bluuebunny/crossref_metadata_2025 huggingface dataset:
Heart failure in human immunodeficiency virus-infected patients
Authors: Goryacheva O. G. , Koziolova A. N.
Published: February 2020

Aim. To determine the features of heart failure (HF) development in patients with human immunodeficiency virus (HIV) infection.

Material and methods. In a general hospital, 160 patients were examined during the year. All of them were divided into 2 groups: group 1 (n=100) — HIV-infected patients with specific clinical picture of HF; group 2 (n=60) — patients without HIV infection and with HF verified by echocardiography and concentration of N-terminal prohormone of brain natriuretic peptide (NT-proBNP).

Results. In comparison with group 2, HIV-infected patients had the following statistically significant differences: lower left ventricular ejection fraction (LVEF), lower prevalence and severity of left ventricle diastolic dysfunction, higher LV mass index (LVMI), and lower NT-proBNP. HIV-infected patients had statistically significant moderate inverse relationship of LVEF (r=-0,43; p=0,015), E/e’ (r=-0,32; p=0,045), LVMI (r=-0,46; p=0,002) and strong relationship of NT-proBNP (r=-0,54; p<0,001) with CD4 T-lymphocyte count in 1 mm3 in the presence of HF symptoms and signs and an increase in NT-proBNP over 125 pg/ml. In group 1, there was a significantly higher prevalence of smoking, chronic alcoholism, drug use, chronic hepatitis C and cirrhosis (especially manifested by hepatomegaly and splenomegaly in combination with ascites and hepatic cytolysis), chronic pancreatitis, pneumonia and inflammatory diseases accompanied by higher erythrocyte sedimentation rate and C-reactive protein concentration, and lower hemoglobin level. HIV-infected patients were statistically less likely to use all groups of drugs for HF treatment, with the exception of spironolactone, and more likely to use drugs for multimorbidity treatment.

Conclusion. The HF prevalence in hospitalized HIV-infected patients, estimated on the basis of symptoms and NT-proBNP increase >125 pg/ml, was 54%; on the basis of LVEF decrease <50% — 32%. The clinical picture of HIV-infected patients is characterized by various symptoms, including those typical for HF with normal NT-proBNP level, due to the high prevalence of comorbidities and concurrent medication.
Intraperitoneal Therapy of Ovarian Cancer
Authors: Markman Maurie
Published: February 2020

Purpose. This is a review of the rationale for the intraperitoneal administration of antineoplastic agents in the management of ovarian cancer.

Patients and Methods. Patients have been treated in a number of clinical trials to define the toxicity profile and efficacy of intraperitoneal therapy in this clinical setting.

Results. Phase I-II trials have confirmed that a number of cytotoxic and biological agents can be administered into the peritoneal cavity as treatment of ovarian cancer with an acceptable toxicity profile and with the attainment of surgically documented responses (including complete responses). In addition, a recently reported phase III trial comparing initial treatment of small-volume residual advanced ovarian cancer with either intravenous or intraperitoneal cisplatin concluded that the intraperitoneal route of drug administration was associated with a longer survival and less toxicity.

Discussion. In the salvage (second-line) setting, responses to intraperitoneally administered antineoplastic agents are seen principally in individuals with small-volume residual disease (largest tumor mass ≤ 0.5-1 cm in maximum diameter) who have previously responded to initial systemic treatment (i.e., documented chemosensitive cancers). Patients with cancers resistant to initial systemic chemotherapy or with larger tumor bulk should probably be treated by alternative strategies. Initial treatment of ovarian cancer with cisplatin delivered by the intraperitoneal route is a reasonable therapeutic option, based on currently available data.

Conclusion. The intraperitoneal delivery of antineoplastic agents remains an interesting and potentially important management strategy for a select group of individuals (small-volume residual disease) with advanced ovarian cancer. Further exploration of a more defined role for this therapeutic approach in ovarian cancer is indicated.
Can Surgical Treatment Results in Gastric Cancer Be Improved?
Authors: Songun Ilfet , Velde Cornelis J.H.
Published: February 2020

Patients with gastric cancer have a poor prognosis. Surgery is the only treatment modality offering hope for cure. However, even after curative surgery, the five-year survival rate is still about 30%. Even though the incidence of early gastric cancer is up to 40% of all cases (surgically curable) in Japan, in Western countries most of the patients are diagnosed at an advanced stage, when curative surgery is no longer possible. Most patients die of locoregional recurrence or distant metastasis. Therefore, every attempt should be made to increase early diagnosis and to find additional prognostic factors which can be determined preoperatively. Operations with extended lymphadenectomy are associated with higher morbidity and mortality rates, while a possible survival benefit is not proven in Western countries. The five-year survival results of two large prospectively randomized, controlled trials (the Dutch Gastric Cancer Trial and the British Medical Research Council Trial) comparing limited lymphadenectomy (D1) to extended lymphadenectomy (D2) are still being awaited. In light of increased morbidity and mortality rates associated with extended lymphadenectomy, the limits of surgical possibilities for the treatment of gastric cancer seem to be reached. Adjuvant radiotherapy and chemotherapy are demonstrated to not give an additional survival advantage compared to surgery only. Development of more active combination chemotherapy regimens and results in locally advanced gastric cancer are encouraging. Therefore, to evaluate the place of preoperative chemotherapy in potentially operable gastric cancer, two randomized trials have been initiated in the Netherlands and Great Britain. Gastric cancer should be considered a malignancy which requires a multidisciplinary approach of a specialized team consisting of committed specialists. New treatment modalities should only be applied to patients in clinical trial settings with dedicated clinicians.
Staging Laparotomy in the Management of Hodgkin's Disease: Is it Still Necessary?
Authors: Multani Pratik S. , Grossbard Michael L.
Published: February 2020

