Tumor-related Symptoms Research Articles

Diagnosis and Differential Diagnosis of Neurological Adverse Events during Immune Checkpoint Inhibitor Therapy.

Therapy with immune checkpoint inhibitors (ICIs) has improved overall survival and cancer-related morbidity of cancer treatment even in cancer entities with poor prognosis. Since the approval of the first ICI, ipilimumab, for treatment of advanced melanoma by the Food and Drug Administration (FDA) in 2011, the spectrum of indications and approved ICIs has grown, rapidly. Up to now, seven different ICIs for more than 20 indications are available. However, their mechanisms of action can lead to immune-related adverse events (irAEs). In particular, neurological irAEs are clinically relevant. Although they are rare, an early and accurate diagnosis is challenging and neurological disease course and sequelae are potentially fatal. Between 08/2017 and 03/2020, 31 patients received ICI treatment at Hannover Medical School and presented with neurological adverse events (N-irAEs). Treated malignancies were metastatic melanoma, bronchial carcinoma, and urothelial cell carcinoma. All patients received comprehensive neurological diagnostics including clinical examination and magnetic resonance imaging (MRI). Cerebrospinal fluid (CSF) analysis was obtained in 21 patients and electroneurography was performed in 22 patients. Although N-irAEs were suspected in all 31 patients, 11 patients had other conditions leading to neurological symptoms including tumor metastases in seven patients and hemorrhagic or ischemic stroke in four patients. In the following, these patients are referred to as the differential diagnosis (DD) group. Patients with N-irAEs suffered from immune mediated neuropathy (9/20), myositis and/or myasthenic syndrome (6/20), or encephalitis/cerebellitis (5/20). Except for cell count, CSF results did not differ between the N-irAEs and the DD group. Symptoms related to N-irAEs are rather unspecific potentially mimicking other tumor-related symptoms such as metastases. Patients with malignancy are predominantly not treated by neurologists. Because of the complexity of neurological symptoms, detailed neurological investigations in specialized institutions are necessary in patients with new neurological symptoms and need to be critically discussed with treating oncologists.

IMMU-03. UPDATES ON BRAINCHILD-01, -02, AND -03: PHASE 1 LOCOREGIONAL CAR T CELL TRIALS TARGETING HER2, EGFR, AND B7-H3 FOR CHILDREN WITH RECURRENT CNS TUMORS AND DIPG

We report preliminary results of three Phase 1 trials of repetitively dosed locoregional CAR T cells for children with recurrent/refractory CNS tumors, targeting HER2 (BrainChild-01), EGFR (BrainChild-02), and B7-H3 (BrainChild-03). Cells are delivered into the tumor cavity (Arm A) or ventricular system (Arm B and BrainChild-03’s DIPG-specific Arm C). Primary endpoints are feasibility and safety. Successful CAR T cell manufacture occurred in 2/2 subjects (BrainChild-01) and 2/3 (BrainChild-02). All subjects tolerated intra-patient dose escalation from 1x107 to 2.5x107 cells/dose without DLTs. Two subjects were evaluable on BrainChild-01 (S-001: glioblastoma, Arm A, survival 173 days post-first infusion, received 6 infusions; S-002: ependymoma, Arm B, survival 111 days, 9 infusions). One subject was evaluable on BrainChild-02 (glioblastoma, Arm A, withdrew from trial at 49 days, 5 infusions). One enrolled patient on BrainChild-03 has not begun treatment. None of the subjects developed new neurologic toxicities, although transient worsening of baseline tumor-related signs and symptoms were seen. Secondary endpoints are efficacy and disease response. No objective radiographic responses have been observed. Both BrainChild-01 subjects had transient systemic CRP elevations following infusions (S-001: peak of 3.9 post Course 1 Week 1; S-002: peak of 2.3 post Course 2 Week 1), possibly indicating an inflammatory response. Both subjects had post-infusion CSF cytokine elevations (CXCL10, GCSF, GM-CSF, IFNa2, IFNg, IL-10, IL12-p40, IL12-p70, IL-15, IL-1a, IL-3, IL-6, IL-7, TNFa, VEGF) without concurrent systemic changes. In summary, we provide preliminary evidence of safety and feasibility of intracranial delivery of CAR T cells for pediatric CNS tumors.

