bluuebunny/crossref_metadata_2025 huggingface dataset:
Response to primary chemotherapy (CHT) in advanced epithelial ovarian cancer (EOC) patients (pts) and molecular characterization of CHT-resistant tumor cell populations: Findings from the Arianna 02 Project
Authors: Zamagni C. , Wirtz R. M. , De Iaco P. , Altimari A. , Roth K. , Rosati F. , Rosati M. , Massari F. , Cacciari N. , Martoni A. A.
Published: March 2020

16059

Background: Despite a high response rate to CHT the prognosis of pts with advanced EOC remains poor. The molecular analysis of pre- and post-CHT tumor specimen may enable the identification of CHT resistant tumor cell populations and thereby lead to adapted treatment options. Methods: Stage III-IV EOC pts diagnosed by laparoscopy and biopsy and not suitable for optimal debulking surgery were eligible. Gene-expression profiles generated from total RNA using the Affymetrix U133A oligonucleotide microarray containing over 22,000 probe sets were obtained at diagnosis and on surgical specimens after 6 courses of primary carboplatin/paclitaxel CHT. Initial comparative analysis focused on proliferative and invasive tumor activity, and on growth factor- and hormone receptors expression. Results: 30 pts were enrolled and data were analyzed according to response to CHT and to time to relapse after surgery. Initial expression analysis results reveal that the quantitative determination of growth factor- and hormone receptors in pre- and post-treatment samples can be used to discriminate responders from non-responders and relates to clinical outcome. Moreover, multiple CHT-resistant tumor cell populations displayed pronounced estrogen receptor expression suggesting a role of hormone receptors in the development of CHT resistance. Conclusions: While hormonal therapies are used in the treatment of other endocrine related tumors, they are not approved for the treatment of EOC. Treatment of EOC cell lines with estrogens down-regulates GnRH activity and promotes cell growth, while tamoxifen has an opposite effect. However, further biological data are lacking in this setting and only few clinical trials have addressed this possibility so far. We have found that the expression of hormone receptors in vivo persists in CHT-resistant tumor cell populations after CHT for EOC. We suggest that hormone receptor activity contributes to the initial development of CHT resistance; hence endocrine therapies particularly in an early setting may be advantageous to a subset of pts and are worth studying.

No significant financial relationships to disclose.
A phase II study of irinotecan and docetaxel in patients with platinum-resistant relapsed epithelial ovarian cancer
Authors: Matsumoto T. , Hiura M. , Oshita T. , Hirata E. , Shiroyama Y. , Wroblewski J. , Yokoyama T. , Nogawa T.
Published: March 2020

16062

Background: Patients with epithelial ovarian cancer are often diagnosed with advanced-stage disease. Although clinical complete remissions are obtained in the majority of patients through a combination of cytoreductive surgery and chemotherapy, relapse is common. Relapsed patients with a short treatment-free interval (TFI) after prior chemotherapy have a poor prognosis. We conducted a pilot study of irinotecan (CPT-11) and docetaxel (DTX) in patients with platinum-resistant relapsed epithelial ovarian cancer. Methods: Eligible patients must have at least one platinum and paclitaxel-containing regimen, and recur with a TFI of less than 6 months. CPT-11 60 mg/m2 and DTX 30 mg/m2 were administrated on days 1, 8, 15 of a 28-day cycle. Eligibility included preserved organ function, aged 20–75, and ECOG performance status 0 or 1. The primary endpoint was response rate, and secondary objectives were duration of response, time to progression (TTP) and safety. Toxicity was assessed using NCI-CTCAE ver.2.0. Results: Between 12/2000 and 4/2005, 26 patients were enrolled, 24 of whom were eligible. The median age was 57.5 years (range 35–75). A total of 99 cycles were analyzed, median number of cycles was 3 (range 1–12). Grade 3/4 hematologic toxicities occurred in 33.3% for anemia, 4.2% for thrombocytopenia, 50.0% for leucopenia, and 62.5% for neutropenia. Non-hematologic grade 3/4 toxicities were not observed. Efficacy based on RECIST criteria was available for 20 patients, and the overall response rate was 10% (2 PR) with SD in 40%. In addition, of 4 patients with no measurable diseases, 2 patients had a confirmed PR by CA125 criteria (GCIG). Over all, clinical benefit (PR, SD) was seen in 63.6% of patients. The median duration of response was 17 weeks (range 2–49). The median TTP was 31 weeks (range 7–86). Conclusions: These results suggest that weekly treatment with CPT-11 and DTX is feasible and effective chemotherapy regimen for platinum-resistant relapsed ovarian cancer.

No significant financial relationships to disclose.
A phase II trial of radiation therapy with concurrent paclitaxel chemotherapy in high-risk endometrial cancer patients after staging operation: An interim analysis of a prospective multicenter trial (KGOG2001)
Authors: Kim J. , Jeong J. , Nam B. , Kim S. , Cho C. , Kim B. , Lee J. , Kim Y. , Bae D. , Kang S.
Published: March 2020

