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Background: Personalized and effective treatments for pancreatic ductal adenocarcinoma (PDAC) continue to remain elusive. Novel clinical trial designs that enable continual and rapid evaluation of novel therapeutics are needed. Here, we describe a platform clinical trial to address this unmet need., Methods: This is a phase II study using a Bayesian platform design to evaluate multiple experimental arms against a control arm in patients with PDAC. We first separate patients into three clinical stage groups of localized PDAC (resectable, borderline resectable, and locally advanced disease), and further divide each stage group based on treatment history (treatment naïve or previously treated). The clinical stage and treatment history therefore define 6 different cohorts, and each cohort has one control arm but may have one or more experimental arms running simultaneously. Within each cohort, adaptive randomization rules are applied and patients will be randomized to either an experimental arm or the control arm accordingly. The experimental arm(s) of each cohort are only compared to the applicable cohort specific control arm. Experimental arms may be added independently to one or more cohorts during the study. Multiple correlative studies for tissue, blood, and imaging are also incorporated., Discussion: To date, PDAC has been treated as a single disease, despite knowledge that there is substantial heterogeneity in disease presentation and biology. It is recognized that the current approach of single arm phase II trials and traditional phase III randomized studies are not well-suited for more personalized treatment strategies in PDAC. The PIONEER Panc platform clinical trial is designed to overcome these challenges and help advance our treatment strategies for this deadly disease., Trial Registration: This study is approved by the Institutional Review Board (IRB) of MD Anderson Cancer Center, IRB-approved protocol 2020-0075. The PIONEER trial is registered at the US National Institutes of Health (ClinicalTrials.gov) NCT04481204 ., (© 2021. The Author(s).)

Aim: Hepatocellular carcinoma (HCC) is a potentially life-threatening cancer. In the current study, anti-HCC efficacy of amygdalin, or metformin alone or in combination in comparison to doxorubicin was studied., Main Methods: Both in-vitro and in-vivo based models. HepG-2 and Huh-7 cell lines as established in-vitro model for HCC were treated with different concentrations of indicated drugs to evaluate the cytotoxicity and determine IC 50 for 24, 48 and 72 h. Moreover, the effect of different treatments on apoptosis and cell cycle using flow cytometric analysis were studied. Hepatocellular carcinoma induced in rats by diethyl-nitrosamine and carbon tetrachloride was established, to further investigate the efficacy of indicated drugs. Aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase were measured by spectrophotometer, alpha-fetoprotein, cytochrome-c, caspase-3 and malondialdehyde were measured by ELISA, and liver biopsies were also evaluated histopathologically., Key Findings: In-vitro results showed that the combination has a promising effect when compared to amygdalin or metformin alone as it is more cytotoxic and have higher ability for induction of apoptosis and arresting cell cycle. In-vivo doxorubicin has a good effect for treating HCC. Also, the combination showed a promising prognostic effect depending on the cytotoxic activity and tumor marker when compared to amygdalin or metformin alone., Significance: Based on the current data, it was hypothesized that amygdalin and metformin especially when used in combination will be a promising approach with low side effects for enhancement of HCC., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Abstract: Limited data exist on patients with limb liposarcoma (LLS) with metastasis at presentation Moreover, the potential prognostic factors of this patient population are poorly documented because of its rarity. Therefore, we conducted this study to evaluate the clinicopathologic characteristics and prognostic factors for patients with metastatic LLS.All patients with LLS with metastasis at presentation from 1975 to 2016 were identified by using the Surveillance, Epidemiology, and End Results (SEER) database. The following clinical data were derived from this clinical database: age, sex, histologic grade, subtype, size of tumor, surgery, radiotherapy, chemotherapy, vital status, cause of death, and survival duration. The Kaplan-Meier method was performed to calculate median survival time and draw survivorship curves. Cox-proportional hazards regression model was used to reveal the statistical independence between various variables.The present study collected 184 cases from SEER database for survival analysis. Mean age was 57.8 years with 63.6% (n = 117) men. The 3-year overall survival (OS) and cancer-specific survival (CSS) rates of this population were 27.8% and 30.1%, respectively. Univariate analysis revealed that age, tumor grade, and surgery were significantly correlated with survival. Sex and tumor size did not reach significant predictor status of survival. Multivariate analysis revealed that age at diagnosis <60, low tumor grade, and local surgery were significantly correlated with improved OS and CSS.Patients with LLS with metastasis at diagnosis experienced quite poor prognosis. Currently, surgery for the primary tumor significantly prolonged the survival of those patients, whereas chemotherapy and radiotherapy need to be further confirmed., Competing Interests: The authors report no conflicts of interest, (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: Primary female genital tract lymphomas are sporadic neoplasms, accounting for 0.2% to 1.1% of all cases of extranodal lymphoma. The most common genital localizations are the cervix, the uterine corpus and the ovary, while primary lymphomas of the fallopian tube are quite unusual. According to literature searching in PubMed, this is the first reported case of primary diffuse large B-cell lymphoma of the fallopian tube., Patient Concerns: A 52-year-old woman presented with a more than 2 months history of intermittent lower abdominal pain. The gynecological examination showed that the uterus, as big as 3 months of pregnancy, had weak activity and no tenderness. The uterine rectum lacuna was like a hard nodule of about 3 × 2 cm, and an irregular solid mass was fixed and inactive in the right adnexa., Diagnoses: In accordance with Ann Arbor staging system, a stage IE primary diffuse large B-cell lymphoma of fallopian tube was diagnosed for this patient, based on the tumor pathology, the results of bone marrow biopsy and computed tomography (CT) scan., Interventions: After gynecological/urinary ultrasound, blood test, pelvic contrast enhanced CT scan and CT angiography of iliac artery, exploratory laparoscopy and following hysterectomy with bilateral salpingo-oophorectomy were performed. After the surgery, the patient was treated with combined Rituximab and chemotherapy and got complete response (CR)., Outcomes: After the operation and R-CHPOP, following up for more than 1 year so far, the patient has no tumor recurrence and is still in good condition., Lessons: It is very difficult to diagnose the primary diffuse large B-cell lymphoma of fallopian tube, not only because of its rarity, but also because of its non-specific clinical manifestations. It easily be treated as late ovarian cancer by gynecologist. So the pathology diagnosis and surgeons' decision is very important. Because lymphoma is pretty sensitive to chemotherapy and easy to get complete response, so we no need to do an operation like ovarian cancer and should put chemotherapy as a primary method for lymphomas of the female genital tract., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The medical and surgical treatment strategies for women with epithelial ovarian cancer continue to evolve. In the past several years, there has been significant progress backed by landmark clinical trials. Although primary epithelial ovarian cancer is still treated with a combination of surgery and systemic therapy, more complex surgical procedures and novel therapeutics have emerged as standard of care. Cytotoxic chemotherapy and maximal surgical effort remain mainstays, but targeted therapies are becoming more widespread and new data have called into question the role of surgery for women with recurrent disease. Poly ADP-ribose polymerase inhibitors have improved progression-free survival outcomes in both the frontline and recurrent settings, and their use has become increasingly widespread. The recent creation of treatment categories based on genetic changes reinforces the recommendation that all women with epithelial ovarian cancer have germline genetic testing, and new biomarker-driven drug approvals indicate that women may benefit from somatic molecular testing as well. To continue to identify novel strategies, however, enrollment on clinical trials remains of the utmost importance. With the evolving data on surgical approaches, targeted therapies such as antiangiogenics and poly ADP-ribose polymerase inhibitors, and the new therapeutic agents and combinations in development, we hope that advanced epithelial ovarian cancer will eventually transition from an almost universally fatal disease to one that can increasingly be cured., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: Resource limitations because of pandemic or other stresses on infrastructure necessitate the triage of time-sensitive care, including cancer treatments. Optimal time to treatment is underexplored, so recommendations for which cancer treatments can be deferred are often based on expert opinion., Objective: To evaluate the association between increased time to definitive therapy and mortality as a function of cancer type and stage for the 4 most prevalent cancers in the US., Design, Setting, and Participants: This cohort study assessed treatment and outcome information from patients with nonmetastatic breast, prostate, non-small cell lung (NSCLC), and colon cancers from 2004 to 2015, with data analyzed January to March 2020. Data on outcomes associated with appropriate curative-intent surgical, radiation, or medical therapy were gathered from the National Cancer Database., Exposures: Time-to-treatment initiation (TTI), the interval between diagnosis and therapy, using intervals of 8 to 60, 61 to 120, 121 to 180, and greater than 180 days., Main Outcomes and Measures: 5-year and 10-year predicted all-cause mortality., Results: This study included 2 241 706 patients (mean [SD] age 63 [11.9] years, 1 268 794 [56.6%] women, 1 880 317 [83.9%] White): 1 165 585 (52.0%) with breast cancer, 853 030 (38.1%) with prostate cancer, 130 597 (5.8%) with NSCLC, and 92 494 (4.1%) with colon cancer. Median (interquartile range) TTI by cancer was 32 (21-48) days for breast, 79 (55-117) days for prostate, 41 (27-62) days for NSCLC, and 26 (16-40) days for colon. Across all cancers, a general increase in the 5-year and 10-year predicted mortality was associated with increasing TTI. The most pronounced mortality association was for colon cancer (eg, 5 y predicted mortality, stage III: TTI 61-120 d, 38.9% vs. 181-365 d, 47.8%), followed by stage I NSCLC (5 y predicted mortality: TTI 61-120 d, 47.4% vs 181-365 d, 47.6%), while survival for prostate cancer was least associated (eg, 5 y predicted mortality, high risk: TTI 61-120 d, 12.8% vs 181-365 d, 14.1%), followed by breast cancer (eg, 5 y predicted mortality, stage I: TTI 61-120 d, 11.0% vs. 181-365 d, 15.2%). A nonsignificant difference in treatment delays and worsened survival was observed for stage II lung cancer patients-who had the highest all-cause mortality for any TTI regardless of treatment timing., Conclusions and Relevance: In this cohort study, for all studied cancers there was evidence that shorter TTI was associated with lower mortality, suggesting an indirect association between treatment deferral and mortality that may not become evident for years. In contrast to current pandemic-related guidelines, these findings support more timely definitive treatment for intermediate-risk and high-risk prostate cancer.