Upper Gastrointestinal Cancer Management in the COVID-19 Era: Risk of Infection, Adapted Role of Endoscopy, and Potential Treatment Algorithm Alterations.

IntroductionThe safety of upper gastrointestinal cancer patients in the SARS-CoV-2 outbreak is extremely important and most surgeons need to establish a contingency management.AimIn this study, we present the surgical outlines of patients suffering from upper gastrointestinal cancers.Materials and MethodsData were obtained from PubMed, Cochrane Database of Controlled Trials, and SCOPUS of reports up to September 2020.ResultsThe COVID-19 outbreak makes surgical procedures extremely difficult to be performed. The most common criteria to prioritize patients for surgical treatment are stage, tumor biology, presence of tumor-related symptoms, the risk of tumor to become non-resectable, and time interval from neoadjuvant therapy. The multidisciplinary teams can help assigning a priority level to each clinical case.ConclusionWe have to continue providing treatment to oncologic patients in the face of COVID-19 uncertainty, with higher caution and responsibility in order to develop a safer and more effective personalized treatment plan.

Improved chemosensitivity following mucolytic therapy in patient-derived models of mucinous appendix cancer

Abundant intraperitoneal (IP) accumulation of extracellular mucus in patients with appendiceal mucinous carcinoma peritonei (MCP) causes compressive organ dysfunction and prevents delivery of chemotherapeutic drugs to cancer cells. We hypothesized that reducing extracellular mucus would decrease tumor-related symptoms and improve chemotherapeutic effect in patient-derived models of MCP. Mucolysis was achieved using a combination of bromelain (BRO) and N-acetylcysteine (NAC). Ex vivo experiments of mucolysis and chemotherapeutic drug delivery/effect were conducted with MCP and non-MCP tissue explants. In vivo experiments were performed in mouse and rat patient-derived xenograft (PDX) models of early and late (advanced) MCP. MCP tumor explants were less chemosensitive than non-MCP explants. Chronic IP administration of BRO + NAC in a mouse PDX model of early MCP and a rat PDX model of late (advanced) MCP converted solid mucinous tumors into mucinous ascites (mucolysis) that could be drained via a percutaneous catheter (rat model only), significantly reduced solid mucinous tumor growth and improved the efficacy of chemotherapeutic drugs. Combination of BRO + NAC efficiently lyses extracellular mucus in clinically relevant models of MCP. Conversion of solid mucinous tumors into mucinous ascites decreases tumor bulk and allows for minimally invasive drainage of liquified tumors. Lysis of extracellular mucus removes the protective mucinous coating surrounding cancer cells and improves chemotherapeutic drug delivery/efficacy in cancer cells. Our data provide a preclinical rationale for the clinical evaluation of BRO + NAC as a therapeutic strategy for MCP.

Unique Interplay Between Molecular miR-181b/d Biomarkers and Health Related Quality of Life Score in the Predictive Glioma Models.

In the last decade, an increasing amount of research has been conducted analyzing microRNA expression changes in glioma tissue and its expressed exosomes, but there is still sparse information on microRNAs or other biomarkers and their association with patients’ functional/psychological outcomes. In this study, we performed a combinational analysis measuring miR-181b and miR-181d expression levels by quantitative polymerase chain reaction (qPCR), evaluating isocitrate dehydrogenase 1 (IDH1) single nucleotide polymorphism (SNP), and O-6-methylguanine methyltransferase (MGMT) promoter methylation status in 92 post-surgical glioma samples and 64 serum exosomes, including patients’ quality of life evaluation applying European Organization for Research and Treatment of Cancer (EORTC) questionnaire for cancer patients (QLQ-30), EORTC the Brain Cancer-Specific Quality of Life Questionnaire (QLQ-BN20), and the Karnofsky performance status (KPS). The tumoral expression of miR-181b was lower in grade III and glioblastoma, compared to grade II glioma patients (p < 0.05). Additionally, for the first time, we demonstrated the association between miR-181 expression levels and patients’ quality of life. A positive correlation was observed between tumoral miR-181d levels and glioma patients’ functional parameters (p < 0.05), whereas increased exosomal miR-181b levels indicated a worse functional outcome (p < 0.05). Moreover, elevated miR-181b exosomal expression can indicate a significantly shorter post-surgical survival time for glioblastoma multiforme (GBM) patients. In addition, both tumoral and exosomal miR-181 expression levels were related to patients’ functioning and tumor-related symptoms. Our study adds to previous findings by demonstrating the unique interplay between molecular miR-181b/d biomarkers and health related quality of life (HRQOL) score as both variables remained significant in the predictive glioma models.

