bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond the bevacizumab resistance, combined effects of erlotinib in heavily pretreated patients with recurrent ovarian cancers.
Authors: Kikuchi Yoshihiro , Takano Masashi , Ikeda Yuji , Kikuchi Ryoko , Kudoh Kazuya , Sasaki Naoki , Sakamoto Masaru , Kita Tsunekazu , Terao Yasuhisa , Takeda Satoru
Published: March 2020

e16505

Background: In heavily pretreated ovarian cancer patients, bevacizumab (B) combined with conventional chemotherapy has been reported to improve the response. However, responses to B are usually transient and resistance inevitably develops. The vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) are valid targets in many solid tumors, and their inhibitors have synergistic effects in preclinical studies. Methods: In 13 patients with heavily pretreated ovarian cancers, after development of B resistance erlotinib (E) (150 mg/day, 3 week, one week rest) and B (2 mg/kg/week, 3 week, one week rest) were administered with cytotoxic agents until development of disease progression or unmanageable adverse effects (AE). The primary endpoint in this study was response rate (RR) and progression-free survival (PFS). Results: Of 13 patients, 3 patients were not evaluable for response evaluation criteria in solid tumors (RECIST). Of 10 patients, 3 (30%) patients had partial responses (PR), 4 (40%) had stable diseases (SD), resulting in 70% clinical benefit rate (CBR). The PFS lasts more than 6 months in 4 (40%) patients. Although main AEs by E were rash, diarrhea and mucositis, all cases were manageable and tolerable. Conclusions: E administration after development of B resistance can reverse effects of B in 70% of heavily pretreated patients with recurrent ovarian cancers. AE of E was manageable and tolerable. These results warrant further studies in such clinical settings.
Is adjuvant chemotherapy after secondary debulking surgery for recurrent ovarian cancer necessary?
Authors: Takekuma Munetaka , Mori Keita , Komeda Satomi , Kuji Shiho , Tanaka Aki , Takahashi Nobutaka , Abe Masakazu , Hirashima Yasuyuki
Published: March 2020

e16507

Background: Secondary debulking surgery (SDS) for recurrent ovarian cancer is recognized as a valuable options. However, to our knowledge, the value of chemotherapy after SDS has not been reported. Methods: Between November 2003 and November 2011, 30 patients with recurrent ovarian cancer underwent SDS at our hospital. We statistically analyzed which variables influenced survival. Results: After SDS, the median follow-up was 22.9 months, and the median survival was 26.7 months (range, 0.1-61 months). Twenty-five patients (83.3%) had no residual tumor after SDS. With Fisher's exact method, the patients who had serum CA125 levels ≥ 40 U/ml tended to show disease progression after SDS (p = 0.13). Adjuvant chemotherapy after SDS had no significant clinical benefit with regard to disease progression (p = 0.25). Moreover, log-rank test showed median progression free survival to be 31.8 months for patients who had serum CA125 levels < 40 U/ml as compared with 8.9 months for patients who had serum CA125 levels ≥ 40 U/ml (p = 0.0351). For patients who received adjuvant chemotherapy after SDS, the median progression free survival was 13.0 months, versus 8.0 months for patients not given adjuvant chemotherapy after SDS (p = 0.5871). Conclusions: We suggest that a serum CA125 level < 40 U/ml should be used as a selection criterion for offering SDS. Adjuvant chemotherapy after SDS does not appear to prolong survival. We advocate that a randomized trial to verify the necessity of chemotherapy after SDS be initiated to confirm this finding.
Centralized independent disease status adjudication for maintenance treatment evaluation in advanced ovarian cancer setting: A critical analysis of the MIMOSA trial experience.
Authors: Scartoni Simona , Pfisterer Jacobus , Sabbatini Paul , Berek Jonathan S. , Bertolotti Monica , Contini Mariapaola , Cristina Goso , Otranto Isabella , Melani Lorenzo , Poggiali Giulia , Maggi Carlo Alberto , Capriati Angela , Simonelli Cecilia ,   on behalf of Mimosa Investigators
Published: March 2020

e16510^

Background: Progression free survival (PFS) is an accepted surrogate of Overall Survival (OS) often used as the primary endpoint in phase III trials evaluating maintenance treatment in advanced ovarian cancer (AOC). Methods: We compare the centrally assessed PFS (PFS-CA) vsthe locally assessed PFS (PFS-LA) data collected in the Mimosa Trial, a randomized, double blind, placebo controlled, Phase III study of Abagovomab maintenance therapy in AOC patients in complete response after standard chemotherapy. PFS was assessed at pre-fixed time points by pelvis/abdomen CT scan, which were centrally and blinded reviewed by trained radiologists for radiological assessment (RA) of recurrence status and date (PFS-RA). An independent blinded committee, including one radiologist and one oncologist, reviewed all the CT scans and any additional imaging records AND/OR clinical data (when locally required for patients’management) to adjudicate the recurrence status and date (PFS-CA). PFS-CA was used for the primary analysis; sensitivity analyses were carried out on PFS-LA as well as on the strictly defined PFS-RA data. Results: 888 patients were randomized 2:1 to receive Abagovomab or placebo. In the ITT population (n = 886) time to PFS-CA was 403 and 402 days in Abagovomab and placebo group, respectively; in the sensitivity analyses time to PFS-LA was 407 and 409, and finally time to PFS-RA was 414- 487 days respectively, without any statistically significant differences between groups or PFS assessments. Conclusions: No differences were seen in PFS assessed centrally or locally when RA and clinical data are considered, whereas a slightly longer PFS was observed when it was assessed exclusively by the independent radiological review although this is not statistically different. The centralised independent assessment of recurrence status for ovarian cancer patients treated in the remission setting appears not to add value to the local blinded assessment. Clinical trial information: NCT00418574.
The impact of an automatically generated survivorship care plan on patient reported outcomes (ROGY Care): Results of a pragmatic cluster randomized controlled trial among endometrial cancer patients.
Authors: van de Poll-Franse Lonneke V. , Nicolaije Kim A.H. , Ezendam Nicole P.M. , Vos M. Caroline , Boll Dorry , Pijnenborg Johanna MA , Roukema Jan A. , Kruitwagen Roy F.P.M.
Published: March 2020