Approximately 3,500 cases of stage I and II Hodgkin's disease are diagnosed each year in the United States. Traditionally, those patients who are considered candidates for primary radiation therapy undergo staging laparotomy (pathologic staging) to rule out definitively the presence of occult subdiaphragmatic disease. An appreciation of the risks of laparotomy and a recognition of the effectiveness of salvage chemotherapy in patients who fail primary radiation therapy have permitted the increased use of clinical staging as the basis for treatment of these patients. This article summarizes the literature regarding the need for staging laparotomy in early stage Hodgkin's disease and suggests alternative approaches to the management of these patients based on clinical criteria and prognostic factors.
Interleukin 12: Basic Biology and Potential Applications in Cancer Treatment
Authors: Robertson Michael J. , Ritz Jerome
Published: February 2020

Interleukin 12 is a heterodimeric cytokine that has potent effects on innate and adaptive immunity. Interleukin 12 induces interferon γ secretion by T cells and natural killer cells, enhances the proliferation of activated T cells and natural killer cells, augments the cytolytic activity of cytotoxic T lymphocytes and natural killer cells, and supports the differentiation of Th1 helper effector cells. Interleukin 12 stimulates in vitro antitumor activity of lymphocytes from patients with cancer and in vivo antitumor activity in many murine tumor models. Current data indicate that CD4 T cells, CD8 T cells, natural killer cells and interferon γ may contribute to the antitumor effects of interleukin 12 therapy. However, further investigation is required to elucidate the precise mechanisms involved in the antitumor activity of interleukin 12.
Pediatric Clinical Trials
Authors: Pratt Charles B.
Published: February 2020

Clinical trials specifically tailored to the unique tumors and leukemias of children have resulted in increased survival rates approaching or exceeding 70% for most diseases. These studies have been carried out by investigators at large, independent institutions or through the auspices of the Children's Cancer Group or Pediatric Oncology Group. The National Cancer Institute has also supported pediatric disease—focused efforts for rhabdomyosarcoma, Wilms tumor, Ewing's sarcoma, osteosarcomas and other diseases. The present-day training of pediatric hematology/oncology fellows assures continuing contributions to the biology of childhood malignant lesions through applications of translational research.
Alternative and Complementary Cancer Treatments
Authors: Cassileth Barrie R.
Published: February 2020

Alternative and complementary therapies differ importantly, and the distinction between the two is crucial for clinical oncologists. “Alternative” or unproven therapies are treatments used independent of surgery, radiation and chemotherapy. They can be dangerous directly and also by delaying patients' receipt of mainstream care. In contrast, complementary therapies typically are adjuncts to mainstream medicine. They can provide symptom control and noninvasive palliation with minimal side effects, improve patients' well-being and enhance cancer medicine. Complementary therapies represent a desired addition and balance to technologically sophisticated cancer care.
The Importance of Drug Scheduling in Cancer Chemotherapy: Etoposide as an Example
Authors: Hande Kenneth R.
Published: February 2020

Etoposide is a drug whose antineoplastic activity is dependent on the schedule of drug administration. This article reviews the rationale for a prolonged schedule of etoposide administration and the therapeutic results of use of such a schedule in the treatment of cancer. The pharmacology of etoposide is also reviewed, with particular attention paid to the pharmacokinetics of oral etoposide and etoposide plasma concentrations associated with cytotoxicity.
New Concepts for the Development and Use of Antifolates
Authors: Chu Edward , Grem Jean L. , Johnston Patrick G. , Allegra Carmen J.
Published: February 2020

Approximately one-third of all cases of colorectal carcinoma present in an advanced and, therefore, incurable stage. For these patients, the development of new chemotherapeutic strategies is of central importance. Biochemical modulation of 5-fluorouracil (5-FU) has resulted in approximately a twofold increase in activity of 5-FU. Recent preclinical investigations suggest that interferon can also modulate the activity of 5-FU and may result in enhanced response rates in patients. One of the critical mechanisms of resistance to 5-FU appears to be the acute induction in thymidylate synthase (TS) levels following therapy with inhibitors of this enzyme. This mechanism is based on a novel autoregulatory feedback pathway wherein the TS protein regulates its own translational efficiency. Regulatory function of the enzyme is dependent on its state of occupancy by either the physiologic ligands or inhibitors, including fluoropyrimidines and antifolates. Ongoing efforts are directed toward utilizing knowledge of this protein/messenger RNA interaction for therapeutic benefit. Given the importance of TS, our laboratory has developed antibodies capable of quantitating the levels of this enzyme in fresh or paraffin-embedded tissues. Preliminary investigations suggest that the level of TS has prognostic importance in patients with rectal carcinoma and may be used to predict responsiveness to fluoropyrimidine agents. Novel strategies utilizing dual modulation of 5-FU with leucovorin and interferon are under investigation in both the advanced and adjuvant disease settings. Emerging mechanistic concepts regarding TS, along with the development of new, more potent inhibitors will hopefully result in future therapeutic gains.
Management of Tracheal Neoplasms
Authors: Compeau Christopher G. , Keshavjee Shaf
Published: February 2020