Effect of Football on Fatigue of Patients with Breast Cancer Treated with Nano-Chemotherapy

Cancer-related fatigue is one of the most common and uncontrollable subjective and persistent fatigue feelings in patients after breast cancer surgery, which seriously affects the rehabilitation effect and quality of life of patients. The purpose of this study was to investigate the effect of football intervention on cancer-related fatigue and quality of life in patients with breast cancer after nano-chemotherapy. The objective of this study is to explore the exercise program that can make patients actively carry out rehabilitation exercise and achieve good rehabilitation effect, so as to provide a theoretical and empirical basis for the study of cancer fatigue and quality of life of patients after breast cancer surgery. In this study, a quasi-experimental study method was used to conveniently select 60 breast cancer outpatients with tumor-related fatigue symptoms in a tertiary hospital in Liaoning Province. According to the convenience group, they were divided into a control group and an intervention group, 30 cases in each group. The control group received routine hospital nursing, while the intervention group received football intervention for 6 months on the basis of routine hospital nursing. The intervention measures include explaining the related knowledge of cancer-related fatigue, helping patients develop football projects, guiding patients to record football sports diaries, checking patients’ football sports diary records at the beginning of each chemotherapy cycle, and discussing football sports feelings with patients. After six months of intervention, the researchers assessed cancer-related fatigue symptoms and quality of life. Football can improve the fatigue, physiological, psychological, and psychological states of breast cancer patients after nano-chemotherapy; reduce fatigue, anxiety, and depression; improve sleep; and ultimately improve the quality of life.

Clinical and Molecular Characterization of Incidentally Discovered Lower-Grade Gliomas with Enrichment of Aerobic Respiration.

PurposeIncidentally discovered diffusely infiltrating lower-grade gliomas (incidental LGGs, iLGGs) are defined as gliomas occasionally found in patients without tumor-related symptoms. At present, very few in-depth research studies on incidental LGGs were reported. We aimed to find out the inherent difference between iLGGs and LGGs with tumor-related symptoms.Patients and MethodsWe enrolled 2486 all-grade gliomas and screened 1594 lower-grade gliomas for further analysis. Medical records were retrospectively reviewed for iLGGs. Clinical and mRNA sequencing data were collected for in-depth analysis.ResultsWe found that with increasing grade, the proportion of incidental glioma patients decreased obviously. In 1594 patients who underwent craniotomy for LGG, 80 (5%) patients were discovered incidentally. Grade II patients (88%) and patients bearing 1p/19q co-deletion in their tumors (23%) were more likely to be diagnosed as iLGGs. Regular radiological screening (48%) and trauma (24%) were the main complaint for brain imaging for iLGGs. Kaplan–Meier survival analysis indicated that iLGGs patients lived a significantly longer survival and Cox regression analysis revealed that iLGGs were an independent indicator of better prognosis. Subsequent gene set enrichment analysis and differential expression analysis based on the gene expression profile revealed that mitochondrial aerobic respiration process was enriched in iLGGs. Moreover, we found that iLGGs tended to generate energy by unique mitochondrial aerobic respiration.ConclusionThese results provided a primitive exploration of iLGGs, which may potentially assist clinical neurosurgeons with personalized management of iLGGs.

Radiation therapy for primary tumor of de novo stage IV breast cancer.