e16517

Background: More patient tailored information for cancer survivors is needed. Evidence on effects of implementing Survivorship Care Plans (SCPs), is limited. Aim of this pragmatic cluster randomized trial is to assess the impact of SCPs in routine clinical practice. Primary endpoint is patient satisfaction with information. Secondary endpoints are QoL and health care use. Methods: We built an SCP-application in the web-based Registrationsystem Oncological GYnecology (ROGY), used in our area since 2006. By clicking the SCP-icon in ROGY, a personalized SCP is automatically generated. Twelve hospitals were randomized to usual care or SCP care. In usual care, gynecologists did not have access to the SCP-icon. In SCP care, SCPs are personally discussed and handed to patients. All newly diagnosed endometrial cancer patients (age ≥ 18) were asked to complete a questionnaire after surgery, 6, 12 and 24 months after diagnosis. The questionnaire included the EORTC INFO25 and asked whether patients actually received an SCP. We expected 150 endometrial cancer patients: 75 per arm. We hypothesized that patients receiving SCP care are more satisfied with the information. Results: 201 patients (74%) returned a questionnaire after surgery: 109 SCP arm, 92 usual care arm. Of the patients in the SCP arm, 69% reported receiving an SCP. Analyses according to randomization arm showed that patients in both arms reported similar scores on all scales of the INFO25, including satisfaction with care (87% vs. 82%, SCP vs usual care, p=0.20). Analyses according to actual care received showed that patients who received SCP care reported significantly higher scores (4-18 points) on all scales of the INFO25, including satisfaction with care (91% vs. 78%, SCP vs usual care, p=0.046) compared to those who did not receive SCP care. Conclusions: Even in a situation where SCPs are automatically generated, still one third does not receive an SCP. But, those who receive SCP care report better information provision and satisfaction. Follow-up measures will show whether this ultimately results in better QoL and decreased health care use. Clinical trial information: NCT01185626.
Novel approach to outpatient endometrial biopsy to detect endometrial cancer.
Authors: De Leon Maria B. , Howard Wu , Del Priore Giuseppe
Published: March 2020

e16522

Background: Currently there is no consensus on the best device and technique for obtaining endometrial biopsies to rule out cancer. Outpatient methods available include aspiration devices (Pipelle) and disruption devices (Tao brush). This study evaluated a new device which combines Global endometrial Disruption using a brush with a built in suction Process (GDP-Tao). Methods: After IRB approval, endometrial specimens were collected using the GDP-Tao from fresh uteri after completion of hysterectomies. Endometrial pathology results from the new device were compared to the final hysterectomy diagnosis by blinded review. Results: Patients (n = 33) were 29-86 years old (median 56), 67% obese, 52% menopausal. Uterine sounds were 2.5-11cm (median 6.6 cm), weight 45-3500g (median 238g), 15% of cervical os were stenotic but all allowed the device to pass without other instrumentation with overall diagnostic rate of 91% (30/33) 15/15 pathologically confirmed malignant specimens were correctly identified by the new device including 2 GDP-Tao specimens with atypical hyperplasia (AH) and hysterectomy pathology with AH and focal adenocarcinoma. Classifying any atypia from the GDP-Tao as “positive” then the detection rate for malignancy was 100% (PPV). 11/11 samples were benign in GDP-Tao and final pathology. There were 3 non-diagnostic (ND) samples from GDP-Tao with final pathology of benign endometrium. One specimen was ND due to absence of tissue from prior endometrial ablation. There was one device result of “proliferative endometrium” with final pathology of focal complex atypical hyperplasia and one device result of “rare atypical cells” with final diagnosis of endometrial polyp. Sensitivity and specificity were 94% and 92%, and negative predictive value was 82% for the identification of both atypical hyperplasia and malignancy. When stratified by uterine size, benign or malignant, the results were similar. Conclusions: Our validation study showed encouraging data thatthis new endometrial sampling device, which combines tissue disruption and aspiration into a single process, provides a reliable mean of obtaining adequate sample to accurately detect endometrial cancer with a high negative and positive predictive value.
Impact of treatment strategies on local control and survival in uterine carcinosarcomas.
Authors: Yalcin Selim , Dizdar Omer , Kucukoztas Nadire , Rahatli Samed , Ozen Ozlem , Dursun Polat , Haberal Nihan , Tarhan Cagla , Yildiz Ferah , Altundag Ozden , Ayhan Ali
Published: March 2020

