, 20–42), for an overall response rate of 43% (95% CI, 31–55). The treatment with lapatinib plus capecitabine was well tolerated, with grade 3–4 toxicity reported in few patients, and no treatment-related deaths were noted. Of note, no cardiac toxicity was reported in this highly pretreated group of patients or in the subgroup of 10 elderly patients.

Conclusions

Our data confirm that lapatinib plus capecitabine is an active regimen even in heavily pretreated patients with visceral and brain metastases and is feasible and active also in selected elderly patients.
Changes in Lymphocyte Count Induced by Repeated Cycles with Low-Dose Interleukin-2 and Interferon-α in 146 Patients with Renal Cell Carcinoma
Authors: Buti Sebastiano , Rovere Rodrigo Kraft , Donini Maddalena , Passalacqua Rodolfo , Pezzuolo Debora , Buzio Carlo
Published: February 2018

Aims and Background

The exact mechanism by which recombinant interleukine-2 and interferon-a modulate the immunological response, inducing long-term responses in metastatic renal cell carcinoma, is still not clear. The aim of the study was to analyze the modifications in peripheral blood lymphocytes during cycles of low-dose immunotherapy as a marker of the biological response to the treatment in 146 patients with renal cell carcinoma (advanced and localized disease).

Methods and Study Design

Peripheral blood lymphocytes were evaluated before and after every cycle of treatment.

Results

We found a statistically significant overall difference between pre- and post-cycle values (mean increase of 39%). The differences between pre- and post-cycle lymphocyte counts for each cycle were significant. Also, the post-cycle lymphocyte count of each cycle remained higher than the baseline value. Furthermore, pre-cycle lymphocyte counts of each cycle were still higher than the baseline value, with no difference between a pre-cycle lymphocyte mean value and the other one (except that between the first and second cycle). From the end of each cycle, but before starting the next one, the absolute value of lymphocytes fell on the average by 15–30%, concurring with the fact that, even starting from pre-cycle values higher than baseline, the immune system remains sensitive to chronically repeated stimulation by immunotherapy. We also found that non-metastatic patients had a higher number of peripheral blood lymphocytes than metastatic patients, whereas the latter had a lower immune response to therapy.

Conclusions

The results support the idea that “maintenance” immunotherapy may not develop resistance over time in terms of biological response and thus may have a role as chronic therapy in combination with other drugs such as target therapy. We suppose that the immune system of patients with metastases is in a state of relative impairment, resulting in less sensitivity to immunostimulating agents.
Clinical Study of Concurrent Chemoradiotherapy or Radiotherapy Alone for Esophageal Cancer Patients with Positive Lymph Node Metastasis
Authors: Han Jihua , Zhu Weiguo , Yu Changhua , Zhou Xilei , Li Tao , Zhang Xiaoye
Published: February 2018

Aims and Background

Esophageal cancer patients with pathologic lymph node involvement generally have a poor prognosis. Many randomized controlled trials have not achieved consistent results similar to those of the RTOG8501 trial, and the long-term survival rate has not increased. The present study aimed to compare the efficacy and toxic side effects of concurrent chemoradiotherapy and radiotherapy alone to treat N1 esophageal carcinoma.

Methods and Study Design

A total of 130 N1 esophageal carcinoma patients were enrolled and randomly divided into two groups: concurrent chemoradiotherapy group (n = 65) and radiotherapy group (n = 65). Both groups received three-dimensional conformal radiotherapy with a total dose of 64–66 Gy. Meanwhile, to the concurrent chemoradiotherapy group, an additional chemotherapy protocol (nedaplatin, 20 mg/m2/d, 5-FU, 500 mg/m2/d for four days) was given from day 1, and such treatment was repeated until day 29. From day 21 after radiotherapy, two cycles of a consolidated chemotherapy protocol were given at an interval of 28 days.