Despite recent advances in multimodality treatments such as endocrine therapy, chemotherapy, molecularly targeted therapy, and radiation therapy, it is still very difficult to cure de novo stage IV breast cancer patients completely. The traditional role of radiation therapy for these patients has been a palliative treatment strategy that aims to control tumor progression and suppress tumor related symptoms. Recently, several non-randomized retrospective studies on de novo stage IV breast cancer have revealed that locoregional radiation therapy (LRRT) might confer a survival benefit. However, there is no high level evidence to support the impact of LRRT on survival among patients with de novo metastatic disease so far. This article aimed to summarize the literature and to discuss whether treating the primary lesion with radiation therapy could improve clinical survival outcomes among de novo stage IV breast cancer patients. The issue of patient selection will be discussed because not all de novo stage IV breast cancer patients could benefit from LRRT. This article also explores the clinical evidence regarding LRRT for de novo metastatic disease across various cancers such as prostate, uterine cervical, non-small-cell lung, and head and neck cancers. Many retrospective trials have shown the impact of locoregional treatment (LRT) on survival in de novo metastatic breast cancer. However, since the backgrounds of patients treated with LRRT are quite different from those of patients who did not receive LRRT and the treatment consists of surgery and/or radiation therapy, the role of radiation therapy alone remains unclear. Several reports investigated prognostic factors to detect the benefits of LRRT, which still remains conflicting and no consensus exists. However, selected patients with de novo metastatic disease with better performance status, low tumor burden, and estrogen receptor positivity should be considered for the addition of radiation therapy delivered to the primary site. To explore proper decision-making regarding LRRT, further prospective randomized trials are eagerly awaited.

Intranodal Administration of Neoantigen Peptide-loaded Dendritic Cell Vaccine Elicits Epitope-specific T Cell Responses and Clinical Effects in a Patient with Chemorefractory Ovarian Cancer with Malignant Ascites

ABSTRACT Chemorefractory ovarian cancer has limited therapeutic options. Hence, new types of treatment including neoantigen-specific immunotherapy need to be investigated. Neoantigens represent promising targets for personalized cancer immunotherapy. We here describe the clinical and immunological effects of a neoantigen peptide-loaded DC-based immunotherapy in a patient with recurrent and chemoresistant ovarian cancer. A 71-year-old female patient with chemorefractory ovarian cancer and malignant ascites received intranodal vaccination of DCs loaded with four neoantigen peptides that were predicted by our immunogenomic pipeline. Following four rounds of vaccinations with this therapy, CA-125 levels were remarkably declined and tumor cells in the ascites were also decreased. Concordantly, the tumor-related symptoms such as respiratory discomfort improved without any adverse reactions. The reactivity against one HLA-A2402-restricted neoantigen peptide derived from a mutated PPM1 F protein was detected in lymphocytes from peripheral blood by IFN-γ ELISPOT assay. Furthermore, the neoantigen (PPM1 F mutant)-specific TCRs were detected in the tumor-infiltrating T lymphocytes post-vaccination. Our results showed that vaccination with intranodal injection of neoantigen peptide-loaded DCs may have clinical and immunological impacts on cancer treatment.

The UPMC Hillman Cancer Center Approach to the Management of Colorectal Cancer During the COVID-19 Pandemic Era

The UPMC Hillman Cancer Center Approach to the Management of Colorectal Cancer During the COVID-19 Pandemic Era

A Snapshot of Elective Oncological Surgery in Italy During COVID-19 Emergency: Pearls, Pitfalls, and Perspectives.