e16526

Background: Carcinosarcoma is a biphasic neoplasm composed of a mixture of malignant epithelial and mesenchymal components. Uterine carcinosarcomas comprise only 3% of all uterine malignancies, however they account for a disproportionally higher rate of mortality from uterine cancer because of their agressive nature. No standardized treatment has yet been established. The purpose of this study was to determine the clinical characteristics, patterns of recurrence and survival outcomes in patients with uterine carcinosarcoma treated in our institution. Methods: Records of the patients with uterine carcinosarcoma were retrospectively evaluated and 29 pts with carcinosarcoma diagnosed between 2007 and 2012 were identified. All patients were initially treated surgically by the same surgeon with comprehensive staging, i.e. total abdominal hysterectomy, bilateral salphingooopherectomy , bilateral pelvic and paraaortic lymph node dissection and omentectomy. Demographic features, tumor characteristics, treatment regimens and patient outcomes in terms of relapse-free survival (RFS) and overall survival (OS) were analyzed. Results: Median age was 63 (range 43-78). 13 patients (45%) had stage I disease, 5 patients (17%) had stage III and 11 patients (38%) had stage IV disease at diagnosis. Median tumor size was 6 cm (range 1.7-20 cm) and lymphovascular invasion was present in 17 patients 59%). Twenty patients (69%) received chemotherapy (90% with paclitaxel and carboplatin) for 6 cycles. One patient received radiotherapy. Median follow up was 13 mos. Seventeen patients (59%) relapsed and 20 patients (69%) died on follow up. Two patients had vaginal cuff recurrence, 4 had pelvic, 4 had abdominal and 7 had distant recurrences. All recurrences were fatal. 3 year RFS was 31%. 3 year OS was 15%. Conclusions: Our data show that uterine carcinosarcomas tend to be more at more advanced stage at diagnosis and despite the use of chemotherapy and radiotherapy, overall prognosis is poor. Surgery remains the mainstay of treatment. More effective adjuvant strategies are needed to reduce relapse and death rates because recurrences are generally fatal.
Efficacy and safety outcomes in heavily pretreated patients (pts) with relapsed ovarian cancer (ROC) after single-agent trabectedin.
Authors: Salutari Vanda , Ferrandina Gabriella , Vincenzi Bruno , Marinaccio Marco , Naglieri Emanuele , Loizzi Vera , Carpano Silvia , Lorusso Domenica , De Vincenzo Rosa Pasqualina , Maria Grazia Distefano , Amadio Giulia , Tonini Giuseppe , Scambia Giovanni
Published: March 2020

e16538

Background: Trabectedin is a marine-derived antineoplastic agent, initially isolated from the tunicate Ecteinascidia turbinata and currently produced synthetically. In combination with pegylated liposomal doxorubicin, trabectedin is approved in Europe for the treatment of pts with platinum-sensitive (PS) ROC. The aim of this multicenter, retrospective study was to evaluate the efficacy and safety of single agent trabectedin in the palliative treatment of heavily pretreated patients with ROC. Methods: Patients with measurable ROC and at least 2 prior treatments were eligible. Patients received single agent trabectedin (1.3 mg/m2, n = 56; 1.1 mg/m2, n=42) as a 3-hour i.v. infusion every 3 weeks. An analysis of the overall response rate (ORR; primary end point) as per RECIST, time to progression (TTP) and overall survival (OS) were performed. Results: Overall, 98 pts were enrolled: median age at diagnosis of recurrence was 53 years (range: 29-79). Forty-four pts (44.9%) were fully PS, while 23 (23.5%) were partially PS and 31 (31.6%) were platinum-resistant. Median number of previous chemotherapy regimens was 4 (range: 2-6). The ORR was 28.6% (5 complete and 23 partial responses); 32 pts (32.6%) experienced stabilization of disease, which lasted ≥6 months in 2 pts, while 38 (38.8%) pts progressed during treatment. The ORR was higher in PS pts (38.6%) compared to partially PS (26.1%) and platinum resistant cases (16.1%), although the statistical significance was not reached (p=0.071). No difference in the ORR was found according to number of prior treatments or trabectedin dose. After a median follow-up of 8 months, median TTP and OS were 5 and 13 months, respectively. The most common grade 3/4 toxicities were transient and non-cumulative anemia and neutropenia in 6.1% and 17.5% of cases, respectively. AST and ALT were increased in 7.1% and 13.3% of pts. Cardiac toxicity was documented in 4 anthracycline pretreated pts, of whom one died due to acute arrhythmia. Conclusions: Single agent trabectedin represents a valid approach in the palliative treatment of pts with heavily pretreated ROC with meaningful clinical benefit and acceptable and manageable safety profile.
Quality of life in patients of carcinoma cervix treated with chemoradiotherapy: A prospective study.
Authors: Lachi Pavankumar , Malik Monica , Adavikolanu Kesava Ramgopal , Kothwal Syedakram , M Deepajoseph , Syed Fayaz ahmed , Pamidighantam Suresh , K.V Jagannathraonaidu
Published: March 2020

e16545

Background: The standard of care in locally advanced carcinoma cervix is concurrent chemoradiotherapy. The aim of the study is to prospectively assess quality of life (QoL) in patients of carcinoma cervix treated with chemoradiotherapy. Methods: Between June 2011 and June 2012, 20 patients of carcinoma cervix were included in the study. All patients received conformal external beam radiotherapy (EBRT) on Linear accelerator to a total dose of 50Gy, 2 Gy per fraction, 25 fractions to the pelvis and intracavitary brachytherapy by High dose rate brachytherapy, 7 Gy per fraction, 3 fractions to a total dose of 21 Gy. Patients received concurrent chemotherapy with Cisplatin 40 mg/m2 weekly for five weeks. QoL was assessed using EORTC QLQ-C30 and QLQ-C24 questionnaires at baseline and at six months following completion of treatment. The collected data was analyzed using standard statistical software package (SPSS version 20.0). Results: Median age of the patients in the study was 52years ( range 34 – 69 years), 13 (65%) patients were stage II and seven (35%) were stage III. Mean duration of treatment is 37 days (range 34- 70 days). Local control rate at six months was 95%. Compliance with completion of QoL scores was high. A statistically significant improvement (p = 0.001) was seen at six months post treatment in Global health score and in function scales like physical function, role function, emotional function, social function and cognitive function. There was a significant improvement in symptom scales of urologic and vaginal symptoms. The difference in sexual function at six months showed a trend towards significance (p = 0.052). Conclusions: Patients of carcinoma cervix have a significant improvement in quality of life following treatment with radiotherapy and chemotherapy.
Uroporphyrinogen decarboxylase gene expression in oral squamous cell carcinomas.
Authors: Kottayasamy Seenivasagam Rajkumar , Ganesan Arun Kumar , Ramamurthy Rajaraman , Kannan Munirajan Arasambattu , Rao Deva Magendhra
Published: March 2020