Patients with tracheal involvement from primary or secondary neoplasms usually present with relatively nonspecific symptoms of cough, wheeze, and shortness of breath. Prompt diagnosis often requires a high index of suspicion. Tomography or computed tomography of the chest will often confirm the presence of a tracheal lesion. A detailed rigid bronchoscopic assessment by an experienced thoracic surgeon is essential for establishing the extent of tracheal involvement. Although advanced tumor stage often precludes surgical resection, the application of current operative techniques allows a significant number of tracheal tumors to be completely excised and primarily reconstructed. Adjuvant radiotherapy is often employed with surgical resection to improve local control and enhance the potential for cure.
Peripheral Blood Stem Cells: Transplantation and Beyond
Authors: Lie Albert K.W. , To L. Bik
Published: February 2020

Peripheral blood stem cells are rapidly becoming a major source of hemopoietic stem cells for transplantation in patients with various hematological and oncological conditions. Clinical results of peripheral blood stem cell transplantation (PBSCT) have shown benefits of earlier hemopoietic recovery, lower morbidity, and greater cost-effectiveness compared with conventional bone marrow transplant. Moreover, the relative ease of obtaining large amounts of stem cells has made multicycle transplantation a viable option in the treatment of malignancies, allowing further escalation of chemotherapy dose intensity. The extension of PBSCT into the use of allogeneic and cord blood cells so far has been met with encouraging results, and the latter holds promise to increasing donor availability to patients requiring transplantation. Developments in cytokine research and ex vivo manipulation of hemopoietic stem cells are enabling new approaches to anticancer treatment involving tumor purging, immunomodulation, ex vivo expansion of stem cells and gene therapy. PBSCT may also become a therapeutic option in certain nonmalignant diseases. This review will discuss the current clinical practice and future developments in PBSCT.
The Role of CA-125 in the Management of Ovarian Cancer
Authors: Markman Maurie
Published: February 2020

Over more than a decade of clinical use, CA-125 has proven itself to be one of the most useful tumor markers in cancer medicine. The major clinical utility of this serum marker is in following the clinical course of women with known ovarian cancer. Other potential uses of CA-125 include the evaluation of the effectiveness of new antineoplastic agents in this malignancy, and in the modification of treatment strategies in individuals whose CA-125 levels fail to decline at an acceptable rate following the institution of therapy. At the present time, the use of CA-125 as a method to screen for ovarian cancer should be considered investigational.
Genetic Testing for Cancer Risk Assessment: A Review
Authors: Grogan L. , Kirsch I.R.
Published: February 2020

Both environmental factors and an inherited predisposition influence carcinogenesis. The direct role of inheritance in the development of cancer is evident in familial cancer syndromes. These syndromes predispose to cancer through the inheritance of a mutation in a single gene in affected carriers. While many inherited cancer syndromes are rare, an inherited predisposition is directly responsible for 5%-10% of all colon and breast cancers. Complex multigenic inheritance plays an important role in cancer predisposition for the population at large. The identification of genes responsible for an inherited predisposition to colon and breast cancer syndromes has directed public attention to genetic testing for susceptibility to cancer. Assays are currently available to determine individual susceptibility to specific cancers. Cancer genetic testing is currently a time-consuming and complex procedure which requires expertise in its application, interpretation, and follow-up strategic planning. This review discusses cancer genetics and its application to individual and family cancer risk assessment with particular emphasis on breast and colon cancer.
Megakaryocyte Growth and Development Factor: A Review of Early Clinical Studies
Authors: Abraham Rick , Basser Russell L.
Published: February 2020

Megakaryocyte growth and development factor (MGDF), a Mpl ligand, recently entered clinical trials worldwide and has been demonstrated to have potent biological activity. MGDF administration causes a dose-dependent increase in platelet count but no effect on white cell count or hematocrit. These platelets are morphologically and functionally normal. When administered following moderately myelosuppressive chemotherapy, MGDF significantly enhances platelet recovery, although scheduling in relation to chemotherapy may be important in optimizing the full effects. MGDF mobilizes progenitor cells of multiple hematopoietic lineages, and may enhance the effects of filgrastim on peripheral blood progenitor cell levels after chemotherapy. MGDF is well tolerated and does not cause toxicity similar to that observed with other thrombopoietic cytokines. Numerous studies are under way to help determine the precise role of MGDF in clinical practice.
Burnout: Caring for the Caregivers
Authors: Penson Richard T. , Dignan Fiona L. , Canellos George P. , Picard Carol L. , Lynch Thomas J.
Published: February 2020

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members.

