bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral mucositis is associated with increased resource use among patients receiving treatment for cancers of the head and neck
Authors: Keefe D. M. , Garden A. , Barasch A. , Tischler R. , Brennan M. , Trotti A. , Vera-Llonch M. , Oster G. , Elting L. , Sonis S. 
Published: March 2020

6070 Background: Oral mucositis (OM) is the oral manifestation of mucosal injury (MUI), and is a common, bothersome, and treatment-interrupting toxicity of chemoradiation therapy for squamous cell cancers (SCC) of the head and neck. Retrospective studies have reported that OM increases healthcare resource use. We present interim results of an international, multicenter, prospective study undertaken to characterize the clinical and economic burden of OM in patients with cancers of the oral cavity (OC), oropharynx (OP), larynx (L) and hypopharynx (HP). Methods: Patients (pts) with histologically proven SCC of the designated anatomical sites, whose planned treatment included full-cycle conventional or intensity modulated (IM) radiation therapy (RT) with or without chemotherapy, were enrolled at least one week prior to the start of treatment. Pts completed the Oral Mucositis Daily Questionnaire (OMDQ), a validated questionnaire developed to document patient-reported symptoms of OM and MUI including mouth and throat soreness (MTS), at baseline and daily throughout RT. MTS was assessed using a 5-point numeric rating scale, ranging from 0 (“no soreness”) to 4 (“extreme soreness”). Results: Of the first 61 pts to complete RT, 72% had cancers of the OC or OP, 49% received IMRT with concomitant chemotherapy, and 68% were male. 95% of pts reported OM symptoms (MTS>0); 80% had one or more scores =2. Pts with OC or OP cancers reported more symptoms than those with L or HP tumors (mean maximum score: 3.3 vs 2.8; p= 0.12). MTS scores were positively related to levels of resource use. Conclusions: Symptoms of radiation-induced OM are positively correlated with levels of resource utilization in patients with head and neck cancers. No significant financial relationships to disclose. [Table: see text]
Biweekly gemcitabine and oxaliplatin (GEMOX) in first-line metastatic or recurrent nasopharyngeal carcinoma (NPC)—An early report
Authors: Chan A. T. , Ma B. , Tung S. , Hui E. P. , Yuen K. K. , King A. , Leung S. F. , Chan I. , Chan M. , Zee B. 
Published: March 2020

6071 Background: This multicenter phase II study evaluated the activity & safety of oxaliplatin (Ox), a 3rd generation platinum, in combination with gemcitabine (GEM) for the first time in the palliative setting for patients (pts) with undifferentiated/ poorly differentiated NPC. Methods: Pts with untreated metastatic (M1) or locoregionally recurrent (LR) NPC were treated with a biweekly ‘GEMOX’ regimen (D1: GEM, 1,000 mg/m2 at 10 mg/m2/min; D2: Ox, 100 mg/m2 over 2 hrs) for a max. of 12 cycles. Intrapatient dose escalation of GEM to 1,250 mg/m2 was allowed from cycle 2 onwards if no significant toxicity occurred in cycle 1. Response was assessed every 4 cycles (RECIST criteria). Results: 23 pts accrued before 31st July 06 were evaluated for toxicity & response; cut-off date for data analysis was 15th Oct 06. The median age was 53 yrs (range 38–72); 19 were men, all had ECOG status of 0–1. At enrolment, 7 pts (29%) had M1 disease only, 3 (12%) pts had LR only, & the rest both M1 & LR. All 7 pts with only LR received radical radiotherapy (RT) at initial diagnosis. A median of 11 cycles (range 3–13) were administered. Best overall response rate was 52%, with 12 partial responses & 11 stable diseases. The median duration of response was 7 months (range 0.8–15). Grade (gr) 3–4 hematological toxicities (CTCAE ver 3) included neutropenia in 7 pts (30%, only 1 pt had fever), thrombocytopenia in 5 pts (26%, 1 gr 4 case with mild gum bleeding). Gr 3–4 non-hematological toxicities included gr 3 diarrhoea in 2 pts, gr 4 Ox-related hypersensitivity reaction in 1 pt, gr 3 epistaxis in 2 pts. The commonest non-hematological toxicities were gr 1–2 Ox-related sensory neuropathy (22pts). There were no treatment-related deaths & only 1 pt withdrew from study due to drug-related toxicity. Conclusions: GEMOX is a promising regimen among pts with metastatic & recurrent NPC. Accrual is ongoing with a planned total sample of 40 pts. No significant financial relationships to disclose.
Cisplatin plus gemcitabine (GC) as induction chemotherapy in locally advanced head and neck cancer (HANC)
Authors: Jamshed A. , Hussain R. , Ahmed S. , Rehman K. , Shehzad K. , Muhammad B. , Hameed S. , Shah M. A. , Azhar R. , Faruqui Z. 
Published: March 2020

