bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized phase III trial comparing induction chemotherapy using cisplatin (P) fluorouracil (F) with or without docetaxel (T) for organ preservation in hypopharynx and larynx cancer. Preliminary results of GORTEC 2000–01
Authors: Calais G. , Pointreau Y. , Alfonsi M. , Sire C. , Tuchais C. , Tortochaux J. , Bourhis J. , Guerrif S. , Garaud P. 
Published: March 2020

5506 Background: Induction chemotherapy (CT) with PF followed by RT in case of objective response is an alternative to total laryngectomy (TL) for patients with locally advanced larynx (L) and hypopharynx (H) cancer. Data have suggested that T may add to the efficacy of PF. The objective of this trial was to determine whether the addition of T to PF could increase the L preservation rate. Methods: Patients with L and H cancer for whom surgical procedure required TL were randomized to receive PF or TPF. Inclusion criteria were: adequate organ function, WHO PS 0 or 1, age from 18 to 70, signed informed consent. Treatment arms were PF = P 100 mg/m2/d1 and F: 1000 mg/m2 continuous infusion (CI) d1 to 5, TPF = T: 75 mg/m2/d1, P: 75mg/m2/d1 and F: 750mg/m2 CI d1 to 5 for 3 cycles with 21 days interval. Patients with complete or partial response and who recovered normal L mobility received RT to 70 Gy. Non responders underwent TL followed by RT. The primary endpoint was 3-year larynx preservation rate. To detect an absolute difference of 15% the sample size was 210. Results: 220 patients were randomized (108 to PF, 112 to TPF). Patients characteristics (age, sex, PS, primary site, TN) were well balanced. The TPF arm showed greater grade 3–4 alopecia (19% vs 2%) and neutropenia (57% vs 35%) while the PF arm showed greater grade 3–4 mucositis (9% vs 4%) and febrile neutropenia (6% vs 2%).Compliance to CT was better in the TPF. The specified treatment was delivered in 81.2% of patients in the TPF vs 67.4%. The overall response rate (T and N) was 82.8% in the TPF vs 60.8% (p = 0.0013). 60.6% of patients achieved a complete endoscopic response vs 46.7%. L preservation was offered for 80% of patients in the TPF vs 57.6%. A high hemoglobin level (>14 gr/l) and a compliance to treatment >80% are associated with a better response rate. With a median follow up of 35 months the 3-year actuarial L preservation rate is 73% following TPF vs 63% using the PF regimen. Conclusion: In advanced L and H cancer, TPF demonstrated significantly superior overall response rate compared to the PF regimen. The TPF is better tolerated and preliminary results suggest that L preservation could be achieved for a higher proportion of patients. No significant financial relationships to disclose.
Clinical features of joint symptoms observed in the ‘Arimidex’, Tamoxifen, Alone or in Combination (ATAC) trial
Authors: Buzdar A. U. 
Published: March 2020

551 Background: Aromatase inhibitors have been associated with higher rates of adverse events associated with the joints, or ‘joint symptoms’ (JS) than tamoxifen. Details of these were reviewed in the ATAC study. JS were reported spontaneously at a higher frequency with anastrozole (A) than with tamoxifen (T), and here we present a detailed assessment of these events. Methods: Adverse events related to the joints were coded into four COSTART terms: arthralgia, arthritis, arthrosis and joint disorder. Time of onset, duration of symptoms and their effect on treatment adherence were reviewed. Results: At 68 months’ median follow-up 1100/3092 (35.6%) patients in the A arm and 911/3094 (29.4%) patients in the T arm experienced JS. Almost half (46%) of patients with JS reported these as an exacerbation of a pre-existing condition in the joints and in most cases the location was generalized. The majority of first events developed within 24 months of initiation of treatment (A 68%, T 59%) with a peak occurrence at 6 months (A 29%, T 20%). Review of all available data showed that half of the patients who recovered from JS were symptom-free within 6 months of onset and in 75%, symptoms resolved within 18 months. Median time to resolution for these events was 5.5 months for the A arm and 5.9 months for the T arm. Sixty percent of patients experiencing JS received treatment, with >90% of these patients managed with an NSAID alone or in combination with mild analgesics. Although the difference in overall prevalence between treatment arms was statistically significant (p<0.0001), a similar occurrence of serious adverse events of JS was reported (A 10.6%, T 10.4%), and only a small number of patients experiencing JS required treatment withdrawal (A 2.1%, T 0.9%). Conclusion: 68-month data from the ATAC trial showed that treatment with A was associated with a modest increase in the incidence of JS compared with T. In most patients the events were mild-to-moderate in intensity and did not lead to withdrawal of treatment. [Table: see text]
RK-0202 for radiation-induced oral mucositis
Authors: Chambers M. S. , Welsh D. V. , Scrimger R. A. , Zehn W. , Epstein J. B. , Troha J. , Sonis S. T. 
Published: March 2020