Objective:To analyze the impact of COVID-19 emergency on elective oncological surgical activity in Italy.Summary of Background Data:COVID-19 emergency shocked national health systems, subtracting resources from treatment of other diseases. Its impact on surgical oncology is still to elucidate.Methods:A 56-question survey regarding the oncological surgical activity in Italy during the COVID-19 emergency was sent to referral centers for hepato-bilio-pancreatic, colorectal, esophago-gastric, and sarcoma/soft-tissue tumors. The survey portrays the situation 5 weeks after the first case of secondary transmission in Italy.Results:In total, 54 surgical Units in 36 Hospitals completed the survey (95%). After COVID-19 emergency, 70% of Units had reduction of hospital beds (median −50%) and 76% of surgical activity (median −50%). The number of surgical procedures decreased: 3.8 (interquartile range 2.7–5.4) per week before the emergency versus 2.6 (22–4.4) after (P = 0.036). In Lombardy, the most involved district, the number decreased from 3.9 to 2 procedures per week. The time interval between multidisciplinary discussion and surgery more than doubled: 7 (6–10) versus 3 (3–4) weeks (P < 0.001). Two-third (n = 34) of departments had repeated multidisciplinary discussion of patients. The commonest criteria to prioritize surgery were tumor biology (80%), time interval from neoadjuvant therapy (61%), risk of becoming unresectable (57%), and tumor-related symptoms (52%). Oncological hub-and-spoke program was planned in 29 departments, but was active only in 10 (19%).Conclusions:This survey showed how surgical oncology suffered remarkable reduction of the activity resulting in doubled waiting-list. The oncological hub-and-spoke program did not work adequately. The reassessment of healthcare systems to better protect the oncological path seems a priority.

Managing Metastatic Thymoma With Metabolic and Medical Therapy: A Case Report

Thymomas consist of neoplastic thymic cells intermixed with variable numbers of non-neoplastic lymphocytes. Metastatic thymomas are typically managed with non-curative chemotherapy to control tumor-related symptoms; no prolonged survival is expected. Metabolic-based approaches, such as fasting and ketogenic diets, target cancer cell metabolism by creating an increased reliance on ketones while decreasing glucose, glutamine, and growth factor availability, theoretically depriving cancer cells of their metabolic fuels while creating an unfavorable environment for cancer growth, which may be beneficial in metastatic thymoma. We report the case of a 37-year-old woman with myasthenia gravis, diagnosed with an inoperable type AB, stage IVA thymoma, who pursued a metabolic intervention consisting of periodic fasting (7-day, fluid-only fasts every 1–2 months), combined with a modified ketogenic diet on feeding days, for 2 years. Fasting-related adverse effects included cold intolerance, fatigue, and generalized muscle aches, all of which resolved during the second year. She experienced two myasthenia relapses, each associated with profoundly reduced oral intake, marked weight loss, and tumor regression-the first relapse was followed by a 32% decrease in tumor volume over 4 months, the second relapse by a dramatic 96% decrease in tumor volume over 4 months. The second relapse also required prednisone to control the myasthenia symptoms. We hypothesize that 2 years of fasting and ketogenic diet therapy metabolically weakened the neoplastic thymic cell component of the thymoma, “setting the stage” for immune activation and extreme energy restriction to destroy the majority of cancer cells during both relapses, while prednisone-induced apoptosis eradicated the remaining lymphocytic component of the thymoma during the second relapse. This case is unique in that a metabolic-based fasting and ketogenic diet intervention was used as the primary management strategy for a metastatic cancer in the absence of surgery, chemotherapy, or radiotherapy, culminating in a near-complete regression. Nearly 3 years after being diagnosed with inoperable metastatic cancer, our patient shows no signs of disease and leads a full and active life.

Efficacy and safety of CT-guided 125I brachytherapy in elderly patients with non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) has become the most common cancer type and the leading cause of cancer-associated mortality worldwide. The aim of the present retrospective study was to evaluate the efficacy and safety of computed tomography (CT)-guided 125I brachytherapy alone in elderly patients with NSCLC. A total of 26 elderly patients with NSCLC stage I–III who had an inoperable lesion or progressive disease following radio-chemotherapy were treated with CT-guided 125I seed implantation for lung lesions and included in the present study. The prescribed dose of 125I brachytherapy was 80–140 Gy, and dosimetric verification was performed immediately after the procedure. The response rate (RR) and local control rate (LCR) were analyzed according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Survival was estimated using the Kaplan-Meier method. Safety and complications were also documented. All patients were aged 65–85 years (median age, 77 years) and successfully completed the procedure, and the median follow-up time was 9.4 months (range, 3–31 months). After a 6-month follow-up, for pulmonary lesions, complete response (CR) was achieved in 11 (42.3%) cases, partial response in 9 (34.6%) cases, stable disease in 4 (15.4%) cases and progressive disease in 2 (7.7%) cases. The 6-month RR and LCR were 76.9 (20/26) and 92.3% (24/26), respectively. The mean overall survival (OS) time was 11.7±7.6 months and the 0.5- and 1-year OS rates were 90.1 and 73.3%, respectively. Tumor-related symptoms in patients were significantly alleviated following the procedure. No severe complications occurred during and after the procedure of 125I seed implantation. In conclusion, CT-guided 125I brachytherapy is a feasible, effective and safe therapy and may be considered as an alternative option to surgery and radiotherapy for elderly patients with NSCLC.