6073 Background: Cisplatin/infusional 5-fluorouracil chemotherapy is routinely administered as standard induction chemotherapy in advanced HANC. However, the optimum treatment remains to be defined. Gemcitabine is an active agent in HANC and few studies have evaluated induction GC in HANC. We have explored the activity and toxicity of GC as induction treatment in HANC and report the results. Methods: From August 2005 to September 2006, 55 patients with locally advanced HANC had induction chemotherapy with GC at Shaukat Khanum Memorial Cancer Hospital and Research Centre. We reviewed the medical records and prospectively collected data to determine activity and toxicity of induction GC. M:F ratio was 64%:36% with a median age of 50 years (range 19–80). All patients had histologically confirmed squamous cell carcinoma. The site of disease was nasopharynx, paranasal sinuses, oral cavity, oropharynx, larynx and hyopharynx in 4% (2), 11% (6), 51% (21), 2% (1), 11% (6) and 22% (11) respectively. According to AJCC staging 7% (4) had stage III and 93% (51) had stage IVa/IVb disease (T3N0 7%, T3N+ 2%, T4N0 38% and T4N+ 53%). Induction chemotherapy consisted of 2 cycles of cisplatin 75 mg/m2 day 1 and gemcitabine 1000 mg/m2 day 1 and 8 with treatment repeated three weekly. Fifty-three (94%) patients received 2 cycles as planned. Toxicity was scored after each cycle according to the NCI.CTC criteria. Response was assessed following completion of induction chemotherapy by clinical examination/MRI scan. Results: All patients were available for assessment of toxicity and response. A total of 111 cycles were delivered. The response rates are: complete 24% (13), partial 62% (34), no response 7% (4) and progression 7% (4). The overall response rate was 86% (complete 24%, partial 62%). No treatment related deaths occurred. Haematological G3/G4 toxicity included neutropenia (13%/7%) and thrombocytopenia (5%/0%). The non-haematological toxicity observed (nausea, vomiting and diarrhoea) was only G1/G2. Conclusions: GC is well tolerated with low toxicity and high anti tumour activity as neoadjuvant chemotherapy treatment in squamous cell head and neck cancer. Combination GC arm should be included in future trials. No significant financial relationships to disclose.
Prognostic value of P53 and thymidylate synthase (TS) overexpression in patients with squamous cell carcinoma of the head and neck treated with neoadjuvant chemotherapy
Authors: Abderkader M. E. , Elsawy W. H. , Abdalla M. , Dorgham Y. T. , Elnemr M. M. 
Published: March 2020

6081 Background: Neoadjuvant cisplatin-based chemotherapy has been widely used in the last decade for organ preservation or unresectable disease in advanced stage head and neck cancer. Thymidylate synthase (TS) and p53 are central molecules in the regulation of cell growth. Differences in the intracellular expression of these proteins by tumor cells may have predictive value for response to chemotherapy and early failure in patients with squamous cell cancer of the head and neck (SCCHN). We examined the expression of P53 and TS that have been associated with chemotherapy resistance. Methods: Immunohistochemistry was used to assess the tumor cell expression of TS and p53 in pre-therapy biopsies from 65 patients with SCCHN treated with induction chemotherapy. Results: The overall response rate for cisplatin-based neoadjuvant treatment was 80%. The expression of P53 and TS was associated with resistance to neoadjuvant treatment, but none reached statistical significance. Overall survival (OS) was strongly correlated with the absence of p53 expression. The OS at 3 years was 80% in the p53-negative group, whereas it was 29% in the p53-positive group for patients treated with neoadjuvant chemotherapy (P < 0.0001). Expression of TS was also significantly correlated with decreased OS after neoadjuvant treatment. In the TS-negative group, the 3-year OS rate was 69% compared with 38% in the TS-positive group (P = 0.0063). Conclusions: Our data showed that p53 and TS may be clinically important predictors of survival in patients receiving neoadjuvant chemotherapy for head and neck cancer. No significant financial relationships to disclose.
Antitumor activity of imatinib in progressive, highly expressing KIT adenoid cystic carcinoma of the salivary glands: A phase II study
Authors: Guigay J. M. , Bidault F. , Temam S. , Janot F. , Raymond E. , Faivre S. 
Published: March 2020