After more than two decades of intensive research, tremendous progress has been achieved in the management of Human Epidermal Receptor-2 overexpressing (Her2+) Early Breast Cancer (EBC). In the latest years, major clinical trials have explored the neoadjuvant scenario, in addition to the prognostic role of pathologic complete response (pCR) and the possibility of a 'tumor biology-driven' patient selection provided by the assessment pathologic response. However, the introduction of new agents has been a major burden for financially-constrained healthcare systems-which includes those from most emerging markets (currently representing 85% of the world population) but also, to some extent, public systems from welfare states. This manuscript addresses evidence-based opportunities to promote a more rational utilization of the available resources in Her2+ EBC, in addition to areas of interest for future research in cost-efficiency., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The experience of older women during breast cancer treatment is insufficiently described by quantitative studies. This study aimed to systematically review qualitative data describing factors that influence older women's (≥65 years old) experience with breast cancer treatment., Methods: A systematic review was performed in accordance with Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA) principles. MEDLINE, CINAHL, PsycINFO, and EMBASE were searched (inception - 2020). Quality assessment of essential item reporting was performed using the Standards for Reporting Qualitative Research (SRQR) criteria. Common ideas were coded, thematically organized, and synthesized within a theoretical framework., Results: Of 7,773 studies identified, twelve were included. The median SRQR score was 13.4 (range 11.3-15.9) (maximum score: 21). Data synthesis revealed that older women experienced breast cancer as a journey with challenges during each phase. During diagnosis, they delayed seeking medical help despite symptoms. Age and experience gave them perspective on the impact of their diagnosis. During decision-making, preconceptions and personal values determined choices. In the treatment phase, women experienced medical and social barriers to care. During the post-treatment phase, many experienced treatment adverse effects, but could move on or compartmentalize as coping mechanisms., Conclusion: Older women with breast cancer have unique challenges specific to each phase of their treatment journey. Older women may benefit from proactive treatment discussions with health care providers to address their specific needs, individualize care, and assist with cancer care navigation., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Cancer patients are at higher risk to be infected with COVID-19 and to develop a more severe form. Breast cancer (BC) treatments, including chemotherapy (CT), targeted therapy and immunotherapy can weaken the immune system and possibly cause lung problems. For all these reasons Salah Azaiez Institute's department of Medical Oncology took drastic actions to protect patients. In this article we will discuss protocol adjustments taken during the COVID-19 pandemic for breast cancer patients.

Background: Adolescent and young adult (AYA) cancer survivors have high risks of late effects. Little is known about the late-effect information needs of AYAs early in treatment or their role in treatment decision making. This study evaluated the importance, quality, and implications of information about late effects in AYAs recently diagnosed with cancer., Methods: This study surveyed 201 AYAs with cancer who were 15 to 29 years old and were treated at the Dana-Farber Cancer Institute (Boston, Massachusetts). Patients were approached within 6 weeks of their diagnosis and were asked about their late-effect and infertility information needs, treatment decision making, and communication outcomes., Results: Forty-five percent of the participants were female; 88% were white. Most AYAs (87% [173 of 200]) considered information about the risks of late effects to be extremely or very important; 80% (159 of 200) valued information about infertility. Many were distressed by information about late effects (53% [105 of 200]) and infertility (45% [89 of 200]); those who considered late-effect information distressing were more likely to value this information (P < .0001). Consideration of late effects (41% [82 of 201]) and infertility (36% [72 of 201]) greatly influenced many patients' treatment decision making. Although 92% of the patients (184 of 199) reported receiving high-quality information about the diagnosis, 57% (113 of 199; P < .0001) and 65% (130 of 199; P < .0001) felt that they had received high-quality information about late effects and infertility, respectively., Conclusions: Most AYAs with cancer value early information about the risks of late effects and infertility, yet many patients felt that they had not received high-quality information about these topics. The development of age-appropriate late-effect communication strategies that recognize high AYA distress may help to address the gap between desired information and perceived information quality., (© 2020 American Cancer Society.)

Chemotherapy drugs are one of the most common causes of serious and fatal medication errors, especially during prescribing, where computerized physician order entry (CPOE) take on importance. This study proposes the description of the post-implementation status of a CPOE in a highly specialized hospital between January and June 2018, among patients older than 18 years. Results: a total of 8835 protocols were indicated using the specific CPOE (93% use rate over all protocols) 91% completed the administration, 1.2% were rejected by pharmacy, and 6.8% was canceled. The most frequent cause of rejection by pharmacy and cancellation by oncologist was an inadequate dose. Most of the protocols indicated using the CPOE implemented, with a reject by pharmacy rate of 1.2%, indicates the utility of CPOE as an error prevention strategy.

Objective: The aim of delivering radiotherapy for pancreatic ductal adenocarcinoma patients was to sterilize vessel margin, increase R0 resection rate and delay local progression. Whether preoperative radiotherapy could prolong overall survival of surgical candidates remained unknown., Methods: Pancreatic ductal adenocarcinoma patients receiving radical resection from surveillance, epidemiology and end result database were enrolled. Propensity score matching was conducted to balance difference in baseline characteristics, and survival analyses were performed to compare overall survival between preoperative radiotherapy and upfront resection groups. Cox proportional hazard regression model and subgroup analyses were utilized to identify prognostic factors., Results: A total of 11 665 and 597 pancreatic ductal adenocarcinoma patients receiving upfront resection and preoperative radiotherapy followed by resection from 2004 to 2016 were identified, respectively, while baseline characteristics were distinct between groups. After propensity score matching, preoperative radiotherapy was not associated with better overall survival (upfront resection vs preoperative radiotherapy, 26 vs 27 months). Subgroup analyses showed that preoperative radiotherapy was a protective factor in pT4 (hazard ratio = 0.64, 95% confidence interval: 0.47-0.88) but a negative predictor in pT1 (hazard ratio = 1.79, 95% confidence interval: 1.08-2.97) patient populations. Survival analyses showed that preoperative radiotherapy improved overall survival of patients with pT4 stage (upfront resection vs preoperative radiotherapy, 19 vs 25 months) and involvement of celiac axis, superior mesenteric artery and aorta (upfront resection vs preoperative radiotherapy, 20 vs 27 months), while preoperative radiotherapy was associated with worse overall survival in patients with pT1 tumor (upfront resection vs preoperative radiotherapy, 39 vs 24 months)., Conclusion: Preoperative radiotherapy could improve survival of resected pancreatic ductal adenocarcinoma patients with pT4 stage or with celiac axis, superior mesenteric artery and aorta invasion., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