16069

Background: This is an interim report of a prospective multicenter phase II trial to evaluate 2-year disease free survival rate, toxicity, overall survival rate and recurrence rate in high-risk endometrial cancer patients who received concurrent chemoradiotherapy after staging operation. Methods: Thirty four patients with endometrial cancer from 17 medical centers in Korea have enrolled the study. The cell types were all endometrioid type and they had no prior chemotherapy. They were in either stage III or IV and all received staging operation including total hysterectomy, bilateral salpingo-oophorectomy, pelvic and paraaortic lymph node dissection and washing cytology. Concurrent chemoradiotherapy was performed with paclitaxel (60 mg/m2/weekly, 6 cycles) and external field irradiation (5 fractions/week, total 4,500–5,040 cGy). Primary end point was 2-year disease free survival rate. Overall survival rate and recurrence rate were secondary end points. Toxicity of the treatment was also evaluated. Results: The expected number of subjects to complete the trial is 56. The trial was activated on 5th June 2005 and median follow up period is 5.8 (0–11) months until December 2006. 19 patients (55.8%) have completed treatment regimen and 14 patients (41.1%) are still receiving treatment. 1 patient (2.9%) died during treatment of the disease and 1 patient (2.9%) was lost during the follow up period. Disease free survival is 94.1% (32/34) and no recurrence has occurred so far. Toxicities have occurred in 52.9% (18/34) with gastrointestinal symptoms (13/34, 38.2%) such as diarrhea and constipation being the most common ones. Conclusions: This interim report suggest a possibility that a concurrent chemoradiotherapy for high-risk endometrial cancer may be an optimal treatment option to improve disease free survival rate.

[Table: see text]
Toxicity of adjuvant sequential chemo- and radiotherapy of high-risk endometrial carcinoma (HREC)—Results of a phase II multicenter feasibility NOGGO study
Authors: Koehler G. , Sehouli J. , Sommer H. , Blohmer J. , Bartz K. , Belau A.
Published: March 2020

16074

Background: Isolated adjuvant radio- or chemotherapy (CHT) only reduces local or distant relapses in HREC without impact on overall-survival. Therefore a multicenter feasibility study on adjuvant sequential chemo- and radiotherapy of HREC was initiated in order to evaluate safety and toxicity. Planned number of patients was 40, if after 17 pts. no termination of therapy because of toxicity was necessary, study can be closed and a phase III-study can be initiated. The data on toxicity are presented. Methods: Eligibility criteria: adenocarcinomas G1/G2 stage IC or G3 stage IA-IC or all stages II and IIIA (histological), all tumours with more than 2 cm diameter in size or non endometrioid cancers stage IA-C, II and IIIA and all cases with vessel invasion. Surgery: abdominal hysterectomy with bilateral adnexectomy without lymphadenectomy or with pelvic and para-aortic lymphadenectomy and positive lymph nodes. Further: Karnofsky-Index > 70, normal bone marrow, kidney, and liver function with laboratory tests not higher than 1.5 times of the normal local reference values. CHT: 175 mg/m2 paclitaxel plus carboplatin AUC 5, q 3 weeks for 4 cycles beginning latest 6 weeks after surgery. Within 6 further weeks after CHT an external beam irradiation (total dose 50.4 Gy, 28 fractions with 1.8 GY/d) plus 3 intracavitary HDR-iridium-192- brachytherapy courses with 3 x 5 GY were performed. Results: To date 17 pts (mean 64.1 years) completed 68 cycles CHT and following radiotherapy. There was no termination of therapy. Grade III leucopenia was observed in 9 % with 2 pts. requiring prolongation of treatment interval. There were 3 and 1 % grade II anemia and thrombocytopenia respectively. Further grade II toxicity: alopecia 38, fatigue 12, nausea/emesis 3, sensory neuropathy 12 %. Administration of G-CSF (pegfilgrastim) and epoitin (darbepoetin) was necessary in 2 and 6 % of cycles. Conclusions: Adjuvant sequential chemo- and radiotherapy of HREC is feasible by safety and toxicity and a phase III study can be initiated.

No significant financial relationships to disclose.
Radical surgery (RS) plus intraperitoneal hyperthermic perfusion (IPHP) with oxaliplatin followed by intravenous docetaxel in the treatment of peritoneal carcinosis from platinum-sensitive recurrent ovarian cancer (OC): A pilot study
Authors: Fagotti A. , Ferrandina G. , Paris I. , Mari A. , Legge F. , Fanfani F. , Facchini G. , Scambia G.
Published: March 2020

16077

Background: Much attention has been focused on the efficacy of radical surgery (RS) plus intraperitoneal hyperthermic perfusion (IPHP) in peritoneal carcinosis from recurrent OC. Methods: A pilot study aimed at analyzing the feasibility, morbidity, and toxicity of RS/IPHP and adjuvant chemotherapy has been carried out. Patients with recurrent, platinum-sensitive OC (PFI->6 months), have been enrolled. RS has been performed with peritonectomy procedures. The perfusion of the abdominal cavity has been achieved using 2 liters/m2 of 5% dextrose solution with oxaliplatin 460 mg/m2, preheated (41.5°C), and infused through the closed abdomen technique. After RS/IPHP, patients have received systemic chemotherapy with docetaxel (75 mg/mq), day 1, every 21 days, for 6 cycles. Results: As of December 2006, 14 patients underwent RS/IPHP: median age was 48.5 yrs (range 34–62). Ten (71.4%) patients had an ECOG PS=0. Median PFI was 24 months (range 7–72). TMedian value of PCI was 6 (range 2–10). Completeness of cytoreduction was 0 in 12 cases and 1 in 2 cases. Median EBL was 700 cc (range 400–1,600) and median number of blood transfusion was 3 (range 0–11). Median length of hospitalization was 15.5 days (range 8–27). We documented 3 cases of sepsis, 1 case of wound dehiscence requiring surgical intervention, 1 case of pleural effusion requiring thoracentesis, and 6 cases of post-operative haemorrhage, treated with surgical re-intervention (n=1), endoscopic cauterization (n=3), or blood transfusions (n=2). Ten patients underwent chemotherapy (total number of cycles= 49): grade 3 and 4 leukopenia occurred in 1, and 2 cases. Three patients (21.4%) experienced severe onicolysis and conjunctivitis. No deaths from this regimen was registered. With a median follow up of 7 months (range 1–18), 2 progressions of disease were observed. Conclusions: RS/IPHP utilizing intraperitoneal oxaliplatin followed by i.v. adjuvant docetaxel was shown to be a feasible approach to peritoneal recurrence of ovarian cancer.