e17002

Background: Oral cancer is one of the most common cancers in India. Uroporphyrinogen decarboxylase (UROD), a key regulator of heme biosynthesis, has recently been suggested as a novel tumor-selective radiosensitizing target against head and neck cancers. Further, a recent study has suggested that tumors with UROD expression may have poorer outcomes and higher rates of recurrence. We tested the expression of UROD splice variants in oral cancer patients who were treated in our hospital to study its expression and impact on the patients. Methods: The expression of both coding and noncoding splice variants of UROD gene was tested in 42 patients (31 male, 11 female) with oral cavity squamous cell carcinomas treated in 2011-12. Pretreatment tumor biopsies were collected and mRNA was extracted using Quiagen RNeasy kit method. cDNA was synthesized using Superscript III and subjected for UROD expression using specific primers. UROD expression and clinical data of patients were analyzed using IBM SPSS 20 Software. Results: The mean age of the patients was 52 years (range 32-70). Buccal mucosa (n=17) and tongue (n=13) were the most common subsites. Seventy six percent had locally advanced disease (T3/T4 and node-positive) and high-grade (70%) cancers. Chemoradiotherapy (CRT) (n =25) and chemotherapy (CT) (n = 10) was given in 35 patients of which 5 had progressive disease. The mean follow up was 11 months. Thirty seven patients were operated, 5 developed locoregional recurrence and 2 developed spine metastases and died during follow-up. UROD was expressed in 23 (54.8%) patients (coding variant = 52.8%, noncoding = 26%). There was no correlation between UROD expression and age, sex, subsite, stage, grade or node positivity. Patients with UROD expression had a slightly poorer response to CRT/CT (30.4% vs 24.1%; p =NS). Similarly, though they had a slightly higher incidence of recurrence, the difference was not significant. Both patients with spinal recurrence had UROD expression. Conclusions: UROD is highly expressed in oral cancer patients in India. Its proposed radiosensitizing and prognostic role in treatment and outcomes though promising needs further evaluation in a larger number of patients.
Chemotherapy with irradiation in salivary gland carcinomas (SGC): A Rare Cancer Network study (RCN).
Authors: Thariat Juliette , Aranguren Dawn , Gozde Yazici , Studer Gabriela , Krengli Marco , Ghadjar Pirus , Demiroz Candan , Cem Onal , Igdem Sefik , Ozkok Hale Basak , Akyurek Serap , Khanfir Kaouthar , Sun xu Shan , Miller Robert Clell
Published: March 2020

e17019

Background: To report the role of combined chemotherapy in SGT. Methods: 251 patients with SGC treated in 2001-2011 were included in a collaborative IRB-approved retrospective RCN study. Chemotherapy is empirically administered based on extrapolation from conventional head and neck squamous cell carcinoma (Ca) (SCC) and data on systemic treatment in localized SGC are lacking. Results: Median age was 60 yo with 2/5 females/males. Tumor sites were the parotid 74.9%, submandibular 16%, sublingual 2.8% or minor gland 4%. Histologic findings were adenoid cystic (ACC) 17.3%, mucoepidermoid (MEC) 19.8%, adenoCa 15.6%, salivary duct (SDC) 10.3%, acinic cell (Aci) 6.2%, ex-pleomorphic 7.8%, undifferentiated 4.9%, myoepithelial 3.3%, epithelial myoepithelial 1.6%, basal cell 1.2%, lymphoepithelial 1.2%, others 4.0%. Surgery was performed in 95.1% (complete resection 38.1%). T stages 1, 2, 3 and 4 were 17.2%, 41.2%, 18.1% and 23.5% respectively. N stages were N0 61%, N1 13%, N2 24%, N3 2%. Perineural, vascular or lymphatic emboli were present in 47%, 24%, 27% respectively. Irradiation was performed postoperatively 96% or exclusively 4% (unilateral 84%, performed w/ photons only 78%, IMRT 41%). Chemotherapy was administered in 18%, dependent on grade, N stage, and emboli (p ≤ .05). None of 17 ex-pleomorphic, 25% of undifferentiated, 36% of SDC, and 66.7% of lymphoepithelial Ca received chemotherapy (p NS). With a median follow-up of 42 months for living patients, crude local, regional, metastatic relapse rates were 112% (in field 85%), 10%, 25%, respectively. Crude death rate was 28% including 77% from SGC. 5-year survival (5y OS) was 63%. The only prognostic factor was nodal involvement (p .002). However, 5y OS differed by histology: ACC 79%, MEC 84%, Aci 67%, SCC 43%, adenoCa NOS 40%, SDC 37%. Chemotherapy did not improve survival whatever histology. Conclusions: Further prospective studies are warranted to define the role of chemotherapy by histology in the setting of localized SGT. Also molecular profile-driven systemic treatments should be investigated.
Immunonutrition limits pro-inflammatory and pro-oxidant effects of radiochemotherapy in cancer patients.
Authors: Vasson Marie-Paule , Talvas Jeremie , Goncalves-Mendes Nicolas , Kwiatkowski Fabrice , Bienvenu Jacques , Bachmann Patrick , Bouteloup Corinne
Published: March 2020

