Evaluating the biological effects of pre-operative intravenous administration of JX-594 (thymidine kinase-deactivated Vaccinia virus plus GM-CSF) prior to planned surgical resection of locally advanced/poor prognosis or metastatic cancers.

Pelvic osteosarcoma has a poor prognosis compared to osteosarcomas in other locations, and the reasons for this remain unknown. Surgical resection of pelvic osteosarcoma is technically demanding and often results in dysfunction and complications. In this study, we investigated the reasons underlying the poor prognosis of pelvic osteosarcoma by comparing it to femoral osteosarcoma using data from the Bone Tumor Registry in Japan. We used propensity score analysis to determine whether surgical resection of pelvic osteosarcoma improved its prognosis. We demonstrated that pelvic osteosarcoma had a poor prognosis because it occurred more often in the elderly, often had larger tumor size, and had metastasis at presentation more often in comparison to femoral osteosarcoma. These three factors were also associated with the non-surgical treatment of pelvic osteosarcoma, which also led to a poor outcome. The overall survival rate was only comparable in pelvic osteosarcoma and femoral osteosarcoma in cases treated with surgical resection. Propensity score analysis revealed that surgical treatment improved the prognosis of pelvic osteosarcoma. As such, we propose that surgical resection should be considered based on tumor stage and patient age in order to improve the prognosis of pelvic osteosarcoma.

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Predictors of Survival in Adrenocortical Carcinoma: An Analysis From the National Cancer Database

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2018-00918 ◽

2018 ◽

Vol 103 (9) ◽

pp. 3566-3573 ◽

Cited By ~ 13

Author(s):

Sri Harsha Tella ◽

Anuhya Kommalapati ◽

Subhashini Yaturu ◽

Electron Kebebew

Keyword(s):

Surgical Resection ◽

Adrenocortical Carcinoma ◽

Poor Prognosis ◽

Stage Iv ◽

Tumor Grade ◽

Disease Stage ◽

Survival Outcomes ◽

National Cancer Database ◽

Stage Iv Disease ◽

Comorbidity Index

Abstract Context Adrenocortical carcinoma (ACC) is rare; knowledge about prognostic factors and survival outcomes is limited. Objective To describe predictors of survival and overall survival (OS) outcomes. Design and Patients Retrospective analysis of data from the National Cancer Database (NCDB) from 2004 to 2015 on 3185 patients with pathologically confirmed ACC. Main Outcome Measures Baseline description, survival outcomes, and predictors of survival were evaluated in patients with ACC. Results Median age at ACC diagnosis was 55 (range: 18 to 90) years; did not differ significantly by sex or stage of the disease at diagnosis. On multivariate analysis, increasing age, higher Charlson-Deyo comorbidity index score, high tumor grade, and no surgical therapy (all P < 0.0001); and stage IV disease (P = 0.002) and lymphadenectomy during surgery (P = 0.02) were associated with poor prognosis. Patients with stage I-III disease treated with surgical resection had significantly better median OS (63 vs 8 months; P < 0.001). In stage IV disease, better median OS occurred in patients treated with surgery (19 vs 6 months; P < 0.001), and postsurgical radiation (29 vs 10 months; P < 0.001) or chemotherapy (22 vs 13 months; P = 0.004). Conclusion OS varied with increasing age, higher comorbidity index, grade, and stage of ACC at presentation. There was improved survival with surgical resection of primary tumor, irrespective of disease stage; postsurgical chemotherapy or radiation was of benefit only in stage IV disease.

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Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma

BioMed Research International ◽

10.1155/2015/840542 ◽

2015 ◽

Vol 2015 ◽

pp. 1-26 ◽

Cited By ~ 20

Author(s):

Chen-Yi Liao ◽

Ching-Chang Lee ◽

Chi-chang Tsai ◽

Chao-Wen Hsueh ◽

Chih-Chiang Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Natural Products ◽

Multidrug Resistance ◽

Intracellular Signaling ◽

Poor Prognosis ◽

Biological Effects ◽

Herbal Medicines ◽

Chemopreventive Agents ◽

Intracellular Signaling Pathways ◽

Anticancer Effects

We would like to highlight the application of natural products to hepatocellular carcinoma (HCC). We will focus on the natural products known as flavonoids, which target this disease at different stages of hepatocarcinogenesis. In spite of the use of chemotherapy and radiotherapy in treating HCC, patients with HCC still face poor prognosis because of the nature of multidrug resistance and toxicity derived from chemotherapy and radiotherapy. Flavonoids can be found in many vegetables, fruits, and herbal medicines that exert their different anticancer effects via different intracellular signaling pathways and serve as antioxidants. In this review, we will discuss seven common flavonoids that exert different biological effects against HCC via different pathways.