No significant financial relationships to disclose.
Cystatin C, an additional marker of ovarian cancer extent: A pilot study
Authors: Wcislo G. , Bodnar L. , Szarlej-Wcislo K. , Gasowska-Bodnar A. , Szczylik C.
Published: March 2020

16080

Background: Cystatin C is a cysteine protease inhibitor which has been recommended as the marker of glomerular filtration rate (GFR). We investigated significance of cystatin C in relation to ovarian cancer extent and its feasibility in assessment of renal function in patient with ovarian cancer (OC) who underwent chemotherapy. Methods: We prospectively included consecutive patients with OC who underwent chemotherapy : cisplatin 75 mg/m2 plus 24-hour infusion of paclitaxel 135 mg/m2 every three week after surgery. Before chemotherapy serum renal markers were noted as: creatinine (Cr), cystatin C (Cys C), albumin, creatinine clearance (ClCr) calculated by using 24-hour urine collection per 1.73 m2, creatinine clearance estimated with formulas Cocroft- Gault (ClCG) and Modification of Renal Disease (MDRD1), respectively. Results: Between February 2003 and January 2006 37 patients were enrolled onto this study. Median age 54 year (range from 28 to 68). Cystatin C and CrCl weakly correlated (R Spearman= -0.36; p=0,03). There were no correlation between cystatin C and other markers of GFR (serum creatinine, ClCG, MDRD1). We showed correlation between cystatin C and tumor extent revealed by spiral CT- scan (> 1 cm diameter) after surgery (R Spearman= 0.4; p=0.01), and CA 125 (R Spearman= 0.4, p=0.03). Cut-off values were established as medians for both factors, and patients with high and low values had no statistical differences in overall survival (log- rank test, p=0.9). Conclusions: We believe that cystatin C could imply OC extent in patients.This factor weakly was correlated with CrCl, and no correlated with other GFR parameters.

No significant financial relationships to disclose.
The correlation of the AKT/mTOR/p70S6K1 pathway and VEGF in human epithelial ovarian cancer
Authors: Trinh X. , Tjalma W. A. , Dirix L. Y. , Vermeulen P. B. , Van Den Eynden G. G. , Van Laere S. J. , Van Der Auwera I. , van Dam P. A.
Published: March 2020

16081

Background: The Akt/mTOR/p70S6K1 (Amp) pathway is activated in a proportion of epithelial ovarian cancers. The ribosomal protein pS6 and p4EBP1 are downstream targets and presumed representative for the pathway's activity. VEGF and angiogenesis in ovarian cancer play an important role as bevacizumab induces high response rates and prolongs progression-free survival in women with relapsed ovarian cancer in two phase II trials. The Amp pathway has proven to be correlated with HIF1alfa and VEGF A expression in vitro. Material and Methods: Our primary objective was to evaluate correlation between this pathway in human subject tissues and angiogenesis using VEGF A and pVEGFR2. Our second objective was to evaluate if different metastatic abdominal (peritoneal and/or omental) lesions show the same pathway hyperactivity and/or angiogenesis as the primary tumour, because relapses usually involve metastatic abdominal lesions. Epithelial ovarian cancer paraffin imbedded material from 1999–2004 was collected. A tissue micro array was build with three samples per paraffin block. Immunohistochemical staining was performed using pS6, p4EBP1, pAKT, VEGF and pVEGFR2. Results: 89 patients were collected with a median age of 69.8y. Patients were FIGO stage I in 21%, stage II in 4%, stage III in 62% and 11% stage IV. Histological examination showed in 53% serous papillary tumours, 25.8% endometroid tumours, clear cell carcinoma in 11.2% and mucinous tumours in 4.5%. 65 patients had available tissue material of both primary tumour as well as other (multiple) metastatic abdominal disease tissue. The results of the immunohistochemical staining as well as the correlation analysis will be presented. Conclusion: Although anti-angiogenesis seems to be very active against human epithelial ovarian cancer, it is at present associated with unacceptable treatment induced toxicities. Inhibiting the Amp pathway with mTOR inhibitors could potentially also inhibit angiogenesis in ovarian cancer with the potential of more manageable side effects. This study will provide some evidence on the relationship between the Amp pathway and the VEGF pathway in human epithelial ovarian cancer.

No significant financial relationships to disclose.
Beyond race: The impact of ethnicity on the treatment outcome of locally advanced head and neck cancer
Authors: Calfa C. J. , Escalon M. , Zafar S. , Lopez E. , Patel V. , Patel S. , Feun L. , Raez L. E.
Published: March 2020

