bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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 &gt;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

Abstract
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

AbstractBackground. 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

Abstract
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

Abstract
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

Abstract
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) &lt;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

Abstract
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

AbstractThe 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.
PENGELOLAAN COBAN UNTUK WISATA EDUKASI DENGAN PELIBATAN KELOMPOK SADAR WISATA (POKDARWIS) DESA PAIT, KABUPATEN MALANG
Authors: Ihsom Moh , Nurhadi Nurhadi , Raharjo Kukuh Miroso , Zulkarnain Zulkarnain 
Published: February 2020

Potensi wisata alam yang dapat dikembangkan di Desa Pait antara lain Coban (air terjun) Kethak, Coban Tangkil, Coban Bara’an. Coban Kethak merupakan air terjun dengan ketinggian 25 meter dengan luas wilayah ± 4 ha disekitarnya ditumbuhi tanaman alpukat dan pohon durian, aliran dua coban ini mengalir ke arah dusun Slatri dan dusun Pait Kulon, disamping dimanfaatkan untuk usaha pertanian, aliran sungai ini dimanfaatkan sebagai tubing yang sangat menarik, khususnya pada musim penghujan. Tujuan yang dicapai dari kegiatan ini adalah Pokdarwis dapat mengembangakan dan mengelola potensi wisata yang pada akhirnya memiliki dampak pada kesejahtraan mayrakat. Solusi yang ditawarkan untuk menjawab dan memecahkan permaslahan diatas adalah menjabarkan strategi dan membagi peran atau Tugas pokok masing-masing pengurus dalam pengembangan dan pengelolaan wisata, pelatihan Pemandu Wisata dan promosi obyek-obyek wisata. Hasil kegiatan ini mampu mengekplorasi keberadaan dan keunikan obyek yang ditawarkan didukung bentuk promosi yang bersifat elektronik maupun bentuk yang lain, serta terbentuknya visi yang sama dengan pemerintah daerah untuk pengembangan wisata edukasiKata kunci—CobanKethak, CobanTangkil, CobanBara’an, Pokdarwis, wisata edukasi.AbstractPotential natural attractions that can be developed in Pait Village include Coban (waterfall) Kethak, Coban Tangkil, Coban Bara’an. Coban Kethak is a waterfall with a height of 25 meters with an area of ± 4 ha around it is overgrown with avocado plants and durian trees, the flow of these two coban flows towards the Slatri hamlet and Pait Kulon hamlet, besides being used for agricultural business, the river flow is used as a tubing very interesting, especially in the rainy season. The goal achieved from this activity is Pokdarwis can develop and manage tourism potential which ultimately has an impact on the welfare of the mayor. The solution offered to answer and solve the problems above is to describe the strategy and divide the role or main tasks of each board in the development and management of tourism, training of tour guides and promotion of tourist objects. The results of this activity are able to explore the existence and uniqueness of the offered objects supported by electronic and other forms of promotion, as well as the formation of the same vision with the local government for the development of educational tourism.Keywords—CobanKethak, CobanTangkil, CobanBara’an, Pokdarwis, educational tour
SOUVENIR BATIK MOTIF BANGUNAN KAMPUNG HERITAGE DENGAN TEKNIK SMOK SEBAGAI MODAL KEMAMPUAN BERWIRAUSAHA MASYARAKAT KAYUTANGAN MALANG
Authors: Sidyawati Lisa , Ponimin Ponimin , Anggriani Swastika Dhesti 
Published: February 2020