5523 Background: This study evaluated the effect of RK-0202, administered as an oral rinse, on the incidence of severe oral mucositis in patients being treated with of radiation therapy (RT) for tumors of the head and neck. Methods: This was a prospective, randomized, placebo-controlled, double-blind study that compared the effect of 2 concentrations of RK-0202 with placebo on the incidence of severe oral mucositis at a cumulative RT dose of 60 Gy in 110 subjects. Twenty-seven subjects received RK-0202 5%, 38 received RK-0202 10%, 29 received placebo and 16 received standard of care. Subjects began dosing just prior to RT and continued dosing six times daily throughout RT. Oral mucositis was assessed twice weekly throughout RT by trained oral evaluators. Results: The higher dose of RK-0202 (10%) successfully attenuated severe oral mucositis as measured by WHO or NCI-CTC v.3 criteria. The incidence of WHO grade 3 or 4 oral mucositis by a cumulative RT dose of 60 Gy was 35% in the RK-0202 group vs. 54% in the placebo group (p = NS). By 50 Gy the incidences in the RK-0202 and placebo groups were 25% and 54%, respectively (p = 0.053). Similarly, the incidence of NCI grade 3 or 4 oral mucositis by 60 Gy was 64% in the RK-0202 cohort vs. 92% for subjects being treated with placebo (p = 0.005). Subjects treated with RK-0202 required less feeding tube placement compared to placebo recipients (3% vs. 22%, p = 0.037) and less opiate analgesia. The median percent of time on opiates was 6% on RK-0202 vs. 21% on placebo. The overall incidence of serious adverse events was significantly lower in subjects treated with RK-0202 (8% vs. 31%, p = 0.024). In general, there was no benefit noted among subjects who received RK-0202 as a 5% solution. Conclusions: RK-0202 significantly reduced the incidence of severe mucositis in subjects treated with radiotherapy for head and neck cancer and was not associated with significant adverse events. [Table: see text]
Neck dissection following organ preservation protocols prolongs feeding tube dependence in patients with advanced head and neck cancer
Authors: Lango M. , Ende K. , Ahmad S. , Feigenberg S. J. , Ridge J. A. 
Published: March 2020

5525 Background: Organ preserving strategies employed in the treatment of advanced stage head and neck cancer frequently result in significant organ dysfunction including dysphagia and feeding tube dependence. While the acute and chronic effects of radiation and chemotherapy are known to contribute to swallowing impairment, the effect of a neck dissection, performed 6–8 weeks following the completion of treatment is unknown. Methods: Retrospective review of Stage III/IV squamous carcinoma patients treated with primary radiation with/without chemotherapy and a post-treatment neck dissection, who remain free of locoregional or distant failure for a minimum of two years. Predictors of prolonged feeding tube dependence (>24 months following the completion of treatment) were evaluated using univariate and multivariate analysis. To determine the independent effect of neck dissection on length of feeding tube dependence, patients matched for covariates were also compared. Results: 79 patients treated at the Fox Chase Cancer Center between 1992 to 2003 were included in this study. 61 (77.2%) received chemotherapy and 37 (46.8%) underwent a neck dissection. The surgical specimen was positive for residual carcinoma in 12 patients (33%). 57 patients (71.3%) underwent placement of a feeding tube. The median time to removal of feeding tubes was 12 months [7–17 months, 95% CI]. Feeding tube-free status at 24 months was associated with use of standard radiotherapy (p = 0.031), N0 vs N+ neck stage (p = 0.041) and management without a neck dissection (p = 0.003). There was no association with age, T-stage, tumor site or use of chemotherapy. On multiple regression, only neck dissection remained a predictor of retained feeding tube at 24 months (p = 0.013). In patients matched for N-stage and treatment selection, those who underwent a neck dissections required a feeding tube a median of 36 months compared with 10 months for those without a neck dissection [32–57 months versus 7–13 months, 95% CI, p = 0.021]. The two year frequency of feeding tube dependence was 14/34 (41%) versus 3/30 (10%), respectively (p = 0.005). Conclusions: Neck dissection may contribute dysphagia experienced by head and neck cancer patients treated with organ preservation protocols. No significant financial relationships to disclose.
Outcomes of radical conformal radiotherapy and concomitant cisplatin chemotherapy for olfactory neuroblastoma—Review of a single centre experience
Authors: Nikapota A. D. , Sevitt T. , Lund V. J. , Howard D. , Spittle M. F. , Prior T. , Saunders M. I. , Varughese M. , Carnell D. M. 
Published: March 2020

