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California: Cancer Organizations Cancer Centres in California Latest Research Publications from CaliforniaCalifornia: Cancer Organizations (15 links)
Founded in 1993, PCF has grown into a global Foundation which has funded hundreds of research studies in over 16 countries. The Website includes detailed information about prostate cancer, research and personal accounts of prostate cancer. Head office in Santa Monica.
California Breast Cancer Research Program
The CBCRP program, established 1993, is responsible for administering funding for breast cancer research in the State of California.
A population-based registry established 1985, run by the California Department of Public Health. The Web site includes data querying, resources for researchers and registrars, publications etc.
This is a camp in Northern California for kids with cancer and siblings of kids with cancer run by the Okizu Foundation. It also has a variety of family camp sessions as well as a program for teen and twenties.
Jacob’s Heart Children’s Cancer Support Services
A non-profit organisation founded in 1998 to provide support for children with cancer and their families. The site includes details of the Association, services, contact information and links.
Los Angeles Breast Cancer Alliance
A grassroots, nonprofit organization dedicated to helping in the eradication of breast cancer through advocacy, education, and community involvement. Formed in 1992, LABCA serves all of Los Angeles County and the surrounding counties.
Medical Oncology Association of Southern California
MOASC was founded in 1990 and is a professional organization representing oncologists and their patients in Southern California.
Northern California Melanoma Center
Saint Mary's Medical Center, San Fransisco. The web site includes details about NCMC and services, research, news and information about melanoma.
Stanford University School of Medicine - Department of Radiation Oncology
The Department is involved in clinical care, education and training, and research.
State Cancer Profiles: California
National Cancer Institute
Generate stats by cancer type and map incidence rates by county.
Teen Impact Program - Childrens' Hospital of Los Angeles
Group-based psychological, emotional and social support program of the Children's Center for Cancer and Blood Diseases; support groups, annual retreat and special activities, mentor and health specialist education.
University of Southern California - Department of Radiation Oncology
Women's Cancer Resource Center of Berkeley
Founded in 1986 to provide support and advocay for women with cancer in the San Francisco Bay Area. The web site includes details of services, events, articles and information, links etc
Cancer Centres in California (16 links)
A nonprofit corporation covering California’s Alameda and Contra Costa counties. The institute is involved in research, patient information, nursing education, and consultations for head and neck cancer+melanoma.
Chao Family Comprehensive Cancer Center
An NCI designated Comprehensive Cancer Center at the University of California, Irvine. Established 1989.
Childrens Hospital Los Angeles: Center for Cancer and Blood Diseases
CHLA was founded in 1901 and is a non-profit hospital. The Children's Center for Cancer is a regional referral center. The website includes details about the Center, programs, services, and staff.
City of Hope Comprehensive Cancer Center
An NCI designated Comprehensive Cancer Center. Established 1913.
Hyundai Cancer Institute - Children's Hospital of Orange County
The Website includes details of treatment programs at the center.
Jonsson Comprehensive Cancer Center
An NCI designated at the University of California at Los Angeles. Established 1974.
Ludwig Institute for Cancer Research - San Diego Branch
Based at the University of California San Diego, the branch focuses mainly on research into cancer genetics, cell signaling, gene regulation and the mechanisms of cell division.
Orange County Foundation for Oncology Children and Families
An all-volunteer organisation formed in 1982 serving pediatric cancer patients and their families in Orange County. This web site gives details of the events the OCF-OCF support, in particular their summer camp for cancer kids.
An NCI designated Cancer Center conducting research (not treatment). Established 1970.
An NCI designated Cancer Center at the at Stanford University. Established 2003.
Part of Sutter Health Sacramento Sierra Region, the Sutter Cancer Center was established in 1983, now with a regional cancer program with additional locations.
UC Davis Comprehensive Cancer Center
An NCI designated Davis Comprehensive Cancer Center at the University of California at Davis. Established 1991.
UC San Diego Moores Cancer Center
An NCI designated Comprehensive Cancer Center at the University of California at San Diego. Established 1978.
UCSF Helen Diller Family Comprehensive Cancer Center
An NCI designated Comprehensive Cancer Center at the University of California at San Francisco. Established 1948.
USC Norris Comprehensive Cancer Center
An NCI designated Comprehensive Cancer Center at the University of Southern California. Established 1971.
Cancer Centers in the USALatest Research Publications from California
Chari A, Vogl DT, Gavriatopoulou M, et al.
Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma.
N Engl J Med. 2019; 381(8):727-738 [PubMed] Related Publications
Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma.
N Engl J Med. 2019; 381(8):727-738 [PubMed] Related Publications
BACKGROUND: Selinexor, a selective inhibitor of nuclear export compound that blocks exportin 1 (XPO1) and forces nuclear accumulation and activation of tumor suppressor proteins, inhibits nuclear factor κB, and reduces oncoprotein messenger RNA translation, is a potential novel treatment for myeloma that is refractory to current therapeutic options.
METHODS: We administered oral selinexor (80 mg) plus dexamethasone (20 mg) twice weekly to patients with myeloma who had previous exposure to bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent and had disease refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab (triple-class refractory). The primary end point was overall response, defined as a partial response or better, with response assessed by an independent review committee. Clinical benefit, defined as a minimal response or better, was a secondary end point.
RESULTS: A total of 122 patients in the United States and Europe were included in the modified intention-to-treat population (primary analysis), and 123 were included in the safety population. The median age was 65 years, and the median number of previous regimens was 7; a total of 53% of the patients had high-risk cytogenetic abnormalities. A partial response or better was observed in 26% of patients (95% confidence interval, 19 to 35), including two stringent complete responses; 39% of patients had a minimal response or better. The median duration of response was 4.4 months, median progression-free survival was 3.7 months, and median overall survival was 8.6 months. Fatigue, nausea, and decreased appetite were common and were typically grade 1 or 2 (grade 3 events were noted in up to 25% of patients, and no grade 4 events were reported). Thrombocytopenia occurred in 73% of the patients (grade 3 in 25% and grade 4 in 33%). Thrombocytopenia led to bleeding events of grade 3 or higher in 6 patients.
CONCLUSIONS: Selinexor-dexamethasone resulted in objective treatment responses in patients with myeloma refractory to currently available therapies. (Funded by Karyopharm Therapeutics; STORM ClinicalTrials.gov number, NCT02336815.).
METHODS: We administered oral selinexor (80 mg) plus dexamethasone (20 mg) twice weekly to patients with myeloma who had previous exposure to bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent and had disease refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab (triple-class refractory). The primary end point was overall response, defined as a partial response or better, with response assessed by an independent review committee. Clinical benefit, defined as a minimal response or better, was a secondary end point.
RESULTS: A total of 122 patients in the United States and Europe were included in the modified intention-to-treat population (primary analysis), and 123 were included in the safety population. The median age was 65 years, and the median number of previous regimens was 7; a total of 53% of the patients had high-risk cytogenetic abnormalities. A partial response or better was observed in 26% of patients (95% confidence interval, 19 to 35), including two stringent complete responses; 39% of patients had a minimal response or better. The median duration of response was 4.4 months, median progression-free survival was 3.7 months, and median overall survival was 8.6 months. Fatigue, nausea, and decreased appetite were common and were typically grade 1 or 2 (grade 3 events were noted in up to 25% of patients, and no grade 4 events were reported). Thrombocytopenia occurred in 73% of the patients (grade 3 in 25% and grade 4 in 33%). Thrombocytopenia led to bleeding events of grade 3 or higher in 6 patients.
CONCLUSIONS: Selinexor-dexamethasone resulted in objective treatment responses in patients with myeloma refractory to currently available therapies. (Funded by Karyopharm Therapeutics; STORM ClinicalTrials.gov number, NCT02336815.).
Related: 
Myeloma Myeloma - Molecular Biology
Myeloma Myeloma - Molecular Biology
Screening for Pancreatic Cancer: US Preventive Services Task Force Reaffirmation Recommendation Statement.
JAMA. 2019; 322(5):438-444 [PubMed] Related Publications
Importance: Pancreatic cancer is an uncommon cancer with an age-adjusted annual incidence of 12.9 cases per 100 000 person-years. However, the death rate is 11.0 deaths per 100 000 person-years because the prognosis of pancreatic cancer is poor. Although its incidence is low, pancreatic cancer is the third most common cause of cancer death in the United States. Because of the increasing incidence of pancreatic cancer, along with improvements in early detection and treatment of other types of cancer, it is estimated that pancreatic cancer may soon become the second-leading cause of cancer death in the United States.
Objective: To update the 2004 US Preventive Services Task Force (USPSTF) recommendation on screening for pancreatic cancer.
Evidence Review: The USPSTF reviewed the evidence on the benefits and harms of screening for pancreatic cancer, the diagnostic accuracy of screening tests for pancreatic cancer, and the benefits and harms of treatment of screen-detected or asymptomatic pancreatic cancer.
Findings: The USPSTF found no evidence that screening for pancreatic cancer or treatment of screen-detected pancreatic cancer improves disease-specific morbidity or mortality, or all-cause mortality. The USPSTF found adequate evidence that the magnitude of the benefits of screening for pancreatic cancer in asymptomatic adults can be bounded as no greater than small. The USPSTF found adequate evidence that the magnitude of the harms of screening for pancreatic cancer and treatment of screen-detected pancreatic cancer can be bounded as at least moderate. The USPSTF reaffirms its previous conclusion that the potential benefits of screening for pancreatic cancer in asymptomatic adults do not outweigh the potential harms.
Conclusions and Recommendation: The USPSTF recommends against screening for pancreatic cancer in asymptomatic adults. (D recommendation).
Objective: To update the 2004 US Preventive Services Task Force (USPSTF) recommendation on screening for pancreatic cancer.
Evidence Review: The USPSTF reviewed the evidence on the benefits and harms of screening for pancreatic cancer, the diagnostic accuracy of screening tests for pancreatic cancer, and the benefits and harms of treatment of screen-detected or asymptomatic pancreatic cancer.
