bluuebunny/crossref_metadata_2025 huggingface dataset:
Dosimetric analysis for thyroid disorders after radiotherapy to the neck
Authors: Akgun Z. , Atasoy B. , Ozen Z. , Gulluoglu B. , Abacioglu M. U.
Published: August 2020

e17025

Background: In our study, we aimed to evaluate the possible predictors of thyroid disorders after radiotherapy to the neck, focusing on radiation dose-volume factors. Methods: Thyroid function was measured in 65 patients treated with radiation ports including the thyroid, between 2005 and 2008. All of the radiation-induced thyroid dysfunction was determined with an endpoint of abnormal thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and thyroxine (fT4), thyroglobulin antibodies (ATG), thyroid peroxidase antibodies (TPA), thyroid binding globulin (TBG) levels. In 65 patients, radiation dose-volume parameters were calculated; e.g. total volume of the thyroid, mean radiation dose to the thyroid, and percentage of the thyroid volume which received radiation doses of no less than 10–50 Gy (V10-V50). The evaluated risk factors for thyroid dysfunction included these dose-volume parameters, sex, age, treatment modality and primary disease. Results: Most patients (72.3%) had a normal thyroid function, 17 (26.2%) hypothyroidism, 1 (1.5%) hyperthyroidism, and 12 (18.4%) thyroiditis with normal thyroid function. Four of 17 patients with hypothyroidism had overt hypothyroidism. In our analysis, DVHs (dose volume histograms) were calculated and no associations were found between the V10, V20, V40, and V50 percentages and thyroid disorders. V30 and minimum absorbed thyroid dose (Dmin) more than 25 Gy appeared to be correlated with high TSH values (p = 0.01 and p = 0.04, respectively). The patients with hypothyroidism were between 40–60 years. Female gender was associated with a higher incidence of TBG abnormality. Baseline TSH values were available in 16 patients, and hypothyroidism was diagnosed in 4 (25%) of them. No correlation was found between tumor-related variables and incidence of thyroid disorders. Conclusions: Thyroid disorders after radiation therapy to the neck still represent a clinically underestimated problem. Further prospective well designed studies on dose-effect relationship for radiotherapy-induced thyroid toxicity are therefore needed, and thyroid should be considered as an organ at risk in all patients treated for head and neck tumors.

No significant financial relationships to disclose.
Cetuximab versus cisplatin concurrent with IMRT in locally advanced head and neck cancer (LAHNC)
Authors: Galper S. L. , Deshpande H. , Rose M. G. , Decker R. H.
Published: August 2020

e17030

Background: Concurrent chemoradiation of LAHNC with cetuximab or cisplatin improves survival. The purpose of this study is to compare cetuximab chemoradiation (ExRT) with cisplatin chemoradiation (ChRT) in patients treated with IMRT. Methods: Between January 2005 and August 2008, 24 patients with LAHNC were treated with definitive chemoradiation utilizing IMRT. ExRT was reserved for those whose age or comorbidities precluded ChRT. 15 patients were treated with ChRT and 9 patients were treated with ExRT. Patient charts and Tumor Registry data were reviewed for acute and late toxicity and for local/regional failure (LRF), distant metastases and death. Results: The ExRT cohort was significantly older (median age 71 vs 58, p=0.005) and had more larynx/hypopharynx primaries (44% vs 27%). The cohorts were otherwise balanced with respect to T- and N-stage. Median follow-up for the ExRT and ChRT cohorts was 11 and 12 months, respectively. Overall treatment time in compliant patients was lower in ExRT patients (46 vs 50 days, p=0.05), reflecting increased use of accelerated radiation fractionation (66% vs 40%). See Table for toxicity outcomes. There was a trend toward increased ≥G3 acute mucositis in the ExRT group (p=0.07). However, there was less weight loss (p=0.05). There were similar acute epidermitis and hospitalizations for malnutrition/hydration rates and a nonsignificant decrease in prolonged mucosal toxicity. 1 patient developed skin necrosis and another osteoradionecrosis in the ChRT group. 1-year freedom from LRF was 89% in the ChRT group vs 56% in the ExRT group (p=0.07). Overall survival (OS) at 1 year was 100% (ChRT) vs 88% (ExRT). Conclusions: ExRT showed a trend toward worse acute mucosal toxicity but not late toxicity despite increased rates of altered fractionation with a higher daily dose. ExRT was associated with worse LRC and OS. A randomized study would best compare outcomes and toxicity profiles. Until such analysis, cetuximab should be reserved for patients unable to tolerate ChRT. [Table: see text]