Burnout describes the end result of stress in the professional life of a physician or caregiver and combines emotional exhaustion, depersonalization and low personal accomplishment. This problem is common in health care workers in every specialty and may affect not only personal satisfaction, but also the quality of care delivered to patients. Burnout is particularly relevant in oncology where caregivers work closely with patients who have life-threatening illnesses and therapy often has only a limited impact. Burnout was discussed in the rounds with an emphasis on factors which precipitate or prevent stress among health care workers. Presentations were made by Dr. Canellos of the Dana Farber Cancer Institute, and Dr. Picard of the Institute for Health Professions. Staff discussed the main issues contributing to burnout including the health care system, lack of time and inadequate training. They considered preventative measures including psychological support of the health care team, communication and management skills, and effective coping mechanisms.
Coexistence of Pregnancy and Malignancy
Authors: Pavlidis Nicholas A.
Published: February 2020

Cancer complicating pregnancy is a rare coexistence. The incidence is approximately 1 in 1,000 pregnancies. The most common cancers are those more frequently seen during the reproductive age of a woman. Breast cancer, cervical cancer, Hodgkin's disease, malignant melanoma, and leukemias are the most frequently diagnosed malignancies during gestation.

The diagnostic and therapeutic management of the pregnant patient with cancer is especially difficult because it involves two persons, the mother and the fetus.

In this paper we review: A) the therapeutic and diagnostic management of these patients; B) the safety of diagnostic and therapeutic procedures; C) the metastatic pattern of the maternal tumors to the placenta and fetus, and D) the potential recommendations for therapeutic abortion.
Hyperprogression and Immune Checkpoint Inhibitors: Hype or Progress?
Authors: Adashek Jacob J. , Kato Shumei , Ferrara Roberto , Lo Russo Giuseppe , Kurzrock Razelle
Published: February 2020

There are currently seven approved immune checkpoint inhibitors (ICIs) for the treatment of various cancers. These drugs are associated with profound, durable responses in a subset of patients with advanced cancers. Unfortunately, in addition to individuals whose tumors show resistance, there is a minority subgroup treated with ICIs who demonstrate a paradoxical acceleration in the rate of growth or their tumors—hyperprogressive disease. Hyperprogressive disease is associated with significantly worse outcomes in these patients. This phenomenon, though still a matter of dispute, has been recognized by multiple groups of investigators across the globe and in diverse types of cancers. There are not yet consensus standardized criteria for defining hyperprogressive disease, but most commonly time to treatment failure less than 2 months and an increase in pace of progression of at least twofold between pre-immunotherapy and on-treatment imaging has been used. In some patients, the change in rate of progression can be especially dramatic—up to 35- to 40-fold. MDM2 amplification and EGFR mutations have been suggested as genomic correlates of increased risk of hyperprogression, but these correlates require validation. The underlying mechanism for hyperprogression is not known but warrants urgent investigation.
Exercise Intolerance in Anthracycline-Treated Breast Cancer Survivors: The Role of Skeletal Muscle Bioenergetics, Oxygenation, and Composition
Authors: Beaudry Rhys I. , Kirkham Amy A. , Thompson Richard B. , Grenier Justin G. , Mackey John R. , Haykowsky Mark J.
Published: February 2020

Background

Peak oxygen consumption (VO2) is reduced in women with a history of breast cancer (BC). We measured leg blood flow, oxygenation, bioenergetics, and muscle composition in women with BC treated with anthracycline chemotherapy (n = 16, mean age: 56 years) and age- and body mass index–matched controls (n = 16).

Materials and Methods

Whole-body peak VO2 was measured during cycle exercise. 31Phosphorus magnetic resonance (MR) spectroscopy was used to measure muscle bioenergetics during and after incremental to maximal plantar flexion exercise (PFE). MR imaging was used to measure lower leg blood flow, venous oxygen saturation (SvO2), and VO2 during submaximal PFE, and abdominal, thigh, and lower leg intermuscular fat (IMF) and skeletal muscle (SM).

Results

Whole-body peak VO2 was significantly lower in BC survivors versus controls (23.1 ± 7.5 vs. 29.5 ± 7.7 mL/kg/minute). Muscle bioenergetics and mitochondrial oxidative capacity were not different between groups. No group differences were found during submaximal PFE for lower leg blood flow, SvO2, or VO2. The IMF-to-SM ratio was higher in the thigh and lower leg in BC survivors (0.36 ± 0.19 vs. 0.22 ± 0.07, p = .01; 0.10 ± 0.06 vs. 0.06 ± 0.02, p = .03, respectively) and were inversely related to whole-body peak VO2 (r = −0.71, p = .002; r = −0.68, p = .003, respectively). In the lower leg, IMF-to-SM ratio was inversely related to VO2 and O2 extraction during PFE.

Conclusion

SM bioenergetics and oxidative capacity in response to PFE are not impaired following anthracycline treatment. Abnormal SM composition (increased thigh and lower leg IMF-to-SM ratio) may be an important contributor to reduced peak VO2 during whole-body exercise among anthracycline-treated BC survivors.

