bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and psychometric properties of the Prostate Cancer Radiation Toxicity Questionnaire
Authors: Rodrigues G. , Bauman G. , Lock M. , D'Souza D. , Mahon J.
Published: March 2020

15631

Background: The objective of this study was to construct a prostate cancer late radiation toxicity (PCRT) questionnaire with associated health-related quality of life (HRQoL) domains. Methods: A literature review of prostate cancer toxicity scales and HRQoL instruments generated a list of potential items for inclusion into the PCRT. An initial questionnaire was subjected to both patient (n=8) and expert (n=7) opinion. A pilot study (n=37) assessed patient feedback, ease of administration, and acceptance. Item reduction (n=100) based on response heterogeneity, factor analysis and Cronbach's alpha analysis was performed. Reliability testing (n=274) was performed using test- retest methodology and calculation of intraclass correlation coefficients (CC). Validity testing (n=274) consisted of discriminant and various construct validity tests (1. calculation of Pearson CC between the PCRT and different HRQoL instruments, and 2. comparison of mean brachytherapy versus external-beam radiation therapy domain scores by Student's t-test). Results: Construction of an initial 29 item (5 point Likert scale) questionnaire with genitourinary, gastrointestinal, and sexual symptom and bother items was performed. The pilot study demonstrated that the PCRT was comprehensive (94%) and easy to administer (1.3% missing data). Item reduction resulted in three HRQoL subscales: (4 item GU alpha = 0.639, 12 item GI = 0.859, 5 item sexual = 0.700). Test-retest reliability demonstrated intraclass correlation coefficients of 0.811 (GU), 0.842 (GI), and 0.740 (sexual). Discriminate validity analysis demonstrated Pearson CC of 0.449 (GU-GI), 0.200 (sexual-GU), and 0.09 (sexual-GI). Content validity analysis demonstrated significant correlations between analogous subscales between PCRT and the PCQoL (range 0.35–0.78). Smaller correlations exist between the PCRT and FACT-G (0.19–0.39) and SF-36 (0.03–0.34). Difference scores between brachytherapy and external-beam favoured brachytherapy [4.13 (GI, p=0.02), 3.50 (sexual, p=0.36), and 3.63 (GU, p=0.14)]. Conclusion: The HRQoL subscales generated from the PCRT have been shown to have good internal consistency with documented reliability and validity.

No significant financial relationships to disclose.
Induction of complete remission in metastatic hormone-refractory prostate cancer: A combined anti-inflammatory therapy approach
Authors: Reichle A. , Walter B. , Berand A. , Vogelhuber M. , Bross K. , Wilke J. , Wieland W. , Andreesen R. , Rogenhofer S.
Published: March 2020

15636

Background: The present multi-centre phase II study was designed to support the hypothesis that networking agents binding to ubiquitous accessible targets in metastatic hormone-refractory prostate cancer (HRPC) may counteract neoplasia-specific aberrant cellular functions, thereby mediating objective response (primary endpoint). Method: Patients with metastatic HRPC, received both an anti- inflammatory and angiostatic therapy consisting of low-dose chemotherapy with capecitabine 1 g twice daily for 14 days every 3 weeks, day 15+, COX-2 blockade with etoricoxib 60 mg daily, day 1+, combined with two transcription modulators, pioglitazone 60 mg daily, day 1+, plus dexamethason 1 mg daily for 14 days, every 3 weeks, day 15+, until disease progression. The study was planned using the Simon optimal design. Results: Thirty-six consecutive patients (N= 22 (61%) chemo-naive, n= 14 (39%) with preceding chemotherapies, mean 2.1 regimen) with metastatic HRPC, confirmed PSA increase, assessable response, and ECOG 0–2 were enrolled between 1/03 to 5/06. Objective response occurred in 10 of 13 cases (N/n: 41%/7%) with PSA (and C-reactive protein) response >50% (N/n: 45%/21%). Median time to PSA response was 2.4 months (range 1.0 to 7.3 months). Two of three patients responding with PSA <4 ng/ml achieved complete remission after 9 and 16 months, 16 patients stable disease (N/n: 41%/64%), and 5 patients experienced progressive disease (N/n: 14%/14%). Median progression-free survival (PFS) was 3.6 months (range 0.5 to 28.5) and median overall survival (OS) 14.4 months (range 0.6 to 37.2). Multivariate analysis recognized pre-treatment with chemotherapy as negative predictor for both OS (hazard ratio 2.26 (CI 95%: 0.970; 5.277), p=0.05) and PFS (HR 2.47 (CI 95%: 1.146; 5.348), p= 0.02), and <50% PSA response as negative predictor for PFS (HR 0.38 (CI 95%: 0.171; 0.857), p= 0.01). Toxicities > WHO grade II were reported: Hand-foot syndrome (n=1), anemia (n=6), edema (n=1), cushing syndrome (n=1), hydronephrosis (n=1). Conclusions: This is the first study reporting continuous complete remissions in HRPC with a biomodulatory therapy approach. Further, the study may clinically support the upper mentioned hypothesis.