e17022

Background: Peri-operative immunonutrition improves digestive surgical outcomes of cancer patients reducing complications and length of stay. Radiochemotherapy (RCT) generates deleterious effects on nutritional and immune status limiting functional capacities of patients. This study aimed to evaluate if immunonutrition enriched in arginine, EPA & DHA and nucleotides could limit these side effects in Head&Neck (HN), and oesophageal cancer patients. Methods: A double-blind randomized clinical trial was driven with two groups receiving either an Immune Enteral Nutrition (IEN, n=13, Impact, Nestlé) or a Standardized Enteral Nutrition (SEN, n=15) during all RCT (5-7 weeks). Nutritional status, plasma antioxidant capacity (TEAC, FRAP) and functional capacities (WHO score, Karnofsky index) were assessed at the beginning (Db) and at the end (De) of RCT. Immune functions were assessed by leukocytes phenotyping, ex vivo PMN ROS production, and PBMC cytokines & eicosanoids (PGE2) secretion and gene expression. Results: At De vs Db, a significant improvement in total body weight (+2.1kg) was observed in IEN patients as well as albuminemia and NRI in IEN malnourished patients. TEAC and FRAP were increased (+100µM EqTrolox) in IEN patients and higher at De than for SEN patients. Functional capacities were maintained upper the autonomy threshold only in IEN patients. The PMN density of chemo-attractant receptors (CD62L, CD15) and ROS production (+30%) were significantly increased in IEN patients at De vs Db. PBMC PGE2 secretion was unchanged at De in IEN patients and lesser than for SEN patients (65.9±56.8 vs 106.8±59.3 ng/ml, p<0,05). Folding ratios (De/Db) of PBMC mRNA expression were strongly increased for antioxidant response genes (catalase, gpx1&4, sod1&2) and for bactericidal NOX system (cybA, rac1&2). Conclusions: Immunonutrition in adjunction to RCT contributes to maintain functional capacities of patients through improvement of nutritional, anti-oxidant and immune status. Immunonutrition could provide a higher bactericidal capacity and limit inflammatory and oxidative responses induced by RCT in immune cells of HN and oesophageal cancer patients. Clinical trial information: NCT00333099.
Comparison between the common neoadjuvant regimens in locally advanced squamous cell cancer of oral cavity.
Authors: Roy Rakesh , Chatterjee Indranil , Chatterjee Indranil
Published: March 2020

e17024

Background: In locally advanced squamous cell carcinoma of the oral cavity, neoadjuvant chemotherapy induces a high response rate that may facilitate definitive surgery or radiotherapy. Patients have an acceptable long-term survival.A strategy was developed in a tertiary care cancer hospital in India to treat patients with locally advanced oral cancers with induction CT followed by surgery if possible.In our centre selection of neoadjuvant regimens were based on following criteria: age, performance status, financial status, accessibility, comorbid illness, and lab parameters. Methods: 32 patients with locally advanced cancers of the oral cavity and inoperable upfront were selected for neoadjuvant chemotherapy. All were male patients, age ranging from 32 – 65 years, with a performance status ECOG 0-1. All had been tobacco users in some form and hailed from east and northeast parts of India. HPV data were unavailable. 2 patients had controlled diabetes. No other comorbidity was found. 20 patients got DCF (docetaxel, 5FU, cisplatin), 8 patients received PCF (paclitaxel, 5FU, cisplatin), 4 patients received PC (paclitaxel, carboplatin). 20-hr infusional 5FU daily was given over a period of 3 days in both the DCF and PCF arms unlike the 5 day infusion. All received growth factors as primary prophylaxis. Results: Patients who received DCF showed the best response followed by PCF and finally PC. Complete response (CR) was found in 6 patients, all of whom received DCF. All underwent surgery. Amongst toxicity neutropenia was highest with DCF arm but none developed febrile neutropenia. Patients exposed to 5FU had grade 1-2 diarrhoea in 90 % cases. No grade 3-4 mucositis were recorded. Diabetic patients who received PC and PCF and did not experience additional neurotoxicity. Dose reduction or modification was required in one patient who received DCF. Conclusions: Neoadjuvant chemotherapy is an useful treatment option for locally advanced cancers of the oral cavity. DCF regimen is most effective and well tolerated in Indian patients. Judicious selection of patient is necessary.
Panobinostat, a novel histone deacetylase inhibitor, in advanced medullary and iodine-refractory differentiated thyroid cancer: A Wisconsin Oncology Network trial.
Authors: Traynor Anne M. , Leverson Glen E. , Elson Diane F , Hernan Hilary R , Larson Martha M. , Blank Jules Harris , Fareau Gilbert G , Wisinski Kari Braun , Mattison Ryan J. , Chen Herbert , Sippel Rebecca S
Published: March 2020