One of the sequelae of head and neck cancer treatment is secondary lymphedema, with important impact on breathing, swallowing and vocal functions. The aim of the study was to assess the presence, staging characteristics and relationship of external and internal lymphedema and dysphagia after head and neck cancer treatment. The MDACC Lymphedema Rating Scale in Head and Neck Cancer was employed for the assessment and staging of face and neck lymphedema; the Radiotherapy Edema Scale for internal lymphedema; and a fiberoptic endoscopic evaluation of swallowing (FEES) for swallowing. The sample consisted of 46 patients with a diagnosis of head and neck cancer. Lymphedema was detected in 97.8% (45) of the evaluations with predominance of the composite type (73.9%-34). A high percentage of external lymphedema of the neck (71.7%-33) and submandibular (63%-29) were detected, with predominance of the more advanced levels. Internal edema was found in almost all structures and spaces at moderate/severe level. At FEES, residue (higher percentage in valleculae and pyriform sinus), penetration and aspirations were observed. The residue was detected in higher occurrence in patients with composite lymphedema (p = 0.012). The combined treatment with radiotherapy was related to submandibular external lymphedema (p = 0.009), altered pharyngolaryngeal sensitivity (0.040), presence of residue (p = 0.001) and penetration to pasty (p = 0.007) and internal edema in almost all structures. There was also a higher percentage of residue in cases with internal altered pharyngolaryngeal sensitivity, residue, penetration and aspiration. Combined treatment with radiotherapy is an associated factor of edema. Cervicofacial and pharyngolaryngeal lymphedema is a frequent event after treatment for HNC, with important impact on swallowing performance characterised by altered pharyngolaryngeal sensitivity, residue, penetration and aspiration. Combined treatment with radiotherapy is an associated factor.

Competing Interests: Competing interests: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author), and declare no conflicts of interest.

Background: Young women with breast cancer (YWBC) are more likely to have aggressive disease, carry mutations for hereditary cancer genes, and experience higher mortality. They also may face reduced fertility because of the toxicity of chemotherapy., Objectives: This article aims to present a review of YWBC treatments, sequelae of treatment, and psychosocial challenges., Methods: The authors performed a review of guideline-supported treatment options, patient resources, and nursing implications., Findings: Because of high-risk cancers and a lack of specific treatment guidelines, healthcare providers may consider aggressive treatments for younger patients. However, studies indicate that the foundation for treatment decisions for YWBC are best based on disease stage and National Comprehensive Cancer Network guidelines.

Importance: Multiple randomized clinical trials have shown that definitive therapy improves overall survival among patients with high-risk prostate cancer. However, many patients do not receive definitive therapy because of sociodemographic and health-related factors., Objective: To identify factors associated with receipt of nondefinitive therapy (NDT) among patients aged 70 years and younger with high-risk prostate cancer., Design, Setting, and Participants: This cohort study identified 72 036 patients aged 70 years and younger with high-risk prostate cancer and Charlson Comorbidity Index scores of 2 or less who were entered in the National Cancer Database between January 2004 and December 2014. Data analysis was conducted from November 2018 to December 2019., Exposure: Receipt of NDT as an initial treatment approach., Main Outcomes and Measures: Survival rates were compared based on receipt of definitive therapy or NDT, and sociodemographic and health-related factors were associated with the type of therapy received. Residual life expectancy was estimated from the National Center for Health Statistics to calculate person-years of life lost., Results: A total of 72 036 men with a median (range) age of 63 (30-70) years, Charlson Comorbidity Index scores of 2 or less, and high-risk prostate cancer without regional lymph node or distant metastatic disease were analyzed. Among eligible patients, 5252 (7.3%) received NDT as an initial therapeutic strategy. On univariate and multivariate analyses, NDT was associated with worse overall survival (univariate analysis hazard ratio, 2.54; 95% CI, 2.40-2.69; P < .001; multivariate analysis hazard ratio, 2.40; 95% CI, 2.26-2.56; P < .001). Compared with patients with private insurance or managed care, those with no insurance, Medicaid, or Medicare were more likely to receive systemic therapy only (no insurance: odds ratio [OR], 3.34; 95% CI, 2.81-3.98; P < .001; Medicaid: OR, 2.92; 95% CI, 2.48-3.43; P < .001; Medicare: OR, 1.36; 95% CI, 1.20-1.53; P < .001) or no treatment (no insurance: OR, 2.63; 95% CI, 2.24-3.08; P < .001; Medicaid: OR, 1.71; 95% CI, 1.45-2.01; P < .001; Medicare: OR, 1.14; 95% CI, 1.04-1.24; P = .004). Compared with white patients, black patients were more likely to receive systemic therapy only (OR, 1.93; 95% CI, 1.74-2.14; P < .001) or no treatment (OR, 1.46; 95% CI, 1.32-1.61; P < .001), and Hispanic patients were more likely to receive systemic therapy only (OR, 1.36; 95% CI, 1.13-1.64; P = .001) or no treatment (OR, 1.36; 95% CI, 1.14-1.60; P < .001). Between 2004 and 2014, patients without insurance or enrolled in Medicaid had 1.83-fold greater person-years of life lost compared with patients with private insurance (area under the curve, 77 600 vs 42 300 person-years of life lost)., Conclusions and Relevance: In this study, receipt of NDT was associated with insurance status and race/ethnicity. While treatment decisions should be individualized for every patient, younger men with high-risk prostate cancer and minimal comorbidities should be encouraged to receive definitive local therapy regardless of other factors. These data suggest that significant barriers to life-extending treatment options for patients with prostate cancer remain.

Background: As cancer survival rates improve, understanding and preventing the adverse off-target and long-term impacts of cancer treatments, including impacts on fertility, have become increasingly important. Cancer therapy-mediated damage to the ovary and depletion of the primordial follicle reserve are well characterised. However, our knowledge of the full extent of damage to the rest of the female reproductive tract, in particular the uterus, is limited., Objective and Rationale: Improving our understanding of the off-target effects of cancer therapies on the entire female reproductive tract is a critical step towards developing truly effective strategies to protect the fertility of cancer survivors. The objective of this narrative review was to critically evaluate the available literature regarding the capacity for the uterus to sustain a healthy pregnancy following exposure to radiotherapy or chemotherapy., Search Methods: The authors performed PubMed (Medline) searches using the following key words: uterus, cancer survivors, radiotherapy, chemotherapy, pregnancy outcome, fertility preservation, infertility. There were no limits placed on time of publication., Outcomes: Overall, there were major limitations to the current available literature, meaning that interpretations should be taken with caution. Despite these drawbacks, data suggest that the uterus may sustain off-target damage, with the extent of damage dependent on the type of cancer treatment and patient age. Specifically, uterine growth is stunted and resistant to hormone replacement therapy in prepubertal girls receiving abdominal, pelvic or whole-body radiotherapy. In contrast, females treated with radiotherapy post-puberty can benefit from hormone replacement therapy, as demonstrated by increased uterine volume and function. No live births have been reported in women previously exposed to radiotherapy after transplantation of cryopreserved ovarian tissue, even when menstruation returns. However, this technique has proven to be a successful fertility preservation method for women previously treated with chemotherapy. Obstetricians commonly report that women who maintain sufficient ovarian function can achieve pregnancy naturally following radiotherapy, but they have thin and/or fibrotic myometrium at delivery, compromising safe delivery and subsequent pregnancy. Furthermore, women exposed to either radiotherapy or chemotherapy have a higher prevalence of preterm birth and low birth weight infants, even in those with normal ovarian function or when oocyte donation is utilised. The mechanisms of potential uterine damage are poorly understood. While the myometrium, vasculature and endometrial progenitor cells are possibly targets, further studies are clearly required and well-controlled animal models could provide the best avenue for these types of future investigations., Wider Implications: Female cancer survivors experience greater rates of early pregnancy loss and complications, suggesting that cancer therapy-induced damage to the uterus contributes to infertility. Despite clinical reports dating back to 1989, we highlight a surprising lack of detail in the literature regarding the precise nature and extent of off-target damage inflicted to the uterus in response to cancer therapies. Young women requiring cancer treatment, and the clinicians treating them, must be equipped with accurate information to aid informed decision-making regarding cancer treatment regimens as well as the development and use of effective fertility preservation measures. As the current literature on the impacts of cancer treatments is limited, we hope that our narrative review on this subject will stimulate more research in this important field., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The purpose of this study was to investigate doctors' and patients' perceptions of cervical intraepithelial neoplasia 1 (CIN 1) and its treatment methods. A survey questionnaire was offered to obstetrics and gynaecology doctors and patients with CIN 1 in 2017. Only 43% of patients knew of this disease. Regarding perceptions of its aetiology, 64% of the patients perceived human papillomavirus infection to be the main cause of CIN 1. Patients' most preferred treatments were medication (20%), followed by alternative treatment (14%). Among doctors, regular follow-up was the most preferred method for managing CIN 1. The survey showed that current treatment modalities for CIN 1 were satisfactory to only half of doctors (50%) and patients (53%). Overall, 70% of doctors responded that new drug development for CIN 1 is needed. Although, CIN 1 is a low-grade lesion, doctors and patients expressed the desire for new therapeutic agents to manage it.IMPACT STATEMENT What is already known on this subject? In general, treatment is not recommended for CIN 1 because lesions are considered indicative of transient HPV infection and spontaneously regress in most patients. What do the results of this study add? Regular follow-up for CIN 1 were satisfactory to only half of doctors and patients. Thirty-six percent of patients wanted active treatment instead of regular follow-up. In addition, 70% of doctors responded that new drug development for CIN 1 is needed. What are the implications of these findings for clinical practice and/or further research? Our results support the need for therapeutic agents for CIN 1.