Findings: The USPSTF found no evidence that screening for pancreatic cancer or treatment of screen-detected pancreatic cancer improves disease-specific morbidity or mortality, or all-cause mortality. The USPSTF found adequate evidence that the magnitude of the benefits of screening for pancreatic cancer in asymptomatic adults can be bounded as no greater than small. The USPSTF found adequate evidence that the magnitude of the harms of screening for pancreatic cancer and treatment of screen-detected pancreatic cancer can be bounded as at least moderate. The USPSTF reaffirms its previous conclusion that the potential benefits of screening for pancreatic cancer in asymptomatic adults do not outweigh the potential harms.
Conclusions and Recommendation: The USPSTF recommends against screening for pancreatic cancer in asymptomatic adults. (D recommendation).
Higuchi T, Sugisawa N, Miyake K, et al.
Sorafenib and Palbociclib Combination Regresses a Cisplatinum-resistant Osteosarcoma in a PDOX Mouse Model.
Anticancer Res. 2019; 39(8):4079-4084 [PubMed] Related Publications
Sorafenib and Palbociclib Combination Regresses a Cisplatinum-resistant Osteosarcoma in a PDOX Mouse Model.
Anticancer Res. 2019; 39(8):4079-4084 [PubMed] Related Publications
BACKGROUND/AIM: Recurrent osteosarcoma is a recalcitrant disease; therefore, an improved strategy is urgently needed to provide therapy. In order to develop a novel strategy for this disease, our lab has developed a patient-derived orthotopic xenograft (PDOX) mouse model for osteosarcoma. The combination of sorafenib (SFN) and palbociclib (PAL) was shown to be effective of hepatocellular carcinoma. However, whether this combination is efficacious on osteosarcoma has not been reported. The aim of this study was to determine the efficacy of the SFN and PAL combination on a cisplatinum (CDDP)-resistant osteosarcoma PDOX model.
MATERIALS AND METHODS: Osteosarcoma PDOX models were randomly divided into five treatment groups: untreated-control, CDDP, SFN, PAL and the combination of SFN and PAL.
RESULTS: Of these agents, the SFN-PAL combination significantly regressed tumor growth, and enhanced tumor necrosis with degenerative changes in the osteosarcoma PDOX.
CONCLUSION: The SFN-PAL combination is an effective treatment strategy for osteosarcoma and therefore holds promise for clinical efficacy.
MATERIALS AND METHODS: Osteosarcoma PDOX models were randomly divided into five treatment groups: untreated-control, CDDP, SFN, PAL and the combination of SFN and PAL.
RESULTS: Of these agents, the SFN-PAL combination significantly regressed tumor growth, and enhanced tumor necrosis with degenerative changes in the osteosarcoma PDOX.
CONCLUSION: The SFN-PAL combination is an effective treatment strategy for osteosarcoma and therefore holds promise for clinical efficacy.
Yoon SN, Park JH, Lwin TM, et al.
Tumor-sealing Surgical Orthotopic Implantation of Human Colon Cancer in Nude Mice Induces Clinically-relevant Metastases Without Early Peritoneal Carcinomatosis.
Anticancer Res. 2019; 39(8):4065-4071 [PubMed] Related Publications
Tumor-sealing Surgical Orthotopic Implantation of Human Colon Cancer in Nude Mice Induces Clinically-relevant Metastases Without Early Peritoneal Carcinomatosis.
Anticancer Res. 2019; 39(8):4065-4071 [PubMed] Related Publications
BACKGROUND: Surgical orthotopic implantation of human colon cancer tissue to the ceca of mice has been used to mimic behavior of cancer in human patients for the development of precision cancer medicine. However, with the current method of serosal surface implantation (SSI) of pieces of human colon cancer tissue, cancer cells are exposed to the peritoneum, which can artificially increase the rate of peritoneal carcinomatosis (PC) during the disease course. The objective of the present study was to introduce a tumor-sealing method (TSM) and compare it with SSI for the ability to produce clinically-relevant metastases without artificial PC.
MATERIALS AND METHODS: HCT116 colon cancer cells transfected with green fluorescence protein (GFP) were cultured and then injected into the subcutaneous layer of athymic nude mice. Subcutaneous tumors were allowed to grow sufficiently to supply adequate tumor for orthotopic implantation. For SSI, a 1 mm
RESULTS: At 20 days after implantation, PC rates in the SSI group and the TSM group were 80% (12/15) and 20% (3/15), respectively (p<0.001). The liver metastasis rate was 41.7% (5/12) in the SSI group and 50% (5/10) in the TSM group (p=0.696). The lung metastasis rate was 0% (0/12) in the SSI group and 10% (1/10) in the TSM group (p=0.201). The mean survival of mice without PC on the 20th day was significantly longer than that of mice with PC on the 20th day (69.1±14.7 vs. 44.5±12.4 days, p=0.001).
CONCLUSION: These results suggest that TSM might be a more patient-like and useful method as a model of metastatic colon cancer than SSI.
MATERIALS AND METHODS: HCT116 colon cancer cells transfected with green fluorescence protein (GFP) were cultured and then injected into the subcutaneous layer of athymic nude mice. Subcutaneous tumors were allowed to grow sufficiently to supply adequate tumor for orthotopic implantation. For SSI, a 1 mm
RESULTS: At 20 days after implantation, PC rates in the SSI group and the TSM group were 80% (12/15) and 20% (3/15), respectively (p<0.001). The liver metastasis rate was 41.7% (5/12) in the SSI group and 50% (5/10) in the TSM group (p=0.696). The lung metastasis rate was 0% (0/12) in the SSI group and 10% (1/10) in the TSM group (p=0.201). The mean survival of mice without PC on the 20th day was significantly longer than that of mice with PC on the 20th day (69.1±14.7 vs. 44.5±12.4 days, p=0.001).
CONCLUSION: These results suggest that TSM might be a more patient-like and useful method as a model of metastatic colon cancer than SSI.
Matsuura K, Suetsugu A, Satake T, et al.
Choline-deficient-diet Decreases Fibroblasts in the Circulating Tumor Cell (CTC) Microenvironment.
Anticancer Res. 2019; 39(8):4061-4064 [PubMed] Related Publications
Choline-deficient-diet Decreases Fibroblasts in the Circulating Tumor Cell (CTC) Microenvironment.
Anticancer Res. 2019; 39(8):4061-4064 [PubMed] Related Publications
BACKGROUND/AIM: Circulating tumor cells (CTCs) may have an important role in metastasis. CTC clusters, which contain fibroblasts, indicate poor prognosis. In the present study, we used our malignant lymphoma metastatic mouse model to compare the effect of a choline-deficient-diet (CDD) and the control diet (CD) on fibroblasts in CTCs.
MATERIALS AND METHODS: We compared the number and morphology of CTCs in CDD and CD mice using color-coded imaging with fluorescent proteins. Malignant lymphoma EL4 cells expressing RFP were injected in the spleen of transgenic C57B/6-GFP mice, which were fed a CDD or CD. Two weeks later, we harvested and observed the number of CTCs and fibroblast-like cells both in heart blood and portal blood. Imaging of CTC morphology was performed with smeared glass slides and in culture.
RESULTS AND CONCLUSION: There was no significant difference in the number of CTCs between CDD and CD mice. The number of fibroblast-like cells in the CTC microenvironment in CD mouse portal blood was significantly larger than in CDD mouse portal blood. These differences may be caused by deficiency in choline that leads to less metastasis in choline-deficient-diet-induced fatty liver.
MATERIALS AND METHODS: We compared the number and morphology of CTCs in CDD and CD mice using color-coded imaging with fluorescent proteins. Malignant lymphoma EL4 cells expressing RFP were injected in the spleen of transgenic C57B/6-GFP mice, which were fed a CDD or CD. Two weeks later, we harvested and observed the number of CTCs and fibroblast-like cells both in heart blood and portal blood. Imaging of CTC morphology was performed with smeared glass slides and in culture.
RESULTS AND CONCLUSION: There was no significant difference in the number of CTCs between CDD and CD mice. The number of fibroblast-like cells in the CTC microenvironment in CD mouse portal blood was significantly larger than in CDD mouse portal blood. These differences may be caused by deficiency in choline that leads to less metastasis in choline-deficient-diet-induced fatty liver.
Satake T, Suetsugu A, Nakamura M, et al.
Color-coded Imaging of the Fate of Cancer-cell-derived Exosomes During Pancreatic Cancer Metastases in a Nude-mouse Model.
Anticancer Res. 2019; 39(8):4055-4060 [PubMed] Related Publications
Color-coded Imaging of the Fate of Cancer-cell-derived Exosomes During Pancreatic Cancer Metastases in a Nude-mouse Model.
Anticancer Res. 2019; 39(8):4055-4060 [PubMed] Related Publications
BACKGROUND/AIM: Tumor-derived exosomes play important roles in tumor metastases. In this report, we observed the fate of tumor-derived exosomes in pancreatic cancer metastatic nude-mouse models using color-coded imaging.
MATERIALS AND METHODS: Mia-PaCa-2 human pancreatic cancer cells expressing red fluorescent protein (RFP) were transduced by exosome-specific pCT-CD63-green fluorescent protein (GFP) and injected in the spleen of nude mice.
RESULTS: Four weeks after injection of these cells into the spleen, liver metastases developed and tumor-derived exosomes were observed within the metastatic cancer cells and in Kupffer cells. Furthermore, tumor-derived exosomes diffused to bone marrow and lung cells, especially macrophages, without any metastases present.
CONCLUSION: In the present study, we visualized the distribution of cancer-derived exosomes for the first time at the cellular level, in a pancreatic-cancer metastatic model.
MATERIALS AND METHODS: Mia-PaCa-2 human pancreatic cancer cells expressing red fluorescent protein (RFP) were transduced by exosome-specific pCT-CD63-green fluorescent protein (GFP) and injected in the spleen of nude mice.