Results

The survival rates at one, two, and three years were 72.3%, 55.3%, and 40% in the concurrent chemoradiotherapy group, respectively, and 75.3%, 38.5%, and 18.5% in the radiotheray group (P = 0.007), respectively. The survival rates of the patients in the concurrent chemoradiotherapy group who completed one to two cycles and three to four cycles at one, two, and three years were 70%, 53.3%, and 30%, and 74.2%, 57.1%, 48.6% (P = 0.128), respectively. Three-year distant metastasis rates were 10.7% in the concurrent chemoradiotherapy group and 16.9% in the radiotherapy group. Acute toxicity in the concurrent chemoradiotherapy group was higher than in the radiotherapy group. Late toxic side effects were similar in the two groups.

Conclusions

Compared with radiotherapy alone, concurrent chemoradiotherapy in the treatment of esophageal carcinoma with local lymph node enlargement can improve the three-year survival rate. Moreover, completion of three to four cycles of chemotherapy may have better efficacy than one to two cycles.
Activation of Aryl Hydrocarbon Receptor Suppresses Invasion of Esophageal Squamous Cell Carcinoma Cell Lines
Authors: Zhang Jianhao , Zong Hong , Li Shenglei , Zhang Dandan , Zhang Lei , Xia Qingxin
Published: February 2018

Aims and Background

Esophageal cancer is the eighth most common malignancy and sixth leading cause of cancer deaths in the world. Recent studies have shown the potential role of the aryl hydrocarbon receptor (AhR) in tumor development; however, little is known about its role in esophageal squamous cell carcinoma. In the present study, we evaluated AhR expression in esophageal tumor tissues as well as cell lines and investigated the effects of AhR activation by its agonist BNF on esophageal squamous cell carcinoma invasion using Eca109 and TE-13 cells as a model.

Methods

Western blotting was performed to detect the AhR and CYP1A1 protein expression. Transwell migration assays were carried out to study the effects of BNF on esophageal squamous cell carcinoma cell invasion. AhR-specific siRNA was used to knock down the expression of AhR protein.

Results

Our results showed that AhR was highly expressed in esophageal squamous cell carcinoma tissues and cell lines when compared with its expression in normal tissue. AhR siRNA robustly decreased AhR protein expression in both Eca109 and TE-13 cells. BNF significantly inhibited invasion of human esophageal squamous cell carcinoma cells via activation of AhR.

Conclusions

The obtained results provide critical information on the roles of BNF in mediating esophageal squamous cell carcinoma invasion. This information could be useful for future therapeutic intervention in this lethal human disease.
Is the Spiritual Life of Cancer Patients a Resource to be taken into Account by Professional Caregivers from the Time of Diagnosis?
Authors: Miccinesi Guido , Proserpio Tullio , Pessi Maria Adelaide , Maruelli Alice , Bonacchi Andrea , Borreani Claudia , Ripamonti Carla
Published: February 2018

Background and Aim

Spiritual life can be defined as the search for personal contact with the transcendent. Careful assessment of spiritual life can help to value its importance to cancer patients from the moment of their diagnosis.

Methods

This is a cross-sectional study. Two hundred fifty-seven patients undergoing cancer treatment filled in the validated Italian version of the Systems of Belief Inventory (SBI-15R). Patients were also asked to attribute themselves to one of the following, mutually exclusive categories: believer and churchgoer, believer but no churchgoer, and non-believer.

Results

Five patients did not report their religious stance and were therefore excluded from the analysis. Of the remaining 252 patients, 49% declared to be believers and churchgoers, 43% believers but not churchgoers, and 8% non-believers. Of the 20 cancer patients who declared not to have a religious faith, 7 patients agreed with the statement that they felt certain that God exists in some form, and 4 had experienced peace of mind through prayer and meditation. Almost all of the patients who declared to have a religious faith and to be churchgoers explicitly affirmed to have been helped by prayer and meditation in coping with their illness. Among believer churchgoers, only 30% declared to seek out the religious or spiritual community when they needed help.