5555 Background: Olfactory neuroblastoma is rare with 25 new cases annually in the UK. Cranio-facial resection and post operative radiotherapy is standard treatment. The use of concomitant chemotherapy has not been fully evaluated, although chemo-sensitivity has been demonstrated by retrospective series. This study evaluates the use of radical radiotherapy and concomitant chemotherapy. Methods: Since 1978 more than 70 patients have been seen at the Institute of Otology and Laryngology. Eighteen patients treated with radiotherapy between 1999 and 2005 were reviewed. These were all CT planned and treated with conformal radiotherapy ± cisplatin chemotherapy 100 mg/m2 D 1, 22 and 43. The radiotherapy prescribed dose varied from 50Gy to 62 Gy in 1.8 to 2 Gy fractions, 10 (56%) received 60Gy in 30 fractions. Overall survival, disease free survival and treatment related morbidity were assessed. Results: Seventeen patients were post operative and 1 was neo-adjuvant. Mean age was 46 years (range 20–83) and the majority were Kadish stage C. Of the 17 post-operative patients, 13 (76%) had surgery as primary treatment and 4 (24%) for recurrence. Eight patients (44%) received concomitant chemotherapy. At the time of analysis follow up ranged from 4 months to 72 months (median 17.5, mean 28.2), 16 (88.9%) patients were alive and 14 (77.8%) disease free. Four (22.2%) patients developed recurrence and 2 died of disease. Of the 4 patients with recurrence, 3 did not receive concurrent cisplatin chemotherapy and the fourth patient did not undergo radical surgery. No patients reported deterioration in vision or significant morbidity following treatment. Conclusions: Post operative radiotherapy with concurrent cisplatin chemotherapy is effective and well tolerated in the management of olfactory neuroblastoma. Where concurrent chemotherapy was not given, relapse rates were high. Our results, although immature, suggest disease free survival superior to published data. A prospective multi-centre study to evaluate concomitant treatment schedules is required. No significant financial relationships to disclose.
Derangement of p53 and MDM2 is involved in transformation of differentiated into anaplastic thyroid cancer
Authors: Wiseman S. M. , Masoudi H. , Niblock P. , Turbin D. , Rajput A. , Hay J. , Filipenko D. , Melck A. , Gilks B. , Huntsman D. 
Published: March 2020

5556 Background: Anaplastic thyroid cancer arises as a consequence of tumor progression, or transformation, from pre-existing differentiated thyroid cancer. Mutation of the p53 tumor-suppressor gene represents a common event in thyroid tumor progression. MDM2 encodes a protein that complexes with p53, downregulates its function, and leads to its degradation via a ubiquitin-proteasome pathway. The objective of this study was to evaluate the change in p53 and MDM2 expression in the transformation of differentiated to anaplastic thyroid carcinoma. Methods: Of 94 cases of anaplastic thyroid cancer diagnosed and treated in British Columbia Canada over a 20 year period (1984–2004) 32 cases (34%) had adequate tissue available for evaluation and 12 of these cases had associated foci of differentiated thyroid carcinoma. A tissue microarray was constructed from these 12 anaplastic thyroid tumors and their associated differentiated foci. Immunohistochemistry was utilized to evaluate expression of p53 and MDM2 by these tumors. Results: There was decreased expression of p53 and MDM2 by the anaplastic tumors when compared to the differentiated thyroid tumors from which they evolved. The expression of p53 and MDM2 was 17% and 8%, respectively, by the differentiated thyroid carcinoma, and 83% and 25%, respectively, by the anaplastic tumors. Evaluating the anaplastic cancers and the differentiated foci from which they evolved, p53 overexpression developed in 8 (67%) of tumors and MDM2 overexpression developed in 3 (25%) of tumors. All the anaplastic tumors that developed MDM2 overexpression also concurrently developed p53 overexpression. Conclusions: This report is the first to demonstrate derangement of p53, and its regulator, MDM2, is involved in the transformation of a subset of differentiated into anaplastic thyroid tumors. Isolated MDM2 overexpression does not appear to play an important role in anaplastic transformation of thyroid cancer. No significant financial relationships to disclose.
Peripheral blood quantitative PCR analysis of EBV DNA in nasopharyngeal carcinoma
Authors: Sirachainan E. , Trachu N. , Wisetpanit Y. , Panvichian R. , Ratanavila A. , Udomsubpayakul U. , Chintrakarn C. , Sirisinha T. , Ativitavas T. , Ratanatharathorn V. 
Published: March 2020