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Mucinous Adenocarcinoma Associated with Fistula in an 87-Year-Old Managed with Neoadjuvant Chemoradiation and ELAPE at Tata Memorial Hospital, in Mumbai

Global Surgery Case Reports ◽

10.31487/j.gscr.2020.02.09 ◽

2020 ◽

pp. 1-4

Author(s):

Avanish Saklani ◽

Seke Manase Ephraim KAZUMA ◽

Vivek Sukumar ◽

Avanish Saklani

Keyword(s):

Colorectal Cancer ◽

Distant Metastasis ◽

Mucinous Adenocarcinoma ◽

Poor Prognosis ◽

Locally Advanced ◽

Delayed Diagnosis ◽

Neoadjuvant Chemoradiation ◽

Tata Memorial Hospital ◽

The Third ◽

Cutaneous Flap

Colorectal cancer is the third most diagnosed cancer and the fourth leading cancer-related death worldwide. Mucinous adenocarcinoma associated with anal fistula is a rare variant of adenocarcinoma, presents with delayed diagnosis, locally advanced, low nodal, and no distant metastasis. Adenocarcinoma associated with fistula (ACAF) is rare, has delayed diagnosis and poor prognosis but can be managed with neoadjuvant chemoradiation (NACRT) and complete curative resections with reconstruction by V-Y advancement cutaneous flap.

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Treatment of patients with locally advanced Merkel cell carcinoma: A multicenter study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21566 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21566-e21566

Author(s):

Monika Dudzisz-Śledź ◽

Pawel Sobczuk ◽

Katarzyna Kozak ◽

Tomasz Switaj ◽

Hanna Kosela-Paterczyk ◽

...

Keyword(s):

Risk Factors ◽

Lymph Node ◽

Poor Prognosis ◽

Locally Advanced ◽

Male Gender ◽

Merkel Cell ◽

Nodal Involvement ◽

Free Survival ◽

Independent Risk Factors ◽

Clinical Metastases

e21566 Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with a high risk of recurrence and poor prognosis. The treatment of locally advanced disease includes surgery (SUR) and radiotherapy (RTH) to achieve high locoregional control rates. The sentinel lymph node biopsy (SLNB) is recommended procedure in cases without clinical nodal involvement. In selected cases, chemotherapy (CHT) may also be considered, but its role is not confirmed. This study aimed to analyze outcomes for locally advanced MCC pts treated in routine clinical practice. Methods: We conducted the retrospective analysis of data from 156 MCC pts treated with curative surgery in four oncological centers, diagnosed between 01/2010 and 12/2019, with data cut-off on 31/12/2020. The data collected included epidemiological and clinical information. Survival analyses were performed using the Kaplan-Meier method, log-rank test and multivariate Cox regression. Results: The median patient age at diagnosis was 72 years (30-94); 50.6% were male. The primary tumor (PT) locations were lower limbs (33.3%), upper limbs (30.1%), and head and neck (28.2%). MCC with no PT was diagnosed in 3.9%. In 62.0% the PT was located in the sun-exposed skin. The median tumor size was 25 mm (4-170). Lymph node (LN) involvement (clinical or positive SLNB or LND) at diagnosis was found in 26.9% (n = 42). The scar excision was done in 50.0% (positive in 16.6%), SLNB in 36.5% (positive in 10.5 %), 51.9% of pts received perioperative treatment, including RTH- 86.4%, CHT- 21%. The relapse rate was 38.3% (35.8% local-regional, 11.1% distant). With the median follow-up of 2.2-years, the median disease-free survival (DFS), local relapse-free survival (LRFS), and distant metastases-free survival (DMFS) were not reached. The 1-year DFS, LRFS and DMFS rates were 65%, 68%, and 90%. The negative independent risk factors for DFS were male gender (HR 1.42, 95%CI 1.06-3.01), metastases in LN at diagnosis (HR 5.41, 95%CI 2.39-12.26), no SLNB in pts with no clinical metastases in LN (HR 5.45, 95%CI 2.41-12.3), and no perioperative RTH (HR 2.19, 95%CI 1.29-3.76). The median overall survival (OS) was 6.9 years (95%CI 4.64-9.15). The negative independent risk factors for OS were male gender (HR 1.95, 95%CI 1.16-3.27), age above 70 (HR 2.0, 95%CI 1.15-3.48), metastases in LN at diagnosis (HR 3.15, 95%CI 1.49-6.68), and no SLNB in pts with no clinical metastases in LN (HR 2.30, 95%CI 1.10-4.82). PT location, UV-exposure, and perioperative CHT or RTH were not independent risk factors for OS. Conclusions: Our results confirm that the MCC treatment should be done in an experienced multidisciplinary team. Male gender, nodal involvement at diagnosis, and no SLNB in pts without clinical metastases in LN are associated with poor prognosis in DFS and OS. The perioperative RTH improves the treatment outcomes and reduces disease progression risk but does not impact OS. Perioperative CHT does not affect pts survival.