e17025

Background: Histone deacetylase (HDAC) inhibitors suppress tumor cell proliferation in medullary thyroid cancer (MTC) and differentiated thyroid cancer (DTC) in vivo. We conducted a multicenter single arm phase II trial of panobinostat, a potent inhibitor of Class I, II, and IV HDAC enzymes, in MTC and radioactive iodine (RAI)-refractory DTC. Methods: We enrolled 13 patients (pts) with progressive metastatic MTC or RAI-refractory DTC. Panobinostat was given at 20 mg orally TIW until disease progression or intolerable toxicities. The primary objective was anti-tumor response rate; secondary objectives included overall survival (OS), progression-free survival (PFS), tolerability, and changes in serum thyroglobulin (Tg) concentration. Results: Mean age was 61±13 yrs; 7 pts were female. 11 pts had DTC; 2 had MTC. Median study follow-up was 11.8 months (mos). 9 pts required dose holds/reductions due to thrombocytopenia (n=7), hypocalcemia (n=3), neutropenia (n=2), diarrhea (n=1), bone pain (n=1), or asthenia (n=1). Due to protocol specified rules, 2 pts were withdrawn from therapy with thrombocytopenia or neutropenia, both asymptomatic. Of the 3 pts with ≥ grade 3 thrombocytopenia, 2 had no bleeding. The third pt continued to bleed from her chronically erosive tumor without exacerbation. Median duration of treatment was 2.1 mos (range, 0.8-11.8). Stable disease (SD) was seen in 7 pts, with a median duration of 5.8 mos (range,1.8-13.8). All 7 SD pts are currently alive, including 2 with SD 4.9 mo and 11.8 mo on treatment. Progressive disease (PD) occurred, and was the cause of death, in 6 pts.No anti-tumor responses were observed. Median PFS for the 13 pts was 3.6 mos (95% CI, 1.8-5.8), with 2 pts having a PFS longer than 6 mos.Median OS for the 13 pts was 18.4 mos (95% CI, 5.8-not estimable). 5 of 11 pts had reductions of their serum Tg on study; however, changes in serial Tg values did not distinguish PD from SD pts. Conclusions: 20 mg TIW was not tolerated by most pts. However, dose modified treatment yielded SD in half of our previously progressing pts. This promising disease stabilization warrants further evaluation, possibly in combination with a VEGFR TKI. Clinical trial information: NCT01013597.
EGFRv3 and PTEN as prognostic markers in head and neck squamous cell carcinoma patients treated with cetuximab.
Authors: da Costa Alexandre Andre Balieiro Anastacio , Ribeiro Adriana Regina G. , Guimaraes Andrea Paiva , Chinen Ludmilla Thome , Pinto Clovis , Lima Vladmir C.
Published: March 2020

e17032

Background: Cetuximab (CTx) is used in treatment of locally advanced (LAD) head and neck squamous cell carcinoma (HNSCC) in combination with radiotherapy (RT) or in metastatic disease (MD). There is no comparison between CTx plus RT and cisplatin plus RT. Patients treated with CTx in daily clinical practice are frequently different from the selected population treated in clinical trials. There are no biomarkers for efficacy of CTx in HNSCC. EGFR variant 3 mutation (EGFRv3), an extracellular domain mutation of EGFR, has been reported in different frequencies in HNSCC in the last years and its association with prognosis and CTx efficacy is still unknown. Methods: Retrospective review of data from patients with HNSCC treated with CTx at a single institution from 2007 to 2010. We evaluated CTx efficacy and expression of EGFRv3, EGFR, PTEN, CD44 and CD44v6 and their impact in objective response rate (ORR), progression free survival (PFS) and overall survival (OS). Biomarkers were analyzed by immunohistochemistry in tissue microarray. Results: For a median follow-up time of 13 months, 61 patients with LAD treated with RT plus CTx had a median OS of 22.7 months, and a median PFS of 8.0 months. Age adjusted Charlson Comorbidity Index (AA-CCI) and ECOG performance status were the most important predictors of poor prognosis in this population. For a median follow-up time of 10.9 months, 44 patients with MD had a median OS of 13.0 months and a median PFS of 7.0 months, for an ORR of 53.7%. EGFRv3 was expressed in 27.1% of tumor samples and was not associated with any clinical outcome. EGFR positivity was associated to higher ORR in LAD and PTEN negativity was associated with shorter OS in the MD setting. Conclusions: In a non selected population with LAD treatment results with CTx in combination with radiotherapy were worse than expected by the phase III study, median OS 22.7 months vs 49.0 months. This difference may be attributed to different population characteristics with higher ECOG and AA-CCI in our study and warrants an adequate proof of efficacy of CTx in this population. EGFRv3 is present in HNSCC but does not impact prognosis. PTEN and EGFR expression emerged as potential biomarkers in HNSCC patients treated with CTx.
The effect of gaps in chemotherapy in patients with stage IV colorectal cancer.
Authors: Sada Yvonne , Davila Jessica , El-Serag Hashem , Duan Zhigang
Published: March 2020

e17501

Background: Chemotherapy (CT) utilization in patients with stage IV colorectal cancer (CRC) has not been well documented in community practice settings. Further, clinical trial data indicate that time gaps during CT for stage IV CRC patients are associated with worse survival. However, the prevalence of CT gaps and their effect on survival in the general population is unclear. Methods: Using national Surveillance, Epidemiology, and End Results-Medicare linked data, stage IV CRC patients diagnosed during 2000-07 were identified. Those who received CT (based on ICD-9 codes) within 3 months after CRC diagnosis were identified. CT duration during the 2 years following CRC diagnosis and frequency of gaps were calculated. A CT gap was defined as >30 days between 2 CT claims. Data on demographics and clinical factors were collected. Multivariable regression was used to identify determinants of CT gaps. Cox proportional hazard models were used to examine the effect of gaps on mortality. Results: 4015 patients with stage IV CRC were identified. Median age was 74 (IQR: 70-79); 51% were male. A CT gap occurred in 2123 patients (53%). Most patients received <3 months of CT (37%), followed by 7-12 months (26%), 3-6 months (21%), >12 months (16%). Nearly 70% of patients who had >3 months of CT had a gap. Among these patients, 41% had 1 gap, 27% had 2 gaps, and 32% had ≥3 gaps. Median number of days per gap was 42 (IQR: 35-75). Multivariate analysis showed that patients who were Asian (OR 1.8, 95% CI: 1.2-2.70), had >12 months CT (5.1, 4.0-6.5), hospitalized during CT (3.9, 3.3-4.6), or had toxicity (1.5, 1.3-1.8) were more likely to have a gap, while patients with comorbidity index ≥2 (0.7, 0.6-0.9) were less likely to have a gap. 1-yr survival was higher in patients with gaps compared to no gaps (89% vs. 60%) after excluding patients who had <3 months of CT. Cox proportional hazard models showed that patients with gaps had a lower risk of mortality (HR 0.58, 0.52-0.64), adjusting for patient and clinical factors. Conclusions: Over half of patients with stage IV CRC had a gap during CT. Contrary to clinical trial data, CT gaps were associated with a survival benefit. Further studies are needed to confirm these findings and to explore patient and provider reasons for stopping CT.
Utilization of subspecialty care by Hispanic pediatric oncology patients, California 1983-2010.
Authors: Alvarez Elysia , Chamberlain Lisa J. , Marina Neyssa , Saynina Olga , Wise Paul
Published: March 2020

