scholarly journals Outcome of multidisciplinary management of adrenocortical carcinoma: a retrospective study

2020 ◽  
Author(s):  
Jiawei Zhu ◽  
Ziye Zheng ◽  
Jing Shen ◽  
Xin Lian ◽  
Zheng Miao ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Multidisciplinary Treatment ◽  
Local Treatment ◽  
Surgical Margin ◽  
Local Therapy ◽  
Arterial Embolization ◽  
Palliative Radiotherapy ◽  
High Recurrence Rate ◽  
Negative Resection Margin ◽  
College Hospital

Abstract Background: Adrenocortical Carcinoma (ACC) is a rare and highly malignant tumor with a high recurrence rate. Reoperation to attain negative resection margin is recommended for selected patients. However, there is limited data on the outcome of unresectable recurrent tumor treated with palliative radiotherapy (RT) and transhepatic arterial embolization (TAE).Method: A retrospective analysis of the Peking Union Medical College Hospital was conducted. Patients with pathologically confirmed ACC were included.Result: Ninety-two patients fulfilled the criteria. The 5-year, 3-year, 1-year overall survival (OS) rates were 27.2%, 44.6% and 71.7% respectively, and median OS was 32.1 months. Age < 50 years, ENSAT stage I/II, surgery and negative surgical margin were associated with improved OS (all P <0.05). A Ki67 index < 20% was a predictor of better disease-free interval (P =0.011). Of 51 patients with recurrent ACC, local treatment (reoperation, palliative RT and TAE) improved OS after recurrence from 14.5 months to 41.6 months. Local therapy and mitotane were both prognostic factors for improved OS after recurrence.Conclusion: multidisciplinary treatment is the major therapeutic approach for ACC. Resectable cases should receive complete resection to attain negative margin. Local treatment such as palliative RT and TAE may extend OS for unresectable recurrence.

New therapeutic challenges in metastatic breast cancer: the association of CDK4 / 6 inhibitors with radiotherapy. A short review

2020 ◽  
Vol 4 (4) ◽  
pp. 01-03
Author(s):  
Tudor Calistru
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Volume Fraction ◽  
Multidisciplinary Treatment ◽  
Metastatic Breast ◽  
Palliative Radiotherapy ◽  
Short Review ◽  
Fda Approval ◽  
Dose Volume ◽  
Innovative Therapies

FDA approval of CDK4 / 6 inhibitors (Palbociclib, Ribociclib and Abemaciclib) for metastatic and advanced breast cancer, in combination or not with Fulvestrant or Letrozole, has improved the prognosis of this type of patient population. Palliative radiotherapy with antalgic purpose in most of the cases is often part of the multidisciplinary treatment of bone involvement metastatic breast cancer. In the context of the approval of these innovative therapies and of the development of radiotherapy techniques, including stereotactic radiosurgery, it is necessary to identify the best therapeutic sequence and parameters (dose, volume, fraction size) to obtain a synergistic effect. Considering the toxicity profiles of new therapies (especially lymphopenia and neutropenia) and the different mechanisms of the induction of these toxicities towards radiotherapy and chemotherapy, it is also necessary to demonstrate the safety profile of concomitant or sequential irradiation with the administration of CDK4 / 6 inhibitors in combination with radiation therapy.

Multidisciplinary consensus recommendations for the management of non-spine bone metastases: Results of a modified Delphi process in a community-academic partnership.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e24092-e24092
Author(s):  
Noah J Mathis ◽  
Jonathan T. Yang ◽  
Maksim Vaynrub ◽  
Ernesto Santos Martin ◽  
Rupesh Kotecha ◽  
...  
Keyword(s):  
Bone Metastases ◽  
A Priori ◽  
Multidisciplinary Treatment ◽  
Local Therapy ◽  
Delphi Process ◽  
National Guidelines ◽  
Consensus Recommendations ◽  
Modified Delphi ◽  
Pain Specialist ◽  
Strongly Agree

