<i>Background</i>. Until recently, dose intensified radiotherapy was the standard radiation method for localized prostate cancer. Multiple studies have demonstrated similar efficacy and tolerability with moderate hypofractionation. In recent years there has been an increasing focus placed on understanding the cost and value of cancer care. In this study we aimed to assess the economic impact of moderate hypofractionation for payers in the United States.<i> Methods</i>. We performed a population-based analysis of the total cost of external beam radiotherapy (EBRT) for localized prostate cancer in the US annually. The national annual target population of patients treated with definitive EBRT was calculated using the Surveillance, Epidemiology, and End Results (SEER) database. Treatment costs for various fractionation schemes were based on billing codes and 2018 pricing by the Centers for Medicare and Medicaid Services (CMS).<i> Results</i>. We estimate that 27,146 patients with localized prostate cancer are treated with EBRT annually in the US. The cost of standard fractionation in 45 or 39 fractions is US<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.9762802pt" id="M1" height="10.1537pt" version="1.1" viewBox="-0.0498162 -9.17742 6.36303 10.1537" width="6.36303pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M263 363V584C343 572 363 521 380 464L408 470C399 526 392 562 387 596C376 598 367 601 353 604C328 612 296 617 263 617V693H228V615C122 603 67 532 67 453C67 376 123 329 193 300L228 284V41C132 52 93 131 75 189L45 181C54 130 66 71 73 50C113 24 170 9 228 9V-76H263V11C370 24 434 90 434 185C434 275 367 325 292 352L263 363ZM228 376C171 398 136 431 136 484C136 530 164 578 228 584V376ZM263 272L275 267C345 236 359 196 359 150C359 96 325 50 263 42V272Z"/></g></svg> 26,782 and 23,625 per patient, respectively. With moderate hypofractionation in 28 or 20 fractions, the cost is US<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.9762802pt" id="M2" height="10.1537pt" version="1.1" viewBox="-0.0498162 -9.17742 6.36303 10.1537" width="6.36303pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M263 363V584C343 572 363 521 380 464L408 470C399 526 392 562 387 596C376 598 367 601 353 604C328 612 296 617 263 617V693H228V615C122 603 67 532 67 453C67 376 123 329 193 300L228 284V41C132 52 93 131 75 189L45 181C54 130 66 71 73 50C113 24 170 9 228 9V-76H263V11C370 24 434 90 434 185C434 275 367 325 292 352L263 363ZM228 376C171 398 136 431 136 484C136 530 164 578 228 584V376ZM263 272L275 267C345 236 359 196 359 150C359 96 325 50 263 42V272Z"/></g></svg> 17,793 and 13,402 per patient, respectively. The use of moderate hypofractionation would lead to 25-50% annual savings US<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.9762802pt" id="M3" height="10.1537pt" version="1.1" viewBox="-0.0498162 -9.17742 6.36303 10.1537" width="6.36303pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M263 363V584C343 572 363 521 380 464L408 470C399 526 392 562 387 596C376 598 367 601 353 604C328 612 296 617 263 617V693H228V615C122 603 67 532 67 453C67 376 123 329 193 300L228 284V41C132 52 93 131 75 189L45 181C54 130 66 71 73 50C113 24 170 9 228 9V-76H263V11C370 24 434 90 434 185C434 275 367 325 292 352L263 363ZM228 376C171 398 136 431 136 484C136 530 164 578 228 584V376ZM263 272L275 267C345 236 359 196 359 150C359 96 325 50 263 42V272Z"/></g></svg>158,315,472-US<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.9762802pt" id="M4" height="10.1537pt" version="1.1" viewBox="-0.0498162 -9.17742 6.36303 10.1537" width="6.36303pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M263 363V584C343 572 363 521 380 464L408 470C399 526 392 562 387 596C376 598 367 601 353 604C328 612 296 617 263 617V693H228V615C122 603 67 532 67 453C67 376 123 329 193 300L228 284V41C132 52 93 131 75 189L45 181C54 130 66 71 73 50C113 24 170 9 228 9V-76H263V11C370 24 434 90 434 185C434 275 367 325 292 352L263 363ZM228 376C171 398 136 431 136 484C136 530 164 578 228 584V376ZM263 272L275 267C345 236 359 196 359 150C359 96 325 50 263 42V272Z"/></g></svg>363,213,480 in the US.<i> Conclusions</i>. Moderate hypofractionation may have the potential to save approximately US<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.9762802pt" id="M5" height="10.1537pt" version="1.1" viewBox="-0.0498162 -9.17742 6.36303 10.1537" width="6.36303pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M263 363V584C343 572 363 521 380 464L408 470C399 526 392 562 387 596C376 598 367 601 353 604C328 612 296 617 263 617V693H228V615C122 603 67 532 67 453C67 376 123 329 193 300L228 284V41C132 52 93 131 75 189L45 181C54 130 66 71 73 50C113 24 170 9 228 9V-76H263V11C370 24 434 90 434 185C434 275 367 325 292 352L263 363ZM228 376C171 398 136 431 136 484C136 530 164 578 228 584V376ZM263 272L275 267C345 236 359 196 359 150C359 96 325 50 263 42V272Z"/></g></svg>0.16-0.36 billion annually, likely without impacting survival or tolerability. This may lead to lower personal financial toxicity. It would be reasonable for public and private payers to consider which type of radiation is most suited to reimbursement.