Purpose: Cancer-related fatigue (CRF) is the most common and distressing symptom in breast cancer survivors (BCS), with severe impact on quality of life. CRF can be reduced through exercise, but conversely, is also a barrier to exercising. The aim of this article was to apply the intervention mapping protocol (IMP) to develop an exercise adherence intervention for BCS with CRF., Method: The program was developed using the IMP, which consists of six steps. Based on the data from focus group interviews and literature review, we produced a logic model of change., Results: Two performance objectives (survivors adopt and maintain exercise and survivors cope with fatigue) and 17 change objectives were generated. Also, we designed theory-based methods of change, and strategies for practical application. A structured program plan that includes intervention content and methods, ranges, and program data was proposed. Finally, an implementation and evaluation plan was developed., Conclusion: The IMP provided a useful framework to systematically plan an exercise adherence program. This study resulted in a theory and practice-based exercise adherence program, based on behavioral change theories, and practice-based knowledge that fits the needs of BCS with CRF.

Objective: Ductal carcinoma in situ (DCIS) has the potential to progress to invasive carcinoma. The optimal management of DCIS and methods for individualizing treatment of DCIS are still being determined. This evidence map depicts the robustness and topical span of research on DCIS management choice on patient-centered and clinical outcomes., Methods: We searched PubMed, EMBASE, PsycINFO, PubMed Health, PROSPERO, and clinical practice guideline sites to identify systematic reviews of DCIS management options and consulted with topic experts. A bubble plot visualizes the literature volume and research content for patient-centered outcomes. An online decision tree facilitates discussions with patients and guides through the available evidence., Results: In total, 40 systematic reviews met inclusion criteria. The research syntheses addressed DCIS management options, including the role of magnetic resonance imaging, axillary surgery/sentinel lymph node biopsy, and excisional biopsy. The map shows existing evidence for mutually exclusive treatment options including active surveillance, breast-conserving surgery, nipple sparing mastectomy, and simple mastectomy. Research findings for intraoperative radiation, adjuvant radiation therapy, adjuvant hormone therapy, hypofractionation radiotherapy, accelerated partial breast irradiation, radiation therapy plus boost, and combined radiation and hormone therapy, as well as for breast reconstruction after mastectomy and surveillance mammography postsurgery are also displayed. The evidence map highlights a scarcity of robust evidence on patient-centered outcomes., Conclusions: The evidence map provides an overview of DCIS research showing the range of management options and remaining decisional dilemmas that follow a diagnosis of DCIS. It maps the evidence in accessible tools to guide practice and future research. : Video Summary:http://links.lww.com/MENO/A448.

Background: Many advances in the management of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) happened in the last two decades. This study highlights the progress in its management over 17 years, outcomes, recurrence patterns, and follow up protocols., Methods: This retrospective analysis of prospectively maintained database at a single tertiary center included GEP-NEN patients from January 2001 to August 2017. Management protocols were based on European Neuroendocrine Tumor Society guidelines. Recurrences were categorized as follows: localized nodal, regional, distant hepatic, or combined. Patients were divided into cohorts: cohort 1 (2001-2006), cohort 2 (2007-2011), and cohort 3 (2012-2017). Survival patterns were analyzed., Results: One hundred and ninety-two patients were included with 98 (51.04%) grade (G) 1, 64 (33.34%) G2, and 30 (15.63%) G3. One hundred and four (54.16%) underwent curative surgery (58 G1, 27 G2, and 19 G3). Overall follow up ranged from 3 to 276 months; 39 were lost to follow up. Ninety-six patients had recurrences: 44 regional + distant and 40 liver-limited recurrences. One-, 3-, and 5-year survivals show significant differences among different treatment groups (p < 0.05). Significant increase in curative resections, chemotherapy utilization, and reduced recurrences were noted in cohort 3. Curative (R0) resection offered 1- and 3-year overall survival of 93.3% and 66.7% in cohort 1; 95.8% and 83.1% in cohort 2; and 100% and 92.9% in cohort 3., Conclusion: Curative resection is the most significant factor for improved survival. Debulking surgerical procedure have a role whereas upfront peptide receptor radionuclide therapy is questionable. Chemotherapy improves overall survival in inoperable/metastatic setting. Recurrence patterns indicate that a long-term follow up greater than 10 years is necessary.

Background: The standard treatment for high-grade non-Hodgkin lymphoma involves the combination of chemotherapy and immunotherapy. We characterize in-silico the optimal combination protocol that maximizes the overall survival probability. We rely on a pharmacokinetics/pharmacodynamics (PK/PD) model that describes the joint evolution of tumor and effector cells, as well as the effects of both chemotherapy and immunotherapy. The toxicity is taken into account through ad-hoc constraints. We develop an optimization algorithm that belongs to the class of Monte-Carlo tree search algorithms. Our simulations rely on an in-silico population of heterogeneous patients differing with respect to their PK/PD parameters. The optimization objective consists in characterizing the combination protocol that maximizes the overall survival probability of the patient population under consideration., Results: We compare using in-silico experiments our results to standard protocols and observe a gain in overall survival probabilities that vary from 4 to 9 percentage points. The gains increase with the complexity of the potential protocol. Gains are larger in presence of a higher number of injections or of an actual combination with immunotherapy., Conclusions: In in-silico experiments, optimal protocols achieve significant gains over standard protocols when considering overall survival probabilities. Our optimization algorithm enables us to efficiently tackle this numerical problem with a large dimensionality. The in-vivo implications of our in-silico results remain to be explored., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background/aims: To determine strategies to prevent early death (ED) and improve the prognosis of patients with advanced hepatocellular carcinoma (HCC)., Materials and Methods: Patients who were diagnosed with HCC from January 2012 to June 2017 were considered for the study. Those who survived for ≤6 months from the date of diagnosis were classified into the ED group (n=21) and those who survived for ≥12 months from the date of diagnosis were classified into the non-ED group (n=88)., Results: There were significant differences between the ED and non-ED groups in the following conditions: when the patient age was ≥80 years (38.1% vs. 14.8% patients); maximum nodule size was >3 cm (90.5% vs. 27.3%); Child-Pugh class C liver disease was seen (66.7% vs. 26.1%); tumor-node-metastasis (TNM) Stage III-IV tumor was present (85.7% vs. 21.6%); BCLC stage C/D of liver cancer was seen (81.0% vs. 21.6%); JIS score was ≥4 (52.4% vs. 3.4%); serum creatinine level was ≥1.0 mg/dL (52.4% vs. 22.7%); and there was absence of aggressive treatments such as hepatic resection, radiofrequency ablation, transarterial chemoembolization, and chemotherapy (66.7% vs. 4.5%). Logistic regression analysis identified maximum nodule size of >3 cm (p=0.005, OR=58.7, 95% CI=3.43-1003.9), JIS score of ≥4 (p=0.021, OR=12.0, 95% CI=1.44-100.1), and absence of aggressive treatments (p=0.006, OR=24.7, 95% CI=2.47-247.2) as predictive factors for ED. The presence of aggressive treatments significantly improved the 12-month survival rate of advanced HCC patients with BCLC stage C/D (presence vs. absence: 78.3% vs. 7.4%), a maximum nodule size of >3 cm (76.7% vs. 7.7%), and a JIS score of ≥4 (60.0% vs. 0%)., Conclusion: Although delayed detection of HCC strongly increased the onset ED, the aggressiveness of HCC treatment is not readily downgraded, and the most aggressive treatment possible should be considered to prevent ED in patients with advanced HCC.