Palliative Endoscopic Esophageal Stenting for Malignant Esophageal Tumour Complications: A Clinical Case and Single Centre Experience in Latvia

Abstract Esophageal stenting is used in patients with malignant esophageal tumours to reduce dysphagia and inanition. The objective of this study was to analyse the main reasons for esophageal stenting in Rīga East Clinical University Hospital (RECUH) and their association with dysphagia and mortality. A cross-sectional study of all patients hospitalised in RECUH who received esophageal self-expanding metal stents (SEMS) from October 2013 to December 2015 was performed. A total of 29 patients, 24 (82.8%) male and 5 (17.2%) female, with mean age 63.7 ± 11.3 years, underwent the procedure. The most common indications for stenting were tumour-related stenosis (52.9%) and fistulae (17.6%). Mean time from establishing the diagnosis of esophageal cancer to stent placement was 338.6 days. Median survival after stenting was 4.8 months. A complex case of a patient requiring placement of three palliative stents illustrates the challenges of esophageal cancer care. Esophageal stent placement is an effective palliative method for treating tumour-related symptoms but carries risks of stent complications and fistula development over time. SEMS are being successfully used in cancer patient treatment in Latvia.

Usefulness of surgical treatment for asymptomatic patients with extra-peritoneal desmoid-type fibromatosis: a systematic review and meta-analysis.

The purpose of this systematic review is to assess and compare the efficacy of surgical treatment for patients with asymptomatic extra-peritoneal desmoid-type fibromatosis to the wait-and-see policy by evaluating (1) the exacerbation rate (exacerbation; recurrence after surgery or progressive disease following non-surgical treatment) and (2) treatment-associated complications in extra-peritoneal desmoid-type fibromatosis. We evaluated documents published between 1 January 1990 and 31 August 2017. The risk of bias in the selected literature was analyzed using the Cochrane Collaboration Risk of Bias Tool. Quality of evidence was evaluated using Grading of Recommendation, Assessment, Development and Evaluation approach. One prospective cohort study, four case-control studies and five case series studies were identified. Meta-analysis was performed to evaluate the exacerbation rate after treatment on one prospective cohort study and four case-control studies. In comparing surgical and non-surgical treatments, the exacerbation rate was significantly higher in the surgical treatment group (odds ratio: 1.32, 95% confidence interval 1.01-1.73, P=0.05). However, in the case series study, the recurrence rate was 23.4% for the surgical treatment group, while the progressive disease rate was 28.1% for the non-surgical treatment group. The postoperative complication rates associated with surgical treatment in the two studies were 20.8 and 17.2%, respectively. When considering the exacerbation rate, non-surgical treatment might be appropriate for asymptomatic patients with extra-peritoneal desmoid-type fibromatosis. However, if patients with tumor-related symptoms opt for surgery, including those who face difficulties due to the presence of tumors, it is important to fully explain to them the possibility that the recurrence rate and treatment-associated functional failures may increase depending on the site of occurrence.

Phase II study of avelumab plus intermittent axitinib in previously untreated patients with metastatic renal cell carcinoma (Tide-A study).