16500

Background: Self identified racial groups share an unequal burden of head and neck cancer . Recent evidence suggests that outcome among races is different and the causes are multifactorial. Nonetheless, differences among ethnic groups have not been reported. Herein, we decided to analyze differences in treatment response and outcome among our white and Hispanic patient population treated for locally advanced head and neck cancer. Methods: Patients were identified using the tumor registry. We reviewed retrospectively the data from medical records. 100 white Hispanics (WH) and 50 white non-Hispanics (WNH) diagnosed with locally advanced head and neck cancer and treated at our institution from 2004 to 2005, were eligible for the study. Standard statistical analysis, including Kaplan-Meier survival curve and Cox proportional hazard models were used. P value of <0.05 was considered for statistical significance. Results: Preliminary results reveal that, in our study population, median age at diagnosis, gender, performance status (ECOG 0–2) and squamous cell histology did not differ significantly between the two groups. Stage 4 at diagnosis was more commonly observed in Hispanics as opposed to WNH (85.7% vs 68.6%) (P = 0.1). Surgery was more commonly used as an initial treatment option in Hispanics than WNH (42.8% vs 28.6%) (P = 0.18) while chemotherapy was less likely to be used (78.6% vs. 91.4%) (P = 0.15). Hispanics were more likely to smoke than WNH (P = 0.0003) and were equally exposed to chronic alcohol use. Patients from the Hispanic group were more likely to respond to therapy than whites by Chi-squared analysis but this difference was not statistically significant (P = 0.09). No differences were seen in disease free survival. Kaplan-Meier estimate of median overall survival was 16 months for Hispanics vs. 25 months for whites but this difference did not reach statistical significance (P = 0.26). Final analysis will be available at the time of the annual meeting. Conclusion: In our experience, a trend for decrease overall survival was noted in the Hispanic ethnic group. This may be in part due to more advanced stage at presentation. Nonetheless, in order to definitively answer this question, further research is warranted.

No significant financial relationships to disclose.
Elevated thyroglobulin levels and negative I-131 whole body scans: Six-year experience in United Arab Emirate
Authors: Uttamchandani A. , Maarraoui A. M. , Attia N. M. , Latif H. A. , Bakir M. A. , Hanif R. M. , Siddiqui Z. J. , Ashruth A. C. , Zachariyah Y. , Morris L. A.
Published: March 2020

16508

Purpose: This is a retrospective study of thyroid cancer patients seen at Oncology Department at Mafraq Hospital/UAE from 1/1999 to 12/2005. Clinical data, prognostic factors and treatment outcomes were studied, special emphasis was put on patients with elevated Serum Thyroglobulin (TG) and negative I-131 whole body scans. Patients and Methods: Total of 144 patients were fully evaluated, intent to treat analysis was used. All patients were treated surgically and post-op thyroid technician 99 scan were performed. I-131 ablation was given if the tumor size was =1 cm or if =1 cm (micropapillary) and multi-focal. Post ablation scan was done on day 10 and thyroxin was given in suppressive doses. Periodic evaluations were done with TG level, I-131 whole body scan, neck US and CXR. Plain CT scans and PET scans were done in selected cases. Results: Male to female ratio 1:2.42, non-smokers were 90%, non-alcoholics were 99%, Diabetes and Hypertension were associated in 28% of cases, family history of thyroid cancer was noted in 8%, papillary carcinoma was seen in 85.8%, follicular cancer in 11.6%, hurthel cell cancer in 0.83% and medullary cancer in 0.17%. Vascular and lymphatic invasion was noted in 29% of all cases. Interesting all patients with vascular or lymphatic invasion relapsed locally or distantly. Post-operative thyroid scan showed residual thyroid tissue in 96% of cases. During follow up TG levels (cut off 5.0 ng/ml) were elevated in 52 patients (37% cohort). Diagnostic I-131 scans were done in 36 patients and were positive in 24 patients (67%) and negative in 12 patients (33%). In the 12 patient group of research interest with elevated TG and negative I-131 whole body scans, 9 received high dose I-131 therapy. Of these patients 8 (88%) showed positive post therapy scan and 1 (12%) showed negative post therapy scan. Conclusion: 1. TG is more sensitive marker than diagnostic I-131 scan in making treatment decisions. 2. Lympho vascular invasion has adverse prognostic value.

No significant financial relationships to disclose.
Acute and late effects of radical radiotherapy in elderly head and neck cancer patients
Authors: Turaka A. , Mohanti B. K. , Chander S. , Jena R. , Deo S. V.
Published: March 2020

16515

Background: To evaluate the difference between acute and late effects of radical radiotherapy in elderly(above 60 years,Group A) head and neck cancer patients with young patients (below 50 years of age, Group B). Methods: The study was conducted on histologically proven head and neck cancer patients receiving radical radiotherapy (RT),49 patients were in group A and 40 in group B.The acute and late radiation morbidity was assessed using RTOG (phases I,II,&III- Pre RT, During RT & 1 month post RT respectively) and LENT-SOMA scoring systems (phases IV &V-3 & 6 months post RT). Results: In phase II, grade I dermatitis was commonly seen (83.7% in group A,72.5% in group B) and grade II dermatitis was 12.2 % vs 25% of patients.The difference in distribution over age was not significant (p= 0.12 & 0.18 in phase II and III).There was no significant difference in the incidence of late effects between two groups (p=0.91 in phase IV and p=0.99 in phase V).Grade II mucositits was seen in majority of patients in both groups,71.4% vs 72.5% in phase II.The late mucosal changes with worrisome subjective (pain) experiences were observed in 69.4% vs 75% of patients in group A and B, respectively.The difference in distribution over the age was significant (p<0.051) only in phase II.Dryness of mouth was the most common acute and late sequel of RT.The acute salivary gland morbidity was mostly moderate to complete dryness (grade II),seen in phases II and III in 24.5% & 73.5% of patients but the late sequel was seen in 83.37% of patients in group A and 85% in group B and the difference in late effects in both groups was statistically significant except in phase V (p= 0.02). Moderate dysphagia of grade II morbidity was seen in 75.5% vs. 65% in phase II. Grade III dysphagia was seen only 5 patients in group A and one in group B. In phase IV,66.7% patients in group A,72.5% in group B had persistent difficulty in swallowing. Conclusions: Grade I and II mucositis and dermatitis during the course of treatment led to increased morbidity, decreased nutritional intake and pain. Xerostomia is the most common and inevitable acute and late squeal of radical radiotherapy to head and neck cancer region resulting in difficulty in mastication and swallowing. There was no difference in the occurrence of acute and late effects between younger and elderly patients.