Background: Gastric cancer ranks the fifth most common cancer, and the third leading cause of cancer-related deaths worldwide. Gastric cancer with liver metastasis (GCLM) has devastating prognosis, however, optimal treatment of GCLM, especially in elderly patients, has yet to be clarified., Case Presentation: A 75-year-old man was diagnosed with advanced gastric cancer (GC), presenting with acute gastrointestinal bleeding and synchronous metastatic lesion in liver. Based on multidisciplinary team (MDT)'s decision, this patient underwent distal palliative gastrectomy with R1 margin. Histopathological diagnosis was stage IV gastric adenocarcinoma (pT3N2M1), HER2 negative. The patient was treated with chemotherapy and argon-helium cryoablation of liver and lung metastases.HER-2 gene amplification was identified in peripheral blood at later stage of therapy. The patient had been followed-up for 39 months, in sharp contrast to a median survival time of 13.8 months for majority of advanced GC., Conclusions: Palliative distal gastrectomy in combination with chemotherapy and cryoablation significantly prolongs overall survival of an elderly patient with GCLM.

Trimodality therapy is the standard of care for locally advanced resectable esophageal cancer (EC) but carries morbidity and mortality risks; thus, therapy at high-volume facilities (HVFs) may offer advantages. This investigation studied postoperative outcomes and overall survival (OS) in EC patients receiving trimodality therapy at HVFs versus lower-volume facilities (LVFs). The National Cancer Data Base was queried for patients with locally advanced EC receiving trimodality therapy. HVFs referred to the 90th percentile of case volume. Multivariate logistic regression determined factors associated with treatment at HVFs, the Kaplan-Meier analysis compared OS between the HVF and LVF groups, and the Cox proportional hazards modeling determined variables associated with OS. Sensitivity analysis evaluated the impact of varying the HVF definition cutoff on OS. A total of 3,229 patients met study criteria, including 330 (10%) treated at HVFs and 2,899 (90%) at LVFs. Treatment at HVFs was associated with decreased 30-day mortality (1.2% vs. 3.3%, P = 0.044) and trends toward lower 90-day mortality (4.8% vs. 7.8%, P = 0.055) and the length of postoperative hospitalization (11.2 vs. 12.3d, P = 0.059). HVF patients experienced higher median OS (55 vs. 36 months, P = 0.004), which also independently correlated on the Cox multivariate analysis (P = 0.001). Sensitivity analysis showed similar results as the HVF/LVF cutoff was decreased until the 80th percentile. This is the first study demonstrating that the trimodality management of EC at HVFs is associated with improved postoperative outcomes and survival. These data have implications for multidisciplinary oncologic providers, in addition to patient counseling by both referring and treating clinicians., (© The Author(s) 2018. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Rationale: Primary adrenal non-Hodgkin lymphomas are predominant diffuse large B cell lymphoma with frequently bilateral adrenal involvement, but the occurrence of nasal type extranodal NK/T cell lymphoma is relatively rare., Patient Concerns: A 40-year-old woman complaining of left back pain for 2-month was admitted to our department., Diagnosis: Based on the feature of enhanced computed tomography (CT) images which showed huge bilateral well-defined adrenal masses with heterogeneous enhancement, she was tentatively diagnosed as having primary adrenal malignancy. Postoperative pathology revealed the diagnosis of primary adrenal Epstein-Barr virus-associated nasal type extranodal NK/T-cell lymphoma., Interventions: Then, she underwent F-fluoro-2-deoxy-D-glucose (F-FDG) positron emission tomography (PET)/CT examination for staging, which showed homogeneously increased FDG uptake in the right adrenal gland and left thigh subcutaneous lesion, as well as heterogeneous increased FDG uptake in the left adrenal gland region with no abnormal uptake in the nasal cavity. Subsequently, the patient has performed 7 cycles of gemcitabine, L-asparaginase, ifosfamide, dexamethasone, etoposide (GLIDE) regimen and autologous stem cell transplantation., Outcomes: Fortunately, the subsequent 2 follow-up FDG PET/CT scans within 1 year revealed complete resolution with no abnormal FDG uptake in the initially involved sites after 7 cycles of GLIDE chemotherapy and autologous stem cell transplantation., Lessons: The enhanced CT and FDG PET/CT features of primary adrenal extranasal NK/T cell lymphoma are huge bilateral well-defined adrenal masses with heterogeneous enhancement, high FDG uptake, especially with subcutaneous involvement. And the awareness of this entity may help clinicians to differentiate it from other primary adrenal tumors and make reasonable therapeutic strategies. Besides, FDG PET/CT scan is very useful for the treatment follow-up of the primary adrenal extranasal NK/T cell lymphoma.

Biliary tract cancer (BTC) patients have poor prognosis even following radical resection. To improve the current status, more evidence is required clarifying the role of adjuvant chemotherapy. This study aim is to evaluate the efficacy of adjuvant chemotherapy and discuss the regimen choices.We retrospectively analyzed the clinical data of 80 patients who underwent curative-intent R0 resection from 2008 to 2016. Among them, 40 patients had received adjuvant chemotherapy, and the others in the observation group were 1:1 matched by clinical characteristics including gender, age, tumor stage, and ECOG performance status score. Kaplan-Meier analysis was performed to compare DFS and OS. Potential confounding factors were adjusted by Multivariate analysis.In the entire patient cohort, the mean disease-free survival (DFS) time of BTC patients with adjuvant chemotherapy and observation was 18.63 ± 3.63 months versus 10.36 ± 1.67 months, respectively (P = .029). There was no significant difference observed in overall survival (OS) time (33.72 ± 5.02 vs 21.05 ± 4.12 months, P = .114). On multivariate analysis, adjuvant chemotherapy and N factor were found to be significant factors for DFS, and sex, age, T factor were found to be significant factors for OS. Besides, subgroup analysis indicated that combination chemotherapy prolonged DFS time of BTC patients than single-agent to some extent, and oral agents showed efficacy to improve OS.This retrospective study demonstrates that adjuvant chemotherapy contributes to DFS, but is unsatisfactory for improving OS. Combination chemotherapy contained oral agents provides a possibility of therapeutic strategy for improving surgical outcomes of BTC patients.

Background: Cancer has a lot of consequences on patients' quality of life (such as cancer-related fatigue (CRF), sleep difficulties and emotional distress) and on patients' partners and their relationship, such as distress and communication difficulties. These consequences are undertreated, and interventions based on hypnosis often focus on breast cancer patients only. This paper describes the study protocol of a longitudinal randomized controlled trial aiming to assess the efficacy of an 8-week intervention combining hypnosis and self-care to improve cancer patients' CRF, sleep and emotional distress and to indirectly improve their partners' distress., Methods: A power analysis required a total sample of 88 patients. To test the efficacy of the intervention, results of the experimental group receiving the intervention will be compared to those of the control group. Data will be collected by questionnaires, relaxation tasks, an attentional bias task, and everyday life assessments measured at four different times: 1.) before inclusion in the study (baseline); 2.) after the intervention; and 3.) at 4- and 12-month follow-up. Partners' symptoms will also be evaluated with questionnaires at the same measurement times., Discussion: There is a growing interest in alternative approaches (such as hypnosis) in addition to standard therapies in oncology settings. The results of this study should be useful for improving knowledge about long-term efficacy of hypnosis-based group interventions for CRF, sleep and distress among all types of cancer patients and their partners, and to better understand the mechanisms of emotional regulation in cancer patients through the attentional bias task., Trial Registration: ClinicalTrials.gov (NCT03144154). Retrospectively registered on the 1st of May, 2017.

