bluuebunny/crossref_metadata_2025 huggingface dataset:
Lymph node density and number of adjuvant chemotherapy cycles for node-positive resected bladder cancer: University of Iowa experience
Authors: Abu Hejleh T. , O'Donnell M. , Vaena D.
Published: August 2020

e16126

Background: Although its survival benefit is unclear, adjuvant chemotherapy (CT) is commonly utilized for node-positive bladder cancer after radical cystectomy (RC) and lymph node (LN) dissection. The ideal number of CT cycles is also unknown. Previous studies in patients with metastatic disease administered up to 6 cycles. Lymph node density (LND) (ratio of positive LN/total LN) has been shown to be more important than nodal TNM stage in predicting outcomes after RC, and suggested a 20% LND cutoff for prognosis. This finding also accounted for adjuvant chemotherapy (yes vs. no). We evaluated the long-term outcomes of node-positive pts after RC, according to the number of cycles of adjuvant CT received and adjusting for LND. Methods: The study was IRB approved. Patients still alive were required to give informed consent and accrual is ongoing. Pathological and survival variables of pathologically node-positive pts who underwent RC at the University of Iowa in the last 5 yrs and then received adjuvant CT were retrospectively evaluated. Results: 22 pts have been evaluated to date. Median age was 62 (37–86). Median number of LNs resected was 19.5 and median LND was 19% (3–47). Median survival was 17 mo (10–67). 21 pts received a platinum-gemcitabine combination. The table shows the pt distribution according to no. of CT cycles, LND and number of > 2 yr survivors. Median survival was 17 mo both for pts with LND ≤ 20% and >20% . Median survival of pts with ≤ 4 cycles of CT was 16.5 mo (11–67), with 4 patients still alive at 14–67 months. Median survival of pts who received > 4 cycles of adjuvant CT was 17 mo (10–44), with 3 pts still alive at 29–39 months. Conclusions: The pt distribution table suggests that patients with high LND may have been sicker, and thus less able to receive as many CT cycles. This study is limited by its retrospective nature and small current sample. Accrual is ongoing and updated data will be available. Prospective adjuvant trials could stratify or randomize patients based on LND. [Table: see text]

No significant financial relationships to disclose.
Combined brachytherapy and external beam radiation for prostate cancer in a community setting
Authors: Kubicek G. J. , Kubicek G. J. , Brown S. , Redfield S.
Published: August 2020

e16147

Background: Prostate cancer is the most common male malignancy, and there is no one standard treatment modality. One treatment option is the combination of external beam radiotherapy and permanent transperineal brachytherapy seed implant Methods: Retrospective review of prostate cancer and side effect outcomes at a single institution in the community setting. All patients were treated with a combination of low dose rate transperineal brachytherapy seed placement and external beam radiation. Results: A total of 897 patients were analyzed, 781 had a minimum follow-up of one year. Median pre-treatment PSA was 8.1 (range 0.3 to 106) and the median Gleason score was 6. With a median follow-up of 3.6 years, 33 (3.4 %) patients had biochemical failure based on the phoenix definition of Nadir + 2. Not including impotence, acute toxicity greater than or equal to Grade 2 was seen in 115 patients (102 GU and 13 GI) and 193 patients had late toxicity greater than or equal to Grade 2 (155 GU and 38 GI). 563 patients received hormone therapy prior to or concurrent with the radiation. Conclusions: This is the largest series reporting on the outcome of combination brachytherpay implant and external beam radiation in the treatment of prostate cancer. Combination treatment using brachytherapy and external beam radiation is well tolerated, with a low rate of biochemical failure and should be considered one of the treatment options for prostate cancer.

No significant financial relationships to disclose.
Phase III efficacy and safety trial of a new leuprolide acetate 3.75 mg depot formulation in prostate cancer patients
Authors: Shore N. D. , Savulsky C. , Mis R. , Karlin G. , Marberger M. , Leuratti C. , Kaisary A.
Published: August 2020

e16152

Background: Androgen suppression is the standard palliative treatment for metastatic, localized or locally advanced prostate cancer. This phase III, open-label, international multicenter clinical study was conducted to investigate the efficacy and safety profile of a new formulation of leuprolide acetate (Lutrate 3.75mg Depot) in suppressing testosterone levels in prostate cancer patients. Methods: 160 patients with prostate cancer who could benefit from androgen deprivation therapy received single intramuscular injections of Lutrate 3.75 mg Depot every 28 days for a total of six doses. Plasma testosterone was determined at specific times throughout the study. The primary endpoint was the proportion of successful patients over the total number of evaluable patients. Patients’ success was defined as testosterone suppression (<0.5 ng/ml) at day 28 and continuance of castration until day 168, with no missing data at the monthly assessments. An exact two-sided binomial test (5% significance level) with two-sided 95% confidence interval (CI) estimated with exact method was performed to test the null hypothesis of 86% successful patients versus the alternative hypothesis of 94% . Results: The proportion of successful patients over the total number of evaluable patients was 96.8% (152/157); the exact binomial test was satisfied (p=0.000094, 90% CI: 92.7–99.0 %). The 78.7% (122/157) of evaluable patients achieved testosterone suppression by day 21. At day 28, 96.8% of the patients achieved castrate levels and 73.1% achieved testosterone levels ≤0.2 ng/ml. At conclusion of the trial, all patients (100%)maintained castration and 92.8% had testosterone levels ≤0.2 ng/ml. The most common treatment-related adverse event were hot flashes (45%), associated with testosterone suppression. Fatigue, hyperhydrosis, night sweats and headache occurred in ≤6.3% of patients. The most frequently reported local adverse reaction was pain at the injection site, experienced by 8.1% of patients. Conclusions: The results of this study demonstrate that Lutrate 3.75 mg Depot is as effective as presently marketed one-month leuprolide acetate formulations in establishing and maintaining testosterone concentration below castration levels in prostate cancer patients.

[Table: see text]
Serum selenium and risk of prostate cancer in Japanese men
Authors: Nozawa M. , Yoshida M. , Saito Y. , Nakagawa M. , Ozeki T. , Yoshikawa M. , Aono Y. , Uemura H.
Published: August 2020

e16166

Background: Epidemiologic studies suggest that low selenium levels are associated with an increased incidence of prostate cancer, although results are conflicting. We examined the association between serum selenium levels and risk of prostate cancer in men who received a prostate biopsy in our hospital. Methods: Our prospective study included 82 patients who received a prostate biopsy based on elevated PSA levels over 4.0ng/ml. Serum from each patient was sampled to determine the selenium level at the time of biopsy. Of these, 47 patients were diagnosed with prostate cancer (case group) and no malignant lesions in the biopsy specimen were detected in the remains, 35 patients (control group). Results: The mean serum selenium levels in the case and control group were 120.4 (SD, 14.4) ng/mL and 118.5 (SD, 16.1) ng/mL, respectively (p = 0.588). Serum selenium levels at biopsy were not associated with risk of prostate cancer diagnosis. In the case group, the mean serum selenium levels in patients diagnosed with 6 or less in Gleason score and 7 or more were 121.0 (SD, 9.9) ng/mL (n = 14) and 120.1 (SD, 16.1) ng/mL (n = 33), respectively (p = 0.851). Serum selenium levels at biopsy were not associated with Gleason score in the case group. An inverse association between serum selenium and PSA levels at biopsy was observed (p = 0.030). No correlation was observed between serum selenium level and age at biopsy. Conclusions: From this study, serum selenium level cannot predict the result of prostate biopsy. The inverse association between serum selenium and PSA levels may suggest that low selenium levels are associated with an increased incidence of prostate cancer.

No significant financial relationships to disclose.
Differential mitochondrial scoring associated with chemotherapeutic effect on ovarian cancer
Authors: Isonishi S. , Matsumoto R. , Hirama M. , Ochiai K. , Tachibana T. , Ishikawa H. , Yasuda M. , Tanaka T.
Published: August 2020

e16514

Background: We reported mitochondrial (MT) scoring system related to platinum response in ovarian cancer (OC) (Oncol Rep2008). We investigated whether the system could be useful to evaluate cellular drug sensitivity and patients’ prognosis. Methods: Ultrathin sections of surgical specimens prepared from 41 OC patients were examined by electron microscopy. Ovarian carcinoma cell line 2008 and its platinum- or taxane-resistant variant C13 or PX24 were used as control cells. Seven independent MT features including diameter and pattern of cresta structure were examined. Clinical response and in vitro sensitivity to platinum (P), taxane (T), irrinotecan (CPT), and doxorubicine (D) were examined while the MT scoring was performed independently. Results: Of 41 cases, 37 were available for clinical evaluation (stage II-IV, received 6 cycles of TP chemotherapy). Fifteen cases were responsive, while 22 were resistant. Total MT score in 15 responsive cases was 5.13 ± 1.13 (M ± SE) and was 11.41 ± 0.43 in 22 resistant cases (p < 0.001). Receptor operative characteristics (ROC) analysis revealed that resistant total “cut-off” score was ≥ 10 points (p < 0.05; AUC = 0.86). Except for D, the scoring system well related to P, T, and CPT sensitivity (p; <0.001, <0.001, 0.006). ROC analysis revealed resistant “cut-off” score for P, T and CPT were ≥ 11, 5, and 10 points (p < 0.05; AUC > 0.80). With a median follow up of 20 months, 11 patients have relapsed. The progression-free survival (PFS) curves show a difference in favor of low scoring group of patients (N = 14) compared to high scoring group (N = 19) (hazard ratio 3.99, p = 0.045), corresponding to an absolute difference in 6-months PFS 16% (89 vs 73%). Conclusions: This MT scoring system excellently related to clinically diagnosed P sensitivity as well as cellular sensitivity to P, T and CPT. Each drug has its own specific “cut-off” score, suggesting that the MT function might be differentially involved in drug sensitivity.

No significant financial relationships to disclose.
Susceptibility of ascites tumor cells to ex-vivo killing by the oncolytic virus JX-963 in epithelial ovarian cancer
Authors: Davies C. , Garson K. , LeBoeuf F. , Bell J. , Weberpals J.
Published: August 2020

e16537

Background: Epithelial ovarian cancer (EOC) has a poor prognosis, and novel therapies are urgently needed. One-third of patients with EOC will develop clinical ascites, an adverse prognostic factor. The ascitic fluid is rich in tumor cells which can be purified and used as a valuable source of patient material for in vitro analysis. In this study, we describe a method to evaluate the efficacy of ascitic tumor cell killing by the oncolytic virus, JX-963 (vaccinia strain) currently approved for use in a NCIC-CTG phase I trial. Methods: Research ethics approval and patient consent was obtained for this study. 15 samples were collected prospectively with relevant clinicopathologic information. Infection with JX-963 was performed using viral doses ranging from a multiplicity of infection (MOI) of 0.5 to 8. Following a seven-day infection period, viability was assessed using the Alamar Blue metabolic assay and tracked by virally encoded green fluorescent protein (eGFP) expression, immunohistochemistry (IHC) and flow cytometry. Results: A standardized protocol was developed for the collection and purification of EOC cells from patient ascites for subsequent infection and quantification of viral killing. Qualitative analysis using phase contrast imaging of the total cell content showed greater opaque dead cell aggregates with increasing MOI over time. Although variable between individual samples, there was a strong correlation between escalating MOI and enhanced cell death in all patient ascites samples, when quantified by Alamar Blue assay and confirmed by flow cytometry and IHC. Similar cell killing profiles by JX-963 were observed for ascites tumor cells derived from both chemotherapy-naïve patients and chemotherapy-exposed (>1 prior line of chemotherapy) patients. Conclusions: EOC cells from patient ascites show effective but differential susceptibility to viral oncolysis by the JX-963 virus that appears to be independent of prior exposure to chemotherapy. The relevance of this work is that in an individual patient, this assay will allow the testing of panels of oncolytic viruses to identify candidate viral therapeutics which may predict response to treatment.

No significant financial relationships to disclose.
Carbon ion radiotherapy for malignant melanoma of female genital organs
Authors: Kiyohara H. , Kato S. , Ohno T. , Ohkubo Y. , Tamaki T. , Kamada T.
Published: August 2020

e16548

Background: Malignant melanoma of the female genital organs is a very rare tumor and resistant to conventional photon radiotherapy. We report six cases of female genital malignant melanoma those were well controlled locally by carbon ion radiotherapy (CIRT). Methods: Between November 2004 and October 2008, six patients with unresectable female genital malignant melanoma were treated with CIRT. Age of the patients ranged from 55 to 80 years (median; 69 years). Four patients had previously untreated locally invasive tumors and other two had locally recurrent tumors after surgery and adjuvant chemotherapy. The tumor located in the vagina (4 patients), both the cervix and the vagina (1 patient), or both the vagina and the vulva (1 patient). Two patients had inguinal lymph node metastasis and two had distant metastases at CIRT. All patients received a total dose of 57.6 gray equivalent (GyE) in 16 fractions over 4 weeks of CIRT. Three patients received chemotherapy using dacarbazine, ACNU, and vincristine after CIRT. Results: The follow-up durations after CIRT were from 9 to 20 months (median; 13 months). No patient developed severe acute toxicity during CIRT. No late toxicity of greater Grade 2 was experienced, while Grade 1 proctitis was observed in a patient. All tumors completely responded to CIRT. No patient developed in-field recurrence. The four patients without distant metastasis were alive with no evidence of disease for 9–20 months after CIRT. The two patients with distant metastases died from metastatic disease 13 and 18 months after CIRT, respectively. Conclusions: CIRT achieved favorable local tumor control without developing severe acute and late toxicity in the treatment of unresectable malignant melanoma of the female genital organs.

No significant financial relationships to disclose.
A feasibility study of intravenous (IV) paclitaxel, intraperitoneal (IP) carboplatin, and IP paclitaxel in patients with epithelial ovarian carcinoma, fallopian tube carcinoma, or peritoneal carcinoma
Authors: Nagao S. , Oishi R. , Iwasa N. , Shimizu M. , Hasegawa K. , Goto T. , Fujiwara K.
Published: August 2020

e16549

Background: This is a feasibility study for a future trial to assess the feasibility of intravenous (IV) paclitaxel, intraperitoneal (IP) carboplatin and IP paclitaxel (TCipTip therapy) in patients with epithelial ovarian carcinoma, fallopian tube carcinoma or peritoneal carcinoma. Methods: The patients eligible for this study had histologically confirmed, stage IC-IV epithelial ovarian carcinoma, fallopian tube carcinoma or peritoneal carcinoma. IV paclitaxel was administered at 135 mg/m2 followed by IP carboplatin administration based on the area under the curve =6 on day1, and IP paclitaxel was administered at 60 mg/m2 on day 8. To ensure the safety, the three initial patients received 45 mg/m2 of IP paclitaxel on day 8. The toxicity grade was determined by CTCAE version 3. This study has been approved by the institutional review committee. Results: During November 2007 and December 2008, 10 patients were entered in this study. The patients included 7 epithelial ovarian carcinoma (stage IC, 2; stage IIIC, 5), 2 stage IIIC primary peritoneal carcinoma, and 1 stage IIA fallopian tube carcinoma. There were 7 serous adenocarcinoma, 2 endometrioid adenocarcinoma, 1 clear cell adenocarcinoma. The incidences of grade 3/4 hematological toxicities were 48% for neutropenia, 28% for thrombocytopenia, and 48% for anemia. Grade 3/4 neurotoxicity, abdominal pain nor IP catheter related toxicity was not observed. IP paclitaxel at 2nd or 3rd cycle was skipped in 4 patients by grade 3/4 neutropenia (grade 3, 3; grade 4, 1 ). Conclusions: TCipTip therapy is feasible for patients with epithelial ovarian carcinoma, fallopian tube carcinoma or peritoneal carcinoma.

No significant financial relationships to disclose.
Hematologic toxicities before and during bevacizumab chemotherapy in women with gynecologic malignancy
Authors: Bottsford-Miller J. N. , Shafer A. , Deal A. , Filip L. , Fowler W.
Published: August 2020

e16565

Background: Many women undergoing chemotherapy for gynecologic malignancy experience hematologic toxicity that delays therapy or requires supportive intervention. In animal models anti-VEGF antibodies increase erythropoietin levels. We examined the hematologic toxicities experienced by patients prior to (PR) and during bevacizumab (BR) treatment. Methods: Retrospective, single-institution study of women with gynecologic malignancy treated at the University of North Carolina with bevacizumab as part of their therapy from January 2005 to June 2007. Data collected included prior therapies, blood product and growth factor use, and interruptions in therapy. Comparisons were made between individual patients’ hematologic parameters during the PR and BR. Median differences between hematologic nadirs were compared using Wilcoxon Signed Rank Tests. Differences in proportions were compared by Chi-Square or Fisher's Exact tests. Results: 43 patients ware identified, 40 with complete data. Most women were Caucasian (88%) and had ovarian or primary peritoneal carcinoma (77%); median (range) age was 53 (23–73). 32 (74%) received three or more different chemotherapy drugs before starting bevacizumab. The median difference in HCT nadir (31.2 vs. 33, p = 0.01) and ANC nadir (1.2 vs. 1.4, p = 0.04) during the PR and BR were significant in favor of the bevacizumab regimens. The median nadir differences for WBC (2.7 vs. 3.1, p = 0.1) and PLT (129 vs. 150, p = 0.07) were non-significant favoring BR. For HCT toxicity grades, 22 (55%) had the same grade during their PR and BR, 15 (38%) had a lower grade during BR, and 3 (7%) had a higher grade during BR (p = 0.001). Similar trends were seen for WBC (p = 0.27), ANC (p = 0.1), and PLT (p = 0.15). During BR there was a trend toward fewer patients receiving darbepoetin (66% vs. 44%, p = 0.07) and filgastrim (29% vs. 14%, p = 0.1). Conclusions: Patients receiving bevacizumab had no worse hematologic toxicity compared to their prior regimens and may have had less severe anemia. While not statistically significant, there were trends toward less growth factor use with bevacizumab. Patients who have had prior hematologic toxicity should be considered for bevacizumab. The effect of bevacizumab on hematologic toxicity should be evaluated with prospective data.

No significant financial relationships to disclose.
Carcinoma of uterine cervix: Top ranking in our country
Authors: Uddin D. , Begum K. N. , Akthar H. , Faruqui M.
Published: August 2020

e16580

Background: Carcinoma of cervix is worldwide, the most frequent gynecological cancer particularly in developing countries like ours. Carcinoma of the cervix uterine is the second commonest gynecological cancer in the developed countries and top ranking in the developing countries like ours. Methods: One hundred and fifty women having carcinoma of the cervix uteri were prospectively studied in the department of Gynaecology and Obstetrics and Radiotherapy department of Rajshahi Medical College Hospital from January 2004 to December 2007. The cases were diagnosed clinically and confirmed by histopathological examination. Results: In all 150 patients of carcinoma of the cervix were selected for this study. There mean age was 50.12 yrs. Most of the patients (78%) had marriage between the age of 10–15 years; 8% married below 10 years and 14% between 16–20 years of age.In this study the all were multipara; 30% patients had 6 pregnancies throughout life. 10% had more than 10 pregnancies, 8% had 8 pregnancies, 4% had 9 pregnancies, 14% had 5 pregnancies and 16% had 4 pregnancies.The study shows that the distribution of patients according to the staging of the carcinoma. 54 (36%) were of III A stage. 39 (26%) in II B stage, 21 (14%) in III B stage, 9 (6%) in IV A stage, 6 (4%) in I B stage, and 3 (2%) in IV B stage. No patient presented with O or IA stage. Conclusions: The study showed that the majority of the patients were between the ages of 40–50. HPV types 16/18 has a significant role for the development of the disease. Religious practices are of important role for its causation. It is less frequent in Jew and most frequent in Hindu. Histopathologically 90%-95% are squamous cell carcinoma and 1–5% are adnocarcinoma.From the findings it is observed that early marriage, creation of awareness about sex hygiene, discourage to have multiple sexual partners and marriages, discourage to have multiple pregnancies and providing adequate health care and health education to the women could reduce the development of carcinoma of cervix.

No significant financial relationships to disclose.
Cost-effectiveness of cetuximab for the first-line treatment of squamous cell carcinoma of the head and neck (SCCHN) in Canada
Authors: Sambrook J. , Levy A. R. , Johnston K. M. , Ricard N. J. , Bourgault C. , Donato B. M. , Sheehan F. G. , Hotte S. J. , Chasen M. R. , Briggs A. H.
Published: August 2020

e17000

Background: Squamous cell carcinoma of the head and neck (SCCHN) is a disfiguring and potentially fatal condition. Cetuximab is a new therapeutic option which has been shown to improve locoregional control (LRC) and reduce mortality in the treatment of locally and regionally advanced disease. Objectives: To estimate the incremental cost-utility of cetuximab plus radiotherapy (CxRT) versus cisplatin plus radiotherapy (CsRT) among platinum eligible patients and versus RT alone in platinum ineligible patients in Canada. Methods: A lifetime transition model was developed with four health states: 1) acute treatment phase; 2) LRC; 3) disease progression and 4) death. Adverse events were accounted for in the first two states. Efficacy of treatment (LRC and overall survival) was obtained from the literature. Based on network meta-analyses, CsRT and CxRT were assumed to have equal efficacy. Resource use was obtained from published literature and clinical expert opinion. The perspective adopted was that of a provincial ministry of health or cancer agency. Utilities were obtained from a previous study of United Kingdom oncology nurses. Costs (2008 CDN$) and outcomes were discounted at 5% annually. Incremental cost-effectiveness ratios (ICERs) were reported with one-way and probabilistic sensitivity analyses performed to assess robustness of results. A priori sub-group analyses were carried out by baseline Karnofsky Performance Scores (KPS). Results: Among all patients (KPS 60–100), the ICERs comparing CxRT to RT were $19,740/QALY (95% CI: $11,122 to $695,295) among platinum ineligible patients and for CxRT vs. CsRT, $99,147/QALY (95% CI: $75,998 to $148,951) among platinum eligible patients. ICERs decreased with increasing KPS scores. At a willingness to pay of $50,000 among platinum-ineligible patients and $100,000 among platinum-eligible patients, the likelihood that CxRT is cost-effective is 90% and 45% respectively. Sensitivity analyses indicated that time horizon and assumptions about CsRT effectiveness had the largest impact on results. Conclusion: Cetuximab is an economically attractive option for SCCHN patients.

[Table: see text]
Efficacy of neoadjuvant therapy with cisplatin, fluorouracil, and cetuximab in locally advanced nonresectable epidermoid skin carcinoma
Authors: Mamelle G. , Fournier E. , Kolb F. , Janot F. , Duvillard P. , Robert C. , Mateus C.
Published: August 2020

e17008

Background: No standard therapy is known for locally advanced unresectable cutaneous epidermoid carcinoma. Chemotherapy (platin ± fluorouracil) and radiotherapy are commonly used separately or in association (1) mostly as palliative treatments. We report six patients with locally advanced unresectable skin epidermoid carcinomas in whom the association of cisplatin, fluorouracil and cetuximab induced a tumor reduction allowing secondary complete surgical resection. Results: All 6 patients had voluminous tumours located on the face (nose, ear, cheek, forhead). For 5 patients, tumours were recurring after one or several surgical resections. One patient had a rapidly progressing non resectable inflammatory tumour on the nose when he was first diagnosed. All patients received 2 to 3 cycles of chemotherapy associating cisplatin 100 mg/m2 J1, fluorouracil 1,000 mg/m2 J1–5, cetuximab J1-J8-J15 (J1 = J21). Tolerance was manageable. A dramatic response with rapid tumour regression, allowing subsequent surgical resection was observed for all patients. Histology showed a complete sterilisation without any active tumoral residue in 2 patients and complete resection (R0) in the remaining patients. Conclusions: The association of cisplatin, fluorouracil and cetuximab is approved for treatment of metastatic head and neck carcinoma (2, 3) but has not been evaluated yet in cutaneous epidermoid carcinoma. The dramatic tumor responses observed in our 6 patients warrant evaluation of this association both in the neoadjuvant and in the metastatic settings for patients with non resectable skin squamous cell carcinomas.

No significant financial relationships to disclose.
Phase I study of pemetrexed in recurrent/metastatic head and neck squamous cell cancer (HNSCC) and to assess the need for steroid premedication
Authors: Coscio A. , William W. N. , Feng L. , Glisson B. , Ayuste R. , Ginsberg L. , Lee J. J. , Obasaju C. , Lippman S. M. , Kim E. S.
Published: August 2020

e17009

Background: Pemetrexed is a novel antimetabolite that inhibits both purine and pyrimidine biosynthesis. Because its mechanism of action is similar to that of both methotrexate and 5-FU, it may also have activity in recurrent/metastatic HNSCC, a disease with limited treatment options and very poor median survival. Pemetrexed is traditionally prescribed with steroids due to skin toxicities observed in early studies; however vitamin supplementation (B12 and folic acid) was not standard at the time of those studies. No study to date has evaluated the optimal use of steroids with pemetrexed in the era of vitamin supplementation. Methods: All patients had metastatic or recurrent HNSCC, were treated with at least one prior chemotherapy regimen, and had ECOG PS of 0–2. The first cohort of patients received pemetrexed 500 mg/m2 every 3 weeks and the next receiving 600 mg/m2 based on a predefined standard dose escalation design. Within each dose level, patients were randomized to one of 3 premedication regimens: no dexamethasone, 20 mg IV on day 1, or standard 4 mg orally bid for 3 days. All patients received vitamin supplementation. The primary endpoint of the study was to determine the maximum tolerated dose of pemetrexed based on steroid premedication. Results: From October 2005 to March 2008, 36 patients were enrolled and 31 were available for evaluation. Median age was 57 years (range 42–82). 51.5% of patients had more than one prior chemotherapy regimens, 81.8% of patients had prior radiation therapy, and 48.5% of patients had prior surgery. Incidence of rash and combined skin toxicities were: 1/11 (9%) and 3/11 (27%) of patients without steroids, 1/11 (9%) and 3/11 (27%) with single IV dose, and 4/9 (44%) and 5/9 (55%) with oral steroids. No treatment-related grade 3 toxicities were observed. One patient initially received no steroid and required dose reduction and addition of steroid due to grade 2 rash. A partial response was observed in one patient (3.2%), and stable disease in 8 patients (25.8%) for a disease control rate of 29%. Conclusions: This is the first study to report the role of steroids as a premedication for pemetrexed. Our data suggests that no steroid premedication is needed with pemetrexed and vitamin supplementation.

[Table: see text]
Expression of angiogenic mediators in head and neck cancer
Authors: Usó M. , Sirera R. , Jantus Lewintre E. , Mosquera N. , Zapater E. , Cabrera A. , Sanmartín E. , Berrocal A. , Basterra J. , Camps C.
Published: August 2020

e17032

Background: In cancer, systematic analysis of mRNA expression levels can contribute to define a molecular network of lung carcinogenesis and establish predictive and prognostic molecular markers. Altered mRNA expression in certain angiogenic and anti-angiogenic genes such as vascular endothelial growth factor family of ligands and their receptors together with other molecules implicated in angiogenesis could predict disease outcome and add prognostic information at diagnosis. Methods: We performed RT-qPCR in frozen head and neck cancer specimens from untreated patients who had undergone surgical resection (n = 23). Samples were processed for mRNA extraction following standard procedures and quantification of gene expression was expressed as relative concentration normalized by an endogenous gene. The following angiogenic genes were quantified: PDGF-A, PlGF, VEGF-A, VEGF-B, VEGF-C, VEGF-D, COX-2, bFGF, HGF, IL-8; and anti-angiogenic genes: Angiomotin and endostatin. Results: Median age was 56.5 years, range (31–79), 17 patients presented squamous carcinoma of the larynx; 8 patients were stage III and the other 15 stage IV. None of the patients received pre-surgery chemo or radiotherapy and 10 patients reveived post-surgery treatment. Our results show that tumor samples had significant higher expression of PDGF, PlGF, COX-2, and IL-8 and a deep down-regulation of angiomotin. However, those data show no correlation between the levels of expression and stage of the disease. Conclusions: Our results reveal that there is an increase in the expression of the pro-angiogenic mediators PDGF, PlGF, COX-2, and IL-8 and a downregulation of angiomotin that may mediate the inhibitory effect of angiostatin on tube formation and the migration of endothelial cells toward growth factors during the formation of new blood vessels in the tumoral area. This data suggest that more research are needed in other angiogenic mediators that VEGF, that PlGF and angiomotin have some role in cancer progression and could be a promising new biomarker in head and neck cancer.

No significant financial relationships to disclose.
Concurrent chemoradiotherapy of patients with locally advanced squamous cell carcinoma of the oral cavity (stage III, IV)
Authors: Adilbay D. G. , Adilbaev G. B. , Ahmetov D. N.
Published: August 2020

e17034

Background: Randomized trials have showed a good result of concurrent chemoradiotherapy in advanced SCC of the head and neck. But there are only few trials which evaluates separately the different sites of the head and neck. The aim was to evaluate the toxicity and efficacy of concurrent intra-arterial chemotherapy plus radiotherapy with altered fractionation in SCC of the oral cavity. Methods: 43 patients with previously untreated oral cavity SCC (T3–4N0–2M0) received concurrent chemoradiotherapy by followed scheme: first day intra-arterial chemotherapy: docetaxel - 80 mg/m2, cysplatin - 100 mg/m2, from second to 21st day RT (28 Gy by 4 Gy - 3 times week), 22nd day second course of intra-arterial chemotherapy and after RT (total dose- 60 Gy by 2 Gy 5 times week, total equivalent to 70Gy by conventional fractionation), depending on the results salvage surgery if necessary. Results: The clinical effects were pCR in 34 (79.1%) patients, pPR in 9 (20.9%) patients. The following main toxicities of chemoradiotherapy were observed: only 2 cases of grade 3 neutropenia, Non-hemathologic toxicity: 74.4% (32 patients) grade 3 mucosal events. All patients have totally completed the treatment. The 3-year overall survival rate were 83.7%, and 3-year disease free survival were 76.7%. Conclusions: This regimen of concurrent chemoradiotherapy where radiotherapy is used by altered fractionation is feasible, safe and well tolerated.

No significant financial relationships to disclose.
Robotic radiosurgery for severe recurrent and primary head and neck cancer
Authors: Kawaguchi K.
Published: August 2020

e17038

Background: We considered the functional reconstruction following head and neck tumor ablation, however, it was impossible to recover completely the function against the severe postoperative status. Here we describe our aim to improve local control and to obtain organ preservation by using the non-surgical outpatient procedure the CyberKnife frameless radiosurgery (CK). Methods: Between March 2006 and January 2008, 22 patients with severe recurrent, previously treated with conventional methods, and 14 patients with primary lesions were treated with CK in the management of head and neck cancer. All the patients had biopsy confirmation of disease prior to radiation therapy; rT2 (3 patients), rT3 (8), rT4 (9), T2 (5), T3 (3), T4 (6), N1 (4), N2b (3), M1 (1), tongue (11), mandibule (11), maxilla (6), maxillary sinus (4), soft palate (2), with sq. cell ca.(34), adenoid cystic ca.(1), fibrosarcoma (1). The treatment plan was set up based on CT, MRI and PET-CT in Yokohama CyberKnife Center. CK's lightweight linear accelerator always irradiates toward the target from 120 directions with image-guided computer based on CT. Marginal Doses were 2000–4200cGy in 3–5 fractions. Curative effects were evaluated assessed by RECIST included PET. Results: 11/22 (50.0%) of the severe recurrent cases were controlled from 6 to 25 months at follow-up range. The local recurrent cases with non-lymph node metastases were excellently controlled as 10/12 (83.3%). For the primary cases, significant tumor reduction were noted at the third-month follow-up, all the 14 patients went into remission with 5 cases in CR, and 9 cases in PR. Between the 4–6 month follow-up, 4 cases were performed additional CK treatment for the recurrent lesions, however, 3 patients with T4 tongue cancer were not cured. Finally, the total control rate of the primary cases was 10/14 (71.4%), however, 8/9 (88.9%) primary cases except tongue cancer has been controlled treated by CK with chemotherapy. The cases of non-lymph node metastases were cured 8/8 (100.0%) by CK. There have been no seriously complications of treatment caused by CK except severe osteoradionecrosis of the 4 patients irradiated with maximum dose. Conclusions: It is now possible with the development of CyberKnife Radiosurgery to improve our treatments of the local control in head and neck cancer.

No significant financial relationships to disclose.
PET/CT fusion in radiotherapy treatment planning for head and neck cancer
Authors: Xiang Z.
Published: August 2020

e17046

Background: Positron emission tomography/computerized emission tomography (PET/CT) creates fusion images which are a combination of tissue function (PET) and anatomy (CT). It is playing an increasingly important role in radiotherapy of cancer. Aim of this report is to investigate the value of PET/CT fusion in radiotherapy treatment planning for head and neck cancer. Methods: 17 patients with head and neck cancer underwent 18F-FDG PET/CT imaging. The primary lesions were all proved by pathology. PET/CT fusion images, PET images and CT images of the same patient were analyzed frame by frame. TNM stage was analyzed based on PET/CT and CT. PET/CT-GTV and CT-GTV volume were analyzed. Results: 59 malignant lesions were detected by PET/CT in the 17 patients. Among 59 lesions, 31 lesions were detected and displayed definitely by both PET and the plain scan of CT; 23 lesions were detected definitely by PET but not by the plain scan of CT; while 5 lesions were negative by PET but definitely by the plain scan of CT. The sensitivity of PET/CT was higher than PET and the plain scan of CT alone. Changes in TNM stage occurred in 7 patients (41%), based on PET/CT. The median PET/CT-GTV and CT-GTV volume was 84.3 cm3 (range, 46∼364 cm3) and 116.2 cm3 (range, 58∼472 cm3), respectively, showed significant differences (p = 0.0005). Conclusions: PET/CT can increase the accuracy of the staging and defining target volumes for radiation therapy fields for head and neck cancer.

No significant financial relationships to disclose.
Capecitabine-based chemotherapy versus primary treatment for patients with advanced stages of undifferentiated nasopharyngeal carcinoma (UCNT): Preliminary results of a phase II study
Authors: Djedi H. , Bouzid K.
Published: August 2020

e17049

Background: The combination of cisplatin and 5-fluorouracil (5-FU) is considered to be the standard treatment in induction chemotherapy for patients with undifferentiated nasopharyngeal carcinoma (UCNT). Capecitabine is an oral fluoropyrimidine. The aim of our study is to evaluate overall response and toxicity of this drug as a primary chemotherapy based-regimen for patients with advanced stages of UCNT. Methods: From January 2008 through December 2008, 34 chemo-naives patients with UCNT were included, mean age: 45.2 years (range 14–61 years), 12F/22M. One patient was stage IIB, nine patients stage III, 17 patients stage IVA, five patients stage IVB, and two patients stage IVC. All patients received at least 3 to 4 courses of neoadjuvant chemotherapy. The treatment plan included cisplatin at dose of 75 mg/m2 on D1 every 21 days, followed by capecitabine at a dose of 1,000 mg/m2 twice daily from D2 to D 15, with a 1-week rest period. Five patients received this scheme plus docetaxel at a dose of 75 mg/m2 on D1 with prophylactic granulocyte colony stimulating factors: lenograstim or filgrastim. All patients had a clinical evaluation of objective response and toxicity before at each cure . A CT scan was done at the end of treatment before radiotherapy. Results: After a total of 114 courses, all patients (34 pts) were evaluable for toxicity and 26 patients were evaluable for response (8 pts have not yet achieved their treatment). A clinical benefit was obtained for all patients since the first cure of chemotherapy. The overall objective response (CR+PR) was achieved in 96% of cases (25/26pts ), one patient had a stable disease. One of the two patients with stage IVC had a complete response on hepatic metastasis after 3 cures. Grade 3/4 toxicity included: diarrhea 5.2%, nausea/vomiting: 9.6%, hand-foot syndrome 3.5%, febrile neutropenia 4.3%, cardiac toxicity: 0.8%, thrombocytopenia 1.75%. Chemotherapy was interrupted for one patient after only one cure because of the cardiac toxicity. Conclusions: Capecitabine based chemotherapy is a safety and an effective regimen in patients with UCNT. However a longer follow-up is needed to confirm the benefit on disease-free survive (DFS) and overall survivor.

No significant financial relationships to disclose.
Neoadjuvant versus concurrent chemotherapy in the management of carcinoma nasopharynx
Authors: Sharma R. , Kumar D. , Kaur S. , Kalsotra P. , Gupta A.
Published: August 2020

e17053

Background: Chemotherapy is added to radiotherapy in the treatment of nasopharyngeal carcinoma with advanced locoregional disease to enhance therapeutic gain. Thirty percent patients with locally advanced nasopharyngeal carcinoma (LA-NPC) still die of distant metastases despite concurrent chemoradiation being the standard of care. In this retrospective study we performed the pooled analysis of these patients to assess the impact of neoadjuvant chemotherapy versus the concurrent chemoradiation approach. Methods: Between January 2000 and December 2007, 45 patients of stage IIB- IVB nasopharyngeal were treated with 3 cycles of induction chemotherapy with cisplatin and 5FU (n = 23) followed by conventional radical radiotherapy, or concurrent chemoradiation with weekly cisplatin (n = 22). Results: Total numbers of patients eligible for analyses were 45. Median age of the patients was 52 years (range 19–76 years). Median follow up was 17 months (range 6–60 months). At the time of last follow up, 13 patients (out of 23, i.e. 56.53%) were alive and disease free in the neoadjuvant group and 13 patients (out of 22, i.e. 59.1%) were alive and disease free in the concurrent chemoradiation group. The 2-year failure free survival in the concurrent chemoradiation arm was 63% versus 35% in the neoadjuvant arm (p = 0.197). Survival analyses adjusted for the gender male revealed 2-year failure free survival as 81% in the concurrent chemoradiation versus 44% in the neoadjuvant chemotherapy group among male patients (p = 0.0143). On multivariate analysis age and stage were the two significant predictive factors for failure free survival. Conclusions: The neoadjuvant chemotherapy seems to be at least as effective as concurrent chemoradiation in this small cohort of patients.

No significant financial relationships to disclose.
Evaluation of p53 and BCL2 expression, mutation, and aneuploidy status on treatment response in an Indian cohort of primary Ca larynx
Authors: Sahoo R. , Babu V. , Patil G. , Kulkarni J. , Rao S. , Thakur S. , Dondhalay G. , Banerjee A. , Kumar BS A. , Korlimarla A. , Rao M R.
Published: August 2020

e17057

Background: Organ-sparing therapy consisting of cisplatin and 5-fluorouracil, combined with radiation for advanced head and neck squamous cell carcinoma (HNSCC) have been advocated in Ca larynx patients. However, failure of some tumors to respond to treatment or tumor recurrence limits the overall success of these therapies. P53 mutations have been linked to cisplatin resistance in other solid tumors. In this study we evaluate the relationships between P53 overexpression/mutations, BCL2 expression and ploidy status on treatment response in retrospective cohort of Ca Larynx patients. Methods: Samples from 18 patients with histopathologically confirmed Ca Larynx were analysed from our biorepository after consent. Clinical, sociodemographic information and response to treatment were abstracted from case records. P53 and BCL2 over expression were checked by IHC and p53 mutation by PCR and direct sequencing. DNA ploidy and S-phase fractions were also analysed. Bivariate relationships were determined between these variables using Spearmans rank correlation. Independent samples t tests were used to determine changes in P53 over expression, BCL2 expression Ploidy status and S phase fractions in both responders and non responders. Results: There was a trend for increase in P53 over expression and BCL2 expression and decrease in S phase fractions in responders vs non responders. Neither p53 over expression (75% of cases) and BCL2 over expression (17% of cases) correlated significantly with treatment response. However, BCL2 expression correlated negatively with disease stage (r = - 0.57, p = 0.02). Aneuploidy was observed in node positive tumors (p = 0.04). Conclusions: The results suggest poor association of molecular markers with treatment response and should not be relied as a marker for treatment response. Though there is a trend for association a larger sample size is required to demonstrate the findings.

No significant financial relationships to disclose.
Physician and practice characteristics influencing tumor board attendance: Results from the provider survey of the Los Angeles Women's Health Study
Authors: Scher K. , Tisnado D. M. , Rose-Ash D. , Rastegar A. , Adams J. , Ko C. Y. , Ganz P. A. , Kahn K. L.
Published: August 2020

e17501

Background: Coordination of care has grown in importance with the advent of new modalities of treatment requiring specialized expertise. In cancer care, multidisciplinary approaches have shown improvements in quality of care and patient satisfaction. Tumor boards provide a mechanism for improving coordination of care. We evaluated physician and practice characteristics that predict frequency of tumor board attendance. Methods: This cross-sectional study utilizes data obtained by surveying physicians of a population-based sample of women with incident breast cancer. Physicians were queried regarding tumor board attendance, specialty (medical oncologist [MO], radiation oncologist [RO], surgeon indicating that the hospital at which most breast cancer surgeries are performed has an American College of Surgeons accredited program [ACOSSg] and surgeon without such affiliation [non-ACOSSg]), physician characteristics (gender, race, teaching involvement, patient volume, number of offices, ownership interest), and practice setting (practice type, size, reimbursement). Univariate, bivariate, and multivariate analyses were performed for the dependent variable characterizing provider report of frequency of tumor board meeting attendance. Results: Most surveyed physicians (83%) report attending tumor board weekly (58%) or monthly (25%). Weekly participation was reported by 63%, 92%, 47%, and 32% of MOs, ROs, ACOSSgs, and non-ACOSSgs (p < 0.01). Specialty and higher patient volumes are significant predictors of more frequent attendance, after adjustment for practice size and type. In comparison to the most prevalent specialty category (low volume ACOSSgs), high volume MOs attend more (p = 0.01), and low volume non-ACOSSgs attend less frequently (p = 0.00). Conclusions: Tumor board attendance implies increased participation in multidisciplinary care, but specific subsets of providers are less frequent users. This not only has implications for choosing providers, but also for efforts to increase attendance. Tumor board agendas and formalized institution wide policies could be designed to further engage low frequency attendees as a means to promote multidisciplinary care and improve health outcomes.

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