Implications for Practice

Peak oxygen consumption (peak VO2) is reduced in breast cancer (BC) survivors and is prognostic of increased risk of cardiovascular disease-related and all-cause mortality. Results of this study demonstrated that in the presence of deficits in peak VO2 1 year after anthracycline therapy, skeletal muscle bioenergetics and oxygenation are not impaired. Rather, body composition deterioration (e.g., increased ratio of intermuscular fat to skeletal muscle) may contribute to reduced exercise tolerance in anthracycline BC survivors. This finding points to the importance of lifestyle interventions including caloric restriction and exercise training to restore body composition and cardiovascular health in the BC survivorship setting.
Early Phase Pediatric Cancer Trials: Progress Highlights Challenges
Authors: Adamson Peter C.
Published: February 2020

This commentary focuses on the promise of more effective and less toxic treatments for children with cancer in the age of targeted therapy, as well as the challenges still to be overcome to best inform pediatric drug development.
Pilot Study of Hyperfractionated Dosing of Lutetium-177–Labeled Antiprostate-Specific Membrane Antigen Monoclonal Antibody J591 (177Lu-J591) for Metastatic Castration-Resistant Prostate Cancer
Authors: Niaz Muhammad Junaid , Batra Jaspreet S. , Walsh Ryan D. , Ramirez-Fort Marigdalia K. , Vallabhajosula Shankar , Jhanwar Yuliya S. , Molina Ana M. , Nanus David M. , Osborne Joseph R. , Bander Neil H. , Tagawa Scott T.
Published: February 2020

Lessons Learned

Hyperfractionation of lutetium-177 (177Lu)-J591 for patients with metastatic castration-resistant prostate cancer did not appear to have any additional advantage over the single dose 177Lu-J591 or fractionated two-dose 177Lu-J591 therapy. Definite conclusions were challenging because of the small sample size of this study, and so further studies are needed to evaluate the viability of the hypothesis. On the basis of available data, a registration study of 177Lu-J591 (also known as TLX591) is planned and will use the two-dose fractionation schedule (Telix Pharma Q3 2019 update https://telixpharma.com/news-media/).

Background

Phase I and II single-dose studies of lutetium-177 (177Lu)-J591, a radio-labeled antibody binding prostate-specific membrane antigen (PSMA), demonstrated safety and efficacy with dose response. Modest dose fractionation of 177Lu-J591 (2 doses) has less myelosuppression per similar cumulative dose, allowing higher doses to be administered safely. We hypothesized that additional dose fractionation would allow a higher cumulative dose, potentially with less toxicity and more efficacy.

Methods

Men with progressive metastatic castration-resistant prostate cancer and adequate organ function were enrolled. 177Lu-J591 was administered at 25 mCi/m2 every 2 weeks until the emergence of related grade 2 toxicity. 177Lu-J591 imaging was performed and circulating tumor cell (CTC) counts were measured before and after treatment along with standard monitoring.

Results

Six subjects in a single cohort, with a median age of 68.6 years, were enrolled. Patients received three to six doses (cumulative 75−150 mCi/m2). Two (33%) patients had >30% prostate-specific antigen (PSA) decline and three (50%) had CTC count decline. Two (33%) experienced grade (Gr) 4 neutropenia (without fever), three (50%) had Gr 4 thrombocytopenia (without hemorrhage), and two (33%) required platelet transfusions. Following hematological improvement, two patients developed worsening cytopenia during prostate cancer progression; bone marrow biopsies revealed infiltrative tumor replacing normal marrow elements without myelodysplasia. Targeting of known disease sites was seen on planar imaging in all.

Conclusion

Hyperfractionation of 177Lu-J591 is feasible but does not seem to have significant advantages over the two-dose fractionation regimen.
Head and Neck Cancer: Altered Fractionation Schedules
Authors: Saunders M.I.
Published: February 2020

Local control is paramount in the treatment of localized advanced head and neck cancer. Standard radiotherapy cures a high percentage of early tumors—more than 80% of the early laryngeal tumors—but fewer of the advanced tumors. Attempts have therefore been made to improve the therapeutic ratio by: A) hyperfractionation: reducing the dose per fraction to reduce late morbidity; the total dose is then elevated in an attempt to improve local tumor control with equal morbidity, and B) acceleration: reducing the overall treatment time to overcome repopulation during a protracted course of radiotherapy.

The total dose and dose per fraction have been reduced in the accelerated arm in some trials, while in others the total dose has been maintained. Both these strategies have been tested in multicenter randomized controlled trials, but neither have become part of routine clinical practice.