No significant financial relationships to disclose.
A study of complementary therapies in men receiving radiation therapy for prostate cancer: A randomized feasibility trial
Authors: Beard C. , Dean-Clower E. , Dusek J. , Stason W. B. , DeCristofaro S. , Keshaviah A. , Purevjal I. , Rosenthal D. , Webster A. , Benson H.
Published: March 2020

15638

Background: Prostate-cancer patients suffer from substantial distress with both their diagnosis and treatment. Several studies have looked at the use of complementary and alternative medicine (CAM) in patients with prostate cancer to alleviate their stress and effects of therapy. We elected to study Reiki and Relaxation Response Therapy (RRT) in prostate-cancer patients. Methods: Patients receiving an eight-week course of radiation for prostate cancer were eligible. Consented participants were randomly assigned to RRT, to Reiki, or to no CAM therapy during radiotherapy. Reiki was given twice weekly, RRT once weekly. The feasibility of enrolling 60 patients, their compliance with physiologic and psychological testing, and preliminary assessment of the effect of CAM are the study endpoints. Statistical analysis of feasibility is based on the assumption that at least 80% of patients would complete 14/16 Reiki sessions or 7/8 RRT sessions. Patients were tested for outcome measures at baseline, at randomization, halfway through radiation, at completion of radiation and 2 months later. The psychosocial outcome measures used were the STAI, CES-D, FACT-G, FACIT: Fatigue Scale, and EPIC: Hormone Section. Physiological assessment included salivary cortisol, blood samples for interleukin-6, tumor necrosis factor alpha, CD8, natural killer cells, heat shock protein 70 and a validated bowel-and-bladder-symptom questionnaire. Results: We have enrolled 62 of 108 eligible patients (60%) within 18 months. The number of enrollment has been increased to 62 as two patients changed their treatment location. To date five patients dropped out short of completion, 1 became ineligible, 32 have completed the study, 20 are still receiving CAM therapy or are in active follow-up and 2 are awaiting randomization and radiotherapy. Conclusions: Complementary therapy appears to be of much interest to prostate-cancer patients. At the completion of the trial, we will have more data on feasibility, compliance and preliminary results on the effect of CAM intervention in this population.

No significant financial relationships to disclose.
Endometrial carcinoma (EC) in women 35 years of age or younger
Authors: Ali-Fehmi R. , Cote M. , Arabi M. H. , Munkarah A. , Schimp V. , Bryant C. , Morris R.
Published: March 2020

16000

Background: Although the majority of women with EC are postmenopausal, 25% are under the age of 50 years at the time of diagnosis. The aim of this study is to describe the demographic and survival data for women presenting with EC at age 35 years or younger (YOY). Design: Patients with a diagnosis of EC were identified from the Surveillance, Epidemiology, and End Results (SEER) cancer database from 1988 to 2003. Demographic and pathologic data were collected. Chi-square and t-tests were used to examine differences between the younger and older women, and survival analyses were performed using Kaplan Meier and Cox regression models. Results: Of the 61,364 women diagnosed with EC in the study period, 931 patients 1.5% were 35 YOY. Compared to women 36 years of age or older at diagnosis, the young-onset women were more diverse in terms of race/ethnicity (p<0.0001), with white women comprising 48% of the younger population, and 80.4% of the older population. Hispanic 23.7%, black 8.3%, and other race/ethnicities 18.4% were more common in the younger age group. The mean age in the young population was 31.5 years. Mean age at diagnosis was greater for the young whites compared to the other racial groups combined (32.0 years vs. 31.0 years, p<0.0001). Younger women were more likely to be diagnosed in earlier stages and grades compared to their older counterparts (both p<0.0001). The overall stage by AJCC in younger women was 75.4%, 6.6%, 4.1% and 5.2% (stages I-IV, respectively), with 8.7% unstaged. In the younger women, 54.6%, 26.3%, and 9.5% of grade 1, 2, and 3 tumors were reported, respectively. Type II tumors comprised 4% (N=36) of the study population. The overall mean survival was significantly better for younger (75.4 months, 95% CI 71.8–79.0) compared to older women (66.6 months, 95% CI 66.2–67.0). The survival difference was seen for every AJCC stage of disease. Conclusions: The changing race and ethnicity demographics in the US, coupled with the increase in obesity, suggest that EC incidence may be on the rise in younger women. Early stage, well-differentiated EC represents the most common type of EC in the younger patients. As treatment standards differ for younger women who hope to preserve their fertility, it is important to follow the long-term outcomes in this group.

No significant financial relationships to disclose.
Outpatient intraperitoneal chemotherapy for ovarian cancer chemotherapy—A comparison of reimbursement for intraperitoneal versus intravenous therapy
Authors: Schink J. C. , Bamlett-Sherman T. , Anastos L. M.
Published: March 2020

16027

Background: The GOG 172 trial produced compelling evidence that IP chemotherapy produced superior outcomes to IV chemotherapy for women with advanced ovarian cancer (AOC). In January 2006 these results were published along with an NCI Clinical Alert documenting the improved overall survival resulting from IP treatment. However, broad adoption of IP chemotherapy may hinge in part on adequate reimbursement, thus requiring support from governmental and third party payors. This analysis is designed to compare reimbursement for outpatient IP versus IV chemotherapy, assuming that the net effect might affect overall adoption of this important new therapy. Methods: A prospective trial of outpatient IP chemotherapy was initiated 1/2006 for women with AOC. A group of 28 AOC patients received 119 IP treatments between 1/2006 and 10/2006. Reimbursement for these treatments, net of related costs, was compared with that for standard IV chemotherapy. The IP regimen includes: aprepitant, palonosetron and dexamethasone on day 1; followed by docetaxel 70 mg/M2 then amifostine 910 mg/M2 (all IV) then cisplatin 100 mg/M2 IP; concluding with paclitaxel 60 mg/M2 IP on day 8. The IV regimen was carboplatin AUC 5 and taxane (paclitaxel 175 mg/M2 or docetaxel 70 mg/M2). The nursing administration codes for IP were 96445 on days 1 and 8; by comparison, the codes for IV were 96413 for infusions up to 1h, and 96415 for each additional hour. Data on precertification, total drug and administration charges, drug costs, and reimbursement were assimilated and used to compare reimbursement net of select costs. Results: Reimbursement for IP code 96445 was significantly higher than for IV codes 96413 and 96415, with the respective mean billed $2,469 for IP vs $834 for IV. Reimbursement rates for 96445 ranged from 25% to 100% (median 97%, mean 87%). Mean total charges for IP regimen was 1.28 times higher than for IV regimen, and reimbursement rates were comparable. Conclusions: IP chemotherapy for AOC is more effort intense and requires more chemotherapy drug and supportive care medications, resulting in higher charges and higher net revenue when administered on an outpatient basis.