Sejarah kota Malang tidak bisa lepas dari keberadaan Kayutangan. Pada era kolonial Belanda, kawasan ini menjadi pusat bisnis, yang hingga sekarang masih bertahan, bahkan telah ditetapkan sebagai bangunan Heritage ke perwakilan pengelola 32 bangunan di Kota Malang 10 diantaranya berada dalam kawasan Kayutangan. Diantara bangunan-bangunan heritage terdapat gang yang juga dipenuhi rumah-rumah heritage, disanalah terdapat Kampung Heritage Kayutangan. Kampung Heritage Kayutangan sekarang ini menjadi salah satu destinasi wisata, dimana warganya sangat membuka diri dan menyiapkan rumah mereka sebagai titik swafoto. Namun ketika berkunjung ke Kampung Heritage Kayutangam, baik wisatawan lokal maupun wisatawan asing kesulitan mencari souvenir yang khas. Pengebdian ini bertujuan mengajak warga untuk dapat menumbuh kembangkan kemampuan berwirausaha yang selanjutnya mampu mengangkat potensi daerah melalui Pelatihan Pembuatan Souvenir Batik Motif Bangunan Kampung Heritage Kayutangan Malang dengan Teknik Smok. metode yang digunakan adalah Participatory Rural Appraisal. Hasil kegiatan ini terdapat pengembangan Kemampuan Berwirausaha Masyarakat dengan produk unggulan membuat Souvenir Wisatawan terutama bagi wisatawan asing berupa t-shirt dan goodie bag.Kata kunci—Heritage Malang, Kayu Tangan, Teknik SMOK AbstractThe history of Malang cannot be separated from the existence of Kayutangan. In the Dutch colonial era, this area became a business center, which until now still survives, even has been designated as a Heritage building to the representative of the management of 32 buildings in Malang. 10 of them are in the Kayutangan area. Among the heritage buildings there are alleys which are also filled with heritage houses, there is Heritage Kayutangan Village. Kayutangan Heritage Village is now one of the tourist destinations, where the residents are very open and preparing their homes as a selfie point. But when visiting the Kayutangam Heritage Village, both local and foreign tourists have difficulty finding distinctive souvenirs. This service aims to invite citizens to be able to develop and develop entrepreneurial skills which are then able to raise the potential of the region through the Training of Making Batik Motifs in Malang Kayutangan Heritage Village Building with Smok Technique. The method used is Participatory Rural Appraisal. The result of this activity is the development of Community Entrepreneurial Ability with superior products making Tourist Souvenirs especially for foreign tourists in the form of t-shirts and goodie bags.Keywords—Heritage Malang, Hand Wood, SMOK Engineering.
PENDAMPINGAN PENGUATAN PENGELOLAAN ORGANISASI BERBUDAYA WIRAUSAHA BERBASIS TECHNOPRENEUR PADA PESANTREN
Authors: Dharma Buyung Adi , Churiyah Madziatul , Agustina Yuli , Winarno Agung 
Published: February 2020

Tujuan dari pengabdian masyarakat ini adalah Peningkatan pengetahuan dan keterampilan santri pondok pesantren salafiyah Al-Azhar, desa Patok Picis, kecamatan Wajak, kabupaten Malang; Peningkatan kesadaran dalam pemanfaatan lahan pondok serta pengelolaan kebersihannya; Peningkatan wawasan santri sehingga dapat memunculkan motivasi dan semangat berwirausaha; Peningkatan nilai ekonomis sumber daya hasil alam yang ada di pondok pesantren. Metode yang digunakan adalah ceramah, pelatihan dan pendampingan, konten yang dikembangkan mencakup, materi technopreneurship dan kewirausahaan, pengelolaan lingkungan, keterampilan memijat dan pembuatan nugget ikan produk pesantren. Hasil kegiatan ini wawasan wirausaha santri telah meningkat, demikian pula keterampilan dalam pemanfaatan potensi bahan baku lokal untuk produk yang lebih bernilai ekonomi serta pemahaman penerapan teknologi yang lebih efektif untuk penguatan karakteristik pesantren wirausaha.Kata kunci—technopreneurship, santri, wirausaha, pesantreneurship AbstractThe aim of this community service is to increase the knowledge and skills of Al-Azhar Salafiyah Islamic Boarding School students, Patok Picis village, Wajak sub-district, Malang district; Increased awareness in the utilization of cottage land and cleanliness management; Increased students’ knowledge so that it can bring up the motivation and enthusiasm of entrepreneurship; Increasing the economic value of natural resource resources in boarding schools. The methods used are lectures, training and mentoring, content developed includes, technopreneurship and entrepreneurship materials, environmental management, massage skills and the production of pesantren fish nuggets. As a result of this activity, the insight of santri entrepreneurs has increased, as has the skill in utilizing the potential of local raw materials for products that are more economically valuable and understanding the application of more effective technology to strengthen the characteristics of pesantren entrepreneurship.Keywords—technopreneurship, santri, entrepreneurship, pesantreneurship