The biological parameters determining local tumor control and normal tissue effects are being studied at Mount Vernon by an analysis of selected randomized controlled trials, with the aim of designing new schedules of radiotherapy for future studies.
Prolonged Neoadjuvant Chemotherapy with GM-CSF in Locally Advanced Breast Cancer
Authors: Honkoop Aafke H. , Luykx-de Bakker Sylvia A. , Hoekman Klaas , Meyer Sybren , Meyer Otto W.M. , Groeningen Cees J. , Diest Paul J. , Boven Epie , Wall Elsken , Giaccone Giuseppe , Wagstaff John , Pinedo Herbert M.
Published: February 2020

Background. Neoadjuvant chemotherapy improves survival in patients with locally advanced breast cancer (LABC). Usually three to four cycles of conventional-dose neoadjuvant chemotherapy are administered prior to local therapy, and another three cycles thereafter. In an attempt to improve results, we increased the dosages and applied GM-CSF, which, besides being a hematopoietic growth factor, has become increasingly known for its immunostimulatory effects, which might enhance the antitumor effect.

Methods. Forty-two patients with stage IIIA or IIIB breast cancer were treated with doxorubicin (A) (90 mg/m2) and cyclophosphamide (C) (1,000 mg/m2) at three-weekly intervals. In the second and fourth cycle a 10% dose reduction of both agents was applied. On the second day GM-CSF 250 μg/m2/day was started and given for 10 days. Initially, some patients were treated with ≤ four cycles, but as the study progressed and toxicity appeared tolerable, six cycles were given whenever possible. After the chemotherapy, patients underwent surgery and postoperative radiotherapy.

Results. The response rate for the whole group to AC was 98% (95% confidence interval 94%-100%), with a clinical complete response rate of 50% (95% confidence interval 35%-65%). Six patients had a pathological complete response. Median follow-up from the start of chemotherapy is 49 months (range 10-100). The disease-free survival (DFS) at three years is 57% and the overall survival (OS) at three years is 79%. There is a significant trend for improved DFS (p = 0.0000) and OS (p = 0.0002) with increasing number of cycles.

Conclusion. The results of the present study with neoadjuvant dose-intensive AC chemotherapy and GM-CSF compare favorably with previous studies in patients with LABC. This is most apparent in patients who received six cycles of neoadjuvant chemotherapy. We hypothesize that these encouraging results are probably related to the prolonged presence of the primary tumor, and to the long-term administration of GM-CSF with the primary tumor and axillary lymph nodes in situ. Therefore, a randomized study is warranted. We already initiated an international randomized trial in patients with LABC in order to answer two questions. First, does prolonged neoadjuvant chemotherapy result in an improved DFS and OS in comparison with the conventional approach, and secondly, what is the effect of GM-CSF in this approach in comparison with G-CSF?
Gemcitabine: Single-Agent and Combination Therapy in Non-Small Cell Lung Cancer
Authors: Sandler Alan , Ettinger David S.
Published: February 2020

With the advent of several newer agents with single-agent response rates greater than 20% and approximately 30%-40% in combination therapy, non-small cell lung cancer (NSCLC) may now be considered a malignancy that is moderately sensitive to chemotherapy. Examples of these agents include the taxanes, paclitaxel and docetaxel; vinorelbine, a new vinca alkaloid, and the camptothecins, of which CPT-11 is the most actively studied agent. Another new and exciting agent is gemcitabine, a nucleoside analogue structurally related to cytosine arabinoside. Gemcitabine's mechanism of action is activated by deoxycytidine kinase to dFdCMP, dFdCDP and dFdCTP. The latter two compounds, when incorporated into DNA, result in chain termination. Phase I studies using a short infusion schedule given weekly for three weeks followed by one week off established 1,000-1,250 mg/m2/week as the maximum tolerated dose. Single-agent gemcitabine has been extensively studied in patients with chemotherapy-naïve advanced NSCLC with response rates of approximately 20%. Response rates for the combination of gemcitabine plus cisplatin are approximately 28%-54% in phase II trials. Recently, this combination has been studied in randomized phase II and III trials revealing improvements in response rates, time to progression and, in the phase III trial, survival. Current and future studies are evaluating gemcitabine in non-cisplatin combinations (i.e., taxanes).
Race, Ethnicity, and the Patient-Caregiver Relationship
Authors: Dedier Julien , Penson Richard , Williams Winfred , Lynch Thomas
Published: February 2020

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, gives support to caregivers, and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members.

Racial discrimination is a pervasive problem with multiple damaging effects. It is naïve to believe that medicine is somehow immune to race-based practices, but there is a growing literature detailing poorer disease-specific outcomes in minority populations for a range of illnesses. A recent study in the New England Journal of Medicine has implicated physician prejudice as a significant contributing factor. The March 1999 Schwartz Center Rounds sought to explore the influence of ethnic bias on the patient-provider interaction and the quality of health care delivery. Using a different format with a current affairs video clip and an interactive panel discussion, participants were encouraged to identify the often subconscious racial prejudices which may undermine their relationships with patients. Staff members were challenged to think creatively about how institutions and individuals might promote “cultural competence” and a more equitable health care environment.
Is There Any Impact of New Drugs on the Outcome of Advanced NSCLC? An Overview of the Southern Italy Cooperative Oncology Group Trials
Authors: Frasci Giuseppe , Panza Nicola , Comella Giuseppe , Pacilio Giovanni
Published: February 2020

Lung cancer represents the major cause of cancer-related death in Europe and North America, accounting for 28% of all cancer deaths. Seventy to 80% of all lung cancers are non-small cell lung cancers (NSCLCs), and approximately 75% of these patients present with locally advanced or disseminated disease.