No significant financial relationships to disclose.
Primary cytoreductive surgery or neoadjuvant chemotherapy: A retrospective analysis of 214 patients with stage IIIc and IV ovarian, tubal and peritoneal cancer from the Norwegian Radium Hospital
Authors: Silins I. , Elstrand M. B. , Davidson B. , Tropé C.
Published: March 2020

16035

Background: We evaluated clinical prognostic factors in ovarian carcinoma for their association with upfront treatment in advanced stage ovarian cancer patients with effusions. Methods: Our study consists of a retrospective analysis of 214 patients with stage IIIc and IV primary ovarian cancer, primary peritoneal carcinoma and tubal cancer, treated at the Norwegian Radium Hospital (NRH) in the period 1998–2003. One-hundred and thirty-eight patients underwent primary cytoreduction, 51 patients received neoadjuvant chemotherapy followed by delayed debulking and 25 patients received only chemotherapy. Results: Residual disease of less than 1 cm was achieved in 31.9 % of primary surgery patients and in 47.1 % of delayed surgery patients. Standard taxane/platinum treatment was given to 79.7 % and 67.1 % patients in the surgery and neoadjuvant treatment group, respectively. Hazard ratio for relapse was significantly higher for upfront treatment with neoadjuvant chemotherapy (1.69, CI 95 % 1.12–2.55) compared to primary surgery and for suboptimal debulking surgery and/or suboptimal chemotherapy (1.66, CI 95 % 1.14–2.41) compared to optimal treatment. The incidence of disease-related death was also significantly higher for the neoadjuvant chemotherapy group (1.83, CI 95 % 1.21–2.79) and for patients treated suboptimally (1.50, CI 95 % 1.03–2.19). Median cancer-specific survival was 31 months for the primary surgery group and 15 months for the neoadjuvant treatment group. Conclusions: In this retrospective analysis, the two most important prognostic factors for advanced ovarian, tubal and peritoneal cancer with malignant pleural and/or abdominal effusion were surgical treatment as first-line therapy and combination of optimal tumor debulking (<1cm) and taxane/platinum chemotherapy. The role of neoadjuvant chemotherapy is still controversial.

No significant financial relationships to disclose.
Combination gemcitabine and cisplatin for recurrent ovarian cancer
Authors: Richardson D. L. , Kim K. , Seamon L. G. , O'Malley D. M. , Eaton L. A. , Cohn D. E. , Copeland L. J. , Fowler J. M.
Published: March 2020

16037

Background: Recent evidence suggests gemcitabine combined with a platinum drug is active in recurrent ovarian cancer. In an effort to decrease dose-limiting myelosuppression associated with gemcitabine plus carboplatin, cisplatin can be substituted for carboplatin. Our objective is to describe a single institutional experience with day 1 and day 15 (D1/15) gemcitabine (1000 mg/m2) and cisplatin (30 mg/m2) for the treatment of recurrent ovarian cancer. Methods: A retrospective chart review was performed of all patients with recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer who were treated with gemcitabine and cisplatin from 8/2001 through 8/2006 at a single institution. Sixty-seven patients met inclusion criteria. Results: The median number of prior chemotherapy regimens was 2 (range 1–6). The median platinum-free treatment interval was 10 months (range 0–40). While 34 (51%) patients were platinum sensitive, 24 (36%) patients were platinum resistant, and 9 patients (13%) were platinum refractory. Patients were treated with a median of 6 cycles (range 1–31) of gemcitabine plus cisplatin. Fifteen (22%) patients had a complete clinical response with a median progression free survival (PFS) of 16 months (range 5–40); 15 (22%) patients had a partial clinical response (median PFS 6 months, range 2–15). Stable disease was noted in 19 patients, with a median PFS of 24 months (range 4–36). Three (38%) out of eight patients with refractory ovarian cancer had a complete clinical response, and 1 patient had a partial response. Non-hematologic toxicities were most common, occurring in 23% of the patient population (neuropathy, fatigue and pain). Grade 3 and 4 hematologic toxicities were rare, occurring in less than 10% of patients. Conclusions: Gemcitabine plus cisplatin (D1/15) is a well tolerated and active regimen in patients with recurrent ovarian cancer, regardless of previous response to platinum-based chemotherapy.

No significant financial relationships to disclose.
Preoperative evaluation of epithelial ovarian cancer with multidetector computed tomography and its correlation with surgical outcome
Authors: SH C. , Thulkar S. , Srivastava D. , Kumar L. , Hariprasad R. , Kumar S. , Sharma M.
Published: March 2020

