Background

Hospice Africa Uganda has three branches, Mobile Hospice Mbarara, Hospice Kampala, and Little Hospice Hoima project to help patients get treatment for cancer (palliative care). In view of this we aimed to find out the factors which influence their late presentation at Hospitals. The World Health Organization (2015) has reported that cancer is the second most common cause of death and was responsible for over 25000 deaths in 2015, approximately 80% occurring in developing countries. It was projected that thiswill increase by 25% over the next 10 years if nothing is done such as putting adequate screening, treatment and prevention measures in place.

Methods

The study took place across the three sites of Hospice Africa Uganda. It has cared for about 70500 patients of which 55300 are cancer patients. A qualitative study was used to interview the patients so as to get a deep understanding of the reasons why patients with cancer present late for treatment at regional hospitals and national referral hospitals. Using the semi structured questionnaire guided the interviewers because it helped the patients to discuss freely the reasons why they report late. Then, data was transcribed and analyzed. A report was written and shared with the team of Hospice Africa Uganda across the three branches. These patients were interviewed at the three sites of hospice because come for the palliative care and during the outreach only patients with cancer were elegible for the study. The researchers used local language during the interviews since the majority of patients are more fluent in local language than English. A recording tape was used to store all the discussions for flexibility.

Results

Of theses patients, 68.5% did not have financial support to carry out early investigation, were peasant farmers, with little knowledge of cancer,17.9% had the financial support but were lazy to go to the hospital for checkup.14.3% did not give clear reason, while others were coming far away from the health units.

Conclusions

There is a very big role for the government, and health workers to sensitize the public, set up more health facilities and train more healthcare workers.

Legal entity responsible for the study

Hospice

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

Pancreatic cancer (PC) is one of the most aggressive and death-relating malignancy. Gemcitabine (GEM) is the key agent in the first-line standard regimen for advanced PC, which is mostly diagnosed at advanced stage and unsuitable for curative resection. The objective responsive rate (ORR) and medium progression free survival (PFS) of various GEM-based regimens are still unsatisfied. Therefore, development of new therapeutic modalities, including immunotherapy, is needed. This study is to investigate the efficacy, safety and clinical beneficial of combination personalized immunotherapy with GEM and radiotherapy in locally advanced and metastatic PC patients.

Methods

Three locally advanced unresectable and seven metastatic PC patients received at least two cycles of GEM (1000mg/m² on day 1 and day 6), radiotherapy combing with personalized peptide vaccine induced DC vaccination on day 7 and cytotoxic T lymphocyte transfer from day 12 to 15 (repeated every 21 days). The locally advanced unresectable PC patients received stereotactic body radiotherapy (SBRT) with a total amount of 50-66Gy during the first cycle. For metastatic patients, their partial lesions received a low dose radiation (0.5Gy bid*2 days) on day 10 and 11 in each cycle.

Results

Two cases were observed with partial remission (PR), five with stable disease (sd), and three with progressive disease (PD). The disease control rate (DCR) was 70%. Median progression free survival (PFS) was 6.4 months. After the first treatment cycle, the total effectiveness for pain easement and increasing appetite are 100% (8/8) and 66.7%, respectively. Haematotoxicities with a 40% incidence rate were the most common adverse drug reactions. Two patients had grade 1 to 2 neutropenia, two with grade 3 to 4 thrombocytopenia. Three patients suffered grade 1 to 2 gemcitabine-induced skin rash. No treatment-related mortality occurred.

Conclusions

Personalized adoptive immunocyte transfer combined chemoradiotherapy demonstrated an acceptable response and safety in advanced pancreatic cancer patients.

Legal entity responsible for the study

The Comprehensive Cancer Centre of Drum Tower Hospital

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

Chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) are common complications of chemotherapy that can lead to hospitalisation or chemotherapy disturbance. Standard of care is guideline-recommended prophylaxis with granulocyte colony-stimulating factors (GCSF) based on the regimen myelotoxicity and patient risk factors.

Methods

MONITOR-GCSF is a real-world European study of 1447 cancer patients (pts) receiving CIN/FN prophylaxis with biosimilar filgrastim; 77.2% had solid tumours and 22.8% haematological malignancies. We analysed prophylaxis patterns and CIN/FN outcomes in these cohorts and performed multi-level modelling of predictors of outcomes at the patient and cycle level.