e24092 Background: Local therapy for bone metastases is becoming increasingly complex, but national guidelines remain limited. We leveraged a community-academic partnership to develop consensus recommendations for multidisciplinary treatment of non-spine bone metastases which are generalizable to diverse practice settings. Methods: We convened a group of 15 physicians (9 radiation oncologists, 2 orthopaedic surgeons, 2 medical oncologists, 1 interventional radiologist, 1 interventional pain specialist) treating bone metastases across 4 institutions from Apr 2020-Feb 2021. We distributed a survey to identify questions warranting consensus development in the treatment of non-spine bone metastases. A literature review was conducted to inform answer statements, and evidence was rated using the Strength of Recommendation Taxonomy. A modified Delphi process was employed to reach consensus defined (a priori) as ³75% of respondents indicating “agree” or “strongly agree”. Results: A total of 16 questions were identified, including indications for multidisciplinary discussion or referral (n=4), appropriate use and duration of RT (n=4), and handling of systemic therapies during RT (n=5). After 2 rounds of modified Delphi process, consensus has been reached on 9 questions (see Table). Strength of Recommendation was rated A (1/9, 11%), B (5/9, 56%), or C (3/9, 33%). Conclusions: Our consensus process provides guidance for management of non-spine bone metastases that expands upon current guidelines. We also highlight areas where prospective trials are needed, including the role of RT prior to stabilization surgery and the selection of patients for ablative treatment. [Table: see text]

OS06.2A Local immunotherapy of glioblastoma via AAV-mediated gene transfer of checkpoint inhibitors in combination with CAR-NK cells

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii8-ii9
Author(s):  
M I Strecker ◽  
K Wlotzka ◽  
F Strassheimer ◽  
J Reul ◽  
P N Harter ◽  
...  
Keyword(s):  
Side Effects ◽  
Tumor Cell ◽  
Nk Cells ◽  
Cellular Response ◽  
Checkpoint Inhibitors ◽  
Local Treatment ◽  
Local Therapy ◽  
Target Cells ◽  
Dependent Manner ◽  
Local Immunotherapy

Abstract BACKGROUND Glioblastoma (GB) is the most common primary brain tumor which is characterized by low immunogenicity of tumor cells and prevalent immunosuppression in the tumor microenvironment (TME). Since expression of PD-L1 on GB cells has been described, immunotherapy with checkpoint inhibitors (CIs) may be a promising approach for GB treatment. However, systemic administration of CIs bears the risk of autoimmune-like side effects, while the intratumoral drug concentration reached may not be sufficient. METHODS We studied delivery of CIs through targeted Adeno-associated viral vectors (AAVs) encoding an anti PD-1 immunoadhesin (aPD-1) as a novel approach towards local immunotherapy in the syngeneic GL261-HER2 glioma model. Tumor cell-specific delivery was achieved by targeting HER2 via a specific designed ankyrin repeat protein (DARPin). We investigated the effects of this strategy alone and in combination with local injection of HER2-specific CAR-NK cells (NK-92/5.28.z), which have already shown efficacy in preclinical GB models and are currently under investigation in the CAR2BRAIN phase I clinical trial. Furthermore, aPD-1 functionality and cellular response to viral transduction as well as compatibility of both therapy approaches has been evaluated in various in vitro models. RESULTS HER2-AAV transduction efficacy of GB cells correlated with HER2 expression level, while target cells did not show anti-viral responses upon transduction. After transduction with aPD-1 HER2-AAVs, aPD-1 immunoadhesin was secreted in a time-dependent manner, bound its target on PD-1-expressing cells and was able to re-activate T-cells due to PD-1 blockade. AAV-transduction did not interfere with CAR-NK cell mediated tumor cell lysis. Biodistribution studies in mice revealed the presence of aPD-1 up to 10 days after a single HER2-AAV injection. In subcutaneous GL261-HER2 tumors, local treatment with HER2-AAVaPD-1 or HER2-AAVIgG-Fc+ NK-92/5.28.z therapy had no significant effect, whereas combination therapy profoundly delayed tumor growth. CONCLUSIONS Local therapy with aPD-1 encoding HER2-AAVs in combination with NK-92/5.28.z cells is a promising novel strategy for GB immunotherapy with the potential to enhance efficacy and reduce side effects.

Outcomes with definitive local treatment to the primary site in non-nasopharyngeal head and neck squamous cell carcinoma patients with synchronous distant metastasis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18014-e18014
Author(s):  
Steven Borson ◽  
Yongli Shuai ◽  
Barton Branstetter ◽  
Marci Lee Nilsen ◽  
Marion Hughes ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Head And Neck ◽  
Distant Metastasis ◽  
Univariate Analysis ◽  
Local Treatment ◽  
Local Therapy ◽  
Distant Disease ◽  
Neck Disease ◽  
Metastatic Sites ◽  
Synchronous Distant Metastasis