Assaf Moore

Ido Stav

Robert B. Den

Noa Gordon

Michal Sarfaty

Victoria Neiman

Eli Rosenbaum

Daniel A. Goldstein

The Financial Impact of Hypofractionated Radiation for Localized Prostate Cancer in the United States

Osteosarcoma is the most common primary malignancy of bone. Although outcomes of patients with osteosarcoma have improved since the introduction of chemotherapy, outcomes of metastatic or unresectable osteosarcomas are still unsatisfactory. To improve osteosarcoma outcomes, the development of novel systemic therapies for osteosarcoma is needed. Since the 1880s, various immunotherapies have been utilized in patients with osteosarcoma and some patients have shown response to the treatment. Based on recent studies about the role of the immune system in malignancies, immunotherapies including immune modulators such as interleukin-2 and muramyl tripeptide, dendritic cells, immune checkpoint inhibitors, and engineered T cells have been utilized in patients with malignancies. Although there are limited reports of immunotherapies for osteosarcoma, immunotherapy is thought to be a promising treatment option for treating osteosarcomas. In this review, an overview of various immunotherapies for osteosarcoma is provided and their potential as adjuvant therapies is discussed.

Shinji Miwa

Toshiharu Shirai

Norio Yamamoto

Katsuhiro Hayashi

Akihiko Takeuchi

Kentaro Igarashi

Hiroyuki Tsuchiya

Current and Emerging Targets in Immunotherapy for Osteosarcoma

<i>Background</i>. The prognostic value of CD133 and SOX2 expression in advanced cancer remains unclear. This study was first conducted to investigate the association between CD133 or SOX2 positivity and clinical outcomes for advanced cancer patients.<i> Methods</i>. Hazard ratios (HRs) with 95&#x25; confidence intervals (95&#x25; CIs) were calculated to evaluate the correlation between CD133 or SOX2 positivity and overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), cancer-specific survival (CSS), or recurrence-free survival (RFS) from multivariable analysis. Trial sequential analysis (TSA) was also performed.<i> Results</i>. 13 studies with 1358 cases (CD133) and five studies with 433 cases (SOX2) were identified. CD133 positivity was correlated with worse CSS and OS, but there was no correlation between CD133 positivity and DFS. SOX2 positivity was associated with poor DFS and RFS but was not linked to PFS. Stratified analysis by study source showed that only CD133 positivity can decrease OS for Chinese patients. Stratified analysis by treatment regimens indicated that CD133 positivity was linked to poor OS in patients treated with adjuvant therapy. TSA showed that additional studies were necessary.<i> Conclusions</i>. CD133 and SOX2 might be associated with worse prognosis in advanced cancer. More prospective studies are strongly needed.<i> Impact</i>. CD133 and SOX2 may be promising targeted molecular therapy for advanced cancer patients.

Susu Han

Tao Huang

Xing Wu

Xiyu Wang

Shanshan Liu

Wei Yang

Qi Shi

Hongjia Li

Fenggang Hou

Prognostic Value of CD133 and SOX2 in Advanced Cancer

<i>Objectives</i>. Cisplatin (DDP) is one of the most commonly used chemotherapeutic drugs for several cancers, including non-small-cell lung cancer (NSCLC). However, resistance to DDP eventually develops, limiting its further application. New therapy targets are urgently needed to reverse DDP resistance.<i> Methods</i>. The mRNA expression of<i> UBE2C</i>,<i> ZEB1/2</i>,<i> ABCG2</i>, and<i> ERCC1</i> was analyzed by reverse transcription-polymerase chain reaction. The protein levels of these molecules were analyzed by Western blotting and immunofluorescent staining. Cell proliferation was detected by CCK8 and MTT assays. Cell migration and invasion were analyzed by wound healing assay and Transwell assays. Promoter activities and gene transcription were analyzed by luciferase reporter assay.<i> Results.</i> In this study, we examined the effect of UBE2C and ZEB1/2 expression levels in DDP-resistant cells of NSCLC. We confirmed that aberrant expression of UBE2C and ZEB1/2 plays a critical role in repressing the DDP sensitivity to NSCLC cells. Additionally, knockdown of UBE2C significantly sensitized resistant cells to DDP by repressing the expression of ZEB1/2. Mechanistic investigations indicated that UBE2C transcriptionally regulated ZEB1/2 by accelerating promoter activity. This study revealed that ZEB1/2 promotes the epithelial mesenchymal transition and expression of ABCG2 and ERCC1 to participate in UBE2C-mediated NSCLC DDP-resistant cell progression, metastasis, and invasion.<i> Conclusion</i>. UBE2C may be a novel therapy target for NSCLC for sensitizing cells to the chemotherapeutic agent DDP.