16051

Background: In the management of epithelial ovarian cancer (EOC), optimum debulking surgery (residual tumour of 1 cm or less) is the most important prognostic factor and is associated with higher survival We conducted a prospective study to evaluate the role of Multidetector (MD) CT scan to predict optimal debulking in advanced EOC. Methods: Between December, 2004 and October, 2006, 38 previously untreated patients (median age-50 years, range 26 to 70) were evaluated with contrast- enhanced MD CT scan of abdomen and pelvis. All CT scans were performed on four-slice MD CT scanner with thin slice image acquisition. Multiplanar coronal, sagital or oblique images were constructed and all images were reviewed by at least 2 radiologists. The extent of disease was determined and mapped for all areas of abdomen and pelvis. Patients underwent primary debulking surgery in which total abdominal hysterectomy, bilateral salphingo-oophorectomy, omentectomy and optimal cytoreduction was done. CT scan films were reviewed and compared with surgical findings. A CT scan scoring system was developed to predict the optimum debulking using 10 parameters: ascites, pelvic, peritoneal deposits, large bowel, small bowel, omentum, diaphragm, liver, lymphadenopathy and lesser sac. Each factor was assigned a score of 0 to 2. The statistical analysis was done using SPSS version 11 and EpiInfo 6 software. Results: The mean interval between CT scan and surgery was 11 days. 18 of 38 patients had a CT score = 7; all 18 had sub-optimal debulking. Of remaining 20 patients with CT score <7, 17(44.7%) had optimum and 3 had sub-optimal cytoreduction. The sensitivity and specificity was 85.7% (95% CI 62.6–96.2) and 100% (95% CI 77.1–100), respectively. It had positive predictive value of 100% and negative predictive value of 85% with accuracy of 92% in identification of patients who would not benefit from surgery. Presence of tumor at gall bladder fossa, porta hepatis, ligament teres, spleen , stomach, pancreas, lesser sack and pelvic side walls was associated with sub-optimal debulking. Conclusions: Pre-operative CT scan scoring helps to identify patients who are likely to have sub-optimal debulking and may be candidates for neoadjuvant chemotherapy

No significant financial relationships to disclose.
Correlation between immunohistochemical biomarker expression and in vitro drug response factors in stage III-IV ovarian cancer
Authors: Tawfik O. , Peterson L. , Parker R. , Mechetner E. , Davis M. , Chapman J. , Khan Q. , Ma J.
Published: March 2020

16055

Background: The reliability of molecular biomarkers as predictors of treatment outcome remains unclear and, in relation to drug resistance even less is known. Immunohistochemical (IHC) expression of biomarkers and in vitro drug resistance (IVDR) relative to clinical outcome were evaluated in patients with stage III-IV epithelial ovarian cancer (OC) who received combination carboplatin (CAR) plus paclitaxel (TAX) chemotherapy. Methods: We correlated clinical outcome with histopathology and biomarker expression of MIB-1, p53, BCL2, EGFR, ER and PR in 98 OC patients with tumors tested for IVDR by extreme drug resistance (EDR) assay. IVDR was determined following exposures to single agents CAR, cisplatin (CP), TAX, taxotere (TXT), gemcitabine (GCB), topotecan (TP), liposomil doxorubicin, and cytoxan (CT). Percentage cell growth inhibition (PCI) for each drug was compared with PCI from untreated control cultures. Results: Tumors with prior chemotherapy (n=29) were more resistant to CAR (unpaired t-test, p=0.046), and CT (p=0.038), and more sensitive to liposomil doxorubicin (p=0.009), compared to treatment naive tumors (n=53). For 65 tumors, there was a positive relationship between MIB-1 vs p53 (r=0.419; p=0.001), and between ER vs PR (r=0.339; p=0.011). Correlation between biomarkers and drug response showed a significantly inverse relationship between MIB-1 vs liposomil doxorubicin, p53 vs liposomil doxorubicin, EGFR vs CAR, CP, GCB and TAX; and between ER vs TXT and CT, and PR vs CT and TP. With a 53% (33/61) response rate to CAR+TAX, time to progression (TTP) for responders (R) with EGFR+ tumors was longer (median TTP 15.6 mo); and shorter for R with EGFR- tumors (p=0.008). For R and non-R, BCL2+ tumors had longer overall survival (OS) (median OS 23.3 mo; p=0.006). No other significant correlations were seen. Conclusion: Prior chemotherapy increased IVDR to CAR and CT, and increased sensitivity to liposomil doxorubicin. Increased expression of proliferation biomarkers, particularly EGFR, correlated with resistance to several chemotherapeutic agents. EGFR expression in responders was associated with longer TTP. The significance of in vitro correlates of prognostic biomarker expression and IVDR for predicting chemoresistance warrants prospective studies to assess its value in clinical settings.

[Table: see text]
Concurrent chemoradiotherapy for locally advanced cervical cancer: Analysis of a single institutional 10-year experience
Authors: Aoki Y. , Nagai Y. , Toita T. , Hirakawa M. , Toma M. , Yagi C. , Nashiro T. , Inamine M. , Kamiyama K.
Published: March 2020

16056

Background: The purpose of this study was to report the feasibility and efficacy of concurrent chemoradiotherapy (CCRT) for the locally advanced cervical cancer in our institute. Methods: We retrospectively reviewed 147 patients (stage Ib: 9, II: 82, III: 80, and IVa: 7) with squamous cell carcinoma of the cervix treated with CCRT. Cisplatin (20mg/m2/day) was administered for 5 days every 3 weeks for a median of three courses (range: 1–5 courses) during radiotherapy (RT). The patients with paraaortic and/or common iliac lymphadenopathy were excluded. RT consisted of pelvic external beam RT (EBRT) with 40Gy/20 fractions followed by high-dose rate brachytherapy (HDR-BT) with 18Gy/3 fractions and pelvic EBRT with 10Gy/5 fractions using a midline block. Late complications were graded by the RTOG/EORTC criteria. Results: The 5-year actuarial overall survival (OS), disease-free survival (DFS), and pelvic relapse-free survival were 78.5%, 70.7%, and 78.0%, respectively. The 5-year OS by the disease stage was as follows: stage Ib 100%, II 82.0%, III 62.3%, and IVa 35.7%. Multivariate analysis identified pelvic lymphadenopathy, tumor diameter > 7cm, and pretreatment hemoglobin < 9.0g/dl as an independent prognostic factor for both OS and DFS. Only one patient suffered from grade 3 enterocolitis, but no grade 4 complication developed. Conclusions: Our experience suggests that CCRT using HDR-BT for locally advanced cervical cancer could achieve favorable local control without suffering from severe late complications.