e18014 Background: Data on the efficacy of including definitive local therapy to the primary head and neck disease (PHN) for non-nasopharyngeal head and neck squamous cell carcinoma (HNSCC) patients with synchronous distant metastasis are lacking. Methods: In this single institution retrospective study, we evaluated the outcomes of patients treated from 2000-2020 at UPMC for non-nasopharyngeal HNSCC with synchronous distant metastasis whose therapy included definitive therapy to the PHN. We evaluated overall survival (OS), calculated as date of diagnosis to date of death and progression free survival (PFS), calculated as date of diagnosis to date of death or progression. Based on an initial univariate analysis, the potential significant predictors were evaluated further in the multiple covariates Cox model via stepwise procedures. The relative mortality rates were summarized with hazard ratio (HR), with HR > 1.0 corresponding to increased mortality. Results: A total of 40 patients met inclusion criteria. The median age was 61, primary sites included 52.5% oropharynx (48% HPV +), 40% larynx/hypopharynx, 7.5% oral cavity, and 85% had a solitary metastatic lesion, most commonly in the lung. Definitive treatment of the PHN was with surgery (55%) or chemoradiation (45%), and 45% also underwent local treatment for all distant disease. The median PFS was 8.6 months (95% CI, 6.4-11.6), and OS was 14.2 months (95% CI, 10.9-27.5). In the 28% of patients that received induction therapy, there was a two-fold increase in median OS to 27.5 vs. 13.7 months, p = 0.06. In the 33% of patients that received anti-PD-1 mAb immunotherapy (IO), the median OS was significantly increased to 41.7 months (95% CI, 8.7-NR) vs. 12.1 months (95% CI, 8.4-14.4), p = 0.01, with a numeric increase in PFS as well (11.3 vs. 8.2 months respectively, p = 0.07). Notably no difference in PFS or OS was seen with type of local therapy to the PHN, receipt of local treatment to all distant disease, by HPV status, or year of diagnosis. In multivariate analysis including induction and other variables significant in univariate analysis (age, number of metastatic sites), IO was independently associated with improved OS (HR 3.123 (No IO vs. IO) (95% CI, 1.198-8.137), p = 0.02), as was age and number of metastatic sites. In the patients that received IO started as part of induction the median PFS and OS were 19.5 and 45.5 months respectively. Conclusions: We observed impressive survival in select non-nasopharyngeal HNSCC patients with synchronous distant metastasis treated with definitive local therapy to the primary head and neck disease in addition to induction and/or IO, with IO independently associated with improved OS. To our knowledge this is the first evaluation of the efficacy of definitive local therapy and IO in this population. Prospective evaluation is warranted.

scholarly journals Multidisciplinary treatment of deep neck infection associated with descending necrotizing mediastinitis: a single-centre experience

2019 ◽  
Vol 47 (12) ◽  
pp. 6027-6040 ◽  
Author(s):  
Chao Ma ◽  
Lian Zhou ◽  
Ji-Zhi Zhao ◽  
Run-Tai Lin ◽  
Tao Zhang ◽  
...  
Keyword(s):  
Thoracoscopic Surgery ◽  
Multidisciplinary Treatment ◽  
Multiple Organ ◽  
Deep Neck Infection ◽  
Descending Necrotizing Mediastinitis ◽  
College Hospital ◽  
Odontogenic Infections ◽  
Neck Infection ◽  
Medical College ◽  
Mediastinal Drainage

Objective Deep neck infection (DNI) associated with descending necrotizing mediastinitis (DNM) is a highly lethal condition. This retrospective review was performed to share our experience performing multidisciplinary management of DNI associated with DNM during a 7-year period. Methods We reviewed 16 patients who had been surgically treated for DNM at Peking Union Medical College Hospital from April 2010 to July 2017. The clinical outcomes were analysed to determine the most appropriate therapeutic strategy. Results Five women and 11 men were included in this study. Their mean age was 54.9 ± 14.3 years. DNM-associated infections most commonly occurred secondary to odontogenic infections (n = 10). Thirteen patients required tracheotomy because of tracheal compression. All patients underwent unilateral or bilateral cervicotomy. Six patients with DNM localized in the upper mediastinal space underwent transcervical mediastinal drainage, while 10 patients with DNM extending to the lower mediastinum were treated by cervicotomy and video-assisted thoracoscopic surgery. Three patients died of multiple organ failure. Conclusion Multidisciplinary treatment can achieve favourable outcomes in >80% of patients with DNM. Early diagnosis, proper airway management, and adequate surgical drainage are crucial for reducing mortality in patients with DNM, and minimally invasive procedures also play an important role.

scholarly journals Outcome of multidisciplinary treatment of peripheral primitive neuroectodermal tumor

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yidi Liu ◽  
Yan Yuan ◽  
Fuquan Zhang ◽  
Ke Hu ◽  
Jie Qiu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Size ◽  
Therapeutic Approach ◽  
Univariate Analysis ◽  
Multidisciplinary Treatment ◽  
College Hospital ◽  
Small Tumor ◽  
Medical College ◽  
Treatment Plans ◽  
Small Tumor Size