6086 Background: Adenoid cystic carcinoma (ACC) of the salivary glands is a rare orphan disease of the head and neck usually resistant to conventional chemotherapy, that was found to express KIT in 87% (39/45) of cases in our institutions. Methods: This study explored the antitumor effects of imatinib given at 800 mg daily in a phase II study for patients (pts) with recurrent or metastatic ACC failing locoregional treatments, presenting CT-scan documented progressive disease and highly (50–100% of tumor cells) expressing KIT. Primary endpoint of this study was time to tumor progression, secondary endpoints were tumor response and safety. Results. Since 2004, 17 pts (M/F: 5/12, median age 48, range 33–71) were included. Target lesions were pulmonary metastasis (13 pts), renal metastasis (1 pt), locoregional (2 pts) and pulmonary + locoregional (1 pt) recurrences. Previous treatment with chemotherapy was reported in 5 pts. Median duration of treatment was 6 months (range, 1–14 months). Toxicity was mild to moderate except for 2 pts who had grade 3–4 anemia/neutropenia and asthenia requiring dose reduction and early study withdrawal, respectively. Among 15 evaluable pts with tumor progression at study entry, 5 pts were stable after 6+, 8, 9, 12+ and 18+ months of follow-up and 2 pts displayed partial responses of 42% and 35% (RECIST). These objective responses were associated with early symptomatic improvement (dyspnea/pain) and occurred in platinum- resistant pulmonary metastasis and a radiation-pre-treated locoregional recurrence, lasting 14 months and 9+ months, respectively. Final accrual and TTP determinations are ongoing. Conclusion. Although sporadic, objective responses can be observed in patients with progressive ACC treated with imatinib as well as long-lasting tumor stabilisations. No significant financial relationships to disclose.
Effect of adjuvant radiotherapy (RT) on overall survival (OS) for node positive head and neck squamous cell carcinoma (HNSCC)
Authors: Lavaf A. , Genden E. , Packer S. , Kao J. 
Published: March 2020

6087 Background: Although adjuvant RT is often recommended for locally advanced HNSCC, its effect on OS or cancer-specific survival (CSS) has not been clearly demonstrated. Methods: Within the Surveillance, Epidemiology, and End Results (SEER) Database, we selected patients with locally invasive but node negative (SEER stage 2) or node positive HNSCC (SEER stage 3–4) treated either with surgery alone (S) or surgery and radiation (S+RT). This analysis included 13,145 patients from the SEER 17 database diagnosed between 1988 and 2001. Exclusion criteria included distant metastases, no RT records or death within 3 months of surgery. The median follow-up was 4.7 years. Results: Adjuvant RT was utilized in 55% of patients with stage 2 and 84% of stage 3–4 HNSCC. For Stage 2 HNSCC, adjuvant RT was associated with lower 5 year OS on univariate analysis (46.32% for S+RT vs. 49.76% for S, p=0.016) but not on multivariate analysis (HR 1.00, p=0.93). For Stage 3 HNSCC, RT improved 5 year OS associated with RT on univariate analysis (52% for S + RT vs. 41% for S, p<0.001) and multivariate analysis (HR 0.80, p=0.002). For Stage 4 HNSCC, RT significantly improved 5 year OS on univariate analysis (35% for S + RT vs. 25% for S, p<0.001) and multivariate analysis (HR 0.75, p<0.001). The addition of RT improved 5 year CSS for both stage 3 (59.7% vs. 51.4%) and stage 4 HNSCC (42.1% vs. 32.8%). Conclusions: In the largest reported analysis of adjuvant RT in locally advanced HNSCC, adjuvant RT results in an approximately 10% absolute increase in 5-year CSS and OS for node-positive HNSCC compared to S alone. The absolute benefit of RT is underestimated on univariate analysis because patients with poor prognostic factors are more frequently selected for adjuvant RT. Outcomes in this high-risk population remain suboptimal, emphasizing the need for continued investigation of innovative treatment approaches. No significant financial relationships to disclose.
Sentinel lymph node biopsy is associated with a significantly improved survival compared to level Iand II axillary lymph node dissection in node-negative breast cancer patients
Authors: Langer I. , Guller U. , Schmitz S. Hsu , Ladewig A. , Viehl C. T. , Moch H. , Wight E. , Harder F. , Oertli D. , Zuber M. 
Published: March 2020

