bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment timing of life-extending therapies and adherence of corticosteroids among metastatic castration-resistant prostate cancer patients with conditions sensitive to corticosteroid use.
Authors: Bui Cat N , Spalding James , Wang Li , Baser Onur
Published: March 2020

e16080

Background: Corticosteroids (CS) have been integral in metastatic castration-resistant prostate cancer (mCRPC) treatment and can be used alongside life-extending therapies (LETs), despite potential toxicity effects. LET and CS timing and adherence were examined in CRPC patients in the Veterans Health Administration (VHA) dataset with conditions sensitive to CS use. Methods: Diagnosed prostate cancer patients with evidence of medical/surgical castration, at least two following prostate-specific antigen (PSA) increases (third PSA value date was the index), and ≥1 claim for cabazitaxel, docetaxel, or abiraterone acetate 06/2007-05/2012 were examined. Adherence was the total overlapping days of CS and LET prescriptions divided by total LET prescription days (≥0.8). Comorbid conditions were measured for 6 months pre-index date. Descriptive analysis, Cox proportional hazards, and logistic regression models summarized therapeutic/clinical features of CRPC or the CS-adherent patient subset. Results: Common CS-sensitive conditions among 15,585 mCRPC patients included hypertension (58.94%) and hyperlipidemia (42.56%). Fewer glaucoma (hazard ratio [HR]: 0.67), ischemic heart disease (HR: 0.78), and peripheral vascular disease (HR: 0.78) patients were prescribed LETs (all p<0.01). mCRPC treated patients with comorbidities (N=858) were significantly older (71.27 vs. 68.94 years, p<0.01) and more often exhibited bone metastases than those without (42.42% vs. 29.73%, p<0.01). After treatment initiation, mCRPC patients with comorbidities had a shorter LET duration (125.02 vs. 133.08 days, p=0.04) within the 6-month follow-up period. Factors associated with reduced CS adherence (≥0.8) included cerebrovascular disease (odds ratio=0.0107, 95% CI: 0.012-0.966) and peripheral vascular disease (odds ratio=0.523, 95% CI: 0.276-0.991). Conclusions: Conditions sensitive to CS influence the LET receipt and duration and are associated with lower adherence when compared to non-CS-sensitive conditions. Attention should be focused on treatments using alternatives to CS for sensitive mCRPC patients.
Japanese nationwide multi-institutional cohort study of prostate cancer brachytherapy with permanent seed implantation.
Authors: Saito Shiro , Ito Kazuto , Yorozu Atsunori , Aoki Manabu , Koga Hirofumi , Satoh Takefumi , Ohashi Toshio , Shigematsu Naoyuki , Daimon Takashi , Kojima Shinsuke , Dokiya Takushi , Fukushima Masanori , Yamanaka Hidetoshi
Published: March 2020

e16090

Background: Brachytherapy with permanent iodine-125 seed implantation (PI) has been approved in 2003 in Japan. Multi-institutional cohort study (Japanese Prostate Cancer Outcome Study of Permanent Seed Implantation; J-POPS, NCT00534196) assessing the treatment feature, efficacy, safety and health-related quality of life (QOL) has started in July 2005. Six thousand nine hundred and twenty-seven cases were enrolled to this study until December 2010 from 68 institutes around the country, which is approximately 40% of all the cases treated in Japan at that time. Methods: Patient’s background, cancer character, treatment feature such as combined therapy of external beam or hormone, post PI dosimetric information, treatment efficacy with PSA level, voiding symptoms with IPSS and treatment related adverse events according to NCI-CTCAE are investigated. PSA was measured every 3 months and symptoms accompanied to the treatment were assessed 3 to 6 months after the treatment. Backgrounds and treatment assessments of 2,341 patients enrolled in J-POPS during the initial 2 years are evaluated. Results: Patients’ age ranged from 45 to 89 (median 69) year-old and 99.0% of the cases were performance status 0 (ECOG criteria). Family history of prostate cancer was seen in 6.2%. PSA levels on cancer diagnosis were 1.60 to 42.0 (mean 6.80) ng/ml, clinical stage T2a or less was 89.9%, T2b was 5.2%, T2c was 2.9% and T3a-T3b was 0.8%. Gleason score (GS) less than 7 was 56.6%, GS 7 was 39.7%, and GS above 7 was 3.6%. According to NCCN risk classification, 44.2% was classified as low risk, 48.3% as intermediate risk and 5.7% as high risk. Androgen deprivation therapy (ADT) was performed in 48.5% of the patients and 23.4% was combined with external beam radiation therapy (EBRT). CT scan based first post therapeutic month dosimetry revealed that prostatic mean V100 and D90 for the cases treated with seed alone were 94.8% and 160.7 Gy, respectively. As for adequate control of radiation dose at rectum (mean R100 = 0.3 cc) and urethra (mean D5 = 223.4 Gy), high grade toxicities appeared very seldom. Conclusions: Outcomes of J-POPS will produce clinical evidence of PI that can be internationally accepted.
Efficacy and safety of docetaxel-based chemotherapy in Japanese men over 80 years old with castration-resistant prostate cancer.
Authors: Kosaka Takeo , Yasumizu Yota , Mizuno Ryuichi , Miyajima Akira , Kikuchi Eiji , Shinya Morita , Kono Hidaka , Nakagawa Ken , Oya Mototsugu
Published: March 2020

e16094

Background: Docetaxel-based chemotherapy is widely used to treat castration-resistant prostate cancer (CRPC). However, its efficacy in elderly males has not yet been fully elucidated. In Japan, the number of elderly CRPC patients continues to increase. Therefore, it is urgently necessary to evaluate the effect of docetaxel-based chemotherapy in elderly Japanese men with CRPC. Methods: Sixty-eight male patients with CRPC who were treated with first-line docetaxel-based chemotherapy in a single institution from 2006 to 2011 were evaluated retrospectively. Results: The median age was 72.4 ± 6.5 years. Ten patients (14.7 %) were ≥ 80 years old (older group), and 58 (85.3 %) were < 80 years old (younger group). All patients received docetaxel at a dose of 75 mg/m2 once every 3 weeks, and prednisolone 10 mg was given every day orally. The prostate-specific antigen (PSA) levels of the older and younger groups before docetaxel-based chemotherapy were 41.2 ± 37.4 ng/ml and 106.5 ± 184.7 ng/ml, respectively (P = 0.273). The PSA doubling times before docetaxel-based chemotherapy were 91.6 ± 92.6 days and 92.5 ± 91.9 days, respectively (P = 0.977). The performance status of the older group was 0 or 1. In the same group, 7 patients (70.0%) achieved a PSA decline of ≥ 30% and 4 patients (40.0%) achieved a PSA decline of ≥ 50%. In the younger group, the PSA decline was ≥ 30% in 37 patients (63.8%) and ≥ 50% in 26 patients (44.8%). The PSA decline rates of ≥ 30% and ≥ 50% were not significantly different between the two groups (p = 0.68 and p = 0.75, respectively). Progression-free survival (PFS) was also not significantly different between the two groups (PFS 5.3 vs. 7.3 months, p = 0.39). The major grade 3–4 toxicities were myelosuppression. Grade 3/4 neutropenia occurred in 80.0% of the older group and 78.0% of the younger group, and Grade 4 neutropenia occurred in 20.0% of the older group and 24.2% of the younger group. There were no significant differences between the two groups (Grade 3/4; p = 0.89, Grade 4; p = 0.79). Conclusions: Docetaxel-based chemotherapy showed a significant effect with a tolerable adverse event rate in elderly Japanese males over 80 years old with castration-resistant prostate cancer.
Effect of weekly administration of bevacizumab, eribulin, and oxalilplatin in patients with heavily pretreated serous ovarian carcinoma.
Authors: Ikeda Yuji , Takano Masashi , Sasaki Naoki , Kita Tsunekazu , Kikuchi Yoshihiro , Kudoh Kazuya
Published: March 2020

e16506

Background: Eribulin, inhibiting a protein component of tubulin, extend the lifespan of patients with late-stage breast cancer who are not benefiting paclitaxel. Bevacizumab (B) is known to enhance chemotherapeutic efficacy of platinum agents. We evaluated the effect of weekly administration of B with eribulin and oxaliplatin (EriOX) in recurrent or refractory serous ovarian carcinoma patients (ROC) pretreated with paclitaxel and carboplatin. Methods: Thirteen patients with ROC had treated with weekly-B and EriOX consisting of B (2mg/kg), eribulin (1mg/m2) and oxaliplatin (30mg/m2). The response and adverse effects (AE) were evaluated using the response evaluation criteria in solid tumors (RECIST), CA125 Gynecologic Cancer Intergroup (GCIG) criteria, and common terminology criteria for adverse events (CTCAE) version 4.0. Results: One patient is still under treatment of two cycles. We evaluated 12 patients at least two or more cycles of weekly B and EriOX. Ten patients (83%) were primarily stage 3 or 4. Ten patients (83%) had received three or more regimens of chemotherapy. All patients were pretreated with paclitaxel and carboplatin and 9 patients (75%) had been pretreated with platinum containing regimen within 6 months. According to the RECIST evaluation, 2 patients (17%) had a complete response (CR), 1 patient (8%) had a partial remission (PR) and 3 patients (25%) had a stable disease (SD). The response rate (CR+PR) and clinical benefit rate (CR+PR+SD) were 25% and 50%, respectively. Median progression-free survival was 3 months (range: 1-5 months). Hematological AEs with grade 3/4 were observed in 2 patients (17%). Hypo albuminemia and edema with grade 3 were in 1 patient (8%), respectively. However, all AE were manageable and torelable. Conclusions: Weekly B and EriOX administration had significant activity with mild AE in patients with paclitaxel and platinum resistant ROC. These results warrant further prospective study.
Time to vulva cancer relapses in dependence on different factors.
Authors: Nerodo Galina , Ivanova Victoria Aleksandrovna , Nerodo Ekaterina Alekseevna
Published: March 2020

e16513

Background: The time to relapses was investigated in dependence on different factors. Methods: We examined 809 vulva cancer patients to evaluate frequency and average time to relapse depending on grades, invasion depth and method of treatment. Results: We found out that 25.09% (203 from 809) of patients had a relapse. For the I grade the relapse was observed in 18.29% patients after 59.3 months on average, for the II grade – in 20.5% after 46.9 months, for the III grade – in 26.6% after 16.8 months, for the IV grade – in 46.2% patients after 7.2 months respectively. The patients of the II grade with tumor invasion of 1-2 mm had a relapse after 61.2 months, with invasion of 3-4 mm – after 42.1, with more than 5 mm – after 38.5 months on average correspondingly. For patients of the III grade with tumor invasion less than 5 mm the average time to relapse was 19.9 months, with invasion more than 5 mm – 12.6 months. There is not significant difference between the times to relapses of early grades patients treated with combined method or complex method with chemotherapy. However for the patients of the III grade the chemotherapy has prolonged the time to relapse from 13.5 to 18.1 months. Conclusions: The relapses of vulva cancer were observed in 25.09% of all patients. The grade, depth of invasion and chemotherapy as a part of complex treatment of III-IV grades patients have considerable influence on the time to relapse.
Structural indices of erythrocytes membrane in patients with vulvar cancer.
Authors: Goroshinskaya Irina Aleksandrovna , Nerodo Galina , Nemashkalova Ludmila Anatolievna , Surikova Ekaterina Igorevna , Nerodo Ekaterina Alekseevna
Published: March 2020

e16515

Background: The analysis of membranes flow property in the zone of protein and lipid contacts, and of proteins submergence degree into lipid erythrocytes membrane bilayer in patients with vulvar cancer. Methods: 34 patients with vulvar cancer at the different stages of the disease were examined. We studied the characteristics of blood erythrocytes membranes with the use of pyrene probe: flow of protein and lipid contacts zones and lipid bilayer, submergence of proteins into lipid bilayer. Results: The analysis of the data received showed, that the most interesting results were obtained during the study of proteins submergence level. In the group with vulva primary tumor the level of proteins submergence into erythrocytes membrane lipid matrix was authentically higher than 25.9% (0.243±0.012, p < 0.001) as compared with the index the healthy women have (0.193±0.006). The degree of proteins submergence into lipid matrix of the patients, being at the state of remission, was decreasing by 25.1% (0.182±0.013, p < 0.01), as compared with the index in the group with primary tumor, achieving the level of the healthy women. Subsequently, during the progress of the relapse, the proteins submergence increased again (0.242±0.019, p < 0.01), achieving the indices in the group with primary tumor. Also, membrane flow property in the zone of protein and lipid contacts was increasing by 25.1% (0.564±0.053, p < 0.05) in the group with relapse, as compared with the group of the primary tumor (0.451±0.017). Conclusions: According to our observations, the increase of proteins submergence into erythrocytes membrane lipid matrix in patients with vulva cancer in remission preceded the clinical manifestation of the disease’s relapse, thus showing the prognostic significance of blood erythrocytes membranes studying during the progress of vulvar cancer.
Ovarian granulosa cell tumors: Experience of National Institute of Oncology in Morocco.
Authors: Sekkate Sakina , Kairouani Mouna , Serji Badr , el Ghissassi Brahim , Mrabti Hind , Errihani Hassan
Published: March 2020

e16527

Background: The granulosa cell tumors are malignancies with a relatively favorable prognosis. They are characterized by prolonged natural history and tendency to late recurrences. The aim of this study is to investigate the epidemiological and pathological characteristics of granulosa cell tumors, and the prognosis factor for recurrences in the national institute of oncology in Rabat in Morocco. Methods: The clinical data of patients with adult granulosa cell tumors of the ovary treated from January 2003 to december 2010 was investigated retrospectively. Data of age, clinical manifestation, imaging, diagnosis, treatment and follow up of the patients were reviewed and analyzed. Histology was obtained in postoperative for all patients. Results: Twenty-seven cases were retrieved. The median age was 53 years. The most common clinical manifestations at diagnosis were: abdominal pain, vaginal bleeding, abdominal distension and hormonal manifestations. The mean tumor size was 14 cm. The majority of patients had stage I (62,96%, n = 17), while (18,51%, n = 5) had stage III, (7,4%, n = 2) had stage IV, and (11,11%, n = 3) of patients had unknown stage.8 patients received adjuvant chemotherapy (4 : bleomycin etoposide, cisplatin (BEP); 1: bleomycin vepeside cisplatin (BVP); 1: endoxan cisplatin; 1: paclitaxel cisplatin; 1: tamoxifene), and 2 patients received chemotherapy for metastatic disease.For a median follow up of 63,44 months, 5 (18,51%) of patients relapsed. The median time to relapse was 41,8 months, (range : 18-62 months).The overall 5-year survival and 9-year survival rates for all stages were 91.3% and 77.3%, respectively. Following univariate Cox regression modeling, the survival depends on stage, it’s better in localized stages (p = 0,05). Conclusions: Granulosa cell tumor of the ovary is an uncommon neoplasm. The adult form progresses slowly and often is diagnosed in an early stage of disease. Surgery is indicated. A prolonged post therapeutic follow-up is necessary because of the risk of recurrences, late and exceptional for the adult form.
Bevacizumab-based therapy in patients with heavily pretreated ovarian and other Mullerian tract cancers.
Authors: Kurbacher Jutta Anna , Lepique Jutta , Herz Susanne , Wessling Gabriele , Kurbacher Christian M.
Published: March 2020

e16533

Background: Bevacizumab (Bev) is approved for the therapy (Tx) of primary and platinum-sensitive recurrent Mullerian tract cancers (MTC) such as ovarian (OC), fallopian tube (FTC), type II endometrial (EC-II), and peritoneal papillary-serous carcinomas (PPSC). However, the role of Bev in the ≥ 3rd line Tx of MTCs is still unclear.This retrospective study summarizes our long-term experiences with Bev in patients (pts) with heavily pretreated MTC who did not qualify for recruitment into a controlled clinical trial. Methods: A total of 74 intensively pretreated MTC pts (OC, n = 65; FTC, n = 2; EC-II, n = 4; PPSC, n = 3) were included in this study with 43 (58.1%) being platinum-resistant. Pts had failed a median of 4 (range 1-10) prior chemotherapies (CTx ). Tx included Bev monotherapy (group A, n = 17), Bev + metronomic CTx (group B, n = 37), and Bev + conventionally dosed CTx (Group C, n=20). Bev was administered at either 10 mg/kg BW q2w or 15 mg/kg BW q3w. Adverse effects were classified according to CTCAE Vs 4.03. TTP was calculated from the start of Bev until progression, OS was calculated from the start of Bev until death or loss to follow up. Results: Most common Tx related toxicities were hypertension, proteinuria, headache, inflammation/infection, epistaxis, and subileus. Hypertension which often required adequate treatment was limiting in only one case as also were renal toxicity and infection. Median TTP was 27.8 wks and median OS was 53.6 wks with no significant difference between platinum-resistant and –sensitive pts. In regard to both TTP and OS, there was a non-significant trend favoring groups A (33.4/63.0 wks) and B (29.9/61.6 wks) vs group C (19.2/35.4 wks). Conclusions: Bev based Tx was active and generally well tolerated in this hard-to-treat population of pts with recurrent MTC. Both TTP and OS were equal or even superior to any conventional CTx used in this setting. Moreover, clinical platinum-resistance did not predict a worse clinical outcome. Although this is not a randomized trial, our results argue in favor that Bev should be preferably given either as single agent or combined with metronomic CTx in pts with heavily pretreated MTCs. Further clinical trials of Bev in recurrent MTCs may prove useful.
Perioperative epidural analgesia and recurrence-free survival for ovarian cancer surgery: A retrospective analysis.
Authors: Koensgen Dominique , Mustea Alexander , Rosanowski Barbara , Leutzow Bianca , Hesse Thomas , Patrzyk Maciej , Heidecke Claus Dieter , Zygmunt Marek , Wendt Michael , Usichenko Taras
Published: March 2020

e16534

Background: Current experimental and clinical data suggest that perioperative factors may influence the long-term outcome after cancer surgery. Recent retrospective analyses have shown the reduction of cancer recurrence and metastatic spread in patients after tumor surgery receiving perioperative regional and neuraxial analgesia. The aim was to investigate whether perioperative epidural anesthesia is associated with the decreased disease recurrence and increased survival after primary tumor debulking in patients with ovarian cancer. Methods: Retrospective analysis of consecutive patients with primary ovarian cancer who underwent radical multivisceral surgery between 01/2003 and 12/2010 under either general anesthesia plus opioid analgesia (group A) or general anesthesia plus epidural anesthesia (group B), was performed. Cancer recurrence-free survival and total survival times after surgery were compared between the groups using Mann-Whitney test. The analysis was strengthened by Kaplan-Meier survival estimates for each group with comparison using the log-rank test. Results: Data of 105 (88%) of patients (group A: 33; group B: 72) were available for analysis. The median (interquartile range-IQR) follow-up time 27 (17-58) months. The groups were comparable regarding age, body-mass index, ASA physiological status, FIGO staging, tumor residual and use of adjuvant platinum-based chemotherapy. The median (IQR) time to recurrence of cancer was 31 (15-63) months in group A vs. 18 (10-35) months in group B (p = 0.017). Longer recurrence-free survival was associated with general anesthesia and opioid analgesia (hazard ratio 1.52; 95% confidence interval 1.4-1.56; p = 0.008). Conclusions: In contrast to previous investigations, perioperative epidural anesthesia was associated with decreased survival in patients after ovarian cancer surgery.
Correlation of in vitro chemotherapy drug resistance assay to clinical response to carboplatin and paclitaxel combination chemotherapy in ovarian carcinoma.
Authors: Cheng Kit , Shapira Iuliana , Rosen Lisa M , John Veena S. , Lovecchio John L. , Menzin Andrew , Whyte Jill Suzanne , Dos Santos Lisa A. , Contreras Diana , Shih Karin , Roy Rajasree , Lee Annette , Hayes Christi , Ahmad Nazish , Tandon Pragati , Hoffman Mark Allan
Published: March 2020

e16546

Background: Carboplatin sensitivity in drug resistance assays has been shown to be an independent predictor of longer progression free interval with conflicting results in overall survival. We evaluated in vitro drug resistance for carboplatin and paclitaxel combination and its correlation with progression free survival (PFS) and overall survival (OS). Methods: From April 1, 2006 to December 12, 2011, in vitro drug resistance assays were sent after cytoreductive surgery for primary epithelial ovarian cancer. Patients were analyzed according to drug resistance scoring system of low drug resistance (S), intermediate drug resistance (I), and extreme drug resistance (R). Retrospective chart review was performed to evaluate PFS and OS. The Kaplan Meier product limit method was used to estimate OS and PFS. Survival curves were compared between groups using the log rank test. Results: From a total of 142 patients: 57 were S, 52 I, and 33 R; 77% were responsive (S+I) to carboplatin and paclitaxel combination. At median follow-up of 18 months, PFS and OS rates were 58.1 and 91.3% respectively for S, 66.1 and 78.7% for I, and 43.2% and 84.3% for R. At 36 months, the PFS and OS rates were 52.3 and 61.1% for S, 51.3 and 55.3% for I and 39.3% and 48.7% for R. There was OS advantage between the S and I compared to R. There were no significant differences in PFS curves (p<0.281) or OS curves (p<0.46). Conclusions: Although sensitivity to carboplatin/ paclitaxel resulted in longer OS, the results were not statistically significant. Our cohorts were small and we may not have had the power to capture statistical significance. A larger multicenter analysis would be needed to further evaluate this finding. In addition, one of the regimens our patients received on relapse was bevacizumab which was not evaluated in the in vitro assay sensitivity assay. Bevacizumab has also been included in first line treatment in combination with platinum/ taxane regimen. Future analysis of in vitro assays may need to include biologics.
The chemotaxis study of adipose derived stem cells (ADSCs) to adenoid cystic carcinoma (ACC) cells.
Authors: Hua Li , Zhengxue Han
Published: March 2020

e17000

Background: Adenoid cystic carcinoma (ACC) has some properties such as neurotropic, angiotropic and early metastasis, recurrence and metastasis is the leading cause of poor prognosis in sACC. The current theory is that the invasion and metastasis were related to tumor stem cells, and the stem cell microenvironment play an important role in this process. According to the stem cell theory, we hypothesized that normal tissue stem cells may also produce chemotactic migration to tumor stem cell microenvironment, therefore this research was to explore the possibility of adipose derived stem cells as a therapy vector targeted to the microenvironment of ACC. Methods: Conventionally culture ACC cells to logarithmic growth phase, then collected them and cultured in serum-free medium. After 48 h, the culture supernatant was collected, filtered and prewarmed, and then added to each well (24-well plate, the lower chamber of the transwell chamber), 600-800 ul for each. Using the same method, the culture supernatant of T293 cells were joined into the lower chamber as a control. Then, the transwell membrane was gently placed into the well, and 100 ~ 150μl suspension of adipose derived stem cells in the logarithmic growth phase (serum-free media) were added into the upper chamber. After cultured under routine conditions for 24 hours, the transwell chamber were removed , fixed and stained. Under bright field microscope, cells invasived and attached to the transwell membrane were observed and counted, results were statistically analyzed by student test. Results: Selecte five high-power microscopic field randomly, counted the number of adipose derived stem cells migrated to transwell membrane of different cell lines. Results showed that migrated cell number of SACC-LM group was 64.3 ± 7.6, the number of SACC-83 group was 52.3 ± 6.1, both higher than the T293 group (31.8 ± 6.3), and the difference between them was statistically significant (p <0.05). Conclusions: Adipose derived stem cells have obvious chemotaxis to adenoid cystic carcinoma cell culture supernatants, so we can propose that adipose derived stem cells has the possibility and feasibiliy of being used as a targeted therapy vectors for ACC.
Prognostic markers for oropharyngeal cancer after docetaxel, 5-FU, and cisplatin induction chemotherapy followed by concurrent chemoradiotherapy.
Authors: Cho Sang-Hee , Bae Woo Kyun , Shim Hyun-Jeong , Choi Won-young , Hwang Jun-Eul , Choi Yoo-Duk , Lim Sang-Chul , Chung Ik-Joo
Published: March 2020

e17005

Background: HPV is associated with prognosis of oropharyngeal cancer, and the incidence has been increased in not only western countries, but also Asian. This study aims to assess the prognostic role of HPV expression and clinical factors after induction chemotherapy followed by chemoradiotherapy for locally advanced oropharyngeal cancer in Korean patients. Methods: A retrospective review of 74 patients with known HPV status and treated with the induction chemotherapy of docetaxel, cisplatin and 5-FU followed by chemoradiotherapy was performed. HPV infection was evaluated with in situ hybridization (ISH) for HPV and p16 protein expression. Results: The median age is 65 (range 43-80) years with male 69, female 5. Among them, 36 patients (49%) are current smokers and 17 patients (23%) are heavy drinkers. Nine patients (12%) show HPV positive in ISH and 35 patients (47%) expressed p16 protein. In response analysis, there is an increasing trend of complete response (CR) in p16 positive patients (34.3%) compared with p16 negative patients (17.9%; P=0.055). HPV expression had no significance with CR. Tumor recurrence showed significantly higher in HPV-negative patients (P=0.044) and p16 (P=0.015) than HPV and p16 positive patients, respectively. In survival analysis, even though the median value was not reached until this time, it showed better trend of PFS in p16 positive patients than p16 negative patients (P=0.072). In univariate analysis of HPV status and clinical parameters, the expression of p16 or HPV had no significant association with survival. However, performance status (PS), T staging, tumor response are significant factors associated with PFS. And PS (0 vs. 1-2) showed a strong relation with PFS in multivariate analysis (HR: 0.24, P=0.001) Conclusions: p16 is a prognostic marker for oropharyngeal cancer patients treated with triple induction chemotherapy followed by CRT and it would be a better surrogate marker for HPV infection than HPV ISH. In addition to biomarker, clinical parameter such as PS has been still important factor of treatment outcome in oropharyngeal cancer patients.
Predicitve factors of cisplatin (CDDP) discontinuation in concurrent chemoradiotherapy (CCRT) to locally advanced head and neck cancer patients.
Authors: Nakano Kenji , Sato Yasuyoshi , Sato Yukiko , Toshiyasu Takashi , Asari Takao , Shimbashi Wataru , Sasaki Toru , Fukushima Hirofumi , Yonekawa Hiroyuki , Mitani Hiroki , Oguchi Masahiko , Kawabata Kazuyoshi , Takahashi Shunji
Published: March 2020

e17006

Background: CCRT is a standard therapy for locally advanced head and neck cancer patients, but some patients have intolerance to high dose density of CDDP. Predictive factors for CDDP discontinuation need to be investigated for making appropriate treatment decisions. Methods: We retrospectively analyzed nonmetastatic head and neck cancer patients treated with CCRT with CDDP (80 mg/m2 per 3 weeks) from November 2005 to April 2012 in our institute. Radiation therapy was performed as three-dimensional radiotherapy or intensity-modified radiotherapy (IMRT). Results: A total of 164 patients received CCRT, of which 89 (54 %) were Stage IV;. Primary sites were as follows; oral cavity 7, oropharynx 52, hypopharynx 53, larynx 14, nasopharynx 30, paranasal sinus/nasal cavity 3, and unknown primary 5. IMRT was performed to 54 (33 %) patients. Median follow-up time was 19 months (range 1-69 months); 1-year overall survival (OS) and progression free survival (PFS) were 90 % and 78 %. Non-Stage IV; and high creatinine clearance (>70 ml/min) were associated with longer OS in Cox proportional hazard model. As for CDDP treatment, 75 (46 %) patients completed 3 cycles of CDDP, 69 (42 %) patients received 2 cycles, and 20 (12 %) patients received only 1 cycle. The main reasons for CDDP discontinuation were infection (24 patients) and renal dysfunction (18 patients). In logistic regression analysis, male sex, younger age (< 61 years) and high body mass index (BMI) (>25) were associated with 3 cycles completion of CDDP statistically significantly (p = .002, odds ratio 6.622; p = .006, odds ratio 2.602; p = .035, odds ratio 2.655, respectively). Conclusions: In CCRT to head and neck cancer patients, infection and renal dysfunction were the main reasons for CDDP discontinuation. Sex, age and BMI could be predictive of CDDP completion/discontinuation.
The predictive value of pretreatment 18-FDG- PET CT in locally advanced nasopharyngeal cancer patients treated definitively with induction chemotherapy followed by concurrent chemoradiotherapy.
Authors: EL Lathy Hala AHMED , Khder Gehan , Rostom Yousry , Refaat Tamer
Published: March 2020

e17013

Background: This study aimed to evaluate the role of pretreatment [18F] fluorodeoxyglucose positron emission tomography (18F-FDG-PET) as a predictor of disease-free survival (DFS), and overall survival (OS) in locally advanced nasopharyngeal carcinoma (LANC) patients treated definitively with docetaxel-based induction chemotherapy followed by concurrent chemoradiation (CRT). Methods: After obtaining the institutional review board approval, we conducted a retrospective analysis of LANC patients (T1,N1-3 and T2-T4,anyN disease) treated definitively between January 2007 and December 2011 with induction chemotherapy docetaxel , cisplatin, and 5- flurouracil (TPF) followed by CRT utilizing weekly cisplatin and had pretreatment 18F-FDG-PET. We examined the association between the pretreatment primary tumor maximum standardized uptake value (SUVmax) and the treatment outcomes. The disease-free survival (DFS), and overall survival (OS) were calculated by the Kaplan-Meier method, and the differences were evaluated on logrank test. The prognostic significance was assessed by univariate and multivariate analyses. Results: The study included 38 eligible LANC patients. The 4-year OS and PFS rates were 94.9% and 84.7%, respectively. The median OS and PFS intervals were not reached. On univariate analysis, the 4-years DFS was significantly higher in patients with pretreatment SUVmax ≤ 8 compared to > 8 (92.3% vs 56%, P = 0.017). It was also significantly correlated to pretreatment T stage (P=0.001), N stage (P=0.011) and the treatment response (P < 0.001) and treatment breaks (P< 0.001). On a multivariate analysis, the SUVmax category was the only factor correlated with 4-year DFS (hazard ratio = 13.2, 95% C I 1.27-136.8, P= 0. 030) but not for OS (P = 0.068). Conclusions: This study shows that the pretreatment primary tumor SUVmax is a potential independent prognostic predictor of clinical outcomes in patients with LANC treated definitively with TPF induction chemotherapy followed by CRT. Further randomized controlled clinical III trials are needed to provide clear evidence of this benefit.
Key determinants of patient experience in oncology: Results from a national online survey.
Authors: Lis Christopher G. , Wood Steve , Rodeghier Mark , Taylor Harold , Grutsch James F. , Gupta Digant
Published: March 2020

e17502

Background: Evaluation of patient experience provides important data on the patient’s perception of the quality of care and treatment delivered by physicians, paramedical staff and the hospital as a whole. There are limited data on the most significant determinants of patient experience in the oncology setting. In a national sample of cancer patients, we investigated the key self-reported factors influencing overall patient experience. Methods: A national random sample of 724 patients undergoing treatment for cancer in a hospital setting between Jan 2009 and Dec 2011. Using a combination of professional and scholarly literature and focus groups, the survey instrument was developed employing an identified set of 13 patient experience factors, an overall patient experience measure and relevant demographic variables. Patients were invited via messages appearing randomly on oncology-oriented physician profile pages, content pages and hospital profile pages from the Healthgrades web properties. Patients were asked to rate their cancer treatment experience on a 5-point scale from “very poor” to “very good” on the 13 patient experience factors. Participants were also asked to identify factors that contributed the most to their overall patient experience. Results: 181 were males and 543 were females. Age distribution was 5-24 (n=8), 25-44 (n=95), 45-54 (n=197), 55-64 (n=259) and 65+ (n=159). Top 5 tumor types were breast (n=284), gynecological (n=78), colorectal (n=47), lung (n=34) and prostate (n=28). Tumor stage at the time of receiving care was I, 210; II, 149; III, 133; IV, 128; and unknown, 104.481 (66.4%) patients were “very satisfied” with their overall experience. The three most important determinants of patient experience as reported by patients were "a compassionate team of care providers" (49.2%), "a knowledgeable, competent physician” (48.9%) and "treatment as a human being and not just a person with a disease" (28.3%). Conclusions: We identified three key determinants of overall patient experience in oncology. Oncology care providers can use data on patient experience to design and track quality improvement over time as well as recognize and expeditiously resolve unmet needs of patients in real-time.
Accelerating the clinical trial start-up process for early-phase cancer studies: A test of process change to support rapid activation in an academic medical center.
Authors: Hurley Sheilah K , Miller Therica M , Flores Stella Rebecca , Dunn Keren , Schroeder Ryan , Yatawara Mahendra , Figlin Robert A. , Mita Monica M. , Sandler Howard Mark , Piantadosi Steven
Published: March 2020

e17507

Background: Clinical trial sponsors have strong scientific, financial, and regulatory interests in rapidly activating studies at participating sites. Academic medical centers have difficulty activating trials within a few weeks of sponsor agreement because, among other inefficiencies, they engage the necessary committee reviews, regulatory approvals, contracting, and budgeting in serial fashion. Incremental revisions in such workflows do not result in strong improvements. Methods: We redesigned our institutional workflow to complete clinical trial activation tasks within six weeks. Historical procedures were replaced rather than scrutinized. A high level leadership committee was required to change and integrate procedures across the medical center, and engage sponsors to improve their turnaround times. A web-based collaborative workflow tracking tool was created to help coordinate the necessary tasks and measure performance. Six clinical trials from the Cancer Center portfolio were used to test and improve the new workflow. Results: Clinical trial activation redesign took one year. For the six studies used as tests of change, the activation times were 49, 54, 78, 58, 62, and 32 days. Times in excess of 6 weeks were largely due to sponsor delays. Conclusions: Considerable effort is required to significantly alter a complex workflow like clinical trial activation. Appropriate priorities, leadership, staffing, and tools are required. Markedly shortened study activation for a small series of cancer trials taught our academic medical center lessons that will be useful for improving the process for all clinical trials, and will make us a better partner for pharmaceutical and academic sponsors as well as for investigator initiated research. [Table: see text]
The effect of cancer awareness month campaigns on internet search volume and incidence of cancer diagnoses.
Authors: Swenson Wade T. , Lindblom John M. , Reber John
Published: March 2020

e17512

Background: Cancer awareness month campaigns are a health promotion tool used to increase public awareness about a specific cancer, its prevention, and treatment. Cancer awareness month campaigns could be most impactful in promoting awareness of cancers for which established screening guidelines exist. Currently, the United States Preventive Task Force endorses screening the general population for colon, cervical and breast cancers. We aimed to assess the effectiveness of campaigns by identifying internet search volume and monthly cancer diagnoses. Methods: GoogleTrends was utilized to identify the relative monthly volume of search terms from 2004 to 2009 as a proxy for public awareness. Search trends for“breast cancer”, “colon cancer”, and “cervical cancer” were analyzed and an average monthly search volume index (SVI) was determined. Surveillance, Epidemiology and End Result (SEER) data was analyzed during the same time period. These data were compared using Pearson's correlation coefficient and the chi square test for seasonality. The monthly trends were compared to corresponding cancer awareness month campaigns (breast cancer-October, colon cancer-March, cervical cancer-January). Results: Internet search volume was highest for colon cancer and breast cancer in the respective cancer awareness campaign months. The frequencies of breast cancer and colon cancer diagnoseswere not significantly higher in the respective cancer awareness months. Cervical cancer search volume and cancer diagnoses did not correlate with awareness campaign months. Search volume and cancer diagnoses were not well correlated for breast cancer (r=0.089) or cervical cancer (r=0.228); however, they were significantly correlated for colon cancer (r=0.386; p-value=0.0008). Conclusions: Cancer awareness month campaigns appear to raise public awareness as estimated by internet search volume for breast cancer and colon cancer. Cervical cancer awareness month campaigns do not have the same effect. There is no significant correlation between cancer awareness campaign months and cancer diagnosis incidence for either breast cancer or cervical cancer, whereas there is a significant correlation for colon cancer.
Disparities in breast cancer presentation and treatment of older women, by insurance status.
Authors: Ursem Carling , Kimmick Gretchen Genevieve , Anderson Roger T. , Hwang Wenke , Camacho Fabian
Published: March 2020

e17516

Background: Disparities are known to exist in breast cancer outcomes by age and socioeconomic status (SES), but there is little data regarding these disparities in the elderly. We studied older women in North Carolina (NC) using insurance status as an indicator of SES. Methods: From the 1999-2002 NC Central Cancer Registry, we identified women age ≥65 years presenting with nonmetastatic breast cancer, having surgery within 60 days of diagnosis, no neoadjuvant therapy, and insured by Medicare only (M) or dual Medicaid/Medicare (dMM). Chi-square tests followed by Tukey Style Multiple Comparison of Proportions were used to compare baseline characteristics and treatment received. Multivariate analyses including age, race, Charlson comorbidity, tumor size, lymph node status (LN), ER/PR status, HER2 status, and relevant treatment components, were used to determine predictors of use of chemotherapy. Results: The study population, n=3088 with mean age 75 (SD 6.69) years, included 560 dMM and 2528 M insured women. In dMM, tumors were larger (23.5 mm vs 18.5 mm, p<0.001), more likely poorly differentiated (p=0.04), and node positive (p=0.004). dMM were significantly less likely to have breast conserving surgery (vs mastectomy, p<0.001), radiation therapy after surgery (<0.001), adjuvant chemotherapy (0.007), and adjuvant endocrine therapy (<0.001). Significant predictors of receipt of adjuvant chemotherapy were: for dMM, white race (OR 0.22, 95% CI 0.06-0.78), positive LN (vs negative LN; 6.00, 1.44-25.02); for M, age 65-69 (vs 75+; 7.43, 3.64-15.18), age 70-74 (vs 75+; 4.93, 95% CI 2.38-10.22), larger tumor size (1.73, 1.09-2.74), positive LN (9.25, 4.80-17.83), and ER/PR negative (4.98, 2.29-10.85). Conclusions: Breast cancers in low SES, older patients are higher grade, larger, and more advanced, yet they less often receive adjuvant chemotherapy. Future work should focus on interventions to increase receipt of standard of care treatment among this population.
Higher incidence and mortality rates of cervical cancer in African-American women in Louisiana.
Authors: Maronge Genevieve Folse , Wu Xiao-cheng , Chen Vivien , Li Xiangrong , Boulmay Brian C. , Loch Michelle Marie
Published: March 2020

e17522

Background: Cervical cancer [CC] incidence in the United States has decreased over the last thirty years in black and white Americans, however it is recognized that black women [BW] have higher incidence and mortality rates than white women [WW]. We evaluated race-specific incidence of CC, mortality rates of CC, and HPV vaccine usage rates in Louisiana [LA] during the last decade, the state with the second highest proportion of black Americans in the United States [US]. Methods: Data from Surveillance, Epidemiology, and End Results (SEER) registries were analyzed for trends in incidence and mortality rate [MR] in BW and WW in LA and the US. SEER 13 and SEER 18 data were used and standardized to the 2000 US population to estimate annual age-adjusted incidence and mortality rates. Results: The incidence of CC in WW in LA was 8.2 per 100,000 from 2006 to 2009, and 7.9 per 100,000 in WW in US. The incidence in BW in LA was 13.3 per 100,000, as compared to the US at 9.7 per 100,000, a 36% higher incidence in BW. The MR in WW in LA and the US was 2.4 and 2.2 per 100,000. The MR for BW in LA was 5.8 per 100,000 and the US was 4.3 per 100,000, a 37% higher incidence in BW. WW in LA and the US showed a peak in incidence between the ages of 35 and 45 from 2006 to 2009. The incidence in BW in LA peaked at 37.1 per 100,000 at age 85 and the incidence in BW in the US peaked at 25.6 per 100,000 at age 85. HPV vaccination rates for LA females ages 13-15 in 2008 and 2009 were 16.1% and 35.4%. Conclusions: BW in LA were twice as likely to be diagnosed with CC than WW with a higher MR. Though the incidence rate of CC is decreasing in WW and BW in the US and in WW in LA, it is increasing in BW in LA and continues to trend up throughout life in BW compared to WW. The high incidence of CC in BW in LA highlights the need to improve utilization of the HPV vaccine. A screening and treatment program targeting CC was implemented within the last decade in the LA public hospital system with the goal of reducing CC incidence and mortality.
Development of a practice consensus statement of the management of locally advanced breast cancer: Expert consensus and systematic review.
Authors: Leonard Robyn , Hogeveen Sophie , Han Dolly , Wong Audrey , Ebrahim Jalal , Rajmohan Yanchini , Boileau Jean-Francois , Gandhi Sonal , Lee Justin , Dinniwell Robert Edward , Brackstone Muriel , Simmons Christine E.
Published: March 2020

e17526

Background: For locally advanced breast cancer patients (LABC), there are currently limited, if any, up-to-date protocol guidelines. The objective of this paper was to develop a consensus of opinion amongst Canadian oncologists, and to determine if Canadian oncologists agreed with the relevant literature. Methods: A modified Delphi survey protocol was used to determine consensus of opinion amongst 83 Canadian experts identified by peers as leaders in LABC. Consensus was defined as > 85% agreement. Concurrently, a systematic review of the literature was performed to identify randomized controlled trials (RCTs) in this field (limits imposed were “humans”, “English language” and “RCT”). The protocols utilized in the RCTs were compared to the results of the consensus survey to determine if expert opinion in Canada is evidence-based or experiential. Results: Consensus of opinion amongst experts was obtained across all areas of patient management except for use of MRI in the workup of patients with LABC. 81% stated MRI would be required prior to initiation of therapy and 68% stated repeat MRI would be required prior to surgical planning in cases where lumpectomy is considered an option. Expert consensus reflected the published literature well in the areas of: clinical assessment with caliper at each cycle, option of lumpectomy if good clinical response, radiotherapy to loco-regional lymph nodes, and no further adjuvant chemotherapy outside of a clinical trial if residual disease is found at the time of surgery. On most other aspects of patient management the Canadian consensus was more conservative than the published literature, except for the use of salvage radiotherapy in the setting of progression on therapy, where the literature was more conservative than the Canadian opinion. Conclusions: A national practice consensus has been developed for the management of LABC which reflects the published literature or is more conservative than the published literature. The only area of clinical equipoise nationally is on the utility of MRI both pre and post neoadjuvant therapy. A further study assessing the appropriate role of MRI clinically in the treatment of LABC patients is warranted.
Cancer of unknown primary (CUP): A population-based analysis of temporal change and socioeconomic disparities.
Authors: Urban Damien , Rao Aparna , Bressel Mathias , Lawrence Yaacov Richard , Mileshkin Linda R.
Published: March 2020

e17535

Background: CUP is the 4th most common cause of cancer death. With advanced diagnostic investigations and treatment of cancer, we hypothesized that the proportion of cancers diagnosed as CUP and survival outcomes of CUP have changed and examination of these changes may identify socioeconomic disparities in the US. Methods: We analysed trends in CUP diagnosis and outcome within the SEER registry between 1973-2008. The relationship between demographic and tumour characteristics with survival was investigated. Results: The incidence and percentage of all cancers diagnosed as CUP have decreased over time (incidence 8.9 vs 6.2 per 100,000 and percentage 3.9% vs 1.9% of all cancer diagnoses in 1973 vs 2008 respectively). Significantly more females were labelled as CUP without a pathological confirmation (25% vs 20% in males, p<0.001). A higher proportion of CUP was diagnosed in females, blacks and residents of less affluent or less educated counties. The 5 year survival significantly improved in those with squamous histology (SqC) but only marginally in those with non-SqC CUP. The improvement in survival over time within SqCC was more pronounced among some socioeconomic groups (SEG; Table). For the entire cohort, factors associated with a longer survival on multivariate analysis included: white race; female; <65 years old; most recent decade at diagnosis; grade 1; SqC; married; a histologic diagnosis and treatment with radiotherapy (all p<0.001). Despite the improvement in survival with radiotherapy (RT), the use of RT was less frequent in females and blacks. Conclusions: The percentage of cancers diagnosed as CUP is decreasing but prognosis remains poor, particularly in non-SqCC CUP. However, significant disparities in the diagnosis and survival between SEG exist, suggesting inequalities in access to diagnostic investigations and treatment. [Table: see text]