bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA cytometric parameters as prognostic factors of chemoimmunotherapy for ovarian cancer.
Authors: Nerodo Galina Andreevna , Kit Oleg Ivanovich , Novikova Inna Arnoldovna , Ardzha Anna , Verenikina Ekaterina V. , Nikitina Vera P. , Kravtsova Oksana E. , Bondarenko Elena , Mezentsev Stanislav Stanislavovich
Published: September 2018

e17041

Background: The aim of the study was to analyze chemoimmunotherapy influence on DNA cytometric parameters in patients with ovarian cancer. Methods: The study included stage IIIC-IV ovarian cancer patients divided into two groups in dependence on the treatment: group A – 21 patients who did not receive neoadjuvant chemotherapy before surgery; group B – 24 patients who received neoadjuvant chemoimmunotherapy with intraperitoneal administration of interferon-gamma (ingaron) and the following surgery. The groups were identical in terms of the disease stages, age and general condition of patients. DNAs were analyzed in fresh tumor tissues using CycleTEST Plus DNA Reagent Kit (Becton Dickinson, USA). The data were processed using the ModFit LT program allowing analysis of ploidy and distribution of tumor cells in phases of the cell cycle. The proportion of cells with different DNA content in the histogram was calculated as a percentage of the total number of studied cells. Proliferation index (PI) was calculated as the total amount of tumor cells in S and G2+М phases of the cell cycle. Results: Full-volume surgery (panhysterectomy+omentectomy) was performed in 52.4% in group A and in 92% in group B, adnexectomy only – in 38.1% and 8%, respectively; exploratory surgeries were performed in group A only – 9.5%. During 2 years of the observation, recurrence in group A was found in 38% of patients, in group B – in 12.5%. Analysis of DNA cytometric parameters showed the minimal proliferation rates (percentage of cells in S phase) in group B – 12.6±2.3%, compared with 20.7±3.4% in group A. PI was lowest in group B – 13±2.7%, compared with group A – 22.4±3.3% (p≤0.05). Significant decrease in the DNA index by 1.3 times was noted in patients in group B in comparison with group A (1.11±0.01% and 1.4±0.05%, respectively) (p≤ 0.05). Conclusions: Thus,DNA cytometric parameters reflect the effectiveness of chemoimmunotherapy and can be used as prognostic factors.
Survival outcomes in patients with platinum-resistant (PL-R) ovarian cancer (OC): The Princess Margaret Cancer Centre (PM) experience.
Authors: Ethier Josee-Lyne , Wang Lisa , Oza Amit M. , Lheureux Stephanie
Published: September 2018

e17049

Background: PL-R OC is associated with poor prognosis, and clinical trials indicate that overall survival (OS) is less than 12 months. Here, we describe real-world outcomes in patients with PL-R OC. Methods: Patients treated for PL-R OC presenting to PM from 2011-2015 were identified through the Oncology Patient Information System (OPIS) following research ethics board approval. Treatment data were extracted from OPIS. Baseline characteristics and survival data were obtained through linkage with the PM Survival Registry. Data were supplemented through individual chart review. OS was defined as time from first treatment for PL-R OC to date of death or last contact. Univariable and multivariable analyses were performed to assess the effect of patient characteristics (time from diagnosis to platinum resistance, OC subtype, tumor grade, PL-R or platinum-refractory [PL-RF] status, optimal debulking, clinical trial enrolment, number of treatment lines, germline BRCA1/2 status) on OS using cox proportional hazard models. P-values of 0.05 were considered significant. Results: Data from 165 patients with PL-R OC were included. Most patients had high grade (86%) and serous (84%) tumours. BRCA was mutated in 13%, wild-type in 49%, and unknown in 35%. The median number of lines received was 2 (range 1-6). Weekly paclitaxel (41%) and pegylated liposomal doxorubicin (41%) were the most common first-line regimens. Clinical trial participation was 36%. Median OS was 342 days (95% Confidence Interval 285-440), and was longer in PL-R (366 days) compared to PL-RF OC (302 days). Tumor grade and clinical trial participation were significantly associated with OS on univariable but not multivariable analysis. The number of treatment lines received for PL-R OC was independently predictive of OS (hazard ratio 0.63; p < 0.001), but may reflect capacity for continued treatment in surviving patients (immortal time bias). Conclusions: Real-word outcomes in PL-R OC are similar to those observed in clinical trial populations, and are worse in PL-RF disease. Receipt of a greater number of treatments for PL-R disease is associated with longer OS, but may be due to immortal time bias.
Feasibility of bevacizumab combined with gemcitabine in treatment of platinum-resistant epithelial ovarian cancer.
Authors: Kogiku Ai , Nagao Shoji , Suzuki Kazuhiro , Yamamoto Kasumi , Senda Tokihiro , Kitai Miho , Shiozaki Takaya , Matsuoka Kazuko , Sudo Tamotsu , Yamaguchi Satoshi
Published: September 2018

e17064

Background: We assessed the efficacy and safety of a combination chemotherapy comprising gemcitabine and bevacizumab for the treatment of platinum-resistant recurrent ovarian cancer. Here we report the results of the interim analysis. Methods: Eligible patients showed recurrent, measurable tumors that had progressed within 6 months after the completion of platinum-based chemotherapy. Patients received gemcitabine (1000 mg/m2) on days 1and 8 and bevacizumab (15 mg/kg) on day1 every 3 weeks until disease progression or unacceptable toxicity levels were observed. The primary end point was the proportion of patients who completed three cycles of scheduled chemotherapy. Results: Twelve patients were enrolled in this study and three patients are still undergoing chemotherapy. The proportion of patients who completed three cycles of chemotherapy was 77.8 % (7/9), and response rate was 66.7 % (6/9). Grade ≥ 3 neutropenia, thrombocytopenia, and hypertension were observed in five, one, and one patients, respectively. There was no GI perforation or death in our study. Conclusions: Combination chemotherapy of comprising gemcitabine and bevacizumab was safe and effective in patients with platinum-resistant recurrent ovarian cancer. Therefore, it is important to continue this study. Clinical trial information: 000016619.
The first-in-class anti-cancer agent ABTL0812 is effective in preclinical models of human endometrial cancer.
Authors: Colàs Eva Colàs , Eritja Nuria , Muñoz-Guardiola Pau , Sole-Sanchez Sonia , Moiola Cristian , Felip Isidre , Gil-Moreno Antonio , Perez-Montoyo Hector , Alfon Jose Alberto , Domenech Carles , Lizcano Jose M , Matias-Guiu Xavier
Published: September 2018

e17070

Background: ABTL0812 is a first-in-class anti-cancer agent with a unique mechanism of action currently in Phase Ib/IIa clinical development for endometrial cancer and squamous NSCLC. ABTL0812 successfully culminated a Phase I clinical trial showing a high safety profile and long disease stabilizations, including 14-months stabilization in a patient with platinum-unresponsive Grade IIIC endometrial cancer with mutated PI3KCA and Akt. Methods: ABTL0812 synergy with paclitaxel and carboplatin was tested in vitro on Ishikawa cells by MTT assay. ABTL0812 in vivo anti-tumor activity was assessed in a PTEN-null inducible mouse model of endometrial adenocarcinoma development upon tamoxifen injection. In vivo synergy between ABTL0812 and paclitaxel was validated in a xenograft model orthotopically implanted with Ishikawa cells and between ABTL0812 and paclitaxel/carboplatin (P/C) in xenografts derived from a patient (PDX) with grade IIIC2 endometrial carcinoma with mutated PI3KCA. Results: ABTL0812 reduced paclitaxel and carboplatin IC50 by 1.5 and 2.1 times respectively in Ishikawa cells. Synergy with paclitaxel was found in Ishikawa orthoxenografts, showing a maximum Tumor Growth Inhibition (maxTGI) of 56,7±16,9% compared with 34.6±33.2% of paclitaxel group. ABTL0812 alone was effective reducing endometrial intraepithelial neoplasia formation in a mouse model of endometrial adenocarcinoma. Additionally, in an endometrial cancer PDX, ABTL0812 alone showed similar efficacy with reduced toxicity when compared with P/C and improved maxTGI when given in combination (ABTL0812: 45,2±17,5%; C/P*: 38,7±26,9%; ABTL0812+C/P*: 59.3±8.8%; *p=0.031). Conclusions: ABTL0812 has shown efficacy as a single agent and in combination with chemotherapy in preclinical models of endometrial cancer with mutations on PI3K/Akt pathway, which appears frequently over-activated in patients with these cancers. These results supported the application of ABTL0812 as a first line therapy in combination with chemotherapy for the Phase Ib/IIa clinical trial currently ongoing, positioning ABTL0812 as a potential therapeutic agent in the treatment of endometrial cancers bearing these genetic alterations.
Use of a multi-drug regimen gemcitabine, 5-fluorouracil, irinotecan, cisplatin bevacizumab, docetaxel and cyclophosphamide (GFIP/BDC) for heavily pretreated epithelial ovarian (EOC), Fallopian tube (FT) and primary peritoneal (PP) cancer.
Authors: Schwartz Melissa , Cohen Samantha , Dottino Peter Remsen , Beddoe Ann Marie
Published: September 2018

e17073

Background: Despite initial response rates to standard platinum-based chemotherapy for EOC/FT/PP, the majority of patients relapse. The purpose of this study was to describe response and tolerability of GFIP/BDC, a modification of the G-FLIP regimen (Bruckner et al), in patients with persistent or recurrent EOC/FT/PP. Treatment consisted of a 2-day combination of gemcitabine 300mg, 5-fluorouracil 500mg/m2, irinotecan 20-30mg/m2, cisplatin 20mg/m2, bevacizumab 4mg/kg, docetaxel 20mg/m2, and cyclophosphamide 20mg/m2 administered every 14 days. Methods: A retrospective descriptive analysis of 20 patients from a single academic institution who received combination GFIP/BDC therapy from January 1, 2011 to August 31, 2016 for persistent or recurrent EOC/FT/PP. Toxicities were retrospectively graded using CTCAE v4.0. Results: Twenty patients were identified with a median age 57.5 years (range 32-71). 85% of patients were non-Hispanic white, 90% had cancer of high-grade serous histology, and all had a GOG performance status of 0-1. Patients had received a median of 3 prior regimens and 95% were platinum-resistant. Median number of cycles administered was 9 (range 3-48) and patients remained on treatment for a median of 5.1 months (range 1.5-24). Thirteen patients (65%) experienced a clinical response (1 complete, 12 partial) with a median duration of 5 months (range 1.5-20). Eight patients (45%) survived progression free for at least 6 months. Grade 3 adverse events were hematologic (5), constitutional (3), gastrointestinal (3), neurologic (2), and vascular (1). Grade 4 adverse events included severe neutropenia (1) and anaphylaxis (1). Thirteen patients (65%) experienced at least one grade 3/4 adverse event. Patients discontinued treatment due to disease progression 65% (13), toxicity 20% (4), patient preference 10% (2), and one patient (5%) is currently on treatment. Conclusions: Selected EOC/FT/PP patients who have failed multiple lines of conventional cytotoxic treatment may benefit from GFIP/BDC. Toxicity might be a limiting factor for administration.
A retrospective analysis of lymph node status in advanced ovarian, fallopian, and peritoneal cancer.
Authors: Itani Yoshio , Morita Sayuri , Sugimoto Hitomi , Takeda Yoshiki , Sasaki Yoshikazu , Ishibashi Satoko , Shugiura Atsushi , Hirano Hitoshi , Toyoda Shinji , Kita Tsunekazu
Published: September 2018

e17074

Background: The purpose of this study was to assess lymph node (LN) status; greatest dimension (D), D of metastatic LN (LN (+)) foci (MF), number of LN (+) of each patient, and MF area aggregated in each patient affected by LN metastasis in FIGO stage III and IV ovarian, fallopian, and peritoneal cancer. Methods: We researched the consecutive 25 patients who underwent primary debulking surgery or neoadjuvant chemotherapy (NAC) followed by interval debulking surgery including systemic lymphadenectomy from 2004 to 2015. Non-serous histology was 20 % (5/25). LN (+) were detected in 12.6% (169/1344) of lymph node preparations. Results: The patients’ median age was 53 years. Median number of LN (+) and sum of MF area in each patient were 2 (range 0-37) and 2 mm2 (range 0- 498). Mean D of the entire LN and of the MF were 4.7mm (95%Confidence Interval (CI); 4.5,4.9) and 6.1mm(95% CI; 5.2, 7.0). The LN (+) displayed a significantly larger mean D value (7.9 mm, 95% CI: 7.4, 8.5) than the non-metastatic lymph nodes (LN (-)) (4.2 mm, 95% CI: 4.0, 4.4) (p<0.05; student t test). D of MF (mm) was approximated by LN (+) area (mm2) as follows; (D of MF) = 2.58+ 0.094*(LN (+) area)+ 0.062* ( ( LN (+) area)-43.2)2; R2=0.75; p<0.0001. The D of MF with NAC, 5.0 mm (95%CI: 3.6, 6.4) demonstrated smaller than that without NAC, 7.0 mm (95%CI: 5.8, 8.1) (p<0.05; student t test). The proportion of LN (-) patients was significantly higher in the NAC group (44%, 4/9) than in the non-NAC group (6%, 1/16) (p=0.022). D of LN (+), D of MF ≥10 mm, sum of MF area, and number of LN (+) ≥ 2 did not achieve statistical significance in analysis with the relative risk (RR) of death. Conclusions: LN (+) exhibits larger D than LN (-) and D of MF could be estimated by LN (+) area. Some MFs shrink after NAC, and hence, become difficult to detect pathologically. In advanced ovarian, fallopian, and peritoneal cancer LN size and sum of MF area could not show an impact on prognosis.
Clinical relevance of circulating tumor cells in ovarian, fallopian tube and peritoneal cancer.
Authors: Gebauer Gerhard , Banys-Paluchowski Malgorzata Joanna , Neubauer Hans , Krawczyk Natalia , Kaczerowski Anna , Paluchowski Peter , Meier-Stiegen Franziska , Abdel-Kawi Ahmed , Fehm Tanja N.
Published: September 2018

e17080

Background: Presence of circulating tumor cells (CTCs) in peripheral blood is associated with impaired clinical outcome in a variety of cancers. So far, limited data are available on the significance of CTCs in gynaecological malignancies. Aims of the present study were to evaluate the dynamics of CTCs in patients with ovarian, fallopian tube and peritoneal cancer during chemotherapy and to assess the clinical relevance of these changes. Methods: 38 patients with ovarian (n=31), fallopian tube (n=4) and peritoneal (n=3) cancer were included into the study. All patients received chemotherapy in the first-line setting (n=19) or tumor recurrence (n=19). CTC analysis was performed prior to systemic treatment, after three and six cycles of chemotherapy and analysed using CellSearch system (Veridex). A tumor cell was defined as EpCAM+, cytokeratin+, CD45-, and positive for the nuclear stain DAPI. CTC positivity was defined as detection of at least one CTC per 7.5 ml blood. Results: 11 out of 38 (29%) patients were CTC positive at baseline. Positivity rate was 20% in patients with first-line setting and 37% in those with tumor recurrence. 1of the 4 patients with fallopian tube cancer presented with CTCs in contrast to 1 out of 3 patients with peritoneal cancer and 10 out of 31 ovarian cancer patients. Presence of CTCs was not correlated with other prognostic factors, such as the FIGO stage, nodal status, or grading. CTC positivity declined to 8% after three cycles of cytotoxic therapy and no patient was CTC positive after 6 cycles of chemotherapy. 12 patients died during follow-up. Patients with CTCs at baseline had significantly shorter overall survival compared with CTC negative patients (p = 0.002; mean OS 5.8 [95%-CI 2.7-8.9] vs. 15.2 [10.5-19.8] months, median OS 3.0 [1.4-4.6] vs. not reached). In the subgroup of patients with primary cancer, CTC positivity was significantly associated with overall survival in the univariate analysis (p = 0.008). Conclusions: Hematogenous dissemination of single tumor cells is a common phenomenon in ovarian, fallopian tube and peritoneal cancer. Patients with CTCs in the peripheral blood at time of diagnosis are more likely to die than those who are CTC-negative at baseline.
What are the expectations and preferences of patients with ovarian cancer to a maintenance therapy? A NOGGO/GCIG/ENGOT-ov22 survey (Expression IV) in 2101 patients.
Authors: Rohr Irena , Keller Maren , Chekerov Radoslav , Oskay-Özcelik Gülten , Richter Rolf , Heinrich Michaela , Taskiran Cagatay , Joly Florence , Wolfrum-Ristau Pia , Gornjec Andreja , Vergote Ignace , Achimas Patrick , Lorusso Domenica , Maenpaa Johanna Unelma , Sehouli Jalid
Published: September 2018

e17096

Background: The primary aim of the survey was to investigate the expectations of European patients about maintenance therapy. Methods: A 24-item questionnaire was provided to ovarian cancer patients via internet or paper-version in9 European countries (Austria, Belgium, France, Germany, Italy, Romania, Slovenia, Finland and Turkey). Data was captured about demographics, tumor stage and therapy after first line and/ or recurrent disease and particularly about preferences of administration and expectations concerning a maintenance therapy. Results: Overall, 2101 questionnaires of ovarian cancer patients were evaluated. Over 63% of the patients were between 51 and 70 years (range 18-90). The majority of the patients were FIGO stage III at their primary diagnosis. 96% of the patients had a surgery and 93% received a chemotherapy. 38% of respondents had recurrent disease. 45% of the patients had already heard of and 29% received maintenance therapy. 85% of the patients heard about maintenance therapy from the doctor and 10% from other patients and 9% read about it on the internet. The four most disturbing side effects of maintenance therapy were polyneuropathy (37%), nausea (36%), loss of hair (34%) and vomiting (34%). The main objective of maintenance treatment for all patients was to increase the chances of cure (73%), followed by an improvement in the quality of life (47%) and the delay of tumor growth (37%). Many patients are willing to take a maintenance therapy until tumor progression (38%). 39% of the patients would prefer an oral administration and 29% do not have any preference for any specific administration. When we performed cross country sub-analysis between patients with primary diagnosis and relapse, or sub-analysis between patients who are actually receiving maintenance therapy or not, we observed no significant differences of expectations to a maintenance therapy. Conclusions: There is an urgent need for more information regarding side effects and treatment goals of maintenance therapy to avoid misunderstandings by the patient. This information may increase patient’s compliance for maintenance therapy in ovarian cancer.
Effect of older age and comorbitities on outcomes with neoadjuvant chemotherapy (NAC) for epithelial ovarian cancer (EOC).
Authors: Xu Zhaomin , Justiniano Carla Francesca , Becerra Adan Z , Aquina Christopher Thomas , Boscoe Francis P. , Schymura Maria J. , Fleming Fergal J. , Temple Larissa K. F. , Morrow Gary R. , Minasian Lori M. , Temkin Sarah Madhu
Published: September 2018

e17101

Background: Although a survival benefit for NAC has not been shown in the overall population of EOC, some patients may benefit from NAC. This analysis evaluates the role of age and comorbidities on the effect of NAC compared to upfront surgery on survival among EOC patients in New York. Methods: Patients who underwent surgery for stage II-IV EOC from 2006-2013 were included from the New York State Cancer Registry and the Statewide Planning and Research Cooperative System. Elderly age was defined as >70 years. Comorbidity burden was defined with the Charlson Comorbidity Index (CCI). Cox models were used to examine the effect of NAC on 5 year overall survival. The analysis was then stratified by age and comorbidity score to evaluate the role of NAC in specific subgroups. Results: 4617 patients met inclusion criteria of which 25% were elderly and 11% received NAC. Factors associated with receipt of NAC included age > 70, advanced stage, serous histology and high hospital volume (p<0.01). After adjustment for patient, hospital, and surgeon characteristics, NAC was associated with a 27% (p<0.01) increase in 5 year overall mortality in all EOC patients. Among the elderly, NAC did not have a significant effect on overall (p=0.47) or EOC-specific survival (p=0.24). Elderly and non-elderly women without comorbidities had a higher risk of death with NAC than primary surgery. There was a trend towards improved survival among elderly patients with higher comorbidity scores. (Table) Conclusions: The impact of NAC on EOC survival differs dependent on age and comorbidities. Patients with no comorbidities may have better prognosis with upfront surgery. Counterintuitively, those with more comorbidities, particularly the elderly, may derive survival benefit from upfront neoadjuvant therapy. [Table: see text]
18FDG-PET/CT for the detection of residual/recurrent in patients with head and neck cancer: A systematic review and meta-analysis.
Authors: Shang Jinbiao , Gu Jialei , Wang Wendong , Wang Kejing , Xu Yaping
Published: September 2018

e17502

Background: To evaluate the diagnostic accuracy of positron emission tomography (PET) and PET/computed tomography (CT) for detecting residual and/or recurrent local and regional disease in patients with head and neck cancer (HNC) following radiotherapy with or without chemotherapy. Methods: Studies about 18FDG-PET/CT for detecting residual or recurrent disease after treatment in patients with HNC were systematically searched in the MEDLINE and EMBASE databases. The Stata software was used to obtain pooled estimates of sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for 18FDG-PET/CT. Results: 31 articles bulled all inclusion criteria. The pooled sensitivity and specificity of PET and PET/CT for detecting residual or recurrent disease at the primary site was 88.7% and 89.6%, respectively. For residual or recurrent neck disease, the sensitivity and specificity were 75.9% and 92.0%, while for residual or recurrent localregional disease, the values were 89.6% and 87.8%. Conclusions: 18FDG-PET/CT has good diagnostic performance for the detection of residual and/or recurrent in HNC patients.
Co-targeting mTORC and EGFR signaling as a therapeutic strategy in HNSCC.
Authors: Swick Adam D , Prabakaran Prashanth Jyothi , Miller Margot , Javaid Amal M , Fisher Michael , Sampene Emmanuel , Ong Irene , Iida Mari , Nickel Kwang-Ok P , Bruce Justine Yang , Wheeler Deric , Kimple Randall J.
Published: September 2018

e17509

Background: Head and neck squamous cell carcinomas (HNSCCs) are frequently altered along the PI3K/AKT/mTORC signaling axis leading to development of therapeutics targeting this pathway. Despite excellent preclinical data, the use of these compounds as monotherapy has been underwhelming in initial clinical trials and identification of predictive biomarkers remains challenging. The EGFR monoclonal antibody cetuximab remains the only approved targeted agent for HNSCC and has potential use in combination therapy. Methods: Both catalytic mTORC (AZD8055) and PI3K/mTORC(NVP-BEZ-235) inhibitors were tested +/- cetuximab in a panel of HNSCC cell lines and patient derived xenografts (PDX) evaluated for potential biomarkers of PI3K/AKT/mTORC pathway. Cell lines were assayed for response to all three agents by multiple approaches, and confirmed by siRNA knockdown. Five PDX models that presented PIK3CA mutation or intrinsic cetuximab resistance were treated with a combination of cetuximab and AZD8055. Results: In HNSCC cells no likely sensitizing mutations were identified, whereas putative protein biomarkers were elevated in some lines. All lines showed similar response to both PI3K/mTORC and dual mTORC inhibition with cetuximab combination producing modest additive effect with similar results for siRNA knockdown. In PDX models, in vivo single agent mTORC inhibition inhibited growth of a PIK3CA mutant cancer, but had little effect on any PIK3CAWT or a second PIK3CA mutant model. In all models the combination therapy showed greater growth delay than monotherapy. Conclusions: The uniform ability of PI3K and mTORC inhibition to suppress the growth of HNSCC cells highlights the pathway’s role in driving proliferation. In vivo, despite some PDX models meeting likely selection criteria, the single agent therapy was largely ineffective. Conversely improved response of combination treatment suggests the potential for adding a catalytic mTORC inhibitor to cetuximab therapy. Overall, these results add to a growing body of evidence suggesting approaches that attempt to match biomarkers to the optimal therapy in HNSCC remains complex and challenging.
Impact of tobacco and alcohol use on HRQOL in patients with advanced head and neck cancer: Results from a community oncology database.
Authors: Fisher Maxine D. , Fernandes Ancilla , Olufade Temitope O , Miller Paul J. , Walker Mark Stephen , Fenton Moon Jung
Published: September 2018

e17512

Background:Tobacco and heavy alcohol use are important risk factors for head and neck (H&N) cancer. H&N cancer may affect activities of daily life (eg, eating, drinking, swallowing), and can be debilitating to health-related quality of life (HRQOL). This study reports HRQOL findings for patients (pts) with advanced H&N cancer eligible for systemic treatment in multimodality or palliative care. Methods:Medical records from pts diagnosed 1/1/2007–10/1/2015 with stage III–IVc H&N cancer and ≥1 disease progression were retrospectively collected from 10 US community oncology practices. We evaluated specific items and composite measures (physical symptoms, treatment effects, distress, despair, ambulation, and performance) with the Patient Care Monitor (PCM), an 86-item pt-recorded outcomes survey. Linear mixed models (LMM) assessed prespecified effects (eg smoking, alcohol use) and change over time across 2 lines of therapy. Results: The study included 462 pts (median age, 61 y; range, 26–99 y). Of these, 81% were male, 77% white, and 21% African American. The most common tumor locations were hypopharynx/larynx (31.1%) and oropharynx (30.9%). Overall, 41.8% of pts were current tobacco users and 22.3% were current or past alcohol abusers/excessive users. No significant difference was observed for receipt of surgery or radiation therapy in the first or second line for either alcohol or tobacco use. Approximately 1240 PCM surveys were collected from 146 pts. LMM showed effects for past tobacco use vs never/undocumented use for sore throat (1.31), dry mouth (1.46), and changes in taste (1.57); P< 0.05. Effects were seen for alcohol use for increased trouble swallowing (1.87; P= 0.01) among current or past abusers/excessive vs never/undocumented users. LMM showed no impacts of tumor location. Models of composite scores showed that after progression, worsening was seen over time for despair (0.57; P= 0.03), impaired ambulation (0.81; P= 0.05) and performance (0.66; P= 0.05). Conclusions: The study showed smoking and alcohol use were associated with worsening clinical symptoms in pts with advanced H&N cancer. Certain composite scores for symptom burden also worsened with progression.
PTEN loss as a predictive biomarker in head and neck squamous cell cancer (HNSCC) patients treated with cetuximab (C).
Authors: Eze Nnamdi , Chung Christine H. , Neumeister Veronique , Sandoval-Schaefer Teresa , Lee Ju-Whei , Burtness Barbara
Published: September 2018

e17520

Background: No biomarker of C resistance has been identified in HNSCC. PTEN loss is present in approximately 30% of HNSCC. Biomarker analysis of the E5397 study suggested that addition of C to cisplatin in R/M HNSCC improves PFS in PTEN high/PIK3CA wild type patients but not those with PTEN loss or PIK3CA mutation. We hypothesized that PTEN testing may aid patient (pt.) selection for C therapy in HNSCC. Methods: MCC15780 was a phase II randomized trial of C plus sorafenib or C plus placebo in R/M HNSCC. 52/56 pts. in this study received C. PTEN analysis using AQUA as previously described was performed on tumor from 38 pts. Automated image capture was performed with HistoRx PM-2000 using the AQUAsition software. AQUA PTEN cut off determined as 1177 based on the first tertile.Fisher’s exact test used to compare low and high expression group. Event-time distributions estimated by Kaplan-Meier and compared using log-rank. Stratified Cox proportional hazards models used to estimate hazard ratios (HR) and test for significance for OS and PFS. All p-values are two-sided. A level of p < 0.05 is considered statistically significant. Results: 12/37 (32%) tumors were PTEN low. There was statistically significant improvement in PFS in PTEN high tumors compared to PTEN low tumors (HR (high/low) =0.33, 95% CI= (0.14, 0.75), p=0.008); and this remains significant after adjusting for age, sex, race, and ethnicity (HR (high/low) =0.27, 95% CI= (0.11, 0.67), p=0.004). Conclusions: PFS is significantly longer in PTEN high tumors compared to PTEN low tumors (HR=0.33, 95% CI= (0.14-0.75), p=0.008) in patients with R/M HNSCC treated with C. This finding remains significant after adjusting for age, sex, race, and ethnicity (HR=0.27, 95% CI= (0.11-0.67), p=0.004).This warrants PTEN analysis of specimens from larger cetuximab-based RCT. [Table: see text]
Prognostic value of pretreatment 18F-FDG PET-CT for nasopharyngeal carcinoma patients.
Authors: Huang Yecai , Feng Mei , He Qiao , Xu Peng , Lang Jinyi
Published: September 2018

e17521

Background: Nasopharyngeal carcinoma (NPC) is a special subtype of head and neck cancer (HNC), there is no highly specific prognostic parameters for NPC. Prognostic value of pretreatment 18F-PET-CT in NPC patient has controversial conclusion. Methods: The prospective and retrospective observational trails which used the 18F-FDG PET to predict the prognosis of the NPC patients were searched in MEDLINE, EMBASE, Cochrane library, CBM, CNKI and VIP (inception to July 2016). Two authors independently assessed study quality and extracted data. Event-free survival (EFS) was considered as the primary endpoint and overall survival rate (OS) was considered as the secondary endpoint. Results: 14 studies and 1,134 patients were included in our analysis. The HR (Hazard ratio) of SUVmax-T, MTV-T and TLG-T for EFS was 1.71 (95% CI, 1.02-2.86, p= 0.04), 2.38 (95%CI 1.53-3.70, p= 0.0001) and 1.65 (95%CI 0.76-3.59, p= 0.21) respectively. Among studies including TLG-T, those with a fixed SUV of 2.5 had an HR 3.55 (95% CI, 1.42–8.84, p= 0.007). The HR of SUVmax-T and MTV-T for OS was 2.19 (95%CI, 1.47-3.27, p= 0.0001) and 2.69 (95% CI, 1.01-7.17, p =0.05). Among studies including MTV-T, those with a fixed SUV of 2.5 had an HR of 4.07 (95% CI, 2.22–7.46, p< 0.00001). Test for predictive value of pretreatment SUVmax-LN, MTV-LN and TLG-LN for EFS and OS showed no significant results ( p> 0.05). Conclusions: We suggested thatSUVmax, MTV and TLG (with a fixed SUV of 2.5) of primary tumor before treatment may be the independent prognostic factors for NPC patients, while SUVmax, MTV and TLG of metastatic lymph node are not.
Determination of the potential of detecting 3q gain as a valuable biomarker in the management of patients with human papilloma virus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC).
Authors: Hegde Upendra P. , Kershnar Eric , Dowsett Robert , Masternak Sophie , Verma Yogita , Tafas Triantafyllos , Kilpatrick Michael
Published: September 2018

e17534

Background: The most recurrent structural chromosomal aberration in HPV associated cervical cancer is gain of the 3q26 locus testing of which has clinical utility in management of patients with cervical lesions. A significant proportion of OPSCC are HPV mediated, suggesting the possibility of a common disease mechanism. The objective of this study is to determine the potential clinical validity of assessing 3q gain as a biomarker in the management of patients with HPV associated OPSCC. Methods: An oral swab using a cytological brush was obtained of the region containing visualized tumor site in newly diagnosed HPV associated OPSCC patients following written informed consent of an IRB approved protocol at the University of Connecticut. The swabs were obtained at the diagnosis and serially after chemotherapy and/or chemo-radiotherapy as well as at 3 months after treatment completion. The specimens’ 3q gain status was determined by fluorescent in situ hybridization (FISH) analysis, utilizing robotic fluorescence microscopy for detection of rare cells demonstrating high 3q26 copy number Results: 54 specimens were collected from 13 patients, of which slides were prepared, hybridized and analyzed from 50. Data was not available in four specimens due to insufficient cells while for eight patients, multiple specimens were obtained before, during and after 3 months of treatment. Depending on the specimen’s cellularity, up to 170,969 cells were analyzed. Cells with > 4 copies of the 3q26 locus were detected in 32 of the 50 analyzable specimens. For several patients, the number of cells with more than four 3q26 signals detected in the later time points of treatment was lower than the number detected at diagnosis. Conclusions:This preliminary dataset demonstrates the ability to detect gain of the 3q26 locus in cells collected by cytological brushing of the region containing an OPSCC. The approach offers the possibility of a minimally invasive method to determine the 3q26 gain status as a reliable biomarker of HPV associated OPSCC that might have value in early diagnosis and management.
Human papillomavirus detection in head and neck squamous cell carcinoma in Turkey.
Authors: Kemal Yasemin , Kemal Ozgur , Kefeli Mehmet , Bel Ayse , Sahin Nilgun , Atmaca Sinan , Koyuncu Mehmet , Yucel Idris
Published: September 2018

e17538

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer worldwide. In Turkey, 5538 new cases and 2340 deaths from head and neck cancer are estimated to occur every year. Tobacco and alcohol are the most important etiological risk factors but in the past three decads tobacco usage is decreased and Human Papilloma Virus (HPV) has changed HNSCC epidemiology. Many new reports suggests that almost 25% of all cases of HNSCC are related to HPV. But its prevelans shows a wide variation among different populations.Today in Turkey HPV positivity in HNSCC is currently not known and this retrospective study aimed to to evaluate the HPV infection in our HNSCC patients. Methods: We included 125 HNSCC patients diagnosed and treated in our hospital beween January 2010 and December 2016. Oral cavity, oropharyngeal, laryngeal and hypopharyngeal cancers were included. Nasopharyngeal and salivary gland cancers were exculuded. Head and neck cancer tissue samples fixed using 10% Neutral Buffered Formalin and embedded blocks were used. From an initial evaluation of 125 patients records 77 of the paients blocks could be adequate for the HPV testing. Detection and genotyping of HPV genotypes were done using a polymerase chain reaction (PCR) protocol. Results: PCR amplification was succesful in 61 of 77 patients. Among the 61 HNSCC patients only 3 patients were HPV positive(4.9 %). HPV 16 subtype was detected in one patient who was 70 years old male, stage III laryngeal cancer with a smoking history. The subtypes detected in other two patients were different from 16 and 18. One of these patients was 42 years old nonsmoker female stage IVa hypopharyngeal cancer and the other one was 56 years old smoker male with stage II oropharyngeal cancer. Conclusions: In Turkey, this is the first study that evaluated HPV positivity in HNSCC. Our results suggest a low prevelance of HPV in Turkish HNSCC patients; large scale population based studies are needed to confirm our findings.
Prognostic neutrophil-to-lymphocyte ratio in head and neck cancer: A single center experience.
Authors: Ziranu Pina , Massa Elena , Puzzoni Marco , Demurtas Laura , Madeddu Clelia , Pusole Grazia , Cubeddu Alessio , Astara Giorgio , Mascia Roberta , Pusceddu Valeria , Pretta Andrea , Dessi Mariele , Atzori Francesco , Lai Eleonora , Tolu Simona , Liscia Nicole , Pireddu Anna Grazia , Impera Valentino , Puxeddu Roberto , Scartozzi Mario
Published: September 2018

e17540

Background: The Neutrophil-to-Lymphocytes ratio (NLR) represents a potential prognostic and predictive marker in a different tumor types. The purpose of our study was to investigate the prognostic value of the pretreatment inflammatory marker NLR in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Pretreatment NLR were retrospectively investigated for correlation with overall survival (OS). Kaplan-Meier statistic and long rang test were used. Univariate analysis for categorical and descriptive variables were performed. Results: Thirty-nine patients, from local to advanced stage disease, were included in our analysis. At a median follow up of 9.44 months (2.04 – 30.3), of the total patients 30.7% died and 41.9% had progression of disease. The median PFS was 4.6 months (2.9 – 27.2) and the median OS (mOS) was 18.9 months. Following ROC curve analysis the optimum cut-off value of NLR was 3.93 (p = 0.017). Patient with NLR > 3.92 had a mOS of 11.9 months, whereas the mOS for NLR ≤ 3.92 was 30.3 months (Log-rank p = 0.189). The 1 year Kaplan-Meier estimates of OS for NLR ≤ 3.92 vs. >3.92 was 72% vs. 45% respectively (Log-rank p = 0.243). According to COX univariate analysis, the risk of death increases of 7.7% each unitary rise of NLR mean value (p = 0.3407). Conclusions: In our limited case series NLR was not significantly associated with clinical outcome. Therefore, multicenter studied are needed to determine an optimal NLR cutoff value. [Table: see text]
Immunologically relevant gene expression as prognostic biomarker in squamous cell carcinoma of the head and neck.
Authors: Pierce Andrew , Secrier Maria , Jones Emma V , Stokes Michael , Shire Norah , Barker Craig , Harrington Elizabeth A. , Barrett J Carl , Angell Helen
Published: September 2018

e17542

Background: Expression of genes known to be integral to anti-tumour activity may be prognostic for patient outcomes in SCCHN. We hypothesized that broad categories of immune function would be responsible for anti-tumor activity. Methods: A study was conducted using data from patient medical records and analysis of archival tumour samples. Patients were ≥18 years old, diagnosed with SCCHN between 1989 and 2015 (n = 119). We quantified the expression of an annotated list of 71 aggregated genes selected to represent a variety of immunological activities: chemokines and receptors, interferon gamma stimulated genes, immunological checkpoints, HLA class I and II molecules, T cell activation, T cell surface markers, adhesion molecules, cytotoxic granules, immune suppression, inflammation, NK cell associated genes and ‘other functionality’. Results: Using a Cox proportional hazards model starting from consideration of the initial 71 genes and performing 10-fold cross-validation with 100 repetitions, several prognostic gene signatures were derived with overall survival hazard ratios > 2.8 and concordance indexes > 0.7, 95% confidence intervals ranging between [0.709, 0.805]. The signatures remained significantly predictive of outcome when accounting for tumour stage, sex and age of patients, HPV status and smoking habits. A cumulative score per sample taking into account the directionality of association of each gene with outcome and its corresponding expression was derived and this score outperformed tumour staging in distinguishing survival outcomes. The genes CD274 (PD-L1; checkpoints), CD8A (T cell surface markers), CCL11 (chemokines and receptors), GNLY (cytotoxic granules), TNFRSF10A (immune suppression), and EDN1 (other) appeared in all signatures, validating our approach of considering broad categories of functionality to represent the anti-tumor immune system response as an integrated whole. Conclusions: Identification of a prognostic gene signature may have additional utility for evaluating early response to therapy by assessing whether therapy has converted a patient tumour from a prognostically unfavourable to prognostically favourable gene signature status.
AUM voice prosthesis: A $1 novel modified tracheo-esophageal voice prosthesis for total laryngectomy patients (TEP).
Authors: Rao Vishal Uchila Shishir , Chatterjee Sataksi
Published: September 2018

e17549

Background: Patients undergoing total laryngectomy require subsequent voice rehabilitation, which can be done by different modalities. The tracheo-esophageal voice prosthesis provides the clarity of speech and has a high rate of success in terms of acquisition of post laryngectomy speech.In this pilot study we evaluate the functionality of a modified trachea- oesophageal prosthesis to be used in primary and secondary trachea- esophageal puncture in 30 patients of total laryngectomy. Methods: This study was conducted at Health care Global Cancer Centre to evaluate the role of a novel trachea-oesophageal prosthesis for total laryngectomy +/- partial pharyngectomy patients from 2015-2016. 30 patients will be enrolled as an inpatient or outpatient. Post TEP insertion evaluation: Patients, who are undergoing primary TEP insertion, will be evaluated for speech/ voice interval of 6weeks, 12 weeks and 6 months. Objective assessment of speech Assessment of the incidence of TEP leak clinically after a test fluid feed. Through the prosthesis (intra TEP leak) Around the TEP leak (peri TEP leak) Assessment of the extrusion rate of the TEP device Assessment of the complication rate associated with the procedure/TEP Results: On objective assemsmsent of speech, all patients (100%) used prosthesis were able able to phonate and communicate using intelligible speech. 10% patients developed intra TEP leak immediately after insertion of prosthesis, 6% within 3 months of insertion, & 3% developed peri tep leak. All patients were immedaitely given a repalcement prosthesis and leaks corrected. Extrusion was seen in 3% of the patients. None reported any complications. Conclusions: Aum voice prosthesis is a excellent and affrodable tracheo oesophageal prosthetic device to enable and empower patients speeech rehabilitation. Clinical trial information: NCT03039465.
The influence of cisplatin de-escalation on survival outcomes in oropharyngeal head and neck squamous cell carcinoma (OPC).
Authors: Peters Geoffrey David , Milne Robin , Bernard Anne , Roberts Kate Elizabeth , Foote Matthew C , Panizza Benedict , Porceddu Sandro Virgilio , Coward Jermaine
Published: September 2018

e17551

Background: Chemoradiotherapy (CRT) with 3 cycles (#) of high-dose cisplatin (HDC) (100mg/m2 weeks 1,4 & 7) and 70Gy over 7 weeks is associated with improved overall survival (OS) compared with radiotherapy (RT) alone in locally advanced OPC. Human Papilloma Virus (HPV) related tumours have superior outcomes and de-escalating treatment is a contemporary issue. Our study objectives were to determine if 2# HDC were non-inferior to 3#, how this was influenced by prognostic factors including stage, smoking history and p16 status, and to explore toxicity attributed to HDC. Methods: A single centre, retrospective analysis was undertaken for OPC patients who received CRT with HDC between Oct 2009 -Dec 2012. Those with distant metastatic disease or receiving induction chemotherapy were excluded. Data extracted included HPV and smoking status, tumour stage by 7thEd AJCC TNM and ICON-S classification, # HDC completed, toxicity and OS. Log-rank test was used for OS analysis. Results: 63, 96 and 4 patients received 3, 2 and 1 # HDC respectively. Median RT dose was 70Gy (range 66-70). 110 (67.5%) were p16 +, 28 (17.2%) were p16 negative and 25 (15.3%) unknown. 52 had omission of #3 HDC predominantly due to neutropenia (33%), nephrotoxicity (23%) and ototoxicity (12%). 19 had delays in #2 HDC resulting in omission of #3 due to completion of RT. There was no difference in OS between 3 #(mean OS (yrs)+/- SEM: 6.05+/- 0.22) or 2# HDC (5.70+/- 0.21) in all comers (p = 0.255). For RTOG0129 low risk p16+ patients, there was no significant difference (p = 0.896) between 3# (6.33+/- 0.24; n = 24) and 2# (6.18+/- 0.25; n = 44) HDC. Similar results were evident for ICON-S stage I for 3# (6.36+/-0.19; n = 25) vs 2# (6.30+/- 0.19; n = 42) HDC (p = 0.932). For RTOG 0129 intermediate risk p16 + OPC there was a significant difference (p = 0.017) in OS favouring 3# (6.29+/-0.22; n = 20) versus 2# (4.81+/-0.67; n = 10) HDC. For p16 negative patients there was no difference (p = 0.265) in OS between 3# (4.06+/-0.94; n = 9) and 2# (5.17+/-0.48; n = 22) HDC. Conclusions: This data suggests that cisplatin de-escalation does not confer inferior OS in low risk HPV related OPC. Significant toxicities with HDC influenced the ability to complete prescribed treatment.
Neoadjuvant chemotherapy plus concomitant chemoradiation versus concomitant chemoradiation for locoregionally advanced nasopharyngeal carcinoma: A systematic review and meta-analysis of comparative studies.
Authors: Tan Teng Hwee , Soon Yu Yang , Cheo Timothy , Tey Jeremy Chee Seong , Tham Ivan Weng Keong
Published: September 2018

e17552

Background: To determine if addition of neoadjuvant chemotherapy (NACT) to concomitant chemoradiation (CCRT) for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) improves overall survival. Methods: We searched MEDLINE for eligible studies comparing NACT plus CCRT versus (vs) CCRT alone for locoregionally advanced NPC. We assessed the methodological quality of the included studies using the MERGE criteria. We performed the meta-analysis with random effects model using Revman 5.3 to estimate the pooled hazard ratios (HR), confidence intervals (CI), P values (P) and I squared statistic (I2). The primary outcome was overall survival (OS); secondary outcomes include progression-free survival (PFS) and adverse events (AE). We used the GRADE approach to appraise the quality of evidence from randomized trials. Results: We found four randomized and five retrospective comparative studies including 2178 patients with low to moderate risk of bias in their methodologic quality. Pooled estimates from both randomized and retrospective studies demonstrated a benefit in PFS (HR 0.78, 95% CI 0.66 to 0.93, P = 0.006, I2 = 0%) and OS (HR 0.77, 95% CI 0.61 to 0.96, P = 0.02, I2 = 0%) with NACT. In the randomized trials, there was moderate quality evidence that NACT improved PFS significantly (HR 0.73, 95% CI 0.57 to 0.93, P = 0.01, I2 = 0%); trend towards OS benefit (HR 0.76, 95% CI 0.56 to 1.03, P = 0.08, I2= 0%) and was associated with more frequent AE. There were no significant differences in the results between the randomized and retrospective comparative studies (PFS HR 0.73 vs 0.82, interaction P (IP) = 0.58; OS HR 0.76 vs 0.78, IP = 0.93). Conclusions: Neoadjuvant chemotherapy delays disease progression substantially and may improve survival for locoregionally advanced nasopharyngeal carcinoma. There were no divergent results between randomized and retrospective comparative studies. Future trials should test more effective and/or better tolerated agents during the neoadjuvant therapy phase.