609 Background: The sentinel lymph node (SLN) biopsy has emerged as the standard of care in evaluating the axillary lymph node status in early stage breast cancer patients. It is well known that step sectioning and immunohistochemistry of the SLN allow for a more accurate histopathologic examination. Conversely, it remains to be elucidated whether or not the more accurate SLN staging is associated with improved survival. Therefore, the objective of the present investigation was to evaluate if patients undergoing a SLN biopsy have an improved disease-free and overall survival compared to those undergoing ALND. Methods: From our prospective database 355 node negative patients with early stage breast cancer (pT1 und pT2 <=3cm, pN0/pNSN0) were assessed. Patients underwent either ALND (n=178) in the years 1990–1997 or a SLN biopsy (n=177) in 1998–2004. Long-term disease-free and overall survival were analysed for both groups. Log-rank tests were used for unadjusted analyses, a Cox proportional hazard regression model for risk-adjusted analyses. Results: The median follow- up was 48.2 months in the SLN group and 120.0 months in the ALND group. Patients in the SLN group had a significantly better disease-free (p=0.012) and overall survival (p=0.04) compared to the ALND group. In Cox proportional hazard regression analysis, the performed procedure (SLN compared to ALND) was an independent predictor for improved disease-free survival (hazard ratio 0.28, 95% confidence interval 0.11–0.75, p=0.011) and overall survival (hazard ratio 0.36, 95% confidence interval 0.14–0.89, p=0.027). Conclusion: The present analysis - the first one in the literature - provides compelling evidence that patients with a negative SLN have a significantly improved disease-free and overall survival compared to node negative patients undergoing ALND. This relevant finding is most likely due to an improved histopathologic staging accuracy. The significant survival benefit of node negative patients having SLN biopsy highlights yet another important advantage of the SLN concept in breast cancer. No significant financial relationships to disclose.
Evolution of the randomized controlled trial (RCT) in oncology over three decades
Authors: Booth C. M. , Cescon D. W. , Wang L. , Tannock I. F. , Krzyzanowska M. K. 
Published: March 2020

6515 Background: The RCT is the gold standard for establishing new therapies in oncology. Here we document changes with time in design, results, author conclusions and sponsorship. Methods: Reports of RCTs evaluating systemic therapy for breast, colorectal (CRC) and non-small cell lung cancer (NSCLC) published 1975–2004 in 6 major journals were reviewed. Two authors independently abstracted data regarding trial design, effect size and author conclusions. Author conclusions were assigned a score from 1 to 7: 4/7 for a neutral statement, 7/7 and 1/7 for strong endorsement of experimental and control arm respectively. For each study the effect size for the primary endpoint was converted to a summary measure: hazard ratio [HR] for survival endpoints and relative risk [RR] for response rate. Descriptive statistics were used to analyze trends over time. Results: 326 eligible RCTs were included (48% breast, 24% CRC, 28% NSCLC). There was a significant increase in the number and size of RCTs (see Table ). Median rate of accrual increased from 7 patients/month in 1975–84 to 14 patients/month in 1995–2004 (p<0.001). There was an increase in multicenter (55 to 95%, p<0.001), international trials (26 to 52%, p<0.001) and for-profit sponsorship over time (6 to 57%, p<0.001). There was increasing use of survival (13 to 48%,) and decreasing use of response rate (32 to 14%) as primary endpoint (p<0.001). Authors have become more likely to strongly endorse the experimental arm despite no change in effect size over time (p=0.005). Studies sponsored by for-profit organizations were more likely to strongly endorse the experimental agent than studies not sponsored by for-profit groups (median author score 6/7 vs. 4/7, p<0.001). Conclusions: RCTs in oncology have become more common, larger, and are more likely to be sponsored by industry. Authors of modern RCTs are more likely to strongly endorse novel therapies despite no increase in the relative benefit of interventions. For-profit sponsorship is associated with stronger endorsement of the experimental arm. No significant financial relationships to disclose. [Table: see text]
Adverse event (AE) assessment lists for clinical trials (CTs) influence AE reporting rates: An evaluation of AE data collected on North Central Cancer Treatment Group CTs
Authors: Mahoney M. R. , Sargent D. J. , Campbell M. E. , Hobbs B. P. , Kugler J. W. , Alberts S. R. , Buckner J. C. 
Published: March 2020