TPS762 Background: The combination of avelumab plus axitinib has been recently reported to be superior than sunitinib alone for treatment of previously untreated mRCC patients (Motzer, NEJM 2019). The study reported a median PFS of 13.8 for the combination of avelumab plus axitinib compared to 8.4 months for sunitinib (p&lt;0.001) with an ORR of 48% vs 24%, respectively. To improve treatment efficacy and safety, TKI discontinuation has been considered in patients treated with sunitinib leading to a longer definitive progression free survival (22.4 months) and overall survival (34.8 months) with a better safety profile (Ornstein, JCO 2017). Despite a new tumor response at TKI reintroduction, many patients progressed after the first months of treatment discontinuation suggesting the necessity to maintain the previous response. This study aims to test if patients achieving a tumor response with the combination of avelumab plus axitinib, can discontinue the TKI in order to delay the resistance and decrease the toxicity related to the combination of therapies. Methods: The single arm, phase II TIDE-A trial, aims to evaluate the activity of avelumab as maintenance therapy in patients with mRCC who achieved a tumor response after the induction phase of therapy with the combination of avelumab and axitinib. Eligible patients have clear cell carcinoma, ECOG performance status 0 or 1, measurable, no bulky disease without tumor-related symptoms or hepatic metastases. Eligible patient will receive the combination of avelumab plus axitinib for 36 weeks. Patients achieving RECIST 1.1 partial response discontinue the axitinib and continue avelumab. At tumor progression, the axitinib will be restarted for at least six months. If a new tumor response is achieved, axitinib will be discontinued again until tumor progression. Patients with RECIST 1.1 stable disease continue the combination of avelumab and axitinib until progression of disease. The primary endpoint is to evaluate the rate of patients free of progression after 8 weeks from axitinib discontinuation. The study is currently ongoing in twenty centres in Italy.

Proton beam re-irradiation for gastrointestinal malignancies: a systematic review.

Radiotherapy (RT) is part of the standard of care management of most gastrointestinal (GI) cancers. Even with advanced RT, systemic therapy, and surgical techniques, locoregional recurrences or second primary cancers can still occur within previously irradiated fields, which can present challenges in delivering effective and safe treatment. Options for reirradiation are often limited, but given the favorable dosimetric aspects of proton-beam RT, it may provide an effective and safe re-irradiation option for patients with recurrent or second primary GI cancers. We conducted a systematic review as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol, assessing for reports of proton-beam reirradiation for recurrent or second primary GI cancers, primarily via PubMed. From the initial 373 articles identified, 7 articles were ultimately included in the analysis. The 7 included studies reported on proton-beam re-irradiation for the following disease sites: esophageal (n=2), pancreas (n=1), liver (n=2), rectal (n=1), and anal (n=1). Study sizes varied from as few as 1 to as many as 83 patients. Across studies, in patients who presented with tumor-related symptoms, palliation (stability/improvement) was achieved in 80-100% of the cases. Local control rates, with variable follow-up, ranged from 36-100%. All median overall survival values, when reported, were greater than 1 year. Across both liver studies, there were no cases of radiation-induced liver disease (RILD) from proton-beam re-irradiation. Across all studies, there were 2 acute (esophagopleural fistula in esophageal cancer, small bowel perforation in pancreatic cancer) and 1 late (esophageal ulcer in esophageal cancer) grade 5 toxicities, all favored to be due to progressive disease, rather than proton-beam re-irradiation. Two studies (1 esophageal, 1 rectal) generated comparison photon plans. One found that proton therapy reduced mean heart and lung doses, spinal cord dose, and lung V5Gy as compared to photon treatment, while resulting in higher lung V20Gy and V30Gy. The other found that protons decreased bowel V10Gy, V20Gy, and the dose to 200 and 150 cc of bowel, as compared to photons. Based upon the published experiences, proton-beam re-irradiation for recurrent or second primary GI cancers appears effective for palliation, with good disease-control, limited toxicity, favorable dosimetry, and overall compares well with published non-proton-beam experiences. Given short follow-up, additional studies are warranted to determine if dosimetric advantages from proton therapy will translate into comparative toxicity benefits.