RESULTS: Four weeks after injection of these cells into the spleen, liver metastases developed and tumor-derived exosomes were observed within the metastatic cancer cells and in Kupffer cells. Furthermore, tumor-derived exosomes diffused to bone marrow and lung cells, especially macrophages, without any metastases present.
CONCLUSION: In the present study, we visualized the distribution of cancer-derived exosomes for the first time at the cellular level, in a pancreatic-cancer metastatic model.
Related: Cancer of the Pancreas Pancreatic Cancer
Cancer of the Pancreas Pancreatic Cancer
Shanafelt TD, Wang XV, Kay NE, et al.
Ibrutinib-Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia.
N Engl J Med. 2019; 381(5):432-443 [PubMed] Related Publications
Ibrutinib-Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia.
N Engl J Med. 2019; 381(5):432-443 [PubMed] Related Publications
BACKGROUND: Data regarding the efficacy of treatment with ibrutinib-rituximab, as compared with standard chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab, in patients with previously untreated chronic lymphocytic leukemia (CLL) have been limited.
METHODS: In a phase 3 trial, we randomly assigned (in a 2:1 ratio) patients 70 years of age or younger with previously untreated CLL to receive either ibrutinib and rituximab for six cycles (after a single cycle of ibrutinib alone), followed by ibrutinib until disease progression, or six cycles of chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab. The primary end point was progression-free survival, and overall survival was a secondary end point. We report the results of a planned interim analysis.
RESULTS: A total of 529 patients underwent randomization (354 patients to the ibrutinib-rituximab group, and 175 to the chemoimmunotherapy group). At a median follow-up of 33.6 months, the results of the analysis of progression-free survival favored ibrutinib-rituximab over chemoimmunotherapy (89.4% vs. 72.9% at 3 years; hazard ratio for progression or death, 0.35; 95% confidence interval [CI], 0.22 to 0.56; P<0.001), and the results met the protocol-defined efficacy threshold for the interim analysis. The results of the analysis of overall survival also favored ibrutinib-rituximab over chemoimmunotherapy (98.8% vs. 91.5% at 3 years; hazard ratio for death, 0.17; 95% CI, 0.05 to 0.54; P<0.001). In a subgroup analysis involving patients without immunoglobulin heavy-chain variable region (
CONCLUSIONS: The ibrutinib-rituximab regimen resulted in progression-free survival and overall survival that were superior to those with a standard chemoimmunotherapy regimen among patients 70 years of age or younger with previously untreated CLL. (Funded by the National Cancer Institute and Pharmacyclics; E1912 ClinicalTrials.gov number, NCT02048813.).
METHODS: In a phase 3 trial, we randomly assigned (in a 2:1 ratio) patients 70 years of age or younger with previously untreated CLL to receive either ibrutinib and rituximab for six cycles (after a single cycle of ibrutinib alone), followed by ibrutinib until disease progression, or six cycles of chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab. The primary end point was progression-free survival, and overall survival was a secondary end point. We report the results of a planned interim analysis.
RESULTS: A total of 529 patients underwent randomization (354 patients to the ibrutinib-rituximab group, and 175 to the chemoimmunotherapy group). At a median follow-up of 33.6 months, the results of the analysis of progression-free survival favored ibrutinib-rituximab over chemoimmunotherapy (89.4% vs. 72.9% at 3 years; hazard ratio for progression or death, 0.35; 95% confidence interval [CI], 0.22 to 0.56; P<0.001), and the results met the protocol-defined efficacy threshold for the interim analysis. The results of the analysis of overall survival also favored ibrutinib-rituximab over chemoimmunotherapy (98.8% vs. 91.5% at 3 years; hazard ratio for death, 0.17; 95% CI, 0.05 to 0.54; P<0.001). In a subgroup analysis involving patients without immunoglobulin heavy-chain variable region (
CONCLUSIONS: The ibrutinib-rituximab regimen resulted in progression-free survival and overall survival that were superior to those with a standard chemoimmunotherapy regimen among patients 70 years of age or younger with previously untreated CLL. (Funded by the National Cancer Institute and Pharmacyclics; E1912 ClinicalTrials.gov number, NCT02048813.).
Cheng D, Zhang F, Hu K
An unusual case report of multiple pulmonary leiomyomatous hamartoma.
Medicine (Baltimore). 2019; 98(30):e16496 [PubMed] Related Publications
An unusual case report of multiple pulmonary leiomyomatous hamartoma.
Medicine (Baltimore). 2019; 98(30):e16496 [PubMed] Related Publications
RATIONALE: Multiple pulmonary leiomyomatous hamartoma (MPLH) is an extremely rare benign disease that mostly occurs in women of reproductive age.
PATIENT CONCERNS: A 32-year-old female patient recently diagnosed with multiple bilateral pulmonary nodules. She has the symptoms of dry cough, chest tightness, dyspnea on exertion. Chest X-ray identified multiple bilateral pulmonary nodules in the lung, and the diameter of the largest nodule was about 3.1 cm.
DIAGNOSES: Pathology confirmed the diagnosis of MPLH based on morphology and immunohistochemical staining.
INTERVENTIONS: The patient presented with multiple well-defined nodular shadows in chest computed tomography (CT), atypical image and symptoms were detected. Positron emission tomography/CT scan showed mild fluorine-18 fluorodeoxyglucose uptake in the lesions and no abnormal foci in any other parts of her body. She subsequently underwent a video-assisted thoracoscopic surgery with wedge resection of the biggest one of the nodules. Then the patient given symptomatic treatment, without hormone, no further treatment was prescribed.
OUTCOMES: The patient is in the good general condition and without obvious pulmonary symptoms after the follow-up of 1 year, chest CT scan showed no significant changes in the sizes and locations of her bilateral pulmonary nodules.
LESSONS: Due to its rare presentation, the primary MPLH may be undiagnosed. Awareness of main morphologic and immunohistochemical features of MPLH is critical for the recognition of this uncommon disease.
PATIENT CONCERNS: A 32-year-old female patient recently diagnosed with multiple bilateral pulmonary nodules. She has the symptoms of dry cough, chest tightness, dyspnea on exertion. Chest X-ray identified multiple bilateral pulmonary nodules in the lung, and the diameter of the largest nodule was about 3.1 cm.
DIAGNOSES: Pathology confirmed the diagnosis of MPLH based on morphology and immunohistochemical staining.
INTERVENTIONS: The patient presented with multiple well-defined nodular shadows in chest computed tomography (CT), atypical image and symptoms were detected. Positron emission tomography/CT scan showed mild fluorine-18 fluorodeoxyglucose uptake in the lesions and no abnormal foci in any other parts of her body. She subsequently underwent a video-assisted thoracoscopic surgery with wedge resection of the biggest one of the nodules. Then the patient given symptomatic treatment, without hormone, no further treatment was prescribed.
OUTCOMES: The patient is in the good general condition and without obvious pulmonary symptoms after the follow-up of 1 year, chest CT scan showed no significant changes in the sizes and locations of her bilateral pulmonary nodules.
LESSONS: Due to its rare presentation, the primary MPLH may be undiagnosed. Awareness of main morphologic and immunohistochemical features of MPLH is critical for the recognition of this uncommon disease.
Zhang C, Ma YY, Liu J, et al.
Preventive infusion of donor-derived CAR-T cells after haploidentical transplantation: Two cases report.
Medicine (Baltimore). 2019; 98(29):e16498 [PubMed] Related Publications
Preventive infusion of donor-derived CAR-T cells after haploidentical transplantation: Two cases report.
Medicine (Baltimore). 2019; 98(29):e16498 [PubMed] Related Publications
RATIONALE: Relapse is the main cause of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Unfortunately, there are no efficient methods to prevent relapse after allo-HSCT. Chimeric antigen receptor T (CAR-T) cells have achieved favorable outcomes in the treatment of refractory/relapsed acute lymphoblastic leukemia (ALL) because of their strong anti-leukemia activity. However, it is unclear whether the CAR-T cells constructed using viral systems can be used as preventive infusions to prevent relapse after haploidentical HSCT.
PATIENT CONCERNS: Two patients with ALL with high risk received haploidentical HSCT.
DIAGNOSES: Two patients were diagnosed with ALL with high risk.
INTERVENTIONS: Patients received preventive infusion of donor-derived CAR-T cells constructed using viral systems on day 60 after haploidentical HSCT.
OUTCOMES: The CAR-T cells were continually detected, and no graft versus host disease developed. The two patients survived with disease-free for 1 year and 6 months, respectively.
LESSONS: Preventive infusion of donor-derived CAR-T cells after haploidentical HSCT may be safe and that immunosuppressors may not affect the proliferation of CAR-T cells.
PATIENT CONCERNS: Two patients with ALL with high risk received haploidentical HSCT.
DIAGNOSES: Two patients were diagnosed with ALL with high risk.
INTERVENTIONS: Patients received preventive infusion of donor-derived CAR-T cells constructed using viral systems on day 60 after haploidentical HSCT.
OUTCOMES: The CAR-T cells were continually detected, and no graft versus host disease developed. The two patients survived with disease-free for 1 year and 6 months, respectively.
LESSONS: Preventive infusion of donor-derived CAR-T cells after haploidentical HSCT may be safe and that immunosuppressors may not affect the proliferation of CAR-T cells.
Related: Acute Lymphocytic Leukemia (ALL)
Acute Lymphocytic Leukemia (ALL)
Ghoreifi A, Djaladat H
Management of Primary Testicular Tumor.
Urol Clin North Am. 2019; 46(3):333-339 [PubMed] Related Publications
Management of Primary Testicular Tumor.
Urol Clin North Am. 2019; 46(3):333-339 [PubMed] Related Publications
In any man with a solid testicular mass, cancer should be considered until proven otherwise. Radical inguinal orchiectomy is the treatment of choice in patients with testis mass. Placement of a testicular prosthesis is safe with a very low complication rate and should be offered to all patients undergoing radical orchiectomy. In patients with widespread or life-threatening advanced disease, delayed orchiectomy following chemotherapy is recommended. Testis-sparing surgery can be performed in highly selected patients with solitary testicle mass, bilateral testicular tumors, or strong suspicion of a benign lesion.