5557 Background: Epstein-Barr virus (EBV) is the major etiology of WHO type 2, 3 nasopharyngeal carcinoma (NPC). Almost every tumor cell contains EBV genome. Correlation between prognosis, disease status and serum EBV DNA level was recently reported. Methods: We conducted a cross-sectional study to determine the correlation between the EBV DNA level from circulating tumor cells and the status of disease. The subjects were classified into 4 groups: new diagnosis, in remission, recurrent disease and control (healthy volunteers). The number of subjects/group was calculated to be at least 32, using proportion of P0 = 40%, P1 = 10% at α = 0.05 and Power = 80%. Genomic DNA was isolated from buffy coat of peripheral blood sample. Using Taqman probes for latent membrane protein 2 (LMP2) gene in EBV genome and beta actin gene as internal control, real-time quantitative PCR was performed. The LMP2 copy number was adjusted according to the beta actin copy number from the same sample. Results: The LMP2 gene can be quantified in the samples from new diagnosis, in remission, recurrent disease and control groups as following: 11/33 (33.3%), 10/29 (34.5%), 19/33 (57.6%) and 0/32 (0%) respectively. Among the patients with measurable LMP2, the median (range) of LMP2 copy numbers of each patient group are 12.97 (1.89–118.41), 18.75 (11.79–92.08) and 38.26 (2.41–642.76) copies/500 ng DNA respectively. Using Chi-Square test, all three patient groups have significantly higher LMP2 copy number than the control group (p < .001). The recurrent disease group has significantly higher LMP2 copy number than the new diagnosis group (p=.048). There is no significant difference between the in remission group and the other patient groups. The sensitivity of this test is 42.1% and the specificity is 100%. Conclusions: The peripheral blood EBV DNA copy number, determined by Real-time quantitative PCR, may be a potential molecular marker in the screening for NPC. No significant financial relationships to disclose.
Squamous cell carcinoma of the head and neck (SCCHN) in patients reporting human immunodeficiency virus (HIV) infection: A retrospective case series
Authors: Haigentz M. , Jung G. , Garg M. , Owen R. , Schiff B. , Smith R. V. 
Published: March 2020

5570 Background: Although Squamous Cell Carcinoma of the Head and Neck (SCCHN) is a non-AIDS defining malignancy, its risk is greater in HIV-positive populations for unclear reasons. Very limited data exist on the clinical presentation, treatment toxicities and outcomes of HIV infected pts with SCCHN, a population frequently excluded from participation in clinical trials. Methods: We present a large case series of HIV infected pts with SCCHN who were recently treated at a single institution. Retrospective chart reviews were performed by treating physicians. Results are reported with descriptive statistics. Results: Thirty individuals with SCCHN reporting HIV infection have been treated by the collaborating physicians from 1997–2005; all were smokers. The average age at diagnosis of SCCHN was 49.3 years (range 33–62), and interestingly, a relatively large number were female (13 of 30, 43%). The median CD4 count of pts was 374/μL, and most pts reported a history of antiretroviral therapy. The most frequent sites of primary disease were the larynx (13 pts, 43%, mostly supraglottic) and oropharynx (13 pts, 43%). Although most patients (87%) presented with advanced (stage III and IV) disease, a few (4 pts, 13%) had stage II disease. Although 12 pts underwent surgical resections for primary treatment, 16 pts underwent primary nonsurgical therapy, including 8 pts treated with chemoradiotherapy. Therapy related toxicities were expected and did not appear different from those observed in immunocompetent individuals. Eight pts had recurrence (7 locoregional/1 distant), and 5 pts died from recurrent/metastatic disease. Three pts had second primary cancers. Conclusions: HIV-infected individuals with SCCHN are generally young smokers, both male and female, receiving active treatment against HIV. The detection of a proportion of pts with early stage disease further supports the role for aggressive smoking cessation counseling and screening efforts for SCCHN in HIV infected populations. Additionally, HIV infection is not a contraindication to aggressive organ-preserving regimens for SCCHN pts with otherwise good functional status. A case-control clinical and pathologic study of SCCHN in HIV infection is planned. No significant financial relationships to disclose.
A phase II trial of docetaxel and cisplatin combination in patients with locally advanced undifferentiated carcinoma of nasopharyngeal type (UCNT): Study update
Authors: Yamouni M. , Benhadji K. A. , Beldjilali Y. , Lahfa I. , Yekrou D. , Djellali L. , Brahimi M. , Bouzid K. 
Published: March 2020