Even though chemotherapy is now recommended in the majority of cases of unresectable NSCLC, it still fails to substantially modify the fate of these patients. In recent years, several active cytotoxic drugs (paclitaxel, docetaxel, vinorelbine, gemcitabine, and irinotecan) have been developed, showing an overall response rate (ORR) <20% in NSCLC. Phase II/III trials testing these new agents in combination with cisplatin have been carried out in recent years with inconsistent results.

Large randomized trials testing cisplatin-paclitaxel, carboplatin-paclitaxel, and cisplatin-gemcitabine regimens have been reported showing no substantial superiority of these combinations over standard treatments. The ORR remained well below 50%, and the median survival times were quite far from one year. These data could suggest that the addition of a single new agent to a platinum compound could be insufficient to substantially improve the prognosis of advanced NSCLC patients.

In view of these disappointing data, the Southern Italy Cooperative Oncology Group has tried to improve the fate of patients with advanced NSCLC by testing new triplet combinations, which combined cisplatin with two rather than one of the newest chemotherapy agents. To avoid an unacceptable increase in toxicity and/or a marked decrease in dose intensity, the standard schedules of administration of the three agents used in these studies were changed, and the schedule changes were evaluated in phase I trials aimed at determining the maximum tolerated dosages of the drugs. Subsequently, phase II and III trials were conducted.

The present paper summarizes the results of the clinical trials either completed or under way and aims to evaluate whether this stategy will result in a substantial prognostic improvement.
Intensity Modulated Radiation Therapy (IMRT): A New Promising Technology in Radiation Oncology
Authors: Teh Bin S. , Woo Shiao Y. , Butler E. Brian
Published: February 2020

Intensity modulated radiation therapy (IMRT) is a new technology in radiation oncology that delivers radiation more precisely to the tumor while relatively sparing the surrounding normal tissues. It also introduces new concepts of inverse planning and computer-controlled radiation deposition and normal tissue avoidance in contrast to the conventional trial-and-error approach. IMRT has wide application in most aspects of radiation oncology because of its ability to create multiple targets and multiple avoidance structures, to treat different targets simultaneously to different doses as well as to weight targets and avoidance structures according to their importance. By delivering radiation with greater precision, IMRT has been shown to minimize acute treatment-related morbidity, making dose escalation feasible which may ultimately improve local tumor control. IMRT has also introduced a new accelerated fractionation scheme known as SMART (simultaneous modulated accelerated radiation therapy) boost. By shortening the overall treatment time, SMART boost has the potential of improving tumor control in addition to offering patient convenience and cost savings.
Contemporary Management of Malignant Pleural Mesothelioma
Authors: Butchart Eric G.
Published: February 2020

The rapidly increasing incidence of malignant pleural mesothelioma underlines the urgency to achieve a consensus in the management of this tumor, which is biologically distinct from most other tumors. For patients with stage I tumors of epithelial type and good performance status, pleuropneumonectomy combined with chemotherapy and radiotherapy provides the best chance of prolonged survival, but further investigation is required to determine the optimum combination of adjuvant therapy. Debulking pleurectomy/decortication combined with adjuvant therapy is a worthwhile alternative for patients with more advanced disease, impaired performance status or tumors of less favorable histology (sarcomatous or biphasic). More clinical trials are urgently required to identify better adjuvant therapy for tumors containing sarcomatous elements. On currently available evidence, neither radiotherapy nor chemotherapy offer worthwhile prolonged disease control when used in isolation, although both have an important role as part of multimodality therapy. Hyperthermia may enhance the effect of both radiotherapy and chemotherapy, and newer radiosensitizing agents also need evaluating. Research into immunotherapy and gene therapy suggests that these newer approaches may have a place if tumor volume is small. In practice they will probably need to be combined with other therapeutic modalities, and further clinical trials are required. Consensus in mesothelioma management currently remains elusive but it seems clear that the way forward will involve striving for much earlier diagnosis, the use of multimodality therapy and collaboration between centers with special expertise in mesothelioma treatment to organize multicenter trials.
Effects of particle size–strength and size–shape correlations on parallel grading scaling
Authors: Ovalle C. , Dano C.
Published: February 2020

Waste mining rock and rockfill materials contain coarse clasts that could easily reach more than 1 m in size. Small scaling techniques for mechanical testing on such coarse materials require altering the particle-size distribution (PSD), by reducing maximum grain size to be able to fit a sample in a laboratory device. To capture the stress−strain behaviour, it is assumed that the reduced PSD has to be parallel to the prototype grading. However, individual grain properties could change with particle size, such as shape and crushing strength. Parallel scaling techniques have been widely applied in rockfill materials, however, the effects of particle-size correlations have been rarely considered, and its effects remain not well understood. This paper presents experimental data on particle-size correlations with both particle shape and particle strength, together with triaxial tests on parallel graded samples of a shale rockfill material. The results show that inverse particle-size−strength correlation results in decreasing particle crushing in finer samples, while particle size−shape correlation could contribute to increase particle crushing in finer samples comprising more elongated grains. Depending on characteristic particle size, one of these opposed trends will prevail and control the material behaviour.
Feasibility of electromagnetic soil heating using magnetic nanoparticle-coated geotextiles
Authors: Kim Ijung , Best Caroline , Kim Seunghee
Published: February 2020