The present study aimed to design and develop a nanocomposite drug delivery system employing an antineoplastic-loaded antibody functionalized nanomicelle encapsulated within a Chitosan⁻Poly(vinylpyrrolidone)⁻Poly(N-isopropylacrylamide) (C⁻P⁻N) hydrogel to form an in situ forming implant (ISFI), responsive to temperature and pH for cancer cell-targeting following intraperitoneal implantation. The optimum nanomicelle formulation was surface-functionalized with anti-MUC 16 (antibody) for the targeted delivery of methotrexate to human ovarian carcinoma (NIH:OVCAR-5) cells in Athymic nude mice that expressed MUC16, as a preferential form of intraperitoneal ovarian cancer (OC) chemotherapy. The cross-linked interpenetrating C⁻P⁻N hydrogel was synthesized for the preparation of an in situ-forming implant (ISFI). Subsequently, the ISFI was fabricated by encapsulating a nanocomposite comprising of anti-MUC16 (antibody) functionalized methotrexate (MTX)-loaded poly( N -isopropylacrylamide)-b-poly(aspartic acid) (PNIPAAm-b-PASP) nanomicelles (AF(MTX)NM's) within the cross-linked C⁻P⁻N hydrogel. This strategy enabled specificity and increased the residence time of the nanomicelles at tumor sites over a period exceeding one month, enhancing uptake of drugs and preventing recurrence and chemo-resistance. Chemotherapeutic efficacy was tested on the optimal ovarian tumor-bearing Athymic nude mouse model and the results demonstrated tumor regression including reduction in mouse weight and tumor size, as well as a significant (p < 0.05) reduction in mucin 16 levels in plasma and ascitic fluid, and improved survival of mice after treatment with the experimental anti-MUC16/CA125 antibody-bound nanotherapeutic implant drug delivery system (ISFI) (p < 0.05). The study also concluded that ISFI could potentially be considered an important immuno-chemotherapeutic agent that could be employed in human clinical trials of advanced, and/or recurring, metastatic epithelial ovarian cancer (EOC). The development of this ISFI may circumvent the treatment flaws experienced with conventional systemic therapies, effectively manage recurrent disease and ultimately prolong disease-free intervals in ovarian cancer patients., Competing Interests: The authors declare no conflict of interest.

Rationale: Hepatocellular carcinomas (HCCs) with metastases to the right atrium (RA) and lungs are rare, with a poor prognosis. Furthermore, the treatment outcomes in patients with advanced HCCs remain unsatisfactory., Patient Concerns: A 46-year-old man presented to our hospital for dyspnea on exertion and abdominal pain., Diagnoses: HCC and extra-hepatic metastases to the lung and RA., Interventions: Multidisciplinary treatment including radiotherapy (RT), transarterial chemoembolization (TACE), and sorafenib. During a follow-up evaluation computed tomography, he experienced a radio-contrast-induced anaphylaxis. After the event, treatment such as RT, TACE, and sorafenib were continued., Outcomes: His tumor burden decreased, finally leading to a complete response as per the modified Response Evaluation Criteria in Solid Tumors. The patient is still alive, 30 months after the episode. Subsequent blood tests showed increased natural killer (NK) cell activity, which was significantly higher than that seen in other age-matched HCC patients with an identical stage of the tumor, receiving sorafenib. This suggests that the increase in NK cells induced by anaphylaxis influenced the tumor burden., Lessons: We report here a rare case of long-term survival of an HCC patient with multiple metastases treated with multidisciplinary modalities, in which high NK cell activity was observed after a radio-contrast-induced anaphylactic reaction during follow-up investigations.

Patients with unresectable metastatic colorectal cancer live for a median of three years when treated with standard therapies. While the evidence guiding cancer-directed treatment of this disease comes from phase III trials that have mostly enrolled patients with good performance status, some patients present with poor clinical conditions. The best treatment for these patients remains to be determined. We performed a systematic review of the treatment outcomes of patients with metastatic colorectal cancer and poor performance status, defined as Eastern Cooperative Oncology Group performance status ≥2. Eligible articles were prospective or retrospective studies or case reports published in English, Portuguese or Spanish. We searched PubMed, EMBASE, LILACS and the Cochrane Library from onset until October 2017 using specific keywords for each search. We found a total of 18 publications, mostly case reports and retrospective studies (14 articles). One was an uncontrolled prospective trial, two were observational studies and one was an individual patient meta-analysis. Although some studies suggested benefits in terms of symptomatic response with standard chemotherapy, with good safety profiles when dose-reduced regimens were administered, a true survival gain could not be demonstrated. The scientific evidence for treating metastatic colorectal cancer patients with poor performance status is scarce, and more studies evaluating treatment for this population are necessary since this condition is not uncommon in clinical practice, particularly in the public healthcare system and developing countries and among destitute populations.

Trimodality therapy with neoadjuvant chemoradiation followed by surgery has emerged as the standard of care for the treatment of locally advanced esophageal cancer. Yet, there is considerable variation in survival within this population. We sought to analyze factors associated with survival after trimodality therapy in esophageal adenocarcinoma. We identified 4,679 patients from the National Cancer Database (NCDB) of the American College of Surgeons who received chemotherapy and radiation prior to surgery for esophageal adenocarcinoma from 2006 to 2013. We excluded patients with stage IV disease and unknown pathological nodal status. We performed regression analyses using a Cox proportional hazards model to identify independent predictors of overall survival. On multivariate analysis, pathologic characteristics associated with decreased overall survival included stage, lymphovascular invasion, and positive surgical margins. Insurance status, age, and comorbidity index were also associated with decreased survival. We found that pathologically node-positive patients who received additional adjuvant chemotherapy were associated with improved survival. Compared to private insurance, Medicaid (HR 1.45, CI 1.22-1.73, P < 0.0001), Medicare (HR 1.17, CI 1.04-1.31, P = 0.0082), or having no insurance (HR 1.50, CI 1.17-1.92, P = 0.0012) were all negative predictors of overall survival. In patients with esophageal adenocarcinoma who have undergone trimodality therapy, a number of different factors are associated with overall survival. In particular, socioeconomic factors relating to access to care are independent predictors of survival. Despite receiving the standard of care, treatment disparities persist in this population of patients.