5579 Background: The standard treatment of locally advanced undifferentiated carcinoma of nasopharyngeal type (UCNT) is cisplatin based chemotherapy followed by locoregional radiotherapy. The purpose of this study is to assess the antitumor activity and toxicity of a new neoadjuvant chemotherapy regimen combining docetaxel (D) and cisplatin (C). Patients and Methods: Previously untreated patients (pts) with histologically diagnosed locally advanced UCNT (Stages IVa and IVb TNM/UICC 1997) received D 75 mg/m2 and C 75 mg/m2 both on day 1, cycles were repeated every 21 days. Every pts received three cycles in a neoadjuvant setting before radiotherapy (4 to 6 weeks after the third cycle of DC). Pts were evaluated by clinical examination, CT scan of nasopharynx and nasofibroscopy with biopsy. Primary end point was tumor response. Secondary end points were disease free survival (DFS), toxicity and overall survival. Results: 75 pts were enrolled in this trial, 54 males and 21 females with a median age of 41 years (range 18–69), WHO performance status of 0–1 in 71 pts and 2 in 4 pts. 19 pts had stage IVa and 56 pts had stage IVb. Toxicity, tumor response and survival over tree years were assessable in 75 pts. After 225 cycles, grade 3 & 4 toxicity (NCI-CTC 2.0) were: neutropenia (12%), febrile neutropenia (2%), anemia (1%), nausea and vomiting (23%), diarrhea (8%), mucositis (1%), reversible alopecia (70%). Two pts had onycolysis. Response rates for the 75 pts were: complete pathologic response 37% (28 pts), partial response 52% (39 pts), stable disease 8% (6 pts) and progression 3% (2 pts). The overall response rate was 89%. 74 pts (98%) had complete response after radiotherapy and one patient had stable disease. 31 patients had recurrence: 25 locoregional, and 6 metastatic (3 with bone metastasis, 2 hepatic metastasis and 1 cerebral metastasis). DFS and overall survival at 3 years were respectively 57% and 65%. Conclusion: DC chemotherapy followed by radiation therapy is an effective regimen for the treatment of advanced UCNT. This treatment has an acceptable safety profile. These data need to be compared to concurrent chemoradiotherapy to assess the best strategy for the management of advanced UCNT. [Table: see text]
Retrospective analysis of renal toxicity in breast cancer patients following zoledronic acid or pamidronate treatment
Authors: Chen L. , Nikolas T. L. , Markowitz G. , Green J. , Wintfeld N. , Neary M. , Duh M. 
Published: March 2020

564 Background: In breast cancer (BC) patients (pts), reports suggest that some i.v. bisphosphonates (BPs) are associated with an incremental renal toxicity risk. Few studies have investigated this risk in clinical practice. We retrospectively analyzed rates of renal toxicity in BC pts treated with zoledronic acid (ZO), pamidronate (PA), or no BP treatment (NT). Methods: Pts were identified through medical and pharmacy claims and laboratory data from >35 managed care plans between 01/2000 and 12/2004. Inclusion criteria: female pts with ≥2 claims for BC, no gap in health plan coverage, and serum creatinine measurements available from before and after first ZO or PA infusion. BC pts receiving NT provided a separate reference group. Observations were analyzed from first infusion to health plan disenrollment (BP monotherapy) or before BP switch. Renal impairment was defined as a ≥25% decrease in glomerular filtration rate (GFR,abbreviated MDRD formula) from baseline. Andersen-Gill model, adjusted for demographics and baseline comorbidities, was used to analyzer multiple events in a given pt, as physician practice patterns indicate that administration of both BPs continues even after the development of a first nephrotoxic event. Results: 312 ZO pts, 166 PA pts, and 2,862 NT pts were included. ZA and PA groups had comparable baseline characteristics, renal-related comorbidities, and baseline GFR. Both BP groups were more frequently exposed to chemotherapies and nephrotoxic drugs than the NT group (p<0.0001). ZO and PA groups had similar renal impairment rates that were significantly higher than the NT group and increased with treatment duration (ZO 15.8%, PA 15.6%, NT 7.3% in pts treated for <6 months, increasing to ZO 42.0%, PA 40.0%, NT 16.9% in pts treated for ≥18 months). Mean renal impairment events per person-year were significantly higher for ZO than PA (0.93 vs 0.81, p=0.019). Multiple-event analysis showed a significantly higher renal impairment risk for ZO than PA (hazards ratio=1.4, p<0.0001). Conclusions: In this study on BC pts, renal impairment was more commonly seen in ZO and PA pts than in NT pts. ZO and PA pts have similar renal impairment risk, but ZO pts are more likely to experience multiple impairment events after repeated administrations. [Table: see text]