No significant financial relationships to disclose.
Patterns of failures after definitive conformal radiation therapy for head and neck cancers
Authors: Jain S. , Gupta T. , Reenadevi P. , Agarwal J. , Laskar S. G. , Shrivastava S. K.
Published: August 2020

e17037

Background: The primary objective of the study is to analyze patterns of failure in patients with head and neck cancer treated with definitive conformal radiotherapy with a focus on the location of failures in relation to the target volume coverage. Methods: Sixty patients with squamous cell carcinoma (stage: T1–3, N0–2b) were treated definitively on a prospective protocol with conformal techniques to conventional dose-fractionation equivalent of 70 Gy to the gross disease using standardized contouring guidelines. The recurrent or persistent tumor volume (Vf) was defined using positron imaging tomography (PET) and surgical-pathologic findings, and analyzed using dose-volume histograms. The failure was considered marginal when 20%-95% of Vf was within 95% isodose line. Results: At median follow-up of 12 months (range, 4–30) the 3-year actuarial local control, loco-regional control, disease-free survival, and overall survival Kaplan-Meier estimates were 86.4%, 80.5%, 62.6%, and 46.4% respectively. Of 12 (19.3%) patients with disease related events, 10 have loco-regional failures with a median time of 4 months (range, 0–22). Of 10 patients, 8 had in-field, one had marginal and one had failures of both patterns. Of seven (11.3%) local failure events, two were isolated and one had marginal failure. Of seven regional failure events, two were marginal including one with failure at peri-parotid contra-lateral neck. Another one had bilateral multiple nodal levels with supraclavicular recurrence. The remaining events were in-field were “true failures” with no apparent technical cause, none had out-field failures. Two patients were detected to have distant metastases and two developed second malignancies, one out-field and other marginal with upper esophagus carcinoma at gradient zone of previous radiation. Conclusions: Conformal radiotherapy does not compromise loco-regional control as compared to historical controls treated with conventional techniques. PET scans are useful in delineation of failure volumes. The majority of recurrences were ‘in-field‘ motivate studies of dose escalation to the highest risk regions and marginal failures in the high-dose gradient region highlight the potential hazard of high precision techniques and warrants careful consideration.

No significant financial relationships to disclose.
Induction chemotherapy with cisplatin and epirubicin followed by radiotherapy and concurrent cisplatin in locally advanced nasopharyngeal carcinoma observed in a nonendemic population
Authors: Airoldi M. , Garzaro M. , Gabriele A. , Raimondo L.
Published: August 2020

e17040

Background: Chemoradiotherapy (CRT) represents the main therapy choice in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). Aim of this study was the clinical evaluation of neoadjuvant chemotherapy (NACT) followed by CRT in a non endemic population affected by advanced NPC. Methods: Patients with locoregionally advanced NPC were treated with three cycles of induction chemotherapy (CHT) with cisplatin (100 mg/m2) plus epirubicin (90 mg/m2), followed by cisplatin (100 mg/m2) and concomitant radiotherapy (70 Gy). Results: In 40 patients treated with such protocol, after the completion of induction CHT and CRT we observed the objective response rates of 90% and 100% respectively. Treatment tolerability and toxicity were easily controllable. With a median follow-up time of 54.5 months 3- and 5-years disease-free survival was 75% and 65.4% and 3- and 5-years overall survival was 84% and 77.5%. 3- and 5-years loco-regional control was 82.4% and 70.3%, and 5-years distant metastases-free survival was 75%. Conclusions: NACT with cisplatin and epirubicin followed by concomitant CRT represents a feasible, efficient treatment for patients with advanced NPC. This regimen ensures an excellent locoregional disease control and overall survival with a low incidence of distant metastases.