Yan Wu

Dan Jin

Xiaohong Wang

Jing Du

Weihua Di

Jiajia An

Cuijie Shao

Jiwei Guo

UBE2C Induces Cisplatin Resistance via ZEB1/2-Dependent Upregulation of ABCG2 and ERCC1 in NSCLC Cells

Regulatory T cells (Treg cells) are considered one of the main dynamic cell types within the immune system. Because Treg cells suppress immune responses, they have potential roles in immunological self-tolerance and may help to maintain immune homeostasis. Promoting Treg cell function and increasing their numbers might be useful in treating autoimmune disorders, as well as preventing allograft rejection. However, studies of mice and humans demonstrate that Treg cells promote cancer progression and suppress antitumor immunity. Therefore, suppressing Treg cell function or reducing their numbers could support the immune system&#x2019;s response to pathogenic microorganisms and tumors. As a result, there is great interest in investigating the Treg cells role in the treatment of hematological and nonhematological malignancies. Consequently, Treg cells could be a fundamentally important target for pathologies of the immune system. Targeting effector Treg cells could help to distinguish and selectively decrease these cells while preserving other Treg cells needed to suppress autoimmunity. Currently, a promising way to treat malignancies and other autoimmune disorders is stem cell transplantation. Stem cell transplants (SCT) can help to manage the production of Treg cells and also may produce more efficient Treg cells, thereby suppressing clinical disease progression. Specifically, mature T cells within the engrafted stem cells mediate this SCT beneficial effect. During SCT, the recipient&#x2019;s immune system is replaced with a donor, which allows for improved immune system function. In addition, SCT can protect from disease relapse, as graft-versus-host disease (GvHD) in transplant patients can be protective against cancer recurrence. The current review will define the role of regulatory T cells in treatment of malignancy. Additionally, it will summarize current promising research regarding the utility of regulatory T cells in stem cell transplantation.

Rana G. Zaini

Amani A. Al-Rehaili

The Therapeutic Strategies of Regulatory T Cells in Malignancies and Stem Cell Transplantations

Due to HAART and consequent decline in mortality from infectious complications, HIV patients have an increasing burden of non-AIDS defining cancers. Data on their safety and efficacy is unknown as these patients were excluded from clinical trials due to concern of unforeseen side effects.<i> Objectives</i>. The main objective of our study was to evaluate the efficacy and safety profile of PD-1 and PD-L1 inhibitors in HIV patients being treated for advanced cancers and to assess the impact of these drugs on HIV status of the patients specifically CD4 count and HIV viral load.<i> Materials and Methods</i>. This was a retrospective analysis of data of 17 patients HIV treated with one of the PD-1/PD-L1 inhibitors (Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab, or Avelumab) for advanced cancer.<i> Results</i>. 10 out of 17 patients responded to therapy. 7 patients, all of whom had shown response to therapy, were alive and 4 were still on checkpoint inhibitor. 10 patients including all 7 nonresponders had died. Responders had minimum of 15 weeks of response while one had ongoing continued response at 34 weeks. Side effects were seen in 7 patients and only one patient needed cessation of therapy. CD4 counts were stable on treatment while HIV RNA remained undetectable.<i> Conclusion</i>. PD-1 and PD-L1 inhibitors appear to have comparable efficacy and tolerable side effect profile and have no effect on HIV markers when used in HIV patients with advanced cancers.

Shahla Bari

Jameel Muzaffar

Austin Chan

Sanjay R. Jain

Ahmad M. Haider

Marjorie Adams Curry

Christopher J. Hostler

Outcomes of Programmed Cell Death Protein 1 (PD-1) and Programmed Death-Ligand 1(PD-L1) Inhibitor Therapy in HIV Patients with Advanced Cancer

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<p><em>Journal of Oncology</em> publishes research related to breast cancer, lung cancer, gastrointestinal cancer, skin cancer, head and neck cancer, paediatric oncology, neurooncology as well as genitourinary cancer.</p>


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<p>Chief Editor, Professor Bruno Vincenzi, is an Associate Professor of Medical Oncology at University Campus Bio-Medico, Italy. His research interests include urogenital neoplasms and the pathophysiology and treatment of bone metastases.</p>


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Journal of Oncology - Table of contents 2019

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Journal of Oncology publishes research related to breast cancer, lung cancer, gastrointestinal cancer, skin cancer, head and neck cancer, paediatric oncology, neurooncology as well as genitourinary cancer.

Journal of Oncology