Background: Data on colorectal lymphoma in general and on MALT (mucosa-associated-lymphoid tissue) lymphoma, in particular are, very rare. There are no existing recommendations from current guidelines for how to manage these patients. We here report our experience from a clinical series., Aim: The aim of this study is to present clinical features and the endoscopic appearance of colorectal MALT lymphoma and therapeutic approaches., Methods: Seven patients (5 male and 2 female, aged 47 - 75 years) were diagnosed to have colorectal MALT lymphoma. All patients underwent a full staging work-up. A concurrent gastric MALT lymphoma was present in 2 patients. Follow-up was 37 (0 - 53) months., Results: Colorectal MALT lymphoma was diagnosed by screening or staging colonoscopy in 3 and 1 patient, revealing no clinical symptoms, respectively. Two patients complained about fatigue, obstipation, and a change in bowel habits. The endoscopic appearance of the MALT lymphoma comprised obstructive tumors (n = 2), polyps (n = 3), a flat lesion (n = 1), and vascular angiectasia (n = 1). In 6 cases, colorectal MALT lymphoma presented as a solitary lesion. Following endoscopic polypectomy, surgical resection, Helicobacter pylori eradication therapy, or systemic immune-chemotherapy, complete remission of lymphoma was achieved in 5 cases, while the outcome is unknown or cannot yet be estimated in 2 cases., Conclusion: A treatment and management approach based on the clinical and local presentation of the lymphoma and its involvement is proposed., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Gamma Knife radiosurgery (GKRS) is increasingly applied in patients with multiple brain metastases and is expected to have less adverse effects in cognitive functioning than whole brain radiation therapy (WBRT). Effective treatment with the least negative cognitive side effects is increasingly becoming important, as more patients with brain metastases live longer due to more and better systemic treatment options. There are no published randomized trials yet directly comparing GKRS to WBRT in patients with multiple brain metastases that include objective neuropsychological testing., Methods: CAR-Study B is a prospective randomised trial comparing cognitive outcome after GKRS or WBRT in adult patients with 11-20 newly diagnosed brain metastases on a contrast-enhanced MRI-scan, KPS ≥70 and life expectancy of at least 3 months. Randomisation by the method of minimization, is stratified by the cumulative tumour volume in the brain, systemic treatment, KPS, histology, baseline cognitive functioning and age. The primary endpoint is the between-group difference in the percentage of patients with significant memory decline at 3 months. Secondary endpoints include overall survival, local control, development of new brain metastases, cognitive functioning over time, quality of life, depression, anxiety and fatigue. Cognitive functioning is assessed by a standardised neuropsychological test battery. Assessments (cognitive testing, questionnaires and MRI-scans) are scheduled at baseline and at 3, 6, 9, 12 and 15 months after treatment., Discussion: Knowledge gained from this trial may be used to inform individual patients with BM more precisely about the cognitive effects they can expect from treatment, and to assist both doctors and patients in making (shared) individual treatment decisions. This trial is currently recruiting. Target accrual: 23 patients at 3-months follow-up in both groups., Trial Registration: The Netherlands Trials Register number NTR5463. ClinicalTrials.gov registration number NCT02953717 , first received October 27, 2016, 8 patients were enrolled in this study on 31 July 2017.

Ameloblastic carcinoma is a rare locally aggressive odontogenic neoplasm. These tumors are most commonly found to arise from mandible. Because of rarity, there is limited information about the clinical behaviour of such patients. We intended to perform this review of published literature to assess the demographic profile, pattern of care and assess survival outcomes. Two authors independently searched PubMed, Google search, and Cochrane library for eligible studies from 1950 until July 1 2016 published in English language. Data of 199 patients were retrieved from 94 publications for statistical analysis. Median age of the entire cohort was 49 years (range 7-91 years). The analysis revealed that a clear twofold higher incidence in male with male-to-female ratio was 2.4:1 (140:57). Mandible was found to be the commonest tumor location in 66.7% (n = 132) cases followed by maxilla (31.8%) (n = 64). The present analysis revealed that median PFS of 57 months (95% CI 39-120 months) with 5- and 10-year PFS was found to be 47.88 and 29.48%, respectively. Median OS for the entire cohort which was 122 months (95% CI 96-153 months) with 2- and 5-year OS for the entire cohort was 87.16 and 69.08%, respectively. In univariate analysis, patients with an R0 resection were found to have a favourable survival. In addition, patients with localized disease and younger age were found to have a better survival. Adjuvant radiation did not confer any survival advantage. The present analysis revealed excellent outcome for patients treated with an R0 resection. Older patients with high-risk factor may benefit from adjuvant radiation. Role of chemotherapy needs to be evaluated.

Background: Colorectal cancer (CRC) is one of the most common cancers all over the world, but its epidemiology is obviously different in various regions., Methods: The treatment of CRC also has varying characteristics due to differences in economy, geography, disease onset, chemotherapy, and other factors, although international guidelines are used to guide the treatment of CRC in China., Results: This paper summarizes the current status of CRC treatment, including surgical therapy, neoadjuvant radiotherapy and chemotherapy, postoperative chemotherapy, targeted therapy, maintenance therapy, and immunotherapy, according to the clinical situation in China, so as to provide better therapy and improve clinical practice for patients with CRC., Conclusion: This research shows that the treatment of colorectal cancer continues to progress, and the patient's efficacy and quality of life have improved.

Objectives: Data regarding the impact of breast cancer treatment-related neuropathic pain (NP) on sleep quality are scarce. Therefore, we aimed to assess the impact of breast cancer treatment-related NP on patients' sleep quality, during the first year after cancer diagnosis., Materials and Methods: A total of 501 breast cancer patients were followed prospectively. Incident NP was identified through systematic evaluations after treatments and one year after enrolment. NP severity was quantified using the Brief Pain Inventory severity subscale and sleep quality was evaluated through the Pittsburgh Sleep Quality Index (PSQI), at baseline and after one year. Adjusted regression coefficients (β) and 95% confidence intervals (95%CI) were used to quantify the relation between NP and the variation in the PSQI z-scores., Results: The occurrence of NP was associated with a deterioration in sleep quality during the first year of follow-up, more pronounced among those with good sleep quality (PSQI≤5) than those with poor sleep quality at baseline (PSQI>5) (β = 0.44, 95%CI: 0.11 to 0.77 versus β = 0.33, 95%CI: 0.08 to 0.59). These differences were accentuated when only the cases of NP with greater severity were considered (β = 0.86, 95%CI: 0.37 to 1.35 versus β = 0.31, 95%CI: -0.08 to 0.64). Within the PSQI components, daytime dysfunction and sleep duration were the most impaired by NP., Conclusion: Our findings highlight the importance of the promotion of sleep hygiene among breast cancer patients diagnosed with NP, especially among those with good sleep quality before treatments., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Peritoneal metastasis of gastric cancer is the main cause of death in gastric cancer patients. Peritoneal metastasis of gastric cancer is difficult to diagnose in its early stage due to lack of obvious clinical signs and symptoms, and poor treatment outcomes and prognosis are often associated with late stage peritoneal metastasis. Therefore, it is crucial to utilize effective early diagnostic tools and to improve the long-term outcomes and the prognosis of patients with advanced gastric cancer. Recently, systemic chemotherapy and intraperitoneal chemotherapy are the first line therapy, and cytoreductive operation plus abdominal cavity thermochemotherapy may be the best method in the treatment of peritoneal metastasis. However, conversion therapy has been gradually incorporated into the treatment of peritoneal metastasis of gastric cancer because of the better efficacy and the higher survival.

To assess the relationship between the locoregional disease-free interval after treatment of the primary tumor and survival after a recurrence in patients with laryngeal carcinoma. We retrospectively investigated patients treated in our Cancer Center for a laryngeal cancer who subsequently developed a locoregional recurrence and were followed up until death. Post-recurrence survival was defined as the time from the locoregional recurrence to death. One hundred and twenty-three patients were included. Median post-recurrence survival was 7 months. The locoregional disease-free interval (LRDFI) after treatment of the primary was weakly correlated with post-recurrence survival (r = 0.210, p = 0.020). A LRDFI cut-off of 12 months was a significant prognostic factor (p = 0.005; median, 5 months, 95% CI: 2.239-6.761, vs 10 months, 95% CI: 7.270-12.730). The time to locoregional recurrence in laryngeal cancer was a prognostic factor correlated with post-recurrence survival. Locoregional failure within the first year after treatment of the primary tumor was associated with an unfavorable prognosis.

Given the paucity of esophageal small cell carcinoma (SCC) cases, there are few large studies evaluating this disease. In this study, the National Cancer Data Base (NCDB) was utilized to analyze the clinical features, treatment, and survival of patients with esophageal SCC in a large, population-based dataset. We selected patients diagnosed with esophageal SCC from 1998 to 2011. Patients were identified as having no treatment, chemotherapy alone, radiation ± sequential chemotherapy, concurrent chemoradiation, and esophagectomy ± chemotherapy and/or radiation. Overall survival (OS) was analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was conducted to identify factors associated with OS. A total of 583 patients were identified. Most patients had stage IV disease (41.7%). Regarding treatment selection, chemoradiation was the most commonly utilized for patients with nonmetasatic disease, whereas chemotherapy alone was most common for metastatic patients. Esophagectomy (median survival 44.9 months with 3 year OS 50.5%) was associated with the best OS for patients with localized (node-negative) disease compared with chemotherapy alone (p < 0.001) or chemoradiation (p = 0.01). For locoregional (node-positive) disease, treatment with chemoradiation resulted in a median survival of 17.8 months and a 3 year OS 31.6%. On multivariate analysis, treatment with chemotherapy alone (p = 0.003) was associated with worse OS while esophagectomy (p = 0.04) was associated with improved OS compared to chemoradiation. Esophageal SCC is an aggressive malignancy with most patients presenting with metastatic disease. Either esophagectomy or chemoradiation as part of multimodality treatment appear to improve OS for selected patients with nonmetastatic disease., (© 2016 International Society for Diseases of the Esophagus.)