Conclusions

A large proportion of cancer patients find themselves involved with the search for a personal contact with the transcendent, also beyond any specific religious affiliation. These spiritual issues may be important even when they are not expressed as participation in religious rituals or adherence to specific religious beliefs. On the other hand, participation in religious rituals often implies the need for a personal spiritual life, both through those rituals and beyond them, as through personal prayer and meditation. These results ask for more attention on the part of professionals towards spiritual resources among cancer patients. It might be appropriate to look systematically for these resources from the moment of the diagnosis, through the sensitive administration of an easy and valid assessment tool like the SBI-15R.
Ewing Sarcoma of the Thoracic Wall in a 54-Year-Old Man
Authors: Fiorentino Alba , Chiumento Costanza , Caivano Rocchina , Fusco Vincenzo
Published: February 2018

Ewing tumor is the second most common bone tumor in children. Its variant, malignant small cell tumor of the thoracopulmonary region, is infrequent in children and extremely rare in adults. A multimodal treatment approach is preferred for this tumor. We describe a rare case of primitive neuroectodermal tumor/Ewing sarcoma arising from the thoracic wall in a 54-year-old man. He underwent extensive resection of the tumor followed by adjuvant chemotherapy and radiotherapy.
Multifocal Capillary Hemangioma (Hemangiomatosis) of the Spleen
Authors: Ambrosio Maria Raffaella , Rocca Bruno Jim , Di Mari Nicoletta , Ambrosio Alessandra , Lazzi Stefano
Published: February 2018

Background

The spleen is mainly affected by benign tumors that originate from the vascular endothelium. The most common is hemangioma, which presents as a small, localized lesion. Isolated diffuse hemangiomatosis of the spleen is a rare entity in which the entire splenic parenchyma is replaced by a proliferation of neoplastic blood vessels. Here we illustrate the case of a 26-year-old man presenting with splenomegaly due to diffuse hemangiomatosis of the white pulp who underwent a splenectomy.

Methods

Representative samples of the spleen were stained with hematoxylin and eosin, and immunohistochemical analysis was performed for Mib-1, CD20, CD30, CD15, CD34, CD31, CD8, factor VIII, D2–40, CD68PGM1, and LMP1.

Results

Macroscopically, the splenic parenchyma contained multiple, red-brown nodules ranging from 0.4 to 1.5 cm. Microscopically, the nodules were roundish and confluent with an angiomatoid appearance and high positivity for CD34 and factor VIII, while they were negative for D2–40.

Conclusions

The differential diagnosis of splenic tumors includes lymphangioma, lymphangiomatosis, peliosis, littoral cell angioma, hemangioendothelioma, hamartoma, angiomatoid transformation of the spleen, and angiosarcoma. It is debated whether diffuse hemangiomatosis is a malformation of the postsinusoidal venous system or a slowly growing neoplasm arising from the splenic sinuses. The positivity of the cavernous vessels for CD8 seems to be in favor of the malformative nature of the tumor.
Mirror Therapy for Phantom Limb Pain in An Adolescent Cancer Survivor
Authors: Clerici Carlo Alfredo , Spreafico Filippo , Cavallotti Gaia , Consoli Annalisa , Veneroni Laura , Sala Alessio , Massimino Maura
Published: February 2018

Aims and Background

Several pediatric tumors require mutilating procedures in order to be treated effectively. Although the pain caused by the surgery is usually of a transient nature, the perception of pain in the amputated limb may persist. This prolonged pain, which is often refractory to pain-killing medication, may severely affect the patient's quality of life. The phenomenon of phantom limb pain (or phantom limb syndrome) has been investigated using neurological, neurophysiological and psychopathological approaches. Here we discuss the advantages of an unconventional rehabilitation technique, the recently reported mirror therapy, whose positive effects might be due, according to some researchers, to neuronal plasticity mechanisms.

Case Report

We describe the use of mirror therapy to treat phantom limb syndrome in a 39-year-old patient whose right leg had been amputated at the age of 17 because of an osteosarcoma. The patient suffered from frequent episodes of pain, with severely negative effects on his quality of life.

Results

We obtained positive subjective feedback from the patient, who reported having benefited significantly from using the mirror. The beneficial effect was still present six months after the start of mirror therapy.