No significant financial relationships to disclose.
A pilot study of proton beam theary for mucosal melanoma of the head and neck
Authors: Zenda S. , Kawashima M. , Kohno R. , Arahira S. , Nishio T. , Ogino T.
Published: August 2020

e17042

Background: The aim of this study is to clarify the clinical profile of proton beam therapy for mucosal melanoma of the head and neck. Methods: Patients with mucosal melanoma of the head and neck fulfilling the following criteria were enrolled: histologically confirmed malignant melanoma; N0 and M0 disease. Proton therapy was delivered three times a week with planned total dose of 60 GyE in 15 fractions. Results: From January 2004 through January 2007, thirteen patients were enrolled in this study. Patients’ characteristics were as follows: median age, 75 years (range, 56 to 79); male/female, 7/6; T1/2/3/4/rec, 3/2/0/7/1. All could receive the full dose of proton therapy. The most common acute toxicities were mucositis (grade 3: 15%) and dermatitis (grade 2: 15%). One patient had unilateral impairment of visual acuity possibly related with treatment. Initial local control rate was 77.0% (10/13, 95%CI: 46.2–95.0%). With median follow up period of 33.7 months, median progression free survival was 18.9 months and median survival time was not reached. 2-year overall survival rate was 69.7% (95%CI: 31.6–86.1%). Most frequent site of first failure was cervical lymph nodes outside of PTV. Four patients died of disease; cachexia caused by distant metastases in three and carotid blowout because of nodal disease in one. Conclusions: Proton beam therapy for mucosal melanoma of the head and neck achieved favorable results in this limited number of patients, although further investigation about late toxicity is needed. Now, the phase II study of this treatment is ongoing.

No significant financial relationships to disclose.
Use of cystatin C as a marker to detect renal insufficiency in head and neck cancer patients with cisplatin-based chemotherapy
Authors: Bölke E. , Gripp S. , Matuschek C. , Hermsen D. , Peiper M. , Budach W.
Published: August 2020

e17048

Background: Knowledge of the usefulness of cystatin C measurement in the detection of chronic kidney disease in patients with head and neck cancer (HNC) is scant. The purpose of this study was to evaluate the ability of plasma cystatin C- and creatinine-based methods to predict glomerular filtration rate (GFR) and classify chronic kidney disease in HNC patients before receiving cisplatin based chemotherapy. Methods: The study population consisted of 43 HNC patients aged 39–76 years. Comparisons were made between measured plasma creatinine, cystatin C, creatinine clearance and GFR estimated by the Modification of Diet in Renal Disease (MDRD) formula. The plasma clearance of (51)Cr-EDTA served as a reference method. Results: The Pearson correlation coefficients between plasma clearance of (51)Cr-EDTA and the markers of GFR were calculated. The correlation coefficients were 0.765 for cystatin C, 0.688 for plasma creatinine, 0.585 for GFR values estimated by MDRD and 0.568 for plasma creatinine clearance. Conclusions: We recommend using cystatin C for the estimation of the GFR of HNC patients instead of solely creatinine or creatinine clearance in clinical practice.

No significant financial relationships to disclose.
Nasopharyngeal carcinoma at the National Institute of Oncology
Authors: Hassan E. , Afqir S. , Ismaili N. , M’rabti H. , Boutayeb S. , Elghissassi I.
Published: August 2020

e17055

Background: To evaluate the disease characteristics and outcome of patients with nasopharyngeal carcinoma treated at the National Institute of Oncology (NIO) Rabat, Morocco. Methods: Between 1999 and 2001, 468 patients with a diagnosis of nasopharyngeal carcinoma were treated at the NIO. The median age was 42 years (range 10 to 83). The male/female ratio was 2.5/1. Of the 468 patients, 88 (19%), and 380 (81%) had T1-T2, and T3- T4 (TNM International Union Against Cancer staging system, 1997), respectively. Ninety percent presented with nodal metastasis. 163 patients (35%) had lymph nodes >6 cm, and 229 (49%) had bilateral nodes at presentation. Histologically, 405 patients (86%) had undifferentiated carcinoma. Seventy-six percent received neoadjuvant multiagent chemotherapy containing cisplatin, followed by radiotherapy (RT). Results: After a median follow-up of 26 months, the disease-free survival (DFS) and overall survival (OS) rate for the entire group was 27% and 41%, respectively. Kaplan-Meier curves were used for evaluation of prognostic factors and were compared using the log-rank test. Nodal status had a significant impact on OS (p < 0.001). Complete responders to chemotherapy had superior DFS and OS. Conclusions: Combined modality management using chemotherapy and RT resulted in satisfactory locoregional control and OS in patients with nasopharyngeal carcinoma. Nodal involvement and response to chemotherapy were important prognostic factors.