No significant financial relationships to disclose.
Feasibility study of capecitabine (cap) and cisplatin (cis) with radiation therapy (RT) in the management of patients with locally advanced unresectable squamous cell carcinoma of the head and neck (HNSCC)
Authors: Allen J. W. , Vasireddy S. , Kaufman J. , Hughes J. M. , Sebelik M. , Salazar J. E. , Niell H. B.
Published: March 2020

16520

Background: Concurrent chemoradiation has become the standard of care for locally advanced unresectable HNSCC. The most commonly used chemotherapy is cis and 5-fluorouracil (5-FU). We evaluated the feasibility of using cap and cis during RT in this population. Cap is an oral pro-drug of 5-FU that can be given daily with RT in order to enhance the activity of RT. Methods: Between Oct, 2003 and Sept, 2005, 12 male patients aged 46–83 were treated at the VA Medical Center. Patients received cis 100 mg/m2 on days 1 and 29 and cap 450 mg/m2 bid (2 hours prior to RT and 12 hours later) for 5 days of each week concurrent with RT to a total dose of 70 Gy in 35 fractions over 7 weeks. Primary endpoint of the study was toxicity. Results: All 12 patients were able to complete therapy. Treatment delays and/or dose modifications were needed in 7 patients. Treatment related toxicities included 6 patients with grade 3 mucositis and 5 patients with grade 3 dysphagia. Other grade 3 toxicities included 3 patients with dehydration and 1 patient each with leucopenia, constipation, nausea and vomiting, and odynophagia. Percutaneous gastrostomy (PEG) tubes were required in 5 patients. Complete response to chemoradiation was seen in 9 patients, 2 patients obtained partial response, and 1 patient progressed. Median progression free and overall survivals have not been reached with a median follow-up of 21 months. Conclusions: Cis and cap administered concurrently with RT has manageable toxicities and is active in patients with locally advanced unresectable HNSCC.

No significant financial relationships to disclose.
Functional morbidities in patients ≥ 65 years compared with younger patients undergoing organ preservation therapy (OPT) for squamous cell carcinoma (SCC) of larynx (L) or propharynx (OP)
Authors: Ramanarayanan J. , Burstein M. , Brodzik F. A. , Jackson A. I. , Mehdi S.
Published: March 2020

16533

Background: Advanced age is shown to be associated with increased late toxicity and minimal clinical benefit in head and neck cancer patients receiving aggressive or combined modality therapies. Elderly may also have delayed functional recovery after OPT. We conducted a retrospective study in patients = 65 years with L or O SCC undergoing OPT to compare functional outcome/ recovery with younger patients undergoing similar treatment. Methods: Patients with L or O SCC from January 1996-January 2006 who underwent OPT were retrospectively studied and stratified into 2 groups: = 65 or < 65 years based on age at diagnosis. Dysphagia, gastrostomy (g) tube dependence, speech quality and weight loss at diagnosis, 3 and 9 months post therapy were compared. Swallowing and speech were evaluated by 2 specially trained therapists based on the Swallowing Performance Scale and GBRAS Scale (perceptual impression of voice quality) respectively. Student z-test and t-test were used in statistical analysis for comparison between patient proportion and mean values. Results: One hundred and twenty patients (L 74 and OP 46) received OPT, of which 43 were excluded (recurrence/inadequate records). Of the 77 (L 54 and O 23) patients analyzed (KPS 80–100), 44 (57%) were = 65 and 33 (43%) <65; more patients aged <65 had advanced stage; 14 patients (31%) = 65 and 16 (48%) <65 received CRT or altered fractionation RT, rest of the patients received standard RT. Elderly group had greater proportion of patients with continued weight loss and higher incidence of dysphonia (70% vs 43% z-score 2.97, p=0.003) at 3 and 9 months than younger patients. Of 19 patients in the elderly group with g-tube, 13 were g-tube dependant at 3 months (68%) vs 12/23 (52%) in the younger population. Conclusions: Elderly may have persistent functional morbidity compared to younger patients receiving similar OPT. As the goal of OPT is to improve functional outcome, careful assessment of risk benefit ratio in the elderly is warranted before administering aggressive therapies.

No significant financial relationships to disclose.
Intra-arterial chemotherapy using docetaxel and cisplatin + RT with radiomodification in combined treatment of patients with locally advanced SCC of the oral cavity
Authors: Adilbay D. G. , Adilbayev G. B. , Ahmetov D. N. , Kydirbaeva G. Z.
Published: March 2020

16543

Background: Our previous studies of using intra-arterial induction chemotherapy in locally advanced SCCHN have showed a low level of toxicities, we haven't experienced any III grade toxicity, there was only 18,8% of grade I and II leucopenia. So this method allows intensify chemoradiotherapy. The addition of radiomodificant agent to standard RT increases its response rate. In our study we have used radiomodification with Arglabin, which showed a good results in different studies performed in Kazakhstan and Russia. To elevate the effect of intra-arterial induction chemotherapy + RT we have studied intensified preoperative chemoradiotherapy. Methods: 15 patients with previously untreated oral cancer (T3–4N0–2M0) received chemoradiotherapy by followed scheme: 1st day intra-arterial chemotherapy by catheterization of the feeding arteries of tumor through the superficial temporal artery: docetaxel - 80 mg/m2, cysplatin - 100 mg/m2, from 2nd to 21st day RT with intra-arterial radiomodification arglabin-70 mg/m2 (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), depending on the results surgical treatment in necessary volumes. Results: The clinical effects were CR in 12 (80.0%) patients, PR in 3 (20,0%) patients. The following main toxicities of chemoradiotherapy were observed: only 1 case of grade III neutropenia, Non-hemathologic toxicity: 13% grade III mucosal events, alopecia 66,7%. All results have been confirmed by cytomorphology. All patients have being followed up. Conclusions: Using intra-arterial path of delivery allows intensify chemoradiotherapy. And adding radiomodification increases the results of combined treatment. Therefore this method needs further investigations.