e17504

Background: Previous analysis has shown that Hispanic pediatric oncology patients in California have decreased utilization of pediatric cancer specialty centers (PCSC). The purpose of this study was to examine the clinical and non-clinical factors associated with decreased inpatient utilization of PCSCs by Hispanic pediatric oncology patients. Methods: Using the California Office of Statewide Health Planning and Development private database we performed a retrospective population based analysis of Hispanic patient discharges 0-18 years of age to explore the influence of age, gender, payer, income, distance to admission site, tumor type and diagnosis of fever and neutropenia on the utilization of PCSCs by Hispanic patients. Results: Analysis of 82,832 Hispanic pediatric oncology discharges showed concentration of hospitalization in PCSCs increasing from 64% in 1983 to 94% in 2010. In addition, an increased percentage of acute lymphoblastic leukemia discharges was seen for Hispanics (28.3%) compared to all discharges (22.4%). The adjusted regression analysis revealed decreased utilization of PCSCs for patients ages 15-18 (OR 0.466; CI 0.441-0.493) and for those residing 6 - 10 miles from a PCSC (OR 0.927; CI 0.883 - 0.974). Increased utilization of PCSCs was seen for Hispanic patients living in zip codes where household income was >4 times the Federal Poverty Level. Payer status was not significantly associated with discharge from a PCSC. None of these findings changed when Los Angeles County was removed from the analysis. A separate analysis was done on Hispanic pediatric oncology patients with a discharge diagnosis of fever and neutropenia. For this subset decreased utilization was seen for those with private insurance (OR 0.84; CI 0.81-0.887), age <1 (OR 0.719; CI 0.64-0.808), ages 15-18 (OR 0.596; CI 0.558-0.636) and those residing >40 miles from a PCSC (OR 0.913; CI 0.854-0.975). Conclusions: Utilization of inpatient pediatric oncology care by Hispanic patients in California has become regionalized in PCSCs since 1983 and is influenced by age, and geography, with payer status not being a significant contributor. Clinical outcomes as they relate to access to PCSCs for Hispanic patients should be examined.
Clinical impact of an online tool to guide choice of therapy (Tx) for patients (Pts) with advanced renal cell carcinoma (RCC).
Authors: Quill Timothy A , Rini Brian I. , Jonasch Eric , Bowser Andrew , Mortimer Jim A. , Motzer Robert John
Published: March 2020

e17530

Background: Clinical practice guidelines outline multiple treatment options for pts with advanced RCC, but provide little to no guidance on the best Tx for an individual pt. We have previously reported that online interactive decision support tools may help practicing community oncologists identify optimal treatment approaches in breast and lung cancers and CML (ASCO 2011 [abstr 6063]; ASTRO 2012 [abstr 162]; ASH 2012 [abstr 4279]). Here, we assess the impact of a tool on the decisions of clinicians treating pts with advanced RCC. Methods: An online tool was developed based on asurvey of experts who were asked what Tx they would choose for 76 pt case variations. Experts considered patient- and tumor-specific characteristics including histology (clear cell vs nonclear cell), extent of metastases, previous systemic therapy received, MSKCC risk status (good/intermediate vs poor), and ECOG performance score (0 vs 1 vs ≥ 2). The tool was built based on their responses and posted online July 12, 2012. After tool users input specific pt characteristics and indicate their intended Tx plan, a table of expert Tx choices are displayed for that pt scenario. To determine the impact of viewing the expert choices, users are then asked if the expert feedback has confirmed or changed their original Tx plan. Results: Three experts completed the survey. Key factors in the experts’ Tx choices were MSKCC risk status for first-line therapy and previous systemic therapy. Preliminary data of 419 cases entered by participants in the online tool show that expert insight changed or confirmed Tx choice for 81% of participants (changed: 22%; confirmed: 59%). An analysis of expert vs user treatment selections in specific subpopulations will be presented. Conclusions: An online tool designed to provide customized, patient-specific expert advice may increase the number of clinicians who make optimal treatment decisions for patients with advanced RCC. Data indicate that the expert choices influenced clinicians’ Tx decisions and, therefore, may facilitate improvements in pt care and outcomes. The tool was developed through an unrestricted educational grant from Pfizer.
Use of inflammatory markers to triage cancer patients requiring nutritional assessment and interventions.
Authors: Clarke Stephen John , Tan Cindy
Published: March 2020