Abstract Peripheral primitive neuroectodermal tumors (PNETs) constitute very rare and aggressive malignancies. To date, there are no standard guidelines for management of peripheral PNETs due to the paucity of cases arising in various body sites. Therapeutic approach is derived from Ewing sarcoma family, which currently remains multimodal. Our study retrospectively analyzed 86 PNET patients from February 1, 1998 to February 1, 2018 at Peking Union Medical College Hospital with an additional 75 patients from review of literature. The clinicopathologic and treatment plans associated with survival was investigated. Surgery, chemotherapy, female sex, small tumor size, no lymph node metastasis, R0 surgical resection, (vincristine + doxorubicin + cyclophosphamide)/(isophosphamide + etoposide) regimen, and more than 10 cycles of chemotherapy were associated with improved overall survival in univariate analysis. Surgery, more than 10 cycles of chemotherapy, and small tumor size were independent prognostic factors for higher overall survival. Our data indicates that multimodal therapy is the mainstay therapeutic approach for peripheral PNET.

scholarly journals Local treatment of oligometastatic disease: current role

2019 ◽  
Vol 92 (1100) ◽  
pp. 20180835 ◽  
Author(s):  
Moritz T Winkelmann ◽  
Stephan Clasen ◽  
Philippe L Pereira ◽  
Rüdiger Hoffmann
Keyword(s):  
Colorectal Cancer ◽  
Survival Benefit ◽  
Local Treatment ◽  
Local Therapy ◽  
Distant Metastases ◽  
Solid Cancer ◽  
Aggressive Treatment ◽  
Current Role ◽  
Oligometastatic Disease ◽  
Thermal Therapies

The presence of distant metastases has long been a predictor of poor outcome in solid cancer. However, in an oncologic situation called oligometastatic disease (OMD), multiple studies have revealed a survival benefit with aggressive treatment of these metastases. Besides surgery and radiation therapy, local thermal therapies have developed into a treatment option for OMD. Most studies concerning local therapy of OMD are available for colorectal cancer, which is therefore the focus of this article. Furthermore, this review gives a basic overview of the most popular ablation techniques for treatment of OMD.

scholarly journals Local Treatment of Hand-Foot Syndrome with Uridine/Thymidine:In VitroAppraisal on a Human Keratinocyte Cell Line HaCaT

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
J. Hartinger ◽  
P. Veselý ◽  
E. Matoušková ◽  
S. Argalacsová ◽  
L. Petruželka ◽  
...  
Keyword(s):  
Cell Line ◽  
Local Treatment ◽  
Local Therapy ◽  
Anticancer Therapy ◽  
Protective Activity ◽  
Human Keratinocyte ◽  
Human Keratinocyte Cell Line ◽  
Keratinocyte Cell Line Hacat ◽  
Keratinocyte Cell

5-fluorouracil (5-FU) is one of the most commonly used antineoplastic drugs in the anticancer therapy. The hand-foot (HF) syndrome (palmar-plantar erythrodysesthesia) is an adverse effect frequently related to long-term i.v. administration of 5-FU or its orally applicable prodrug capecitabine. Its severity can even lead to interruption of the otherwise effective anticancer therapy. Tentative practice in some clinics has shown that topical application of 10% uridine ointment is beneficial for calming down the HF syndrome. This study is focused on verifying the alleged protective activity of uridine in thein vitromodel of cultured human keratinocyte cell line HaCaT. We also tested the protective effects of thymidine alone or uridine-thymidine combination. The cellular viability time progression was measured in order to evaluate the effect of protective agents by three different types of cytopathogenicity tests—NTCA test (non-destructive test of cellular activity), modified MTT test and RTCA (real-time cell analyser, Roche). All three methods proved the ability of uridine and uridine-thymidine combination to protect keratinocytes against 5-FU damagein vitro. While thymidine alone did not show any remarkable effect, the thymidine-uridine combination demonstrated enhanced protective activity compared to uridine alone. Our findings provided the supporting rationale for using uridine or uridine-thymidine ointments in the HF syndrome local therapy.