This paper reports a new way of soil heating using a woven and a non-woven geotextile coated with magnetic nanoparticles (MNPs) that generate heat when exposed to a magnetic field. The MNPs were synthesised in the presence of the geotextile, creating and simultaneously coating the MNPs onto the geotextile. The fixation of MNPs on the geotextile was confirmed by direct observation by way of scanning electromagnetic images and an induction heating test. When the prepared geotextile was placed inside a soil medium, heat was generated immediately as the geotextile was exposed to a high-frequency alternating magnetic field, subsequently transferring heat from the MNP-coated geotextile to the surrounding soil. The soil heating performance was greater with the non-woven geotextile than with the woven one, which implies a better capacity to retain the MNPs with a rough surface. However, the effect of different soil types (sand and clay) on heating performance was insignificant. A follow-up study on the heat transfer on a field scale will provide a practical strategy for field application. Overall, the innovative heating method can potentially provide additional functionality to geotextiles as an attractive option for soil heating.
Interventions of a clinical pharmacist in a medical intensive care unit – a retrospective analysis
Authors: Cvikl Maja , Sinkovič Andreja
Published: February 2020

Several studies demonstrated a significant decrease in prescription errors, adverse drug events, treatment costs and improved patient outcomes, when a clinical pharmacist (CP) was a full member of a multidisciplinary team in the intensive care unit (ICU). Our aim was to evaluate the activities of a CP, included in a 12-bed medical ICU team of a university hospital in the course of several months. We conducted a retrospective analysis of all the CP’s interventions from March to November 2017, carried out and documented after reviewing and discussing patients’ medical data with the treating ICU physicians. We identified four main categories of CP’s interventions: pharmacotherapy adjustments to kidney function (PAKF category), drug-drug interactions (DDIs category), therapeutic monitoring of drugs with narrow therapeutic index (TDM category), and drug administration by the nasogastric tube (NGT category). During the study period, 533 patients were admitted to the medical ICU. The CP reviewed the medical data of 321 patients and suggested 307 interventions in 95 patients. There were 147 interventions of the PAKF category, 57 interventions of the TDM category, 30 interventions of the NGT category, and 22 interventions of the DDIs category. Fifty-one interventions were unspecified. The majority of all interventions (203/307) were related to antimicrobial drugs. ICU physicians completely accepted 80.2% of the CP’s suggestions. We observed that regular participation of the CP in the medical ICU team contributed to more individualized and improved pharmacological treatment of patients. Therefore, ICU teams should be encouraged to include CPs as regular team members.
Relationship of vancomycin trough levels with acute kidney injury risk: an exposure-toxicity meta-analysis v1
Authors: Bellos Ioannis , Daskalakis Georgios , Pergialiotis Vasilios
Published: February 2020

Vancomycin is a tricyclic glycopeptide antimicrobial agent with activity against gram-positive microorganisms, while nephrotoxicity represents one of its main adverse effects. Several risk factors have been identified including vancomycin dose and patients comorbidities, while measurement of trough levels is recommended in order to ensure treatment efficacy and minimize the risk of toxicity. However, the exact relationship of vancomycin trough levels and acute kidney injury incidence remains unclear. The aim of this meta-analysis is to evaluate the association between trough levels and risk of renal impairment, by defining an exposure-toxicity relationship and assessing their accuracy in predicting the development of acute kidney injury.
The Effect of Quality of Life and Sociodemographic Characteristics of Patients on Health Service Perception
Authors: SARI Aylin , SÜSLÜ Selin , AYAZ Özlem , BİLİR KAYA Başak
Published: February 2020

Aim: To determine the effect of quality of life and sociodemographic characteristics of patients admitted to the outpatient clinic of a Physical Therapy and Rehabilitation Hospital on Health Service Perceptions.
Methods: This cross-sectional study was conducted on a total of 367 patients (236 female, 131 male) who met the criteria of participation in the study and applied to the policlinic at a Physical Therapy and Rehabilitation Hospital between June 15 and September 15, 2019. Data were collected using a structured form measuring the socio-demographic characteristics and satisfaction levels of the patient and Nottingham Health Profile Scale (NHP) to measure the general perceived quality of life of the patient.
Results: A statistically significant correlation was found between age values and total satisfaction mean scores (r = 0.215 p = 0.0001). Total satisfaction average scores of the literate group were found to be significantly higher than the other groups (p = 0.032, p = 0.005).The total satisfaction mean scores of the Hospital Advise (+) group were found to be statistically higher than the Hospital Advise (-) group (p = 0.0001). There was a statistically significant correlation between NHP Pain average scores and total satisfaction mean scores (p = 0.001).
Conclusion: Health service perception may be affected by many different factors in patient-hospital communication. Age, education, hospital referral status and presence of pain are important parameters that we defined in our study. In the development of the health service provided, it will be guided to examine and define all factors in detail.