No significant financial relationships to disclose.
Temporal trends in first-line chemotherapy treatment among elderly stage IIIB/IV non-small cell lung cancer (NSCLC) patients in the United States: Evidence from SEER-Medicare data
Authors: Lang K. , Marciniak M. D. , Faries D. , Stokes M. , Buesching D. , Earle C. , Treat J. , Thompson D.
Published: March 2020

17002

Background: Data regarding first-line chemotherapy treatment among advanced-staged NSCLC patients is lacking. The purpose of this analysis was to assess first-line treatment patterns over time among elderly patients with Stage IIIB/IV NSCLC. Methods: Patients aged 65 years and older diagnosed with Stage IIIB/IV NSCLC between 1997 and 2002 were identified and followed over time using the SEER-Medicare database to evaluate temporal trends in first-line chemotherapy treatment. Results: Chemotherapy use increased from approximately 28% of Stage IIIB/IV patients diagnosed in 1997 to 36% of patients diagnosed in 2002. Among identifiable first-line treatments, cisplatin or carboplatin and taxane (C/CT) doublet therapy was the most common treatment in all years (approximately 50% or greater). The use of single-agent taxanes and gemcitabine increased over time (taxane use increased from 3.3% in 1997 to 7.6% in 2002; gemcitabine use increased from 0.6% in 1997 to 5.1% in 2002), while use of single agent cisplatin or carboplatin (C/C) declined (from 10.0% in 1997 to 3.1% in 2002). Use of doublet therapy with C/C and either a taxane or gemcitabine also increased over time (with the largest increase for the gemcitabine combination from 0.3% in 1997 to 11.8% in 2002). Correspondingly, use of doublet C/C and any other therapy declined markedly (from 18.9% in 1997 to 3.7% in 2002). Use of 3 or more agents as first-line treatment was infrequent across study years (<1.0%). Treatment discontinuation was substantial (>60% for all regimens). Conclusions: Our findings indicate relatively low but increasing use of first-line chemotherapy treatment among elderly Stage IIIB/IV NSCLC patients.

[Table: see text]
Use of colony stimulating factors (CSF) for primary prophylaxis of chemotherapy-induced neutropenia in community oncology practices to reduce risk of febrile neutropenia (FN)
Authors: Wong M. D. , Hershman D. , Morrison V. A. , Ding B. , Malin J. L.
Published: March 2020

17013

Background: In addition to proof of efficacy from randomized controlled trials (RCTs), health care decision makers need data on therapy effectiveness, specifically how well an intervention performs in routine practice. While the efficacy of filgrastim and pegfilgrastim in preventing FN has been established in RCTs, their effectiveness in community practice has not been studied. Methods: Data were obtained from medical records of patients treated with chemotherapy for a variety of malignancies in a random sample of 99 US community oncology practices in 2001 and 2003 (before and after FDA approval of pegfilgrastim in 2002). Patients receiving filgrastim or pegfilgrastim and, in 2003, every third patient not treated with a CSF, were consecutively sampled(n=6148). Only those receiving chemotherapy on 3–4 wk cycles were included in this analysis (n=3,744). Primary prophylaxis was defined as receipt of CSF within 3 days of the 1st cycle of chemotherapy. Multivariable logistic regression, adjusted for patient and treatment characteristics and weighted for patient sampling was used to estimate the odds of FN in patients who received primary prophylaxis versus those who were managed expectantly, i.e. patients who received CSF later during chemotherapy or not at all. Results: Of 3744 patients in the study population, 2966 (79%) received a CSF some time during their chemotherapy treatment. In 2003, approximately 18% of patients received CSF primary prophylaxis. Among patients who did not receive primary prophylaxis but received a CSF later during the treatment, 38% initiated CSF in the 1st cycle after day 3. In a multivariate model, increased risk of FN was associated with receiving myelosuppressive chemotherapy (OR 2.19; 95% CI 1.05–4.56) and having 3 or more drugs (vs. 1) in the regimen (OR 2.13; 95% CI 1.09–4.17). Adjusting for patient and treatment characteristics, the relative odds of FN in patients who received CSF primary prophylaxis was 0.70 (95% CI 0.50–0.98) compared with patients who either received CSF later or not at all. Conclusions: In this community practice setting, patients who received CSF primary prophylaxis had significantly lower odds of developing FN than patients managed expectantly.

No significant financial relationships to disclose.
Trends in chemotherapy (CT) utilization for colorectal cancer: A provincial population-based analysis
Authors: Renouf D. J. , Kennecke H. , Gill S.
Published: March 2020

17014

Background: Significant advances have been made in the treatment of colorectal cancer in both the adjuvant and metastatic setting. The purpose of this study is to examine CT prescribing patterns for adjuvant therapy of colon cancer and metastatic colorectal cancer over the last 15 years in British Columbia, Canada. Methods: All patients (pts) with stage 2 or 3 colon cancer, or stage 4 colorectal cancer at presentation referred to the BC Cancer Agency during a one year period for three time cohorts: 1990, 2000 and 2004, were reviewed. A pt was considered to be treated with CT if they received a cycle of CT within 6 months of referral. Results: A total of 1421 pts were included: stage 2/3 n=915, stage 4 n=506. Chemotherapy utilization increased significantly from 1990 to 2004 for adjuvant CT (1990: 49 (29%), 2000: 129 (45%), 2004: 235 (52%), p<0.001) and for palliative CT (1990: 41(35%), 2000: 100 (51%), 2004 120 (63%), p<0.001). The proportion of pts with stage 2 disease treated with adjuvant CT dramatically increased (1990: 3(4%), 2000: 38 (26%), 2004: 50 (30%), p<0.001). CT utilization was associated with a later time cohort and younger age of presentation ( Table 1 ). The use of palliative CT was significantly associated with male gender (p=0.025). This gender bias was not observed in the adjuvant setting. Among pts >70y, only 25% (99/394) received adjuvant CT [1990: 5(8%), 2000:38 (28%), 2004: 57 (28%] and 31% (50/162) received palliative CT [1990:4 (15%), 2000:17 (24%), 2004:30 (45%)]. Conclusions: In this population-based cohort, adjuvant and palliative CT utilization has increased since 1990 however there is room for improvement. Despite the lack of conclusive evidence, the use of adjuvant CT for stage II disease has increased significantly. Female pts appear less likely to receive palliative CT. Despite evidence that the elderly can accrue similar proportional benefits, the majority of referred pts >70y did not receive adjuvant or palliative CT. Such discrepancies in CT utilization require further investigation.

[Table: see text]

No significant financial relationships to disclose.
Deferasirox for myelodysplastic syndrome patients with transfusional iron overload: A budget impact analysis
Authors: Mody-Patel N. , Goldberg S. L. , Barghout V.
Published: March 2020

17019

Background: Myelodysplastic syndromes (MDS) affect 12–20,000 in the US yearly. Blood transfusions, a mainstay of treatment, place MDS patients (pts) at risk for complications of transfusional iron overload (IO). Although recent data suggests iron accumulation significantly reduces survival in low and intermediate -1 risk MDS, incremental cost of adding chelators to health plan formularies are unknown. The economic impact of treating transfusional IO in MDS with two commercially available chelating agents were estimated from a health care plan (hcp) perspective. Methods: An Excel based model was developed to ascertain the incremental cost per treated MDS pt associated with oral deferasirox (DSX) relative to subcutaneous (sq) deferoxamine (DFO). Annual Per Member Per Month (PMPM) cost was calculated by dividing differences in annual expenditures for DSX and DFO by total plan membership. Data from published literature and pivotal clinical trials were used to estimate MDS prevalence and chelation eligibility. Costs associated with infusing sq DFO were based on medical claims analysis from 2001 to 2004. Medication costs were based on wholesale acquisition costs assuming 100% compliance. Sensitivity analyses were performed by varying model parameters. Results: A hcp of one million pts is estimated to have 119 pts with MDS, of which 22% are eligible for iron chelation therapy. The base-case model resulted in an incremental annual saving of $389.48 per treated MDS pt and an incremental budget impact of $0.0 PMPM of the hcp (function of relatively few MDS pts spread over million in hcp) associated with the use of DSX. Overall, 34.2% of DSX cost was offset by the absence of infusion costs, the key cost driver. Sensitivity analyses of varying pt weight and infusion costs showed the model results were robust. Conclusions: The annual budget impact of switching MDS patients with IO to DSX from DFO will potentially result in cost-savings for US health plans. These results should be considered in the selection of chelation therapy.

No significant financial relationships to disclose.
Differential delays in breast cancer treatment as a function of racial/ethnic background
Authors: Bustami R. T. , Poletick E. B. , Cosico J. N. , Whitman E. D.
Published: March 2020

17023

Differential delays in breast cancer treatment as a function of racial/ethnic background Background: Multiple studies have identified differences in breast cancer treatment and outcome due to racial/ethnic and socioeconomic factors. The purpose of this study was to investigate treatment disparities, both actual and temporal (i.e. time delay), in patients newly diagnosed with breast cancer as a function of racial/ethnic background. Methods: Patients at two affiliated hospitals newly diagnosed with breast cancer were identified and classified from discharge billing data. Time to treatment was defined as the time in days between biopsy proven diagnosis and initiation of treatment including chemotherapy, radiation therapy, lumpectomy and mastectomy. Nonparametric Analysis of Variance (ANOVA) using the Kruskal-Wallis Test examined differences between race groups based on median time to treatment. Types of treatment were analyzed by the Chi-Square test. Results: A total of 1217 patients were identified over a five-year period. Racial background was classified as White, African American, or Asian/Other. Lumpectomy was performed in 47%, 41%, and 38%, respectively (p = 0.15), while 24%, 23%, and 18% received a mastectomy (p = 0.51). There were no significant differences between the racial groups for types of therapy received. Results from ANOVA (table) showed statistically significant differences between the three race groups in terms of time to mastectomy (p = 0.003) and time to radiation therapy (p=0.043). Results from pairwise comparisons showed that (1) African American patients had a significantly longer time to mastectomy than Whites (p = 0.002), (2) patients in the Asian/Other group had a significantly longer time to radiation than their white counterparts (p = 0.015). Conclusion: This study demonstrates racial differences in time to non-surgical and surgical treatment in a group of ethnically diverse breast cancer patients.