No significant financial relationships to disclose.
Dysgerminoma of the ovary: Review of 32 cases
Authors: Streltsova O. , Tjulandin S. , Jordaniya K. , Kuznetsov V. , Kedrova A.
Published: March 2020

16072

Purpose: This study was undertaken to determine the frequency, characteristics, treatment and outcome of patients with dysgerminomas in single institution between 1990 and 2006. Methods: A total of 32 patients with pure dysgerminoma were retrospectively reviewed, among whom 23 patients had primary treatment in NNBRCRC during the period 1990–2006 and referred for follow-up (n=1) or salvage therapy after recurrence (n=9). Results: The median (range) age at presentation was 21 (14–42) years. 17 women (53%) presented with FIGO surgical stage I disease, 2 (6%) had pelvic metastases (stage II), and 9 (28%) had advanced (stage III/IV) disease. 4 patients had no comprehensive surgical staging. 2 women had evidence of dysgenetic gonads with a 46 XY karyotype. Primary surgery was done in all patients. 22 patients (69%) underwent fertility-sparing surgery. 4 (13%) patients received no adjuvant treatment after surgery due to stage Ia. All of them are alive without evidence of disease at a median (range) follow-up of 4,2 (2–6,4) years. Postoperative systemic chemotherapy was administered to 28 (87%) women. 16 of them received adjuvant chemotherapy and 12 received chemotherapy for metastatic disease. Among them 20 received platinum-based chemotherapy. Six patients had disease progression during first-line systemic treatment, all women received non-platinum-based chemotherapy. Three of them were salvage with second-line cisplatinum-based chemotherapy. Two deaths were associated with progressive disease, and one patient died of intercurrent disease. Overall, 29 women (90%) are alive without evidence of disease at a median follow-up of 68 months. Conclusions: Our date confirmed that the majority of patients can be managed with fertility sparing surgery and platinum-based adjuvant treatment without compromising survival.

No significant financial relationships to disclose.
Weekly topotecan as a salvage therapy in heavily pre-treated patients with recurrent platinum-resistant epithelial ovarian cancer
Authors: Marinaccio M. , De Marino E. , Mele E. , Catacchio R. , Meo D. , Iezzoni C. , Conversano C.
Published: March 2020

16076

Background: The prognosis of patients with recurrent epithelial ovarian cancer is extremely poor after several lines of chemotherapy; this situation becomes more and more difficult to manage in the presence of a platinum-resistance condition. Topotecan 1.5mg/m2 on days 1 through 5 of a 21-day cycle is often employed as a second-line chemotherapy also for platinum-resistant epithelial ovarian cancer. In this phase II study we investigated the safety as well response rate of weekly topotecan as a salvage therapy in heavily pretreated patients with recurrent platinum-resistant epithelial ovarian cancer (RprEOC). Methods: To be elegible for the study patients had to be considered resistant to platinum and paclitaxel pretreated. Eleven patients (median age 51 yrs, range 45 - 70) with performance status 0–2 affected by RprEOC with measurable disease, were planned to receive weekly topotecan. They had received at least 3 prior lines of chemotherapy. Topotecan was administered at the dose of 2.0 mg/m2 via a 30-minute i.v. infusion once every week until disease progression or unacceptable toxicity. Results: All patients were evaluable for toxicity and clinical response. All the 11 pts enrolled had stage III-IV disease. Median number of chemotherapy cycles was 5 (range 3 - 8). A total of 62 cycles were administered. Dose reduction was necessary for 12% of the cycles. Main toxicities included anemia (12%), leucopenia (18%), thrombocytopenia (15%) and asthenia (20%). No deaths were attributable to therapy. No one showed complete response, while two partial response (18.2%) and four stable disease (36.4%) were observed. Five pts (45.4%) progressed on therapy. The median progression-free interval was 13 weeks. Conclusion: Salvage therapy for patients with ovarian cancer who failed several platinum and paclitaxel treatments remains a therapeutic challenge. Topotecan administered at low weekly dosage (2.0 mg/m2) is an active option in the subset of heavily RprEOC and it seems also to be a more tolerable regimen compared to the classical 5-day schedule.

No significant financial relationships to disclose.
Doxorubicin and concurrent radiotherapy for anaplastic thyroid cancer: We need to do better
Authors: Lim S. , Lee N. Y. , Fury M. G. , Ghossein R. A. , Shaha A. R. , Wolden S. L. , Pfister D. G.
Published: March 2020