6517 Background: In NCCTG CTs a subset of AEs are assessed at each patient (pt) evaluation based on the known safety profile of agents(s). The NCCTG routinely pre-fills the “known” AE list onto CT Case Report Forms (CRFs). Newly identified AEs may expand the AE assessment list for ongoing CTs. Our survey of NCCTG AE data (JCO 2005), demonstrated that 85% of AEs reported were pre-filled on CRFs, of which, 83% did not actually occur (Grade 0). Extending this work, we evaluated the influence of pre-filling AEs on CRFs, relative to the final AE rates reported. Methods: Our non-random sample contains 507,899 AEs collected from 1/99–6/06 on 74 NCCTG CTs, 13 of which had AEs added to the CRF pre-fill list during the CT (2,604 pts, 3 Ph I/II, 8 Ph II, 2 Ph III, 9 investigational agents). Results: An average of 2.8 AEs (range 1–6) were added to CRFs for ongoing CTs, primarily for Oxaliplatin induced AEs. 58% (21/36) of AEs added during a CT were not reported prior to the addition, 22% (8) were not reported afterwards. 5 CTs had significantly higher AE rates (p<0.01) after expanding the AE list, most notably for required blood chemistries (SGOT/alk phos/creatinine/bilirubin 14.2 vs 0.72%). Overall, the same AEs were 4-fold (range 0–25) as likely to be reported when pre-filled on the CRF. Regardless of pre-filling, only 6% of the newly required AEs were Gr 3+. Conclusions: Our data suggest a significant difference between the AE rates reported if included in the CT CRF assessment list. This may significantly influence the reported results of a CT, explaining differential AE rates reported across CTs of the same agent(s). A prospective study is planned to formally evaluate this observation. Supported by NIH Grant CA25224. No significant financial relationships to disclose.
Uncertainty around individualized predictions using nomograms: The concept of individualized prediction intervals
Authors: Iasonos A. , Schrag D. , Raj G. V. , Russo P. , Panageas K. S. 
Published: March 2020

6526 Background: Nomograms have become popular in the clinical oncology community, because of their simplicity. Clinicians use nomograms to provide individualized prognostic estimates to patients based on their clinical and pathologic characteristics.We aim to evaluate the degree of uncertainty around individualized point estimates derived from a published nomogram. Methods: Predictions were evaluated from a published nomogram (Raj G.V et al, J Urol. 2007;177(1):53–8.), where the predicted outcome was clear cell (CC) histology in renal masses using pre-operative parameters.95% confidence intervals (CI) for each prediction were obtained from logistic regression using the SAS system.CIs depend on the covariate effect in the underlying model and the patient-specific values of the covariates, hence they differ from patient to patient.The width of the CI was used to assess the zone of uncertainty of the predictions for each individual patient in this cohort. Results: Predictions were obtained for each of the 299 patients in the cohort. The median width of the 95% CI around the point estimates was 18% (range 11–47%) indicating that 50% (147/299) of patients have ± 9% uncertainty and 95% (283/299) of patients have less than ±16% uncertainty around the estimate predicted by the nomogram. Only three patients (1%) have more than ±20% uncertainty around the nomogram derived estimate. For example, a 69-year-old male with a 3.9 cm renal mass, without vascular flow on Doppler ultrasound, has 18% probability of CC histology with 95% CI: 10–29%, whereas a 48-year-old female with 9.7cm renal mass without vascular flow has 18% probability of CC histology with 95% CI:7–41%. Conclusions: We demonstrate that patients with equal predicted probability from a nomogram may have different uncertainty around their prediction. When nomograms are used to convey prognostic information to patients, reporting strategies should incorporate the degree of uncertainty around the point estimates that are derived from the underlying regression models.Although, this strategy adds some degree of complexity to the graphical representation of results, it enhances the integrity of the exercise and conveys to patients the important message that uncertainty is inherent in prognostication. No significant financial relationships to disclose.