[Table: see text]

No significant financial relationships to disclose.
Does qualitative radiologic assessment of tumor response measure up to traditional quantitative scoring methods?
Authors: Gottlieb R. , Litwin A. M. , Mashtare T. L. , Wilding G. , Raczyk C. L. , Taylor J. , Fakih M. G. , Gupta B.
Published: March 2020

17034

Background: The Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) radiologic metrics are the standards for tumor response to therapy. However these methods are difficult to use and are limited in their prediction of clinical outcome. We hypothesize a simpler qualitative assessment of tumor response by CT is as reproducible and predictive of clinical outcome as the RECIST and WHO methods. Methods: This was a retrospective evaluation of 23 patients (11 males, 12 females, mean age 56.1 years, range 40–81 years) with biopsy proven metastatic colo-rectal carcinoma treated at our institution between 2002 and 2006 who did not have their primary tumor resected. Only patients with two consecutive CT examinations separated by at least three weeks were included. Two board certified radiologists, blinded to the other's reads, independently interpreted all CT examinations measuring up to five hepatic lesions on both CT examinations using RECIST and WHO criteria and qualitatively assessing all hepatic metastases, categorizing them as increased, decreased, or unchanged between scans. Clinical outcome, using time to progression of disease (TTP), was measured, utilizing a Cox proportional hazards model, to compare the predictive value of all three scoring systems for those patients starting first line chemotherapy (11 patients) at the time of our analysis. Results: Qualitative assessment resulted in agreement in 21/23 patients (91.3%, kappa = 0.78) classifying hepatic metastases as any increase (2 patients), any decrease (17 patients), or no change (2 patients) between scans compared with agreement in 20/23 patients (87.0%) for RECIST (kappa = 0.62) and WHO ( kappa = 0.67) methods placing patients into partial response (2 patients by RECIST and WHO), stable disease (17 patients by RECIST, 16 patients by WHO), and disease progression (1 patient by RECIST, 2 patients by WHO)categories by accepted criteria. No significant difference in prediction of TTP between methods was found. Conclusions: Our pilot data suggests our qualitative scoring system may be at least as reproducible and predictive of patient clinical outcome as the RECIST and WHO methods.

No significant financial relationships to disclose.
Pharmacoeconomic analysis of a combination of capecitabine (X) with docetaxel (D) and trastuzumab (H) first-line in HER2- positive advanced or metastatic breast cancer
Authors: Bonetti A. , Santoro A. , Cirrincione A. , Giuliani G. , Bell R.
Published: March 2020

17036

Background: A recently published (Wardley et al ESMO 2006) randomized phase II trial (CHAT) compared XDH with DH. The primary endpoint, overall response rate, was similar with XDH (71%) and DH (73%), while XDH showed superior time to progression (TTP) (hazard ratio [HR] 0.70, p=0.045, median 18.2 vs 13.8 months, respectively) and a trend toward superior progression-free survival (HR 0.72, p=0.06, median 14.8 vs 12.8 months, respectively). Overall survival data are immature. This analysis evaluates potential pharmacoeconomic impacts of adding X to DH. Methods: Direct medical costs during the study were estimated from the Italian health system perspective. Actual doses of both regimens were modeled from trial data. Grade 3/4 adverse events (AEs) and related medications were analyzed to estimate costs of treating major AEs. Other costs relating to laboratory tests and drug administration were assumed to be the same in both arms. Results: Total direct medical costs were slightly lower for XDH: €15250 vs €15570 for DH. As expected, the main cost drivers were drug costs: €14,370 vs €14,690, respectively. XDH and DH safety profiles were different: XDH resulted in more grade 3/4 non-hematologic AEs than DH (total: 77% vs 68%; hand-foot syndrome: 16% vs <1%; diarrhea: 11% vs 4%, respectively), but less grade 3/4 neutropenia (54% vs 77%), complicated neutropenia (20% vs 24%) and febrile neutropenia (14% vs 23%). The estimated mean AE costs per patient were similar in both arms. Conclusion: With the convenience of oral therapy, adding X to DH does not increase the number and duration of infusion visits or increase costs. For patients, physicians and payers, XDH is a good alternative for the treatment of advanced/metastatic breast cancer.

[Table: see text]
Epidemiology of cancer in the middle age and elderly populations in a developing economy: Need for proper resource allocation and personnel training
Authors: Alese O. B. , Obamuyide H. A.
Published: March 2020

17046

Background: Cancer is emerging as a major cause of death in developing countries. In order to prioritize health care resources, the pattern of occurrence and the current surgical treatment of different cancer types must be determined. We retrospectively reviewed the hospital's operating records, to find out the areas of greatest need with respect to cancer types. Methods: We extracted and analyzed relevant data from the hospital's operating records for the General Surgical Divisions (3). The hospital is a tertiary health care centre, serving as referral for more than 10 million people. All the operations done on patients more than 40 years old, from January 2004 to December 2005 (a 24 month period), were included in the analysis. Results: A total of 210 operations were done for general surgical malignancies in the 3 Divisions over the study period. 50% of the patients were between 41 and 60 years of age. 8% were 70 years and older. The majority were female; 72.4%, with a male to female ratio of 1:2.6. More than half of the cases were breast cancers (51.9%). Others were gastrointestinal (30%; colorectal: 24%, stomach: 6%), soft tissue sarcomas (6%), thyroid cancers (3.3%) and salivary glands (3%). 13.8% of the operations were done on emergency basis; in more than half of the colorectal cases who presented in acute intestinal obstruction. Virtually all the breast cancer operations were modified radical mastectomy. Conclusions: Most cancer operations in the middle age and elderly patients are for breast cancers, especially in the female gender. A significant proportion of the emergency operations are done for colorectal cancers presenting with acute intestinal obstruction. Appropriate health care personnel training and adequate resources are urgently needed in these areas, for effective and modern control of an emerging epidemic in developing economies.

No significant financial relationships to disclose.