Related: Testicular Cancer
Testicular Cancer
Mandel-Brehm C, Dubey D, Kryzer TJ, et al.
Kelch-like Protein 11 Antibodies in Seminoma-Associated Paraneoplastic Encephalitis.
N Engl J Med. 2019; 381(1):47-54 [PubMed] Related Publications
Kelch-like Protein 11 Antibodies in Seminoma-Associated Paraneoplastic Encephalitis.
N Engl J Med. 2019; 381(1):47-54 [PubMed] Related Publications
A 37-year-old man with a history of seminoma presented with vertigo, ataxia, and diplopia. An autoantibody specific for kelch-like protein 11 (KLHL11) was identified with the use of programmable phage display. Immunoassays were used to identify KLHL11 IgG in 12 other men with similar neurologic features and testicular disease. Immunostaining of the patient's IgG on mouse brain tissue showed sparse but distinctive points of staining in multiple brain regions, with enrichment in perivascular and perimeningeal tissues. The onset of the neurologic syndrome preceded the diagnosis of seminoma in 9 of the 13 patients. An age-adjusted estimate of the prevalence of autoimmune KLHL11 encephalitis in Olmsted County, Minnesota, was 2.79 cases per 100,000 men. (Funded by the Rochester Epidemiology Project and others.).
Related: Testicular Cancer
Testicular Cancer
Park JH, Zhao M, Oshiro H, et al.
Peritoneal Metastases in a Patient-derived Orthotopic Xenograft (PDOX) Model of Colon Cancer Imaged Non-invasively
Anticancer Res. 2019; 39(7):3463-3467 [PubMed] Related Publications
Peritoneal Metastases in a Patient-derived Orthotopic Xenograft (PDOX) Model of Colon Cancer Imaged Non-invasively
Anticancer Res. 2019; 39(7):3463-3467 [PubMed] Related Publications
BACKGROUND/AIM: Patient-derived orthotopic xenograft (PDOX) models have patient-like clinical features and may be imaged, in case of some cancers, by passaging of the tumors through transgenic nude mice expressing red-fluorescent protein (RFP) where they stably acquire RFP expressing stroma. The aim of the present study was to quantify red fluorescent area and intensity in colon-cancer peritoneal metastases in PDOX models in non-transgenic nude mice after passage in RFP transgenic nude mice by non-invasive external fluorescence imaging.
MATERIALS AND METHODS: Tumor fragments originating from a colon cancer patient with peritoneal metastases were implanted in transgenic RFP nude mice. Resultant tumors were harvested, and fragments were implanted in the same strain a second time. Passaged tumors stably acquired RFP-expressing stroma from their transgenic hosts. The tumor with RFP-expressing stromal cells were harvested and implanted orthotopically in non-transgenic nude mice. At eight weeks post-implantation, non-invasive external RFP images were obtained. RFP area and intensity were measured and correlated with tumor weight and volume.
RESULTS: Metastatic patient colon cancer can be stably and brightly labeled by passage in transgenic RFP-expressing nude mice such that tumor growth could be non-invasively imaged. Tumor growing could be non-invasively imaged when passaged to non-transgenic nude mice. A strong correlation between fluorescence intensity and area values with tumor weight and volume were established by external fluorescence imaging.
CONCLUSION: This new tumor model of metastatic colon cancer can be used to evaluate novel therapeutics in real time for this recalcitrant disease.
MATERIALS AND METHODS: Tumor fragments originating from a colon cancer patient with peritoneal metastases were implanted in transgenic RFP nude mice. Resultant tumors were harvested, and fragments were implanted in the same strain a second time. Passaged tumors stably acquired RFP-expressing stroma from their transgenic hosts. The tumor with RFP-expressing stromal cells were harvested and implanted orthotopically in non-transgenic nude mice. At eight weeks post-implantation, non-invasive external RFP images were obtained. RFP area and intensity were measured and correlated with tumor weight and volume.
RESULTS: Metastatic patient colon cancer can be stably and brightly labeled by passage in transgenic RFP-expressing nude mice such that tumor growth could be non-invasively imaged. Tumor growing could be non-invasively imaged when passaged to non-transgenic nude mice. A strong correlation between fluorescence intensity and area values with tumor weight and volume were established by external fluorescence imaging.
CONCLUSION: This new tumor model of metastatic colon cancer can be used to evaluate novel therapeutics in real time for this recalcitrant disease.
Detweiler K, Elfenbein DM, Mayers D
Evaluation of Thyroid Nodules.
Surg Clin North Am. 2019; 99(4):571-586 [PubMed] Related Publications
Evaluation of Thyroid Nodules.
Surg Clin North Am. 2019; 99(4):571-586 [PubMed] Related Publications
This is a brief overview of the initial workup of patients with thyroid nodules. Most nodules are incidentally discovered, benign, and do not require surgery, but the clinician's job is to determine which nodules are concerning and what the appropriate workup should be. Ultrasound examination is the best imaging modality to evaluation thyroid nodules and, when biopsy is indicated, fine needle aspiration is the proper technique to sample thyroid nodules.
Related: Thyroid Cancer
Thyroid Cancer
Oronsky B, Scribner C, Aggarwal R, Cabrales P
RRx-001 protects normal tissues but not tumors via Nrf2 induction and Bcl-2 inhibition.
J Cancer Res Clin Oncol. 2019; 145(8):2045-2050 [PubMed] Related Publications
RRx-001 protects normal tissues but not tumors via Nrf2 induction and Bcl-2 inhibition.
J Cancer Res Clin Oncol. 2019; 145(8):2045-2050 [PubMed] Related Publications
BACKGROUND: RRx-001, a minimally toxic next-generation checkpoint inhibitor that targets myeloid suppressor cells in the tumor microenvironment, has also been shown to protect normal tissues from the cytotoxic effects of chemotherapy and radiation. The following experiments were carried out to determine whether the cytoprotective functions of RRx-001 in normal cells were operative in tumor cells.
DESIGN: The effects of RRx-001 on normal cells, and ovarian cancer A2780 and UWB1 cells were evaluated with a colony-forming assay. Western blot densitometry was used to measure Nrf2 nuclear translocation in Caco2 cells after exposure to RRx-001. Following incubation with RRx-001, levels of the antioxidant, NQO1, were determined in Caco2 cells by measuring absorbance over 300 min at 440 nm. RRx-001-mediated cytotoxicity in HCT-116 colorectal cancer cells was evaluated with an MTT assay. In addition, the effect of RRx-001 incubation on the protein expression of Nrf2, PARP, cleaved PARP, procaspases 3, 8, and 9, Bcl-2, and Bax in HCT-116 colorectal cells was determined by western blot analysis.
RESULTS: RRx-001 is demonstrated to induce Nrf2 in normal tissues, mediating protection, and to downregulate the Nrf2-controlled antiapoptotic target gene, B-cell lymphoma 2 (Bcl-2) in tumors, mediating cytotoxicity.
CONCLUSION: Through Nrf2 induction in normal cells and inhibition of Bcl-2 in tumor cells, RRx-001 selectively protects normal cells against lethality in normal cells, but induces apoptosis in tumor cells.
DESIGN: The effects of RRx-001 on normal cells, and ovarian cancer A2780 and UWB1 cells were evaluated with a colony-forming assay. Western blot densitometry was used to measure Nrf2 nuclear translocation in Caco2 cells after exposure to RRx-001. Following incubation with RRx-001, levels of the antioxidant, NQO1, were determined in Caco2 cells by measuring absorbance over 300 min at 440 nm. RRx-001-mediated cytotoxicity in HCT-116 colorectal cancer cells was evaluated with an MTT assay. In addition, the effect of RRx-001 incubation on the protein expression of Nrf2, PARP, cleaved PARP, procaspases 3, 8, and 9, Bcl-2, and Bax in HCT-116 colorectal cells was determined by western blot analysis.
RESULTS: RRx-001 is demonstrated to induce Nrf2 in normal tissues, mediating protection, and to downregulate the Nrf2-controlled antiapoptotic target gene, B-cell lymphoma 2 (Bcl-2) in tumors, mediating cytotoxicity.
CONCLUSION: Through Nrf2 induction in normal cells and inhibition of Bcl-2 in tumor cells, RRx-001 selectively protects normal cells against lethality in normal cells, but induces apoptosis in tumor cells.
Chouliaras K, Senehi R, Ethun CG, et al.
Recurrence patterns after resection of retroperitoneal sarcomas: An eight-institution study from the US Sarcoma Collaborative.
J Surg Oncol. 2019; 120(3):340-347 [PubMed] Related Publications
Recurrence patterns after resection of retroperitoneal sarcomas: An eight-institution study from the US Sarcoma Collaborative.
J Surg Oncol. 2019; 120(3):340-347 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: Resection of primary retroperitoneal sarcomas (RPS) has a high incidence of recurrence. This study aims to identify patterns of recurrence and its impact on overall survival.
METHODS: Adult patients with primary retroperitoneal soft tissue sarcomas who underwent resection in 2000-2016 at eight institutions of the US Sarcoma Collaborative were evaluated.
RESULTS: Four hundred and ninety-eight patients were analyzed, with 56.2% (280 of 498) having recurrences. There were 433 recurrences (1-8) in 280 patients with 126 (25.3%) being locoregional, 82 (16.5%) distant, and 72 (14.5%) both locoregional and distant. Multivariate analyses revealed the following: Patient age P = .0002), tumor grade (P = .02), local recurrence (P = .0003) and distant recurrence (P < .0001) were predictors of disease-specific survival. The 1-, 3-, and 5-year survival rate for patients who recurred vs not was 89.6% (standard error [SE] 1.9) vs 93.5% (1.8), 66.0% (3.2) vs 88.4% (2.6), and 51.8% (3.6) vs 83.9% (3.3), respectively, P < .0001. Median survival was 5.3 years for the recurrence vs 11.3+ years for the no recurrence group (P < .0001). Median survival from the time of recurrence was 2.5 years.
CONCLUSIONS: Recurrence after resection of RPS occurs in more than half of patients independently of resection status or perioperative chemotherapy and is equally distributed between locoregional and distant sites. Recurrence is primarily related to tumor biology and is associated with a significant decrease in overall survival.
METHODS: Adult patients with primary retroperitoneal soft tissue sarcomas who underwent resection in 2000-2016 at eight institutions of the US Sarcoma Collaborative were evaluated.
RESULTS: Four hundred and ninety-eight patients were analyzed, with 56.2% (280 of 498) having recurrences. There were 433 recurrences (1-8) in 280 patients with 126 (25.3%) being locoregional, 82 (16.5%) distant, and 72 (14.5%) both locoregional and distant. Multivariate analyses revealed the following: Patient age P = .0002), tumor grade (P = .02), local recurrence (P = .0003) and distant recurrence (P < .0001) were predictors of disease-specific survival. The 1-, 3-, and 5-year survival rate for patients who recurred vs not was 89.6% (standard error [SE] 1.9) vs 93.5% (1.8), 66.0% (3.2) vs 88.4% (2.6), and 51.8% (3.6) vs 83.9% (3.3), respectively, P < .0001. Median survival was 5.3 years for the recurrence vs 11.3+ years for the no recurrence group (P < .0001). Median survival from the time of recurrence was 2.5 years.
CONCLUSIONS: Recurrence after resection of RPS occurs in more than half of patients independently of resection status or perioperative chemotherapy and is equally distributed between locoregional and distant sites. Recurrence is primarily related to tumor biology and is associated with a significant decrease in overall survival.
Related: Soft Tissue Sarcomas USA
Soft Tissue Sarcomas USA
Hong D, Rasco D, Veeder M, et al.
A Phase 1b/2 Study of the Bruton Tyrosine Kinase Inhibitor Ibrutinib and the PD-L1 Inhibitor Durvalumab in Patients with Pretreated Solid Tumors.
Oncology. 2019; 97(2):102-111 [PubMed] Related Publications
A Phase 1b/2 Study of the Bruton Tyrosine Kinase Inhibitor Ibrutinib and the PD-L1 Inhibitor Durvalumab in Patients with Pretreated Solid Tumors.
Oncology. 2019; 97(2):102-111 [PubMed] Related Publications
BACKGROUND: Ibrutinib, a first-in-class, once-daily inhibitor of Bruton's tyrosine kinase, is approved in the United States for the treatment of various B-cell malignancies. Preclinical data suggest synergistic antitumor activity of ibrutinib with programmed death-ligand 1 (PD-L1) inhibitors in solid tumors. This study evaluated ibrutinib plus durvalumab, a PD-L1-targeting antibody, in patients with relapsed/refractory solid tumors.
METHODS: This open-label, multicenter, phase 1b/2 study enrolled previously treated patients with stage III/IV pancreatic adenocarcinoma, breast cancer, or non-small cell lung cancer (NSCLC). Phase 1b determined the recommended phase 2 dose (RP2D). In phase 2, patients were treated at the RP2D to evaluate the safety and antitumor activity of ibrutinib plus durvalumab.
RESULTS: The RP2D was identified as ibrutinib 560 mg p.o. daily and durvalumab 10 mg/kg i.v. every 2 weeks, with 122 patients treated at the RP2D. Median age was 61 years, and the majority of patients (94%) had stage IV disease. Overall response rates (complete or partial responses) were 2% for pancreatic cancer, 3% for breast cancer, and 0% for NSCLC. Median progression-free survival was 1.7, 1.7, and 2.0 months in the pancreatic cancer, breast cancer, and NSCLC cohorts, respectively. Median overall survival was 4.2, 4.2, and 7.9 months in the pancreatic cancer, breast cancer, and NSCLC cohorts, respectively. The safety profiles observed across tumor types were consistent with the known safety profiles for ibrutinib and durvalumab. Grade ≥3 adverse events in ≥5% of all patients were hyponatremia (10%), dyspnea (7%), maculopapular rash (7%), pneumonia (7%), anemia (6%), and diarrhea (6%).
CONCLUSIONS: The combination of ibrutinib 560 mg daily and durvalumab 10 mg/kg every 2 weeks had an acceptable safety profile. The antitumor activity of the ibrutinib-durvalumab combination was limited in our study population.
METHODS: This open-label, multicenter, phase 1b/2 study enrolled previously treated patients with stage III/IV pancreatic adenocarcinoma, breast cancer, or non-small cell lung cancer (NSCLC). Phase 1b determined the recommended phase 2 dose (RP2D). In phase 2, patients were treated at the RP2D to evaluate the safety and antitumor activity of ibrutinib plus durvalumab.
RESULTS: The RP2D was identified as ibrutinib 560 mg p.o. daily and durvalumab 10 mg/kg i.v. every 2 weeks, with 122 patients treated at the RP2D. Median age was 61 years, and the majority of patients (94%) had stage IV disease. Overall response rates (complete or partial responses) were 2% for pancreatic cancer, 3% for breast cancer, and 0% for NSCLC. Median progression-free survival was 1.7, 1.7, and 2.0 months in the pancreatic cancer, breast cancer, and NSCLC cohorts, respectively. Median overall survival was 4.2, 4.2, and 7.9 months in the pancreatic cancer, breast cancer, and NSCLC cohorts, respectively. The safety profiles observed across tumor types were consistent with the known safety profiles for ibrutinib and durvalumab. Grade ≥3 adverse events in ≥5% of all patients were hyponatremia (10%), dyspnea (7%), maculopapular rash (7%), pneumonia (7%), anemia (6%), and diarrhea (6%).
CONCLUSIONS: The combination of ibrutinib 560 mg daily and durvalumab 10 mg/kg every 2 weeks had an acceptable safety profile. The antitumor activity of the ibrutinib-durvalumab combination was limited in our study population.
Spradlin JN, Hu X, Ward CC, et al.
Harnessing the anti-cancer natural product nimbolide for targeted protein degradation.
Nat Chem Biol. 2019; 15(7):747-755 [PubMed] Article available free on PMC after 17/12/2019 Related Publications
Harnessing the anti-cancer natural product nimbolide for targeted protein degradation.
Nat Chem Biol. 2019; 15(7):747-755 [PubMed] Article available free on PMC after 17/12/2019 Related Publications
Nimbolide, a terpenoid natural product derived from the Neem tree, impairs cancer pathogenicity; however, the direct targets and mechanisms by which nimbolide exerts its effects are poorly understood. Here, we used activity-based protein profiling (ABPP) chemoproteomic platforms to discover that nimbolide reacts with a novel functional cysteine crucial for substrate recognition in the E3 ubiquitin ligase RNF114. Nimbolide impairs breast cancer cell proliferation in-part by disrupting RNF114-substrate recognition, leading to inhibition of ubiquitination and degradation of tumor suppressors such as p21, resulting in their rapid stabilization. We further demonstrate that nimbolide can be harnessed to recruit RNF114 as an E3 ligase in targeted protein degradation applications and show that synthetically simpler scaffolds are also capable of accessing this unique reactive site. Our study highlights the use of ABPP platforms in uncovering unique druggable modalities accessed by natural products for cancer therapy and targeted protein degradation applications.
Related: Breast Cancer
Breast Cancer
Matei D, Filiaci V, Randall ME, et al.
Adjuvant Chemotherapy plus Radiation for Locally Advanced Endometrial Cancer.
N Engl J Med. 2019; 380(24):2317-2326 [PubMed] Related Publications
Adjuvant Chemotherapy plus Radiation for Locally Advanced Endometrial Cancer.
N Engl J Med. 2019; 380(24):2317-2326 [PubMed] Related Publications
BACKGROUND: Stage III or IVA endometrial cancer carries a significant risk of systemic and locoregional recurrence.
METHODS: In this randomized phase 3 trial, we tested whether 6 months of platinum-based chemotherapy plus radiation therapy (chemoradiotherapy) is associated with longer relapse-free survival (primary end point) than six cycles of combination chemotherapy alone in patients with stage III or IVA endometrial carcinoma. Secondary end points included overall survival, acute and chronic toxic effects, and quality of life.
RESULTS: Of the 813 patients enrolled, 736 were eligible and were included in the analysis of relapse-free survival; of those patients, 707 received the randomly assigned intervention (346 received chemoradiotherapy and 361 received chemotherapy only). The median follow-up period was 47 months. At 60 months, the Kaplan-Meier estimate of the percentage of patients alive and relapse-free was 59% (95% confidence interval [CI], 53 to 65) in the chemoradiotherapy group and 58% (95% CI, 53 to 64) in the chemotherapy-only group (hazard ratio, 0.90; 90% CI, 0.74 to 1.10). Chemoradiotherapy was associated with a lower 5-year incidence of vaginal recurrence (2% vs. 7%; hazard ratio, 0.36; 95% CI, 0.16 to 0.82) and pelvic and paraaortic lymph-node recurrence (11% vs. 20%; hazard ratio, 0.43; 95% CI, 0.28 to 0.66) than chemotherapy alone, but distant recurrence was more common in association with chemoradiotherapy (27% vs. 21%; hazard ratio, 1.36; 95% CI, 1.00 to 1.86). Grade 3, 4, or 5 adverse events were reported in 202 patients (58%) in the chemoradiotherapy group and 227 patients (63%) in the chemotherapy-only group.
CONCLUSIONS: Chemotherapy plus radiation was not associated with longer relapse-free survival than chemotherapy alone in patients with stage III or IVA endometrial carcinoma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00942357.).
METHODS: In this randomized phase 3 trial, we tested whether 6 months of platinum-based chemotherapy plus radiation therapy (chemoradiotherapy) is associated with longer relapse-free survival (primary end point) than six cycles of combination chemotherapy alone in patients with stage III or IVA endometrial carcinoma. Secondary end points included overall survival, acute and chronic toxic effects, and quality of life.
RESULTS: Of the 813 patients enrolled, 736 were eligible and were included in the analysis of relapse-free survival; of those patients, 707 received the randomly assigned intervention (346 received chemoradiotherapy and 361 received chemotherapy only). The median follow-up period was 47 months. At 60 months, the Kaplan-Meier estimate of the percentage of patients alive and relapse-free was 59% (95% confidence interval [CI], 53 to 65) in the chemoradiotherapy group and 58% (95% CI, 53 to 64) in the chemotherapy-only group (hazard ratio, 0.90; 90% CI, 0.74 to 1.10). Chemoradiotherapy was associated with a lower 5-year incidence of vaginal recurrence (2% vs. 7%; hazard ratio, 0.36; 95% CI, 0.16 to 0.82) and pelvic and paraaortic lymph-node recurrence (11% vs. 20%; hazard ratio, 0.43; 95% CI, 0.28 to 0.66) than chemotherapy alone, but distant recurrence was more common in association with chemoradiotherapy (27% vs. 21%; hazard ratio, 1.36; 95% CI, 1.00 to 1.86). Grade 3, 4, or 5 adverse events were reported in 202 patients (58%) in the chemoradiotherapy group and 227 patients (63%) in the chemotherapy-only group.
CONCLUSIONS: Chemotherapy plus radiation was not associated with longer relapse-free survival than chemotherapy alone in patients with stage III or IVA endometrial carcinoma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00942357.).
Zang W, Bian H, Huang X, et al.
Traditional Chinese Medicine (TCM)
Anticancer Res. 2019; 39(6):2739-2747 [PubMed] Related Publications
Traditional Chinese Medicine (TCM)
Anticancer Res. 2019; 39(6):2739-2747 [PubMed] Related Publications
BACKGROUND/AIM: The aim of the present study was to investigate the vascular normalization effect of traditional Chinese medicine Astragalus membranaceus (AM) and Curcuma wenyujin (CW) on tumor-derived endothelial cells (TECs).
MATERIALS AND METHODS: TECs were isolated from the xenografted HCC cell line HepG2 expressing red fluorescent protein (RFP). The effect of AM and CW on TECs proliferation was measured using the CCK8 assay. The vascular normalization potential of AM and CW was assessed using a tube formation assay. Immunocytochemistry was performed to assess the effect of AM and CW on the expression of angiogenic maker CD34 and hypoxia-inducible factor HIF1a.
RESULTS: The isolated TECs and endothelioma (EOMA) cells did not differ with regard to the expression levels of endothelial markers CD34, VEGFR-1, VEGFR-2, PDGFR-α and PDGFR-β. All AM, CW, AM+CW and Nintedanib (Nin) showed a dose-dependent increasing inhibition effect on either TECs or EOMA cells. AM, CW and AM+CW significantly reduced HIF1a expression, increased CD34 expression and enhanced endothelial network formation in TECs or EOMA cells compared to the control.
CONCLUSION: AM and CW promoted vascular normalization in tumor-derived endothelial cells of HCC, through increased expression of CD34 and reduced expression of HIF1a.
MATERIALS AND METHODS: TECs were isolated from the xenografted HCC cell line HepG2 expressing red fluorescent protein (RFP). The effect of AM and CW on TECs proliferation was measured using the CCK8 assay. The vascular normalization potential of AM and CW was assessed using a tube formation assay. Immunocytochemistry was performed to assess the effect of AM and CW on the expression of angiogenic maker CD34 and hypoxia-inducible factor HIF1a.
RESULTS: The isolated TECs and endothelioma (EOMA) cells did not differ with regard to the expression levels of endothelial markers CD34, VEGFR-1, VEGFR-2, PDGFR-α and PDGFR-β. All AM, CW, AM+CW and Nintedanib (Nin) showed a dose-dependent increasing inhibition effect on either TECs or EOMA cells. AM, CW and AM+CW significantly reduced HIF1a expression, increased CD34 expression and enhanced endothelial network formation in TECs or EOMA cells compared to the control.
CONCLUSION: AM and CW promoted vascular normalization in tumor-derived endothelial cells of HCC, through increased expression of CD34 and reduced expression of HIF1a.
Zaidi MY, Ethun CG, Liu Y, et al.
The impact of unplanned excisions of truncal/extremity soft tissue sarcomas: A multi-institutional propensity score analysis from the US Sarcoma Collaborative.
J Surg Oncol. 2019; 120(3):332-339 [PubMed] Related Publications
The impact of unplanned excisions of truncal/extremity soft tissue sarcomas: A multi-institutional propensity score analysis from the US Sarcoma Collaborative.
J Surg Oncol. 2019; 120(3):332-339 [PubMed] Related Publications
OBJECTIVE: Our aim was to compare outcomes in patients who underwent unplanned excisions (UE) of soft-tissue sarcomas (STS) against patients with planned excisions (PE).
METHODS: The retrospective 7-institution US Sarcoma Collaborative database was used. Patients with curative-intent resection of truncal/extremity STS between 2000 and 2016 were included. Propensity score weighting analysis (PSWA) was performed. Endpoints were locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-specific survival (DSS).
RESULTS: One thousand five hundred and ninety-six patients were included. Eighty-two percent (n = 1315) underwent PE and 18% (n = 281) underwent UE. Compared with PE, patients with UE were younger with smaller tumors with similar tumor grade. Unmatched analysis revealed PE was associated with worse DMFS (hazard ratio [HR] 1.95, P = .009) and DSS (HR 1.78, P = .039), but not LRFS compared with UE. On PSWA, UE had earlier LRFS (3-year LRFS: 80.5% vs 89.8%, P = .039), but not DMFS or DSS. By grade, patients with high-grade tumors and UE had worse LRFS (1-year LRFS: 90% vs 94%, P = .015), but similar DMFS and DSS compared with PE. In low-grade patients, UE and PE had similar LRFS, DMFS, or DSS.
CONCLUSIONS: UE of STS is not associated with worse prognosis compared to PE, though UE is associated with earlier locoregional recurrence in patients with high-grade tumors. Multimodality therapy is needed to achieve improved outcomes in these patients.
METHODS: The retrospective 7-institution US Sarcoma Collaborative database was used. Patients with curative-intent resection of truncal/extremity STS between 2000 and 2016 were included. Propensity score weighting analysis (PSWA) was performed. Endpoints were locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-specific survival (DSS).
RESULTS: One thousand five hundred and ninety-six patients were included. Eighty-two percent (n = 1315) underwent PE and 18% (n = 281) underwent UE. Compared with PE, patients with UE were younger with smaller tumors with similar tumor grade. Unmatched analysis revealed PE was associated with worse DMFS (hazard ratio [HR] 1.95, P = .009) and DSS (HR 1.78, P = .039), but not LRFS compared with UE. On PSWA, UE had earlier LRFS (3-year LRFS: 80.5% vs 89.8%, P = .039), but not DMFS or DSS. By grade, patients with high-grade tumors and UE had worse LRFS (1-year LRFS: 90% vs 94%, P = .015), but similar DMFS and DSS compared with PE. In low-grade patients, UE and PE had similar LRFS, DMFS, or DSS.
CONCLUSIONS: UE of STS is not associated with worse prognosis compared to PE, though UE is associated with earlier locoregional recurrence in patients with high-grade tumors. Multimodality therapy is needed to achieve improved outcomes in these patients.
Related: Soft Tissue Sarcomas
Soft Tissue Sarcomas
Zhao B, Tsai C, Hunt KK, Blair SL
Adherence to surgical and oncologic standards improves survival in breast cancer patients.
J Surg Oncol. 2019; 120(2):148-159 [PubMed] Related Publications
Adherence to surgical and oncologic standards improves survival in breast cancer patients.
J Surg Oncol. 2019; 120(2):148-159 [PubMed] Related Publications
BACKGROUND: Adherence to evidence-based standards can lead to improved outcomes for patients with breast cancer. However, adherence rates to standards and their effects on patient outcomes are unknown.
OBJECTIVES: To examine adherence rates to standards compiled by the American College of Surgeons Clinical Research Program and its effects on patient outcomes.
METHODS: Using the National Cancer Database (2004-2015), we identified cohorts of breast cancer patients: clinical T1N0M0 under age of 70 (cT1), clinical T2N0M0 or T3N0M0 (cT2/3), and clinical M0 and pathologic N2 or N3 (pN2/3). Standards included negative margins, any adjuvant therapy, and two or more lymph nodes (LNs) examined (for cT1 or cT2/3 patients) or more than 10 LNs examined (for pN2/3 patients). We performed Kaplan-Meier and Cox proportional hazards analysis.
RESULTS: We identified 318 853 (65.0%) cT1, 164 593 (67.3%) cT2/3, and 77 626 (67.7%) pN2/3 patients who met the standards. More than 90% of patients had negative margins and adjuvant therapy, but less than 80% met LN standards. The median overall survival (OS) was significantly longer for patients who met the standards. Individual components of the standards were predictors of improved OS.
CONCLUSIONS: One-third of patients did not meet the evidence-based standards in their treatment for breast cancer. Efforts to improve the knowledge of and adherence to these standards should be emphasized.
OBJECTIVES: To examine adherence rates to standards compiled by the American College of Surgeons Clinical Research Program and its effects on patient outcomes.
METHODS: Using the National Cancer Database (2004-2015), we identified cohorts of breast cancer patients: clinical T1N0M0 under age of 70 (cT1), clinical T2N0M0 or T3N0M0 (cT2/3), and clinical M0 and pathologic N2 or N3 (pN2/3). Standards included negative margins, any adjuvant therapy, and two or more lymph nodes (LNs) examined (for cT1 or cT2/3 patients) or more than 10 LNs examined (for pN2/3 patients). We performed Kaplan-Meier and Cox proportional hazards analysis.
RESULTS: We identified 318 853 (65.0%) cT1, 164 593 (67.3%) cT2/3, and 77 626 (67.7%) pN2/3 patients who met the standards. More than 90% of patients had negative margins and adjuvant therapy, but less than 80% met LN standards. The median overall survival (OS) was significantly longer for patients who met the standards. Individual components of the standards were predictors of improved OS.
CONCLUSIONS: One-third of patients did not meet the evidence-based standards in their treatment for breast cancer. Efforts to improve the knowledge of and adherence to these standards should be emphasized.
Related: Breast Cancer
Breast Cancer
Gannon NP, King DM, Ethun CG, et al.
The role of radiation therapy and margin width in localized soft-tissue sarcoma: Analysis from the US Sarcoma Collaborative.
J Surg Oncol. 2019; 120(3):325-331 [PubMed] Related Publications
The role of radiation therapy and margin width in localized soft-tissue sarcoma: Analysis from the US Sarcoma Collaborative.
J Surg Oncol. 2019; 120(3):325-331 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: Soft-tissue sarcomas (STSs) are often treated with resection and radiation (RT)±chemotherapy. The role of RT in decreasing resection width to achieve local control is unclear. We evaluated RT on margin width to achieve local control and local recurrence (LR).
METHODS: From 2000 to 2016, 514 patients with localized STS were identified from the US Sarcoma Collaborative database. Patients were stratified by a margin and local control was compared amongst treatment groups.
RESULTS: LR was 9% with positive, 4.2% with ≤1 mm, and 9.3% with >1 mm margins (P = .315). In the ≤1 mm group, LR was 5.7% without RT, 0% with preoperative RT, and 0% with postoperative RT (P < .0001). In the >1 mm group, LR was 10.2%, 0%, and 3.7% in the no preoperative and postoperative RT groups, respectively (P = .005). RT did not influence LR in patients with positive margins. In stage I-III and II-III patients, local recurrence-free survival was higher following RT (P = .008 and P = .05, respectively).
CONCLUSIONS: RT may play a larger role in minimizing LR than margin status. In patients with positive margins, RT may decrease LR to similar rates as a negative margin without RT and may be considered to decrease the risk of LR with anticipated close/positive margins.
METHODS: From 2000 to 2016, 514 patients with localized STS were identified from the US Sarcoma Collaborative database. Patients were stratified by a margin and local control was compared amongst treatment groups.
RESULTS: LR was 9% with positive, 4.2% with ≤1 mm, and 9.3% with >1 mm margins (P = .315). In the ≤1 mm group, LR was 5.7% without RT, 0% with preoperative RT, and 0% with postoperative RT (P < .0001). In the >1 mm group, LR was 10.2%, 0%, and 3.7% in the no preoperative and postoperative RT groups, respectively (P = .005). RT did not influence LR in patients with positive margins. In stage I-III and II-III patients, local recurrence-free survival was higher following RT (P = .008 and P = .05, respectively).
CONCLUSIONS: RT may play a larger role in minimizing LR than margin status. In patients with positive margins, RT may decrease LR to similar rates as a negative margin without RT and may be considered to decrease the risk of LR with anticipated close/positive margins.
Related: Soft Tissue Sarcomas
Soft Tissue Sarcomas
Ribas A, Lawrence D, Atkinson V, et al.
Combined BRAF and MEK inhibition with PD-1 blockade immunotherapy in BRAF-mutant melanoma.
Nat Med. 2019; 25(6):936-940 [PubMed] Related Publications
Combined BRAF and MEK inhibition with PD-1 blockade immunotherapy in BRAF-mutant melanoma.
Nat Med. 2019; 25(6):936-940 [PubMed] Related Publications
Oncogene-targeted therapy with B-Raf proto-oncogene (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors induces a high initial response rate in patients with BRAF
Related: BRAF Skin Cancer
BRAF Skin Cancer
Ascierto PA, Ferrucci PF, Fisher R, et al.
Dabrafenib, trametinib and pembrolizumab or placebo in BRAF-mutant melanoma.
Nat Med. 2019; 25(6):941-946 [PubMed] Related Publications
Dabrafenib, trametinib and pembrolizumab or placebo in BRAF-mutant melanoma.
Nat Med. 2019; 25(6):941-946 [PubMed] Related Publications
Blocking programmed death 1 (PD-1) may enhance the durability of anti-tumor responses that are induced by the combined inhibition of BRAF and MEK
Fischer K, Al-Sawaf O, Bahlo J, et al.
Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions.
N Engl J Med. 2019; 380(23):2225-2236 [PubMed] Related Publications
Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions.
N Engl J Med. 2019; 380(23):2225-2236 [PubMed] Related Publications
BACKGROUND: The BCL2 inhibitor venetoclax has shown activity in patients with chronic lymphocytic leukemia (CLL), but its efficacy in combination with other agents in patients with CLL and coexisting conditions is not known.
METHODS: In this open-label, phase 3 trial, we investigated fixed-duration treatment with venetoclax and obinutuzumab in patients with previously untreated CLL and coexisting conditions. Patients with a score of greater than 6 on the Cumulative Illness Rating Scale (scores range from 0 to 56, with higher scores indicating more impaired function of organ systems) or a calculated creatinine clearance of less than 70 ml per minute were randomly assigned to receive venetoclax-obinutuzumab or chlorambucil-obinutuzumab. The primary end point was investigator-assessed progression-free survival. The safety of each regimen was also evaluated.
RESULTS: In total, 432 patients (median age, 72 years; median Cumulative Illness Rating Scale score, 8; median creatinine clearance, 66.4 ml per minute) underwent randomization, with 216 assigned to each group. After a median follow-up of 28.1 months, 30 primary end-point events (disease progression or death) had occurred in the venetoclax-obinutuzumab group and 77 had occurred in the chlorambucil-obinutuzumab group (hazard ratio, 0.35; 95% confidence interval [CI], 0.23 to 0.53; P<0.001). The Kaplan-Meier estimate of the percentage of patients with progression-free survival at 24 months was significantly higher in the venetoclax-obinutuzumab group than in the chlorambucil-obinutuzumab group: 88.2% (95% CI, 83.7 to 92.6) as compared with 64.1% (95% CI, 57.4 to 70.8). This benefit was also observed in patients with
CONCLUSIONS: Among patients with untreated CLL and coexisting conditions, venetoclax-obinutuzumab was associated with longer progression-free survival than chlorambucil-obinutuzumab. (Funded by F. Hoffmann-La Roche and AbbVie; ClinicalTrials.gov number, NCT02242942.).
METHODS: In this open-label, phase 3 trial, we investigated fixed-duration treatment with venetoclax and obinutuzumab in patients with previously untreated CLL and coexisting conditions. Patients with a score of greater than 6 on the Cumulative Illness Rating Scale (scores range from 0 to 56, with higher scores indicating more impaired function of organ systems) or a calculated creatinine clearance of less than 70 ml per minute were randomly assigned to receive venetoclax-obinutuzumab or chlorambucil-obinutuzumab. The primary end point was investigator-assessed progression-free survival. The safety of each regimen was also evaluated.
RESULTS: In total, 432 patients (median age, 72 years; median Cumulative Illness Rating Scale score, 8; median creatinine clearance, 66.4 ml per minute) underwent randomization, with 216 assigned to each group. After a median follow-up of 28.1 months, 30 primary end-point events (disease progression or death) had occurred in the venetoclax-obinutuzumab group and 77 had occurred in the chlorambucil-obinutuzumab group (hazard ratio, 0.35; 95% confidence interval [CI], 0.23 to 0.53; P<0.001). The Kaplan-Meier estimate of the percentage of patients with progression-free survival at 24 months was significantly higher in the venetoclax-obinutuzumab group than in the chlorambucil-obinutuzumab group: 88.2% (95% CI, 83.7 to 92.6) as compared with 64.1% (95% CI, 57.4 to 70.8). This benefit was also observed in patients with
CONCLUSIONS: Among patients with untreated CLL and coexisting conditions, venetoclax-obinutuzumab was associated with longer progression-free survival than chlorambucil-obinutuzumab. (Funded by F. Hoffmann-La Roche and AbbVie; ClinicalTrials.gov number, NCT02242942.).
Robert C, Grob JJ, Stroyakovskiy D, et al.
Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma.
N Engl J Med. 2019; 381(7):626-636 [PubMed] Related Publications
Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma.
N Engl J Med. 2019; 381(7):626-636 [PubMed] Related Publications
BACKGROUND: Patients who have unresectable or metastatic melanoma with a
METHODS: We analyzed pooled extended-survival data from two trials involving previously untreated patients who had received BRAF inhibitor dabrafenib (at a dose of 150 mg twice daily) plus MEK inhibitor trametinib (2 mg once daily) in the COMBI-d and COMBI-v trials. The median duration of follow-up was 22 months (range, 0 to 76). The primary end points in the COMBI-d and COMBI-v trials were progression-free survival and overall survival, respectively.
RESULTS: A total of 563 patients were randomly assigned to receive dabrafenib plus trametinib (211 in the COMBI-d trial and 352 in the COMBI-v trial). The progression-free survival rates were 21% (95% confidence interval [CI], 17 to 24) at 4 years and 19% (95% CI, 15 to 22) at 5 years. The overall survival rates were 37% (95% CI, 33 to 42) at 4 years and 34% (95% CI, 30 to 38) at 5 years. In multivariate analysis, several baseline factors (e.g., performance status, age, sex, number of organ sites with metastasis, and lactate dehydrogenase level) were significantly associated with both progression-free survival and overall survival. A complete response occurred in 109 patients (19%) and was associated with an improved long-term outcome, with an overall survival rate of 71% (95% CI, 62 to 79) at 5 years.
CONCLUSIONS: First-line treatment with dabrafenib plus trametinib led to long-term benefit in approximately one third of the patients who had unresectable or metastatic melanoma with a
METHODS: We analyzed pooled extended-survival data from two trials involving previously untreated patients who had received BRAF inhibitor dabrafenib (at a dose of 150 mg twice daily) plus MEK inhibitor trametinib (2 mg once daily) in the COMBI-d and COMBI-v trials. The median duration of follow-up was 22 months (range, 0 to 76). The primary end points in the COMBI-d and COMBI-v trials were progression-free survival and overall survival, respectively.
RESULTS: A total of 563 patients were randomly assigned to receive dabrafenib plus trametinib (211 in the COMBI-d trial and 352 in the COMBI-v trial). The progression-free survival rates were 21% (95% confidence interval [CI], 17 to 24) at 4 years and 19% (95% CI, 15 to 22) at 5 years. The overall survival rates were 37% (95% CI, 33 to 42) at 4 years and 34% (95% CI, 30 to 38) at 5 years. In multivariate analysis, several baseline factors (e.g., performance status, age, sex, number of organ sites with metastasis, and lactate dehydrogenase level) were significantly associated with both progression-free survival and overall survival. A complete response occurred in 109 patients (19%) and was associated with an improved long-term outcome, with an overall survival rate of 71% (95% CI, 62 to 79) at 5 years.
CONCLUSIONS: First-line treatment with dabrafenib plus trametinib led to long-term benefit in approximately one third of the patients who had unresectable or metastatic melanoma with a
Related: BRAF Skin Cancer
BRAF Skin Cancer
Coppé JP, Mori M, Pan B, et al.
Mapping phospho-catalytic dependencies of therapy-resistant tumours reveals actionable vulnerabilities.
Nat Cell Biol. 2019; 21(6):778-790 [PubMed] Related Publications
Mapping phospho-catalytic dependencies of therapy-resistant tumours reveals actionable vulnerabilities.
Nat Cell Biol. 2019; 21(6):778-790 [PubMed] Related Publications
Phosphorylation networks intimately regulate mechanisms of response to therapies. Mapping the phospho-catalytic profile of kinases in cells or tissues remains a challenge. Here, we introduce a practical high-throughput system to measure the enzymatic activity of kinases using biological peptide targets as phospho-sensors to reveal kinase dependencies in tumour biopsies and cell lines. A 228-peptide screen was developed to detect the activity of >60 kinases, including ABLs, AKTs, CDKs and MAPKs. Focusing on BRAF
Bernthal NM, Upfill-Brown A, Burke ZDC, et al.
Long-term follow-up of custom cross-pin fixation of 56 tumour endoprosthesis stems: a single-institution experience.
Bone Joint J. 2019; 101-B(6):724-731 [PubMed] Related Publications
Long-term follow-up of custom cross-pin fixation of 56 tumour endoprosthesis stems: a single-institution experience.
Bone Joint J. 2019; 101-B(6):724-731 [PubMed] Related Publications
AIMS: Aseptic loosening is a major cause of failure in cemented endoprosthetic reconstructions. This paper presents the long-term outcomes of a custom-designed cross-pin fixation construct designed to minimize rotational stress and subsequent aseptic loosening in selected patients. The paper will also examine the long-term survivorship and modes of failure when using this technique.
PATIENTS AND METHODS: A review of 658 consecutive, prospectively collected cemented endoprosthetic reconstructions for oncological diagnoses at a single centre between 1980 and 2017 was performed. A total of 51 patients were identified with 56 endoprosthetic implants with cross-pin fixation, 21 of which were implanted following primary resection of tumour. Locations included distal femoral (n = 36), proximal femoral (n = 7), intercalary (n = 6), proximal humeral (n = 3), proximal tibial (n = 3), and distal humeral (n = 1).
RESULTS: The median follow-up was 132 months (interquartile range (IQR) 44 to 189). In all, 20 stems required revision: eight for infection, five for structural failure, five for aseptic loosening, and two for tumour progression. Mechanical survivorship at five, ten, and 15 years was 84%, 78%, and 78%, respectively. Mechanical failure rate varied by location, with no mechanical failures of proximal femoral constructs and distal femoral survivorship of 82%, 77%, and 77% at five, ten, and 15 years. The survivorship of primary constructs at five years was 74%, with no failure after 40 months, while the survivorship for revision constructs was 89%, 80%, and 80% at five, ten, and 15 years.
CONCLUSION: The rate of mechanical survivorship in our series is similar to those reported for other methods of reconstruction for short diaphyseal segments, such as compressive osseointegration. The mechanical failure rate differed by location, while there was no substantial difference in long-term survival between primary and revision reconstructions. Overall, custom cross-pin fixation is a viable option for endoprosthetic reconstruction of short metaphyseal segments with an acceptable rate of mechanical failure. Cite this article:
PATIENTS AND METHODS: A review of 658 consecutive, prospectively collected cemented endoprosthetic reconstructions for oncological diagnoses at a single centre between 1980 and 2017 was performed. A total of 51 patients were identified with 56 endoprosthetic implants with cross-pin fixation, 21 of which were implanted following primary resection of tumour. Locations included distal femoral (n = 36), proximal femoral (n = 7), intercalary (n = 6), proximal humeral (n = 3), proximal tibial (n = 3), and distal humeral (n = 1).
RESULTS: The median follow-up was 132 months (interquartile range (IQR) 44 to 189). In all, 20 stems required revision: eight for infection, five for structural failure, five for aseptic loosening, and two for tumour progression. Mechanical survivorship at five, ten, and 15 years was 84%, 78%, and 78%, respectively. Mechanical failure rate varied by location, with no mechanical failures of proximal femoral constructs and distal femoral survivorship of 82%, 77%, and 77% at five, ten, and 15 years. The survivorship of primary constructs at five years was 74%, with no failure after 40 months, while the survivorship for revision constructs was 89%, 80%, and 80% at five, ten, and 15 years.
CONCLUSION: The rate of mechanical survivorship in our series is similar to those reported for other methods of reconstruction for short diaphyseal segments, such as compressive osseointegration. The mechanical failure rate differed by location, while there was no substantial difference in long-term survival between primary and revision reconstructions. Overall, custom cross-pin fixation is a viable option for endoprosthetic reconstruction of short metaphyseal segments with an acceptable rate of mechanical failure. Cite this article:
Related: Bone Cancers
Bone Cancers
Chi KN, Agarwal N, Bjartell A, et al.
Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer.
N Engl J Med. 2019; 381(1):13-24 [PubMed] Related Publications
Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer.
N Engl J Med. 2019; 381(1):13-24 [PubMed] Related Publications
BACKGROUND: Apalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. Whether the addition of apalutamide to androgen-deprivation therapy (ADT) would prolong radiographic progression-free survival and overall survival as compared with placebo plus ADT among patients with metastatic, castration-sensitive prostate cancer has not been determined.
METHODS: In this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT. Previous treatment for localized disease and previous docetaxel therapy were allowed. The primary end points were radiographic progression-free survival and overall survival.
RESULTS: A total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease. At the first interim analysis, with a median of 22.7 months of follow-up, the percentage of patients with radiographic progression-free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P<0.001). Overall survival at 24 months was also greater with apalutamide than with placebo (82.4% in the apalutamide group vs. 73.5% in the placebo group; hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P = 0.005). The frequency of grade 3 or 4 adverse events was 42.2% in the apalutamide group and 40.8% in the placebo group; rash was more common in the apalutamide group.
CONCLUSIONS: In this trial involving patients with metastatic, castration-sensitive prostate cancer, overall survival and radiographic progression-free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT, and the side-effect profile did not differ substantially between the two groups. (Funded by Janssen Research and Development; TITAN ClinicalTrials.gov number, NCT02489318.).
METHODS: In this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT. Previous treatment for localized disease and previous docetaxel therapy were allowed. The primary end points were radiographic progression-free survival and overall survival.
RESULTS: A total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease. At the first interim analysis, with a median of 22.7 months of follow-up, the percentage of patients with radiographic progression-free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P<0.001). Overall survival at 24 months was also greater with apalutamide than with placebo (82.4% in the apalutamide group vs. 73.5% in the placebo group; hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P = 0.005). The frequency of grade 3 or 4 adverse events was 42.2% in the apalutamide group and 40.8% in the placebo group; rash was more common in the apalutamide group.
CONCLUSIONS: In this trial involving patients with metastatic, castration-sensitive prostate cancer, overall survival and radiographic progression-free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT, and the side-effect profile did not differ substantially between the two groups. (Funded by Janssen Research and Development; TITAN ClinicalTrials.gov number, NCT02489318.).
Related: Prostate Cancer
Prostate Cancer
Viswanadhapalli S, Luo Y, Sareddy GR, et al.
EC359: A First-in-Class Small-Molecule Inhibitor for Targeting Oncogenic LIFR Signaling in Triple-Negative Breast Cancer.
Mol Cancer Ther. 2019; 18(8):1341-1354 [PubMed] Article available free on PMC after 01/08/2020 Related Publications
EC359: A First-in-Class Small-Molecule Inhibitor for Targeting Oncogenic LIFR Signaling in Triple-Negative Breast Cancer.
Mol Cancer Ther. 2019; 18(8):1341-1354 [PubMed] Article available free on PMC after 01/08/2020 Related Publications
Leukemia inhibitory factor receptor (LIFR) and its ligand LIF play a critical role in cancer progression, metastasis, stem cell maintenance, and therapy resistance. Here, we describe a rationally designed first-in-class inhibitor of LIFR, EC359, which directly interacts with LIFR to effectively block LIF/LIFR interactions. EC359 treatment exhibits antiproliferative effects, reduces invasiveness and stemness, and promotes apoptosis in triple-negative breast cancer (TNBC) cell lines. The activity of EC359 is dependent on LIF and LIFR expression, and treatment with EC359 attenuated the activation of LIF/LIFR-driven pathways, including STAT3, mTOR, and AKT. Concomitantly, EC359 was also effective in blocking signaling by other LIFR ligands (CTF1, CNTF, and OSM) that interact at LIF/LIFR interface. EC359 significantly reduced tumor progression in TNBC xenografts and patient-derived xenografts (PDX), and reduced proliferation in patient-derived primary TNBC explants. EC359 exhibits distinct pharmacologic advantages, including oral bioavailability, and
Related: Signal Transduction LIFR
Signal Transduction LIFR