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Feasibility and efficacy of neoadjuvant cabozantinib and nivolumab in patients with borderline resectable or locally advanced hepatocellular carcinoma (HCC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.335 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 335-335

Author(s):

Mark Yarchoan ◽

Qingfeng Zhu ◽

Jennifer N. Durham ◽

Nicole Gross ◽

Soren Charmsaz ◽

...

Keyword(s):

T Cells ◽

Adverse Event ◽

Neoadjuvant Therapy ◽

Surgical Resection ◽

Primary Endpoint ◽

Locally Advanced ◽

Borderline Resectable ◽

Advanced Hcc ◽

Surgical Evaluation ◽

Systemic Therapies

335 Background: Only 10-15% of newly diagnosed HCC patients are candidates for a potentially curative resection, and most patients who receive resection eventually recur. Historical systemic therapies including sorafenib, as well as locoregional therapies, have not demonstrated benefit in the perioperative setting. Novel combinations of targeted therapies and immunotherapies demonstrate higher response rates than sorafenib in HCC. Here, we report the feasibility and efficacy of neoadjuvant combination therapy with cabozantinib plus nivolumab, followed by surgical resection, in patients with borderline resectable or locally advanced HCC. Methods: We conducted an open-label, single-arm, phase I study in patients with HCC with borderline resectable or locally advanced HCC (including multinodular disease, portal vein involvement, or other high-risk features). Patients received 8 weeks of therapy with cabozantinib 40 mg oral daily plus nivolumab 240 mg IV every two weeks, followed by restaging and possible surgical resection. The primary endpoint was feasibility, defined by the percentage of patients experiencing a treatment-related adverse event that precluded continuing on to surgery within 60 days of the planned date for surgical evaluation. Results: We enrolled 15 patients of whom 14 patients completed neoadjuvant therapy and underwent surgical evaluation. Adverse events were consistent with prior experience with these agents, and the trial met its primary endpoint, with no patients experiencing a treatment-related adverse event that precluded timely surgical assessment. Of patients completing neoadjuvant therapy, 1 patient declined surgery, 1 tumor could not be resected, and 12 patients underwent successful R0 surgical resection. 5/12 (41.7%) resected patients had a major or complete pathologic response. At a median follow up of one year, 4/5 pathologic responders are without recurrence. We performed an in-depth profiling of the surgical resection biospecimens and identified an enrichment of IFNγ+ effector memory CD4+ and granzyme B+ effector CD8+ T cells as well as tertiary lymphoid aggregates in the pathologic responders. We further analyzed the spatial relationships of cell types in responders and non-responders, which identified distinct spatial arrangement of B cells in responders, and proximity of arginase-1 expressing myeloid cells to T cells in nonresponders. Conclusions: This study is, to our knowledge, the first use of a targeted therapy in combination with an immune checkpoint inhibitor in the neoadjuvant setting in HCC, and the first use of modern systemic therapies to expand surgical resection criteria. Neoadjuvant cabozantinib and nivolumab is feasible, and may result in pathologic responses and long-term disease-free survival in a group of patients who may be outside traditional resection criteria. Clinical trial information: NCT03299946.

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