Conclusions

The reported case highlights the value of an integrated multidisciplinary approach including neurological/physiatric assessment, clinical psychological support, physiotherapy and other, unconventional treatment modalities. This report should guide future studies towards the application of mirror therapy in order to elucidate its effects and efficacy.
PET Scan Contribution in Chest Tumor Management: A Systematic Review for Thoracic Surgeons
Authors: Duranti Leonardo , Leo Francesco , Pastorino Ugo
Published: February 2018

Aims and background

In the 90s, the introduction of positron emission tomography (PET) represented a milestone in the staging of thoracic tumors. In the last 10 years, PET scan has been widely adopted in thoracic oncology, showing high accuracy in diagnosis and staging and with promising issues in defining prognosis. The aim of this systematic review was to focus on the results and pitfalls of PET scan use in the modern management of chest tumors.

Methods and study design.

The literature search was performed on May 2010 in PubMed, Embase, and Cochrane according to PRISMA protocol. The search was restricted to publications in English, using in the same string the word “PET” with 9 different chest tumors; results were then filtered by eliminating technical articles, focusing only on papers in which surgery was considered as a potential diagnostic or therapeutic tool. From 6600 papers initially selected, 99 manuscripts were fully analyzed.

Results

Glucose uptake is a metabolic marker useful in the diagnosis and staging of chest tumors. In lung cancer screening, standard uptake value is helpful in defining the risk of malignancy of isolated pulmonary nodules. The addition of PET scan to conventional staging increases detection of nodal and distant metastases in lung cancer, esophageal cancer and malignant mesothelioma. In thymoma, a close relationship between standard uptake value, histology, and Masaoka stage has been advocated. This link between glucose uptake and prognosis suggests that PET translates biological tumor behavior into clinically detectable findings.

Conclusions

PET scan has a crucial role in thoracic oncology due to its impact on diagnosis, staging and prognosis. PET scan expresses the biological behavior of tumors, opening interesting perspectives in chest tumor management and improving detection and stage grouping in lung cancer. It anticipates the diagnosis in long-incubating diseases such as mesothelioma and increases biological knowledge of rare diseases, such as thymoma and other mediastinal tumors.
Adjuvant Therapy for Resected Stage III Melanoma Patients: High-Dose Interferon-Alpha versus Ipilimumab Combined with Kinases Inhibitors
Authors: Minutilli Ettore , Feliciani Claudio
Published: February 2018

High-dose interferon-alpha remains the first-line treatment in the adjuvant therapy of metastatic melanoma. More recently, high-dose pegylated interferon-alpha-2b has been approved by the US Food and Drug Administration. Actually, an adjuvant therapy alternative to high-dose interferon-alpha is represented by ipilimumab. Moreover, combination therapy of IFN-alpha or ipilimumab with tyrosine kinase inhibitors has been proved in patients with specific mutations. It is mandatory to understand what the best adjuvant treatment is for resected metastatic melanoma patients, particularly at stage III-N1, in terms of overall survival rather than recurrence-free survival. The ECOG 1609 clinical trial compared high-dose interferon-alpha and ipilimumab alone or combined with tyrosine kinase inhibitors for the treatment of early metastatic melanoma. In the past, ECOG 1684, 1690 and 1694 trials showed improvement in recurrence-free survival more than overall survival for high-risk melanoma patients (stage IIB-III) treated with high-dose interferon-alpha, whereas more recently the EORTC 18991 trial reported successful therapeutic results in terms of recurrence-free survival rather than overall survival for stage III-N1 melanoma patients treated with high-dose pegylated interferon-alpha-2b. Toxicity was more acceptable within one year of treatment. Randomized trials have demonstrated that ipilimumab as second-line therapy is able to increase dose-dependent overall survival rates in advanced melanoma patients despite severe but reversible immune-related adverse events. Old tyrosine kinase inhibitors have been used in combination with interferon for the treatment of advanced melanoma patients with moderate benefits and increased toxicity, but new selective drugs seem to be more efficacious. Early metastatic melanoma patients (stage III-N1) should be the principal subset to be treated with the most suitable adjuvant therapy to achieve the best overall survival. New schedules have to be tested with high-dose interferon-alpha and ipilimumab alone or combined with tyrosine kinase inhibitors while waiting for results from ECOG 1609.