Brain metastases in patients with urothelial carcinoma.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 282-282
Author(s):  
Helen Jane Boyle ◽  
Emilie Lavergne ◽  
Jean Pierre Droz ◽  
Nathalie Bonnin ◽  
Aude Flechon
Keyword(s):  
Brain Metastases ◽  
Urothelial Carcinoma ◽  
Metastatic Disease ◽  
Cox Model ◽  
Brain Mri ◽  
Brain Lesion ◽  
Local Treatment ◽  
Local Therapy ◽  
Initial Diagnosis ◽  
Initial Presentation

282 Background: Muscle invasive urothelial cancers are infrequent. Patients (pts) with metastatic disease have poor prognosis. Brain metastases (BM) are rare. The aim of this retrospective study is to analyse the characteristics, the treatment and the evolution of patients with BM treated in a single centre. Methods: Thirty pts with BM were identified among the 1591 pts with urothelial carcinoma seen at the Centre Léon Bérard, between 1994 and 2011. The study population was described, overall survival (OS) from diagnosis of BM was estimated by Kaplan-Meier method and prognostic factors were explored using a Cox model. Results: Twenty seven pts in our series were male. Median age at initial diagnosis was 60 years (range: 33.9-78.9 years). Twenty two pts had primary bladder tumours and 8 upper urinary tract tumours. Twenty four pts underwent surgery for their primary lesion, 2 received chemoradiotherapy and 4 did not receive any radical local treatment. Six pts had metastatic disease at initial presentation: 3 were operated on. Median delay between initial diagnosis and BM was 16.6 months (range: 0-56.4 months), 3 patients had BM at initial presentation. Median time between first metastases and BM was 10 months (range=0-52 months). Eleven patients developed BM as one of the first sites of metastases. BM were symptomatic in 28 pts: specific neurological symptoms (n=25), headaches (n=6), epilepsy (n=2). For the 2 other pts, they were discovered on a systematic brain MRI. Eighteen pts had cerebral metastases only, 5 pts had cerebellar metastases only, 6 had both; the last patient had cerebral, cerebellar and meningeal involvement. Half of the pts had only 1 brain lesion. Five pts were operated on: 4 received postoperative radiotherapy; 19 patients were given radiotherapy alone and 6 did not get any local therapy. In this series, median OS from diagnosis of BM was 3.4 months (IC95% [2.2-10.3]). Only the administration of chemotherapy after the diagnosis of BM was significantly associated with OS; probably because only fit enough patients were offered treatment. Conclusions: Prognosis of patients with urothelial carcinoma and BM is poor; however some patients have long survivals. Treatment is not codified as there is little data in the literature.

The ORCHESTRA trial: A phase III trial of adding tumor debulking to systemic therapy versus systemic therapy alone in multi-organ metastatic colorectal cancer (mCRC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS788-TPS788 ◽  
Author(s):  
Elske C. Gootjes ◽  
Tineke E Buffart ◽  
M.P. Tol ◽  
J Burger ◽  
Dirk J. Grunhagen ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Systemic Therapy ◽  
Local Treatment ◽  
Case Series ◽  
Local Therapy ◽  
Phase Iii ◽  
Locoregional Therapy ◽  
Treatment Modalities ◽  
Type I ◽  
Tumor Debulking

TPS788 Background: In the current multidisciplinary approach of mCRC, local treatment of oligometastases is common practice. Results of large case series of selected patients treated with complete surgical resection of metastatic lesions suggest that this approach substantially improves survival rates to around 30-60%. Other techniques such as radiofrequency or microwave ablation (RFA, MWA), transarterial chemoembolization (TACE) or radiotherapy can also be applied in local treatment. Curative treatment options are generally not available for patients with extensive hepatic and/or extrahepatic mCRC. These patients primarily receive palliative systemic treatment consisting of combination chemotherapy as well as targeted agents. So far, reports on the benefit of local treatment for metastases in multi-organ mCRC have major limitations, including being small, non-randomized, single-center and retrospective. The benefit from local treatment of metastases for these patients should be established to allow for interruption of the standard systemic therapy and exposure to possible adverse events from local treatment. Methods: The ‘ORCHESTRA’ trial is a randomized multicenter clinical trial for patients with multi-organ mCRC, comparing the combination of chemotherapy and maximal tumor debulking versuschemotherapy alone (NCT01792934). We will examine the interplay of both efficacy and toxicity for the combination of systemic chemotherapy and locoregional therapy. Our study design incorporates systemic as well as local therapy in the experimental arm and combines local treatment modalities to pursue maximal tumor debulking. We aim to improve overall survival of patients with multi-organ mCRC by maximal tumor debulking after induction chemotherapy with at least six months. A total of 478 patients will be included to meet the primary endpoint (power 80%, type I error rate 5%). We define local treatments feasible when they can be performed within a 3-month time period to prevent extensive delay of systemic therapy. Currently, 60 patients are included in 22 participating Dutch hospitals. Clinical trial information: NCT01792934.

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