Contribution of Laser Photovaporisation in the Management of Lower Urinary Tract Symptoms Related to Prostatic Tumours: Preliminary Study of 29 Cases at the Saint Camille Hospital of Ouagadougou (Burkina Faso)

The treatment of prostatic tumour-related lower urinary tract symptoms (LUTS) uses a varied therapeutic arsenal. In our country, the treatment is dominated by open surgery. Laser treatment is becoming an efficient alternative to trans-urethral prostatic resection or prostatic adenomectomy. We report our experience with the results of Thulium laser photovaporization in the treatment of prostatic tumour-related LUTS. Materials and Methods: A prospective study was conducted between November 2018 and August 2019 at the Saint Camille hospital of Ouagadougou. The inclusion criteria were the presence of LUTS related to a prostatic tumour with an operative indication. Results: 29 patients were treated with Thulium laser prostatic photovaporization. The average age of patients was 72.58 ± 25.34 years (54 - 84 years). The average vaporization duration was 71.24 ± 21.65 minutes (15 - 210 minutes) for an average prostatic volume of 80.97 ml. The average duration of hospitalization for patients was 1.93 days (1 - 5 days). The average bladder sounding duration was 1.68 days (1 - 4 days). A capsular perforation, a sphincter lesion and urinary retention after removal of the catheter were the complications. Conclusion: Laser photovaporization is a newly used method at the Saint Camille Hospital. The benefit is the reduction of the risk of bleeding, the short duration of hospital stay and bladder sounding. Photovaporization deserves to be popularized in our daily practices.

The clinical utility of 'GRAS' parameters in stage I-III adrenocortical carcinomas: long-term data from a high-volume institution.

Adrenocortical carcinoma (ACC) is a rare cancer with poor survival. We sought to identify prognostic factors and assess its clinical utility in postoperative management of nonmetastatic ACC. We included 65 patients who underwent adrenalectomy and clinicopathological diagnosed as European Network for the Study of Adrenal Tumors (ENSAT) stage I-III ACC in our center from 2009 to 2017. Potential clinicopathological parameters were selected. The prognostic correlation, including overall survival (OS) and recurrence-free survival (RFS), was analyzed using Kaplan-Meier method and univariate and multivariate Cox model. The 2-year and 5-year post-surgery survival rate were 54.6% (95%CI: 42.5-70.1%) and 33.5% (95%CI: 22.3-50.6%), respectively. 46 (70.8%) cases were symptomatic ACC. Tumor-related or hormone-related symptom was identified as independent prognostic factor in OS (HR = 5.5, 95%CI: 1.87-16.16) and RFS (HR = 3.62, 95%CI: 1.28-10.24). Higher tumor grade (Weiss score > 6 or Ki67 index ≥ 20%) was independently associated with poor OS (HR = 4.73, 95%CI: 2.15-10.43). R status (R1/R2/Rx) was independently correlated with worse RFS (HR = 2.56, 95%CI:1.21-5.43). Accordingly, patients with higher GRAS (Grade, R status, age, and symptoms) score were more likely to have poor prognosis (OS: HR = 2.7, 95%CI: 1.43-5.11 and RFS: HR = 3.31, 95%CI: 1.68-6.52, respectively). Symptoms, higher tumor grade and positive/unknown R status were independent risk factors in stage I-III ACC. Comprehensive consideration of GRAS parameters may optimize the prognostic assessment for postoperative patients.

Management of nonmetastatic muscle invasive bladder cancer in the elderly

A substantial increase in the number of elderly patients with muscle invasive bladder cancer (MIBC) is expected in upcoming years due to demographic changes and the peak incidence of bladder cancer in the 8th decade of life. The management of these patients is mainly driven by chronological age, comorbidities, tumor characteristics (unifocality, multifocality, concomitant carcinoma in situ, depth of invasion) and the presence of tumor-related symptoms (hematuria, pain, bladder dysfunction). A potential algorithm for the treatment of elderly patients with MIBC is presented. Ideally these patients are managed by a multidisciplinary team that includes an in-depth geriatric assessment and in centers experienced with MIBC to avoid any delay for—potentially—curative treatment.