Aim: To estimate the number of early progenitors of bone marrow (BM) hematopoiesis in patients with diffuse large B-cell lymphoma (DLBCL) in the late period after high-dose chemotherapy (HDCT) according to the mNHL-BFM-90 program., Subjects and Methods: The investigators analyzed the results of BM immunophenotypic and histological studies in 40 patients (median age, 57 years) with DLBCL who received HDCT according to the mNHL-BFM-90 program at the Hematology Research Center (HRC), Ministry of Health of the Russian Federation (MHRF), in the period 2002 to 2009. A comparison group consisted of 19 patients (median age, 70 years) treated according to the CHOP/R-CHOP program at HRC, MHRF, in the same period. The median follow-up period was 6 years. The results of BM examination were analyzed before and 5-10 years after the end of HDCT. Immunophenotypic study determined the number of early CD34+ hematopoietic progenitors. BM cellularity, the size of erythroid, granulocytic and megakaryocytic lineages, their ratio, the presence of dysplasia signs, and secondary stromal changes were histologically determined. The BM toxic injury signs found for the first time were evaluated as manifestations of late myelotoxicity., Results: At 5-to-10-year follow-ups after the end of HDCT according to the mNHL-BFM-90 program, the patients showed a smaller number of early CD34+ progenitors of BM hematopoiesis in 31 (78%) cases than those treated according to the CHOP/R-CHOP-21 program (n=8 (2%)) (p=0.005). Myelopoiesis with decreased CD34+ cell count was characterized by hypocellularity in 8 (26%) patients (p=0.07), the narrowing of megakaryocytic lineage in 14 (45%) (p=0.006), erythroid one in 7 (23%) (p=0.01), and granulocytic one in 8 (26%) (p=0.92), pronounced secondary stromal changes in 15 (48%) (p=0.03), and grade 1 thrombocytopenia in 13 (42%); p=0.02)., Conclusion: There is evidence that the number of early CD34+ progenitors of BM hematopoiesis decreased in patients with DLBCL in the late period after HDCT. The investigation shows the relationship of the reduction in the number of early CD34+ progenitors of BM hematopoiesis in the late follow-up period to the presence of pronounced secondary changes in the BM stroma (p=0.02). There was no statistically significant relationship of the decreased number of CD34+ cells to the age younger or older than 60 years, to the period after the end of chemotherapy, to gender or presence of specific BM injury.

Objective: To evaluate the impact of therapy on bone mineral density (BMD) and body composition in survivors of acute lymphoblastic leukemia (ALL) treated in accordance with Brazilian protocols by the Brazilian Cooperative Group of Treatment of Lymphoblastic Leukemia in Childhood (GBTLI) LLA-93 and LLA-99., Methods: A cross-sectional study with 101 patients was performed. BMD and body composition were evaluated using bone densitometry and were interpreted according to the age group and the reference population. Values between -1.1 and -1.9 in the group of children under 20 years were considered as risk group for low BMD z-scores. BMD values were compared to clinical characteristics, treatment received and body composition. A chi-square test, Fisher's exact test, likelihood ratio and Student's t-test were applied, with a 5% significance level., Results: The patients presented a frequency of fractures of 2%, of osteonecrosis, 2%, and of low BMD, 2.9%. In the group of 79 patients under 20 years of age, three had low BMD. The 16 that presented risk for low BMD, demonstrated lower valutes in lumbar vertebrae L1-L4 (p=0.01) and whole body (p=0.005), and smaller values of lean body mass (p=0.03). In the group of 22 patients over 20 years of age, ten had osteopenia., Conclusions: The low impact of treatment on BMD of this study confirms the concept that the bone mass gain occurs with increasing age and that the treatment does not influence the process. The population at risk for low BMD values presented lower bone mass values and could benefit from a long-term monitoring for possible bone toxicity.

In recent years, cancers once viewed as relatively homogeneous in terms of organ location and treatment strategy are now better understood to be increasingly heterogeneous across biomarker and genetically defined patient subgroups. This has produced a shift toward development of biomarker-targeted agents during a time when funding for cancer research has been limited; as a result, the need for improved operational efficiency in studying many agent-and-target combinations in parallel has emerged. Platform trials, basket trials, and umbrella trials are new approaches to clinical research driven by this need for enhanced efficiency in the modern era of increasingly specific cancer subpopulations and decreased resources to study treatments for individual cancer subtypes in a traditional way. In this review, we provide an overview of these new types of clinical trial designs, including discussions of motivation for their use, recommended terminology, examples, and challenges encountered in their application.

No standards for staging, systemic therapy or the timing of an operation are defined for patients newly diagnosed with synchronous metastases and a primary in the colon. An expert group of radiologists, medical, radiation and surgical oncologists therefore came together to discuss staging and treatment sequence for these patients and came up with a recommendation based on current evidence of potential therapeutic options. The discussion was organized to debate recommendations centred on 5 topics and therefore the position paper is built upon these titles and their subtitles., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Esophageal cancer is one of the most common digestive tract cancers in our country. Although multimodality therapy has been used in the treatment of esophageal cancer, such as radiotherapy, chemotherapy and targeted therapy, surgery plays its irreplaceable role. With the development of techniques and innovation of instruments, minimally invasive esophagectomy is introduced into practice worldwide. Due to its less trauma and fewer complications, minimally invasive esophagectomy draws great attention, however, controversy exists in the question whether minimally invasive esophagectomy has similar efficacy to open esophagectomy. With the aim of providing suggestions for selecting optimal surgical procedure, this review discusses differences between minimally invasive esophagectomy and open esophagectomy in the following three aspects: perioperative mortality and morbidity, margin status and harvested lymph node number, and postoperative survival. Nowadays, the advantage of minimally invasive esophagectomy has been widely recognized in reducing perioperative morbidity and mortality, however, in the aspect of radicality and prognosis, it is far from reaching a definite conclusion for lack of multicenter, large sample, prospective, randomized controlled trials. Such trials are warrented so as to show the strength and weakness of minimally invasive esophagectomy.

Purpose: A panel of Japanese experts on tumor ablation therapy gathered to reach a general consensus on topics surrounding ablation therapy., Materials and Methods: Questionnaires relating to ablation protocols for radiofrequency ablation (RFA) and cryoablation, as well as ancillary procedures required for safe and secure ablation therapy, were sent to seven institutions. Experts from these institutions discussed each topic based on the evidence and the questionnaire data, and a consensus was reached at an annual meeting of the Japan Image-guided Ablation Group in Maebashi, Japan, in October 2015., Results: A consensus was reached on each of six topics, including "management of antiplatelet and anticoagulation drug therapy"; "pain control in the perioperative period"; "arterial embolization combined with ablation therapy"; "protection of non-target organs"; "RFA and cryoablation protocols"; and "ablative margins.", Conclusions: The consensus achieved here will serve as the framework for tumor ablation therapies in Japan.

Aim: The aim of the study was to analyse the recurrence rates of choroidal melanoma treated with Ru-106 brachytherapy with or without adjunctive transpupillary thermotherapy., Material and Methods: We analysed medical records of 97 patients treated with Ru-106 brachytherapy with or without adjunctive transpupillary thermotherapy who subsequently presented with recurrence. All patients were treated at the Department of Ophthalmology and Ocular Oncology in Krak6w between 1995 and 2006., Results: The mean time to recurrence was 29.15 months and tended to be shorter in larger melanomas. The 5-year recurrence rate determined using Kaplan-Meier estimator was 28.69%. Marginal recurrence was the most common type of recurrence, especially in tumors adjacent to the optic disc. The recurrence rates were the highest for all types of recurrence after the use of COB plaque with or without adjunctive transpupillary thermotherapy., Conclusion: The highest incidence of recurrence was shown in the second year following the Ru-106 brachytherapy and the time to recurrence tended to be shorter in larger melanomas. Marginal recurrence was the most common type of recurrence, especially in tumors adjacent to the optic disc.