e17541

Background: Nutritional status impacts on the outcomes of cancer treatment ( http://www.cancer.gov/cancertopics/pdq/supportivecare/nutrition/ HealthProfessional ). Nutrition is a concern of cancer patients. Many centres lack the resources to undertake formal nutritional assessments on cancer patients. Inflammatory markers have been shown to correlate with nutritional status and cancer treatment outcomes. The NLR is the ratio of the neutrophil and lymphocyte counts in a full blood count (FBC). Our aim was to determine if the NLR can be used to identify cancer patients needing nutritional assessment and intervention. Methods: A prospective observational study evaluated sequential new patients attending a cancer centre. All were assessed for nutritional status using the patient generated scored global assessment (PGSGA) tool and categorized as A (well nourished), or B/C (malnourished). A FBC was done in the week prior to treatment. Receiver operation characteristic (ROC) curves were used to determine optimal cut-points for NLR to predict malnutrition. Results: 234 patients were enrolled - 112 had advanced cancer. The median age was 60 years (range 25-83), 108 (46%) were male and 101 (43%) were malnourished at baseline. The mean NLR was higher in malnourished patients (4.1 vs 2.5 – p<0.001), however this was due to differences in advanced cancer patients. The optimal cut point for NLR in all patients to predict malnutrition was 5.0 (4.3 in advanced patients). In advanced patients, an NLR ≥4.3 had a sensitivity and specificity for malnutrition of 42.2% (95% CI 30.1-54.3) and 97.9% (95% CI 88.9-99.9), respectively, producing a positive predictive value of 0.96 (95% CI-0.82-1.00). Thus, NLR while strongly correlated with malnutrition is not sensitive enough alone to be used to identify malnourished cancer patients. However, as >98% of patients with a raised NLR had malnutrition, the NLR could be used to triage patients for nutritional assessment and thereby reduce the workload for clinical dieticians. Conclusions: The NLR is a useful indicator of nutritional status, which when elevated is specific for malnutrition. A low NLR should be reassuring in regard to nutritional status in advanced cancer patients.
Impact of zoledronic acid (ZA) versus pamidronate (P) on overall survival (OS) in multiple myeloma (MM).
Authors: Sanfilippo Kristen Marie , Luo Suhong , Gage Brian , Vij Ravi , Carson Kenneth Robert
Published: March 2020

e17546

Background: Nitrogen-containing bisphosphonates (BPs) have been shown to improve OS compared to non-nitrogen containing BPs in MM (Morgan et al. Lancet 2010). Treatment guidelines recommend use of ZA or P (both nitrogen-containing) in MM patients with bone disease. No study has compared the effect of these two drugs on OS. We compared the impact of ZA versus P on OS in United States Veterans with MM. Methods: We retrospectively identified patients diagnosed with MM from 10/2002-2/2009 within the Veterans Heath Administration Central Cancer Registry who received ZA (n=482) or P (n=757) by linking registry data to pharmacy records. Cox multivariable analysis was used to estimate the association between choice of BP and OS while controlling for potential confounders: body mass index (BMI), age, race, Charlson comorbidity index, year, treatment, hemoglobin (Hgb), creatinine (Cr), and albumin. Results: The median OS in patients receiving ZA was 34.5 months, compared to 26.4 months in the P group. After adjusting for confounders, ZA reduced the risk of death by 24% compared to P (hazard ratio [HR] 0.76; 95% confidence interval [CI]: 0.66-0.88) at 5 years (Table). A sensitivity analysis that compared ZA only (n=482) versus all patients who received P, regardless if they later received ZA (n=1117) continued to show decreased mortality (HR 0.82; 95% CI: 0.71-0.94) after controlling for the same potential confounders. Conclusions: In this, the largest study to evaluate the association between ZA versus P on OS in MM, we found decreased mortality associated with ZA. Given the similar toxicity profiles, this study supports preferential use of ZA over P and may serve as evidence for re-evaluation of current guidelines for BP use in MM. [Table: see text]
Prospective observational study on fertility preservation in young early breast cancer patients: The PREFER (Pregnancy and Fertility) trial.
Authors: Lambertini Matteo , Anserini Paola , Fontana Valeria , Abate Annalisa , Sozzi Fausta , Merlo Franco , Pronzato Paolo , Bighin Claudia , Levaggi Alessia , D'Alonzo Alessia , Giraudi Sara , Iacono Giuseppina , Miglietta Loredana , Poggio Francesca , Del Mastro Lucia
Published: March 2020

e17548

Background: Approximately 4.5% of breast cancers are diagnosed in women younger than 40 years. Chemotherapy (CT)-induced loss of fertility is a major concern for young patients. Different strategies are available to attempt to preserve ovarian function. We evaluated feasibility and patient preferences of 3 different strategies: oocyte cryopreservation (OC), ovarian tissue cryopreservation (OTC) and temporary ovarian suppression with the administration of LHRH analogue (LHRHa) during CT. Methods: From March 2010 to January 2013 49 breast cancer patients younger than 45 years (median age: 38 [range 25-45]), referred to our institution. They were offered the possibility to reduce the gonadotoxic effects of anticancer treatments: the oncologist proposed both the administration of LHRHa during CT, and a reproductive counselling performed by the gynecologist, where OC and OTC were discussed. The first analysis was planned after 2 years; preliminary data are presented. Results: The majority of patients (42 [85.7%]) accepted the treatment with LHRHa, started at least 1 week before CT. Thirty-eight patients (77.6%) refused the reproductive counselling; the main reason for refusal was previous pregnancies (19 patients [38.8%]). Out of 11 patients (22.4%) who accepted the reproductive counselling, only 3 (6.1%) accepted to undergo OC and 1 (2.0%) OTC. The reasons for refusal were: not eligible for comorbidities 3 patients [6.1%]), fear of delaying cancer treatment (2 patients [4.1%]), fear of the ovarian stimulation required (1 patients [2.0%]) and low successful rate of the technique (1 patients [2.0%]). The 3 patients undergoing OC received a controlled ovarian stimulation with the use of daily injections of recombinant FSH: median length of stimulation was 9 days (range, 8 to 9 days); peak estradiol levels ranged from 280 to 521 pg/ml. An average of 13.3 ± 5.7 oocytes was retrieved, and 8.3 ± 3.1 oocytes cryopreserved per patient. Conclusions: This preliminary analysis suggests that the majority of patients (85.7%) accept the administration of LHRHa during CT and approximately 8.2% of patients undergoes surgical fertility preservation techniques.