No significant financial relationships to disclose.
Environmental effects on head and neck cancer in India
Authors: Mishra A. , Singh V. P. , Verma V.
Published: August 2020

e17059

Background: Head and neck cancer in India has unique demographic profile, environmental exposure, dietary habits, and personal and family history. Methods: 1,000 cases were analysed. Results: Males dominated (82%) in fifth (29%) and sixth (33%) decades. Majority was uneducated (76%) and poor. Passive tobacco smoking was seen in-house (85%) as well as in the work-place (80%). Approximately 69% smoked more than 100 cigarettes/bidis in their lifetime. Majority acquired regular smoking habit in second (73%) and third (18%) decades and continued smoking for more than 20 years (66%) with 10–20 cigarettes daily (range 1 to 43). However 30% never used tobacco. The main alternative forms were bidi (27%) and smokeless-tobacco chewing products (47%). A past history of cancer and the subsequent radiation treatment was found in 3% while GERD in 33%. Multivitamins/minerals for chemoprevention was used in 65% for 1 to 12 months. Alcohol consumption was seen in 26% where the age of initiation was in second and third decade and the total years of consumption mainly varied from 10–30 years. Having a predominant agriculture-based-economy, the majority of males (38%) were farmers with significant exposure to pesticides and fertilizers; while females predominantly housewifes (17%). The family history was appreciated in 1% with natural parents known in all. The most common sites involved were oral cavity (28%), oropharynx (30%), and larynx (32%). Majority presented with advanced stage (III = 39%; IV = 23%). The consumption of fruit and vegetable juice was less common as compared to fresh consumption as such. Green salads, potatoes, and fiber cereals were significantly used (4–6 times a week). Beans, peas, and corn was not common while beef and pork consumption rare owing . The ‘staple’ diet was wheat, rice, pulses with additional meat mainly in Muslims (once a day). The use of cooking oil, butter, eggs biscuits, cheese, cakes, and cookies was uncommon (less than once a week), but milk was abundant. Conclusions: Hence, it seems that poor, education/literacy, poor socioeconomic status, tobacco smoking (passive and active) at an early age for prolonged duration, tobacco-related products and exposure to pesticides/fertilizers predispose Indian population for head and neck cancer, rather than a positive family history, dietary factors, radiation exposure, or alcoholism.

No significant financial relationships to disclose.
Objective measure of patients’ understanding of their role in a randomized trial: A multicenter case-control study
Authors: Leroy T. , Christophe V. , Clisant S. , Antoine P. , Vanlemmens L. , Fournier E. , Penel N.
Published: August 2020

e17500

Background: Informed consent process is the key-element of the ethical considerations of clinical trials. Several reports have shown that even having been through this process, enrolled patients misunderstand the modalities and goals of randomized clinical trials (RCT). The purpose of this study is to compare individuals’ objective understanding about RCT between patients already included (cases) and patients treated under standard care who have never received information about clinical trials (controls). Methods: We submitted a standardized questionnaire to both populations to explore the objective understanding of RCT. This questionnaire includes 10 ended-questions (q) exploring: understanding of underlying legislation (3 q), understanding of conditions of study withdrawal (3 q), understanding of randomization (2 q) and understanding of uncertainty (2 q). Results: 75 cases and 107 controls were included in the present study. Three questions are associated with a rate of good responses close to 70% in both populations: anonymity of collected data (66% in controls vs 81% in cases), existence of legislation protecting patients (73% vs 76%) and right to withdraw in case of toxicity (73% vs 82%). Understanding of cases is statistically better (p < 0.05) for 6 other questions: physicians duty to tell everything about the trial (44% vs 68%), right to withdraw from the study without giving any reason (38% vs 73%), withdrawing does not jeopardies the quality of further care (40% vs 71%), all the patients do not receive the same treatment (56% vs 73%), allocation at random (12% vs 52%) and uncertainty about benefits (20% vs 38%). At last, the rate of correct responses is similar and very low for the question exploring the uncertainty about toxicity (43% vs 44%). Conclusions: Informed consent actually improves enrolled patients’ understanding of RCT. Nevertheless, additional efforts should be made to increase the quality of the transmission of information about randomization and uncertainty.