16506

Background: Anaplastic thyroid cancer (ATC) is a rare, aggressive malignancy. The potential for pathologic misclassification complicates the interpretation of published data. One treatment option for locoregionally (LR) advanced disease is weekly low-dose doxorubicin (D) with concurrent radiation therapy (RT), based on reported 2-year local control rates of 68% (ATC)/77% (other TC histologic subtypes) (Cancer 1987;60:2372). We looked to evaluate our experience with this general approach, but in a larger series which included pathologic confirmation of all ATC cases. Methods: Patients (pts) were identified through the Memorial Sloan-Kettering Cancer Center (MSKCC) Radiation Oncology and Pathology Databases. Inclusion criteria: diagnosis of ATC between 1984–2006, with pathology review at MSKCC; LR disease only, able to be encompassed within a RT portal; treatment at MSKCC with planned weekly D (10 mg/m2) and concurrent radiation. Prior surgery was allowed. Documentation of failure was based on clinical/radiographic assessment. Principal outcomes assessed: LR control (LRC: no failure at the primary site, in the neck, or the mediastinum), progression-free survival (PFS), and overall survival (OS). The Kaplan-Meier method was applied. Results: Thirty-seven patients were included in our analysis (median age 64; 54% female, 46% male). Median RT dose 5760 cGy, >4500 cGy in 32 (87%), administered through hyperfractionated or once-daily schedules. Median number of D treatments received 5.5, >4 in 24 (65%). 2-year outcomes: LRC 25%; PFS 8%; OS 18%. 6 patients remain alive at the time of last follow-up with survival durations of 4.1, 11.4, 11.7, 57.3, 58.5, and 140.7 months, respectively. A subset analysis was performed limited to the 24 patients (65%) who completed >4,500 cGy of radiation and >4 doses of D. 2-year outcomes were improved in this latter group, but remained disappointing, even among these more highly selected pts (LRC 30%; PFS 11%; OS 27%). Conclusions: Better therapy is needed for this poor prognostic disease. Future analyses will evaluate the impact of histologic subtype of ATC, radiation technique/dose, and surgical resection on outcome.

No significant financial relationships to disclose.
Evaluation of epidermal growth factor receptor (EGFR) in nasopharyngeal carcinoma and lymph node metastases: Implications for EGFR targeted therapy
Authors: Huang Y. , Lin T. Y. , Lu T. X. , Luo R. Z. , Niraula S. , He J. H.
Published: March 2020

16510

Background: Epidermal growth factor receptor (EGFR) overexpression is proved to be an independent predictor of poor clinical outcome in Nasopharyngeal Carcinoma (NPC). Expression level of EGFR is also important for EGFR-Targeted therapy but yet unexplored in the primary NPC tumors and lymph node metastases. Aim of this study was to correlate EGFR expression levels in primary tumors and lymph node metastases in NPC to find out whether assessing EGFR status on primary cancer is an effective tool for planning EGFR targeted therapy. Methods: Archived tissue samples of primary tumor and corresponding lymph node metastases of 86 NPC patients (67 males, 19 females; median age = 52 years) diagnosed between 1997 and 2006 were collected from Sun Yat-sen University Cancer Center. Immunohistochemical evaluation of EGFR expression in primary tumors and related lymph node metastasis was performed. According to the UICC 2002 staging system for nasopharyngeal carcinoma, stages Iib, III, IVa, IVb and IVc included 43, 11, 3, 27 and 2 cases respectively. Cervical and supraclavicular lymph nodes were taken in 66 (76.7%) and 20 patients (23.3%) respectively. EGFR status was defined as positive if the percentage of malignant cells stained were =1%. The SPSS 10.0 system was used for statistical analysis and Chi- square test was used to assess the correlation between the EGFR expression in the primary and metastatic tumors. Results: EGFR status was positive in 63 primary tumors (73.2%) and 52 metastatic lymph nodes(60.5%). In 18 EGFR expressing primary tumors (28.6%), the corresponding metastatic lymph node site was negative whereas it was found positive in 7 metastic lymph node (13.5%) of EGFR-negative primary tumors. The difference between these two groups (ie, EGFR-positive to EGFR-negative vs. EGFR-negative to EGFR-positive) was statistically significant (P=0.001). Conclusions: High levels of EGFR protein are frequently observed in NPC and represent potential therapeutic target. However, equivalent expression is not displayed by metastatic nodes, which may limit the effectiveness of anti- EGFR treatment in advanced diseases. These findings have to be considered in future prospective studies.

No significant financial relationships to disclose.
A proposal of pathological classification (pTNM) of patients with head and neck cancer according to capsular rupture (pN- RC)
Authors: Gallego O. , Leon X. , Lopez Pousa A. , Farre N. , Vega M. , Lopez M. , Carreras G. , Carreras G. , Marse R. , Quer M. , Barnadas A.
Published: March 2020

16525

Background: Lymph node metastasis remains one of the most significant prognostic factors of head and neck squamous cell carcinoma survival. Several studies have demonstrated that capsular rupture (CR) significantly decreases survival in patients with a positive neck dissection. We proposed to investigate whether inclusion of CR in the pTNM improves the prognostic capacity of the classification. Methods: We reviewed 841 patients (p) who underwent neck dissection and had a minimum follow-up of two years. The Kaplan-Meier method was used to analyce survival according to presence of neck nodes with CR and number of nodes with CR. Results: We analyzed 841p (151 oral cavity, 97 oropharynx, 136 hypopharynx, 258 supraglotis, 151 glotis and 48 only node; T1, 208 T2, 336 T3, 164 T4; 349 N0, 174 N1, 242 T2 and 78 N3). Treatment was surgery in 220 p and surgery plus radiotherapy in 621p. We treated 465 p with induction chemotherapy. Five-year survival was: 87% for pN0 (n=34), 67.2% for pN1RC-negative (n=118), 74.6% for pN1RC-positive (n=24), 51.7% for pN2RC-negative (n=127), 39.8% for pN2RC-positive only one node (n=58), 17.4% for pN2RC-positive more than one node (n=93) and 21.7% for pN3 (n=72). Conclusions: These results indicate that including CR information in the pTNM improves prognostic capacity of the classification. We propose four pTNM categories: Category 0: pN0; category 1: pN1RC-negative or -positive; category 2: pN2RC-negative or pN2RC-positive only one node; category 3: pN2RC-positive more than one node or pN3.

No significant financial relationships to disclose.
Moving from 2D to 3D conformal radiotherapy (3DCRT) in locally advanced head and neck cancer: A dosimetric comparison
Authors: Billan S. G. , Bakouche V. , Nevelsky A. , Abdah-Bortnyak R. , Uziel R. , Rawashdeh F. , Gez E. , Epelbaum R. , Kuten A.
Published: March 2020

16530

Background: The aim of this study is to evaluate the dosimetric parameters of 3D CRT in head and neck tumors, to compare with hypothetical 2D plans, and to evaluate the acute toxicity. Methods: A total of 33 patients with median age of 62 years (range: 23–87 ) and with histologically proven head and neck cancer were consecutively treated with 3D CRT using a 6-field photon beam technique. 9 patients had supraglottic carcinoma, 5 - glottic carcinoma, 4- nasopharyngeal carcinoma, 4 - thyroid carcinoma, 2- oropharyngeal cancer, 3 - carcinoma of oral cavity, 1- carcinoma of hypopharynx, 1- maxillary sinus carcinoma, 3- unknown primary, 1- recurrent laryngeal carcinoma. 28 patients received concomitant chemotherapy and 13 were treated with neoadjuvant chemotherapy, 5 patients received postoperative radiotherapy and 28 received definitive radiotherapy. A comparative analysis of dose distributions and dose-volume histograms (DVH) between 2D and 3D plans for 11 patients with glottic and supraglottic carcinoma for the initial 50 Gy (since the 20 Gy boost was given almost identical in both technique) was carried out. Toxicity analysis was determined according to RTOG/EORTC toxicity criteria. Results: The mean dose coverage V45 (%) of the primary planning target volume for 2D and 3D plans was 89.6% and 94.8%, respectively (p=0.005). The mean volumes of the hot spots ( 110% of prescribed dose) for primary target volumes for 2D and 3D plans were: 61cc (range: 8.7–130.2 cc) and 26.2 cc (range: 0–49.8 cc), respectively (p=0.005). The mean dose to the parotid glands was significantly lower with 3D CRT (22.1 Gy and 24.7 Gy) compared to 2D technique (45.2 Gy and 46.4 Gy) for right and left parotids, respectively (p=0.003). The maximal spinal cord dose was: mean 45.3 Gy and 41.6 Gy for 2D and 3D CRT, respectively (p=0.003). Gr3 acute toxicity was observed in 3 patients (9%) , and Gr 4 toxicity in 6 patients ( 18%). Treatment was interrupted in 3 patients only. Conclusions: 3DCRT in head and neck cancer permits good coverage of the PTV .The low rate of acute toxicity can be explained by improving the dosimetric parameters of organs of risk and reducing the volume of hot spots in the target. Using 3D CRT for laryngeal carcinoma allows parotid sparing with a mean parotic dose of less than 26 Gy

No significant financial relationships to disclose.
Effectiveness of concurrent radiation therapy combined with peroral chemotherapy (UFT or TS-1 ) for T2N0 glottic cancer in Japanese population
Authors: Niibe Y. , Hayakawa K. , Nakayama M. , Matsubayashi T. , Takahashi H. , Okamoto M.
Published: March 2020

16538

Background: The current study retrospectively reviewed 147 T2N0 glottic cancer patients treated at Kitasato University Hospital to compare concurrent radiation therapy combined with chemotherapy (most of them: UFT or TS-1, peroral anti-cancer drugs), with conventional radiation therapy. Methods: One-hundred and forty-seven patients with T2N0 glottic cancer treated with radiation therapy alone or radiation therapy combined with peroral (UFT or TS-1)or intravenous chemotherapy between 1974 and 2005 at Kitasato University Hospital. The median age of all patients was 64 years (range; 45–86 years). As for gender, 145 were males and the others were females. As for radiation therapy protocol, all except one were treated with 2 Gy per fraction, 5 fractions per week and a total of 60 Gy. Only one patient was treated with 1.8 Gy per fraction, 5 fractions per week and a total of 61.2 Gy. As for chemotherapy protocol, 83 patients were concurrently given UFT, (UFT group). 24 patients given TS-1, (TS-1 group) and 23 patients underwent intravenous chemotherapy using mainly cisplatin (Pt. group). The other 23 patients underwent no chemotherapy. Results: The median follow-up time was 61 months (range; 3–372 months). The 5-year local control rates of all patients was 83.4 %. Stratified by radiation therapy alone group (RT group) and concurrent chemoradiation therapy (CCRT group), The 5-year local control rates of RT group and CCRT group were 82.7%, 83.4%, respectively (p=NS). Stratified by chemotherapy regimens of CCRT group, 3-year local control rates of UFT group, TS-1 group and Pt. group were 90.1%, 100.0% and 73.4%, respectively, which indicated the peroral chemotherapy was not inferior to intravenous chemotherapy. As for morbidity, 2 patients of UFT group experienced severe enteritis . Conclusion: Concurrent radiation therapy combined with UFT or TS-1 for T2N0 glottic cancer might be the one of standard treatments in Japanese Population. Furthermore, concurrent use of TS-1 might perform break-through for T2N0 glottic cancer in terms of local control rate, overall survival and burdens of treatment on patients.

No significant financial relationships to disclose.
Weekly chemotherapy with platinum as radio-sensitizer during concomitant chemoradiotherapy for squamous cell head and neck cancer
Authors: Caramalis A. , Nissel-Horowitz S. , Iqbal U. , Roy R. , Radhakrishnan N. , Thomas A. , Pollack J. , Lebowicz Y. , Mehrotra B.
Published: March 2020

16541

Background: CRT protocols for locally advanced HNC commonly utilize single agent cisplatinum as the radiation- sensitizing chemotherpy. This is typically administered in q 3 weekly doses of 100 mg/sq m concomitantly with XRT. However, many pts are not candidates for this dose and schedule of cisplatinum delivery due to co-morbidities. Limited data are available regarding the efficacy of alternate dosing of platinum analogues.We therefore analysed our experience with alternate dosing of cisplatin or carboplatin administered concomitantly with XRT. Methods: IRB approval was obtained for this retrospective analysis. Tumor registry and pharmacy data were reviewed to identify eligible pts. between 2004–2006 who were treated with alternate dosing of platinum with XRT. Pt characteristics recorded included: age, gender, stage, site of disease, type of chemotherpeutic agent used carboplatin or cisplatinum, number of doses administered, local disease free survival and overall survival. Results: Eleven pts were identified. Median age: 64 years (44–75); Gender: M:F::8:3; Sites: Oral cavity: n=2; Pharynx: n=11; Stage III: n=3; Stage IVa &b: n=8. Cisplatin weekly (doses 30–40mg/sqm): n=8; Carboplatin weekly AUC=2: n=3; Cisplatin weekly, changed to carboplatin: n=1. Nine of 11 pts achieved a local CR (82%); one pt has achieved a near CR and one pt achieved a PR and required salvage laryngectomy. At a median follow up of 14 mos (range: 4–34), all pts remain alive. In addition to the pt that achieved a PR after initial treatment, one other pt has required surgical salvage at 23 mos post CRT. No treatment related mortality occurred in this series. Conclusions: Weekly administration of cisplatin and carboplatin appears to be a feasible alternative to standard dose and schedule of cisplatin with acceptable efficacy. Future studies should compare targetted therapies such as cetuximab with or in combination with weekly platinum regimens during CRT for pts not eligible for standard dose cisplatinum.

No significant financial relationships to disclose.
Geriatrics, oncology, and palliative care for patient-tailored treatment: A Brookdale experience.
Authors: Naik S. G. , Dumlao T. L. , Kalavar M. , Steier W.
Published: March 2020

17028

Background: Patients over 75 years of age are particularly underrepresented in clinical trials. Measures have been used to help characterize the functional age of a patient, to optimize treatment decisions and stratify outcomes, based on factors other than chronological age. The purpose of this study was to evaluate if palliative and social issues influence decision-making in this older population. Methods: The geriatrics oncology patients’ consults from July 2005 to December 2006 were reviewed. In addition to geriatric and oncology tools, palliative measures such as advanced directives, DNR status and social support were incorporated. Results: 89 pts with mean age 80.3 years (range 72–91) and AJCC Stages I (3.3%), II (16.8%), III (28%), and IV (46%) across various malignancies were included. Of the study population, 86% of patients were > 75 years of age, 55% were women, and 75% were widowed; 64% were African- American and 20% were Hispanic. Interestingly, 14 patients (15.7%) had diagnosis of previous cancer (6 breast, 6 prostate). Performance status (KPS and ECOG), activities of daily living (ADL) and instrumental activities of daily living (IADL) scales were assessed. 38.2% had KPS>70, and 31.5% had KPS<40. 22.4% were also independent for instrumental activities of daily living. 33% patients had advanced directives (including DNR status) at diagnosis. Consent was signed by patients themselves in 56% of cases. Social issues included: 22.4% were in NH, 10.11% without social support, 21.3% with falls, and 41.6% with depression in the GDS. Co-morbidities included HTN in 50%, dementia in 19.1%, and multiple medical problems in 21.3% patients. 30.33% pts received aggressive treatment, while19.1% were referred to hospice, with 50% requiring palliation. Pain was the main symptom that needed palliation in 48.3% patients. Supportive care included use of growth factors 24.7% and erythropoietin 48.3%. Conclusions: Social support, advanced directives, consent were the main issues even in patients with good performance status and absence of major co morbidities. Strategies to increase participation of good performance status elderly patients in geriatric clinical trials should include pain and palliative care issues.

No significant financial relationships to disclose.
Truth telling to cancer patients: Views of Myanmar primary care physicians
Authors: Mon S. , Pe A.
Published: March 2020

17030

Background: Due to cultural and social concern, non oncology physicians are still practicing nondisclosure in Myanmar. The views of Myanmar primary care physicians about truth telling to cancer patients were studied. Methods: A Questionnaire about revealing diagnosis and prognosis to cancer patients was prepared and given to 150 qualified Primary care physicians attending the oncology related lecture in CME course for General Practitioners in 2006, Yangon, Myanmar. Results: A total of 145 completed forms (96.66%) were returned. Age of primary care physicians range from 23 yrs to 52 yrs. 90 doctors (62.06%) were under age of 35 yrs (mean 29.94 yrs) and practicing experience ranged from 1 to 10 yrs. The remaining 55 (37.93%) were over 35 yrs of age (mean 44.52 yrs) with practicing duration of 10 to 28 yrs. The common cancer patients they have seen in daily practice were breast cancer (40%), lung cancer (28.96%), GI cancer (15.17%), cervical cancer (8.96%), ovarian cancer (3.4%), head and neck cancer ( 2.06%) and hematological malignancies (1.37%).A total of 73 doctors (50.34%) answered that they let the patient know they were suffering from a serious disease (not mentioning the word cancer) that needs further specialized treatment. Interestingly, 69.09% of physicians over 35 yrs of age agree with this approach, whereas only 38.88% of young physicians prefer it. Besides, 56.6% of senior primary care physicians prefer to reveal the diagnosis and prognosis to one or more family members first. Although all doctors are aware of the psychological distress on patients by painful truth telling, 58.8% of younger generation prefer to practice full disclosure to patients. Altogether, 105 physicians (72.41%) agree that disclosure of diagnosis and prognosis depends on education status of the individual patient. Conclusions: In this study, there were variations in physicians’ attitude and practice of truth telling. Full disclosure was preferred more by young physicians in Myanmar. Further studies on patients’ preference of telling the truth will help to better understand doctor-patient communication in Myanmar.

No significant financial relationships to disclose.