Results

Differences in GCSF prophylaxis patterns were observed between cohorts. The solid tumour cohort vs the haematology cohort included significantly more over-prophylacted pts (29.7% vs 13.7%) and fewer correctly-prophylacted pts (54.0% vs 65.3%) (P = 0.009 for trend). Of note, 16.3% with solid tumours and 21.0% of haematology pts were under-prophylacted. In 60% of solid tumour pts, GCSF was initiated within the recommended time window vs 42% of haematology pts. Cycle-level analyses revealed higher rates of CIN (all grades) and FN in the haematology cohort, but no differences in hospitalisation or chemotherapy disturbance. No differences in patient-level outcomes (“ever” during the study) were found, except for FN (9.1% in haematological patients vs. 5.0% with solid tumours). Across patient- and cycle-level analyses, predictors of poor outcomes common to both cohorts included concomitant antibiotic prophylaxis, Eastern Cooperative Oncology Group performance status > =2 at any time, and CIN of any grade in a prior cycle. A GCSF Initiation Score of 1, indicating biosimilar filgrastim initiation within the 24–72 h window, was a common strong predictor of better outcomes.

Conclusions

Our analyses illustrate the importance of assuring adequate GCSF support in both haematology and solid tumour pts to prevent CIN/FN and related hospitalisations and chemotherapy disturbances.

Clinical trial identification

N/A

Legal entity responsible for the study

Sandoz Biopharmaceuticals

Funding

Sandoz Biopharmaceuticals

Disclosure

M. Aapro: Amgen (honoraria, speakers bureau, expert testimony), Helsinn Healthcare (advisory role, speakers bureau, research funding), Hospira (advisory role, speakers bureau, research funding), Teva (advisory role, speakers bureau), Merck KGaA (advisory role), Merck (advisory role), Sandoz (advisory role, speakers bureau, research funding), Pierre Fabre Medicament (advisory role, speakers bureau, research funding), Vifor Pharma (advisory role, speakers bureau), Tesaro (advisory role, speakers bureau), Novartis (speakers bureau, research funding), Roche (speakers bureau), Johnson & Johnson (speakers bureau). C. Bokemeyer: Hexal AG (personal fees). M. Boccadoro: Celgene (personal fees), Novartis (personal fees), Amgen (personal fees), Sanofi (personal fees). P. Gascón: Sandoz (speakers bureau). K. Denhaerynck: Matrix45 (employment). Matrix45 has been under contract for scientific consulting services to GCSF manufacturers including Hospira, Hexal/Sandoz and Therapeutic Proteins International. By company policy, employees cannot hold equity in sponsor organizations and cannot receive direct personal benefits, financial or other, from sponsor organizations. A. Krendyukov: Hexal AG (employment).

I. Abraham, K. Macdonald: Matrix45 (employment). Matrix45 is under contract with study Sponsor, Hexal/Sandoz, for scientific support services including study design, statistical analysis and manuscript preparation for the MONITOR-GCSF study. Matrix45 has been under contract for scientific consulting services to other GCSF manufacturers including Hospira. By company policy, employees cannot hold equity in sponsor organizations and cannot receive direct personal benefits, financial or other, from sponsor organizations. Matrix45 provides similar services to other biopharmaceutical companies without exclusivity constraints. H. Ludwig: Celgene (speaker’s honoraria), Takeda (research funding, speaker’s honoraria), Amgen (honoraria for advisory boards and speakers board).

Background

Non-coding RNAs, such as microRNAs (miRs), are often affected by loss or amplification of adjacent tumor suppressor genes or oncogenes, respectively. MIR491 is located in close proximity to the CDKN2A locus and is frequently co-deleted with CDKN2A. MIR491 expression has correlated with inhibition of EGFr. Also, knockdown of MIR491 has been shown to increase cellular proliferation and invasion in glioma cells [Li, X et al. Oncogene, 34(13):1619-1628, 2015]. Since MIR491 deletion has been demonstrated in head and neck cancer, we sought to assess the effect of increasing MIR491 expression on EGFr expression as well as downstream signaling events and radiosensitivity.

Methods

Four human head and neck squamous cell carcinoma cells lines were studied (UM-SCC-1, UM-SCC-1R, UM-SCC-6 and UM-SCC-6R). The UM-SCC-1R and UM-SCC-6R cells were developed as cetuximab resistant cells after several months of continuous exposure to cetuximab. Previously published methods were used to transfect cells with MIR491. Also, previously described methods were used for assessments of EGFr and other downstream proteins (by immunoblot), cell proliferation, colony formation and apoptosis (annexin assay). [Bonner JA. Radiother Oncol, 92:338-344, 2009].

Results

MIR491 transfected human head and neck squamous cell carcinoma cells (UM-SCC-1, UM-SCC-1R, UM-SCC-6 and UM-SCC-6R) showed decreased expression of phosphorylated EGFr and phosphorylated AKT by immunoblot. Furthermore, these decreases in EGFr and EGFr-signaling proteins correlated with enhanced radiosensitivity as assessed by cell proliferation and colony formation. This enhanced radiosensitivity correlated with greater radiation-induced apoptosis.

Conclusions

These results suggest that MIR491 is a negative regulator of EGFr in head and neck cancer and that deletions of the non-coding MIR491 gene may be associated with radiation resistance, and may contribute to poor outcomes for certain tumors that are treated with radiotherapy. Further work will be necessary to determine if MIR491 deletions are associated with greater tumor recurrence following radiation or other DNA-damaging cancer treatments.

Clinical trial identification

N/A

Legal entity responsible for the study

James Bonner

Funding

University of Alabama Health Services Foundation

Disclosure

J.A. Bonner: Occasional consultant/honoraria for Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Serono, and Cel-Sci. E.S. Yang: Advisory Board SRATA Oncology, Research Support Eli Lilly, Novartis Research Support-AACR, Bayer C. Willey: North, Pursell & Ramos, PLC - medical-legal consultations for malpractice case review.

All other authors have declared no conflicts of interest.

Background

Prognostic nutritional index (PNI), based on serum lymphocyte counts and albumin levels, has been introduced as a simple and easily measurable biomarker, representing the nutritional and immunological status of cancer patients. However, the nutritional and inflammatory conditions can be different between pre- and post-operative statuses because of eradication of primary tumors, and major surgeries can influence the general condition and immune reaction of a host. Here, we aimed to examine the prognostic role of prognostic nutritional index (PNI) dynamics in the pre- and postoperative periods in patients with renal cell carcinoma (RCC) who underwent radical nephrectomy (RN).

Methods

We analyzed 324 patients with RCC who underwent RN. Overall population was classified into 4 groups according to 4 types of pre- to postoperative PNI dynamics as follows: Group 1 (low → low PNI), 2 (low → high PNI), 3 (high → low PNI) and 4 (high → high PNI). The level of PNI was calculated using the following formula: 10 × serum albumin level (g/dL) + 0.005 × absolute lymphocyte counts in blood (/mm³). Primary and secondary endpoints were cancer-specific survival (CSS) and overall survival (OS), respectively.

Results

Patients with higher pre- and postoperative PNI (> 45) had better survival outcomes than those with lower pre- and postoperative PNI (≤ 45). Notably, patients in Group 4 showed the best CSS and OS rates, whereas patients in Group 1 had the worst survival outcomes. Furthermore, PNI dynamics was identified as an independent predictor for CSS and OS outcomes, in addition to pre- and postoperative PNI, tumor size, and pathologic T (pT) stage. Patients with localized RCC (≤ pT2) showed significant differences in both CSS and OS estimates, while patients with advanced pT stage (≥ pT3) demonstrated a difference only in OS outcomes, according to PNI dynamics.

Conclusions

In summary, PNI dynamics in pre- and postoperative status was identified as a valuable predictor of survival outcomes in patients with RCC undergoing RN. Our study is the first that provides the independent prognostic importance of dynamics of nutritional status for patients with RCC.

Legal entity responsible for the study

Samsung Medical Center, Sungkyunkwan University School of Medicine.

Funding

Korea Health Industry Development Institute (KHIDI)

Disclosure

All authors have declared no conflicts of interest.

Background

Breast cancer is the leading cause of mortality in women and is the second most common malignancy encountered in women of childbearing age. An aggressive clinical course has been reported to occur during pregnancy. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase that cleaves insulin-like growth factor 1 (IGF-1) from a circulating complex formed with insulin-like growth factor binding protein 4 (IGFBP4). Increased bioavailability of IGF1 subsequently impacts on tumour biology. PAPP-A is produced in increasing levels until term by the syncytiotrophoblast cells in the human placenta. High levels of PAPP-A have been associated with progression in other tumour types.

Methods

Eleven breast cancer cell lines were examined to characterise the components of the PAPP-A/IGF axis in breast cancer. PAPP-A mRNA expression was analysed by quantitative RT-PCR. The effect of PAPP-A expression on cell migration in the MDA-MB-453 cell line was subsequently evaluated by using neutralising antibodies. An analysis of The Cancer Genome Atlas (TCGA) publicly available transcriptome profiling dataset was also performed, through specific query of expression clustering.

Results

PAPP-A expression was noted in three of the cell lines. In the MDA-MB-453 cell line, which expressed high levels of PAPP-A, neutralising antibodies to PAPP-A and IGFBP4 significantly reduced migratory capabilities. Analysis of the TCGA dataset revealed that alteration (mainly upregulation) in PAPP-A expression resulted in worse overall survival (n = 1104, p = 0.13). Median survival with alteration in PAPP-A expression was 74 months compared with 113 months in patients without alteration in PAPP-A.

Conclusions

Our data suggest that PAPP-A plays a role in the progression of breast cancer, which may be particularly relevant in pregnancy. The insights gained from this research open up the possibility of indirect and specific therapeutic targeting of IGF to halt the progression of breast cancer.

Legal entity responsible for the study

Olivia Newton-John Cancer Research Institute

Funding

None

Disclosure

J. Cebon: Jonathan S. Cebon Honoraria - Amgen; Bristol-Myers Squibb; GlaxoSmithKline; Merck; Merck Sharp & Dohme; Merck Sharp & Dohme; Merck Sharp & Dohme; Novartis Consulting or Advisory Role - Amgen (Inst); Bionomics; Bionomics (Inst); Bristol-Myers Squibb (Inst); Bristol-Myers Squibb (Inst); Bristol-Myers Squibb (Inst); Bristol-Myers Squibb (Inst); Bristol-Myers Squibb (Inst); Merck Sharp & Dohme (Inst); Merck Sharp & Dohme (Inst); Merck Sharp & Dohme (Inst); Novartis; Novartis (Inst) Research Funding - CSL (Inst); GlaxoSmithKline (Inst) Patents, Royalties, Other Intellectual Property - GlaxoSmithKline Expert Testimony - Bristol-Myers Squibb

All other authors have declared no conflicts of interest.

Background

The expression of human epidermal growth factor receptors 2 (HER2) and hormonal receptors (estrogen receptor and progesterone receptors) on breast cancer are important markers that always be determined on breast cancer patients. Association between HER2 and hormonal receptors (ER and PR) expression are used as a prognostic and predictive factor on breast cancer. This research aimed to determine the association between HER2, ER, and PR on breast cancer.

Methods

This study was an analytical with cross-sectional design. This study was conducted from May 2015 – December 2015 in oncology division of surgery department RSUP DR. M. Djamil, Padang. Research subjects were 373 of breast cancer patients from 2011 – 2015. Chi square analysis test was used to determine the significant relationship between the variables.

Results

This study involved 124 cases with HER2+ and 249 cases with HER2-. Significant differences in the cases were ER+/HER2- (85.2%) compared with ER+/HER2 (14.8%) with p < 0.001. We also obtained the same tendency on PR+/HER2- (82.7%) compared with PR+/HER2 + (17.3%) with p < 0.001.

Conclusions

This study concluded that there were significant differences between expression of HER2 and hormonal receptors (ER and PR).

Clinical trial identification

This is not a trial idetification research

Legal entity responsible for the study

Medical Faculty of Andalas University

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

Concurrent chemoradiotherapy (CCRT) with cisplatin is widely recommended as a treatment option for patients with advanced cervical cancer because of its better prognosis than radiotherapy. However, cisplatin should be reluctantly avoided or reduced for patients with renal dysfunction because of nephrotoxicity. In contrast, carboplatin is adjusted to a dose according to renal function, to insure safety independent of renal function. Here we evaluated the efficacy and feasibility of CCRT with paclitaxel and carboplatin (TC) for patients with advanced cervical cancer with renal dysfunction.

Methods

We retrospectively analyzed the safety and efficacy of TC-CCRT for 11 patients with advanced cervical cancer with renal dysfunction between December 2015 and May 2017 in our hospital (TC-group). Patients who underwent radiotherapy alone between January 2012 and December 2015 (RT-group, n = 15) because of renal dysfunction served as historical controls. Chemotherapy using 135 mg/m2 paclitaxel followed by carboplatin with a dosage at area under the curve = 5 mg/ml/min was given every 3 weeks. Three cycles, maximum, were expected. Radiotherapy of both groups was performed using whole pelvic external irradiation and brachytherapy.

Results

The TC group received triweekly chemotherapy (average 2.4 cycles). All patients received the planned full radiation. Radiotherapy was temporarily discontinued for two patients (18.2%) in the TC-group and for one patient (6.7%) in the RT group because of toxicity. The TC-group required 6.0 days (average) extended radiation therapy, which was not significantly longer than the RT-group (7.0 days). The rates of local complete response did not differ significantly between groups (90.9% vs 86.7%).

Conclusions

TC–CCRT for patients with advanced cervical cancer with renal dysfunction was safe, with minimal postponement of radiotherapy because of toxicity, suggesting that this therapy is effective. The advantage of TC–CCRT for increasing survival compared with RT or CCRT using reduced doses of cisplatin is further evaluated.

Legal entity responsible for the study

Yokohama City University Hospital, Department of Obstetrics and Gynecology

Funding

None

Disclosure

All authors have declared no conflicts of interest.