[Table: see text]
Interobserver and interlaboratory variability of mismatch repair protein expression in ovarian tumors
Authors: Coppola D. , Nicosia S. , Lee J. , Kim J. , Schildkraut J. , Narod S. , Sutphen R. , Sellers T. , Pal T.
Published: August 2020

e17505

Background: Immunohistochemistry (IHC) for mismatch repair (MMR) protein (MLH1, MSH2, MSH6) expression has been a useful strategy for identifying tumors with MMR deficiency. However, despite its wide use, interpretation of results suffers from poor reproducibility. Methods: To assess inter-observer (IO) and inter-laboratory (IL) variability of MMR protein expression, 41 epithelial ovarian cancer (EOC) samples were arrayed in triplicate for construction of a tissue microarray (TMA). Six slides were made from this donor TMA block, of which 3 were stained at the Moffitt Cancer Center (MCC) and 3 were stained at the University of South Florida (USF), using different lab procedures. IHC for MMR protein expression was performed using the avidin-biotin-complex (ABC) method with appropriate controls. Subsequently, all slides were independently scored for protein expression by two pathologists. The Concordance Correlation Coefficient (CCC) value was computed to evaluate IO and IL concordance, with a value >0.75 indicating excellent concordance. Results: The CCC value for the IO analysis was 0.95 (for MCC-stained slides; 95% C.I.: 0.89–0.98) and 0.85 (for USF-stained slides; 95% C.I.: 0.66, 0.93), indicating excellent concordance. The CCC value for IL analysis was 0.53 (95% C.I.: 0.37–0.66). Conclusions: Our findings demonstrate that variability in IHC protocols may contribute to the interpretation of IHC results. Our data suggest that when pathologists are given the same slide, there is excellent agreement between two observers; however, when the same slides are stained in a separate laboratory using the same method (ABC) but different protocol, there may be considerable disagreement. These findings are of great clinical significance due to the widespread use of IHC as diagnostic, prognostic and therapeutic tools in cancer care.

No significant financial relationships to disclose.
The association of pretreatment patient characteristics on the allocation of treatment in stage II ovarian cancer
Authors: Brewster W. R. , Chase D. M. , Fedewa S. , Chen A. , Ward E.
Published: August 2020

e17508

Background: In high-risk early stage ovarian cancer, surgery followed by adjuvant chemotherapy demonstrates improved survival in prospective trials. The objective of this research was to document patterns of care in the treatment of stage II epithelial ovarian cancer and those factors associated with less than optimal treatment. Methods: The study population was selected from patients diagnosed with ovarian cancer in 2003 to 2005 and reported to the National Cancer Database, a hospital-based cancer registry. 2,252 (93.8%) patients had sufficient information for analysis. Demographics, health insurance, Charlson co-morbidity score, area-level income, and facility characteristics were analyzed as factors potentially associated with treatment. Multivariate logistic regression was performed to assess factors associated with optimal treatment versus suboptimal treatment. Results: Among the women 2,252 women included in the study 1,533 (68.0%) received surgery and chemotherapy and 719 (32.0%) received surgery alone. In multivariate analysis, Black and Hispanic patients were significantly less like likely to receive optimal treatment as compared to white patients (OR = 0.54, 95% CI 0.36–0.82; OR = 0.51, 95% CI = 0.34–0.79, respectively). Women 75 years of age or more were significantly less likely to receive optimal treatment (OR = 0.43 95% CI 0.28–0.67) compared to women less than 53 years. Treatment in a comprehensive cancer facility or teaching hospital compared to community cancer hospitals was positively associated with optimal treatment (OR = 1.40 95% CI 1.02–1.92; OR = 1.89 95% CI 1.38–2.59). Among the 719 patients not receiving chemotherapy, 205 had no reason recorded, and the majority with information (456/514) stated that chemotherapy was not part of planned therapy. Only 33 patients (6.4%) were recorded as refusing recommended chemotherapy. Conclusions: Although only a small proportion of newly diagnosed cases, Stage II ovarian cancer patients have a high probability of benefiting from adjuvant chemotherapy, which improves the likelihood of long-term survival and cure. Further studies are needed to address the patient, clinician and health system factors associated with suboptimal treatment.

No significant financial relationships to disclose.
Creation of a library of harmonized standard research variables and case report forms (CRFs) for oncology research
Authors: Reeves D. M. , Helton E. , Speakman J. , Ness E. , Komatsoulis G.
Published: August 2020

e17512

Background: Oncology clinical research can be facilitated through use of a set of core variables to collect, aggregate, analyze and report data across a number of diverse research settings. These elements can be captured in Case Report Form (CRF) templates, and cloned to expedite the activation of a clinical trial and the collection of data. Through the efforts of the Cancer Biomedical Informatics Grid or caBIG community, the creation of a set of CRFs to support NCI-sponsored trials has been underway since the summer of 2007. Methods: A schematic to represent commonly-used CRFs in oncology trials was created as a roadmap for the project. Priorities were established, and community broadcasts used to recruit workgroup members with clinical, biostatistical, and regulatory expertise. CRFs were contributed by the community-at-large, including the pharmaceutical industry and NCI cooperative groups. Variables from a set of CRFs were partitioned into one of four groups: mandatory, conditional, optional, or not to be included in a CRF. After all the variables for a CRF were finalized by consensus, data elements were created and registered into an NCI ISO/IEC 11179 metadata repository that facilitates the reuse of data elements and CRFs. Results: Eight workgroups have completed their work by the end of 2008, with additional groups underway. The results of the first eight groups were harmonized with the Clinical Data Acquisitions Standards Harmonization or CDASH version 1.0, a standard for CDISC. After approval, the variables are assembled into CRFs with instructions that are available through NCI's data standards repository in a variety of electronic formats. The variables will undergo a rigorous change management process with regular review and versioning as required. Conclusions: The identification and reuse of standards to support the conduct of oncology research depends upon our ability to manage data sets that can be aggregated and analyzed in a timely manner. The caBIG CRF harmonization and standardization variables are being implemented now through a series of early adoption activities and a phased deployment plan that will result in the reuse of a single set of variables to support the conduct of oncology clinical trials.

No significant financial relationships to disclose.
Is tumor burden a better predictor of drug activity than progression-free survival?
Authors: Fridlyand J. , Kaiser L. , Fyfe G.
Published: August 2020

e17521

Background: Improving the ability of Phase (Ph) II trials to better predict Ph 3 outcome is critical. Percentage change in tumor burden (%SLD) is a potentially earlier marker of drug activity than an early evaluation of progression-free survival (PFS) and includes aspects of tumor response not captured by PFS. We describe a statistical evaluation of the ability of %SLD vs PFS to identify an active agent in randomized Ph 2 trials. Methods: Ph 2 trials were simulated with data from bevacizumab (B) and trastuzumab (T) mBC and mCRC Ph3 trials of > 1800 patients total. 2/3 B trials and 1 T trial showed improved PFS (+) & OS (+ or trend), and 1 mBC B study was negative. We repeatedly sampled patients, with their treatment assignments, tumor assessments and PFS values from these studies to emulate randomized Ph 2 trials with different sample sizes, enrollment patterns and follow-up. We determined the probability of correctly identifying an approvable regimen, based on 5% 1-tailed tests of PFS (log-rank) and %SLD (last & nadir, Wilcoxon). All endpoints have equal follow up given a landmark. Results: We performed analyses on 6–8 week assessments and on up to 20–24 week assessments in patients enrolled over 6 months. The estimated probability of a correct Ph 3 decision is reported below for a 100-patient Ph 2 trial. We found:1) For B, PFS consistently outperforms %SLD; 2) for T, %SLD is modestly better than an early PFS, especially with shorter patient follow up. The results were similar across other assessments and varying enrollment times. Conclusions: More trial data are needed to determine if the usefulness of %SLD for decision making is dependent on the drug's MOA/indication. For B, its utility is inferior to PFS at all time points, with the last %SLD generally outperforming the nadir %SLD. In the T study the %SLD analyses displayed a slight advantage. PFS and %SLD should be incorporated into Ph 2 design, analysis, and decision making.

[Table: see text]

[Table: see text]
A qualitative study of exceptional survivors of cancer
Authors: Meleth S. , Allen L. , Kvale E. , Meredith R. , Spencer S. , Heslin M. , Nabell L. , Posey J. , Partridge E.
Published: August 2020

e17522

Background: An exceptional survivor of cancer is an individual who has outlived actuarial predictions for his/her particular form of cancer or experienced a complete regression. This pilot study was designed to determine if there were any biological, psychosocial, cultural or lifestyle characteristics exceptional survivors of cancer that can be measured and transferred through interventions to other cancer patients. Methods: The sample consisted of 21 survivors of cancer who were identified by oncologists at UAB as exceptional survivors. The study gathered qualitative data through semi-structured interviews and two validated scales measuring resilience, sense of coherence. A new cancer ‘catastrophizing’ scale based on the pain catastrophizing scale (PCS) was tested for its concordance with the two validated scales. The diagnosis and treatment information on these patients was collected through a questionnaire completed by the patient's oncologist. Results: Eight oncologists referred twenty-five patients to the study. Twenty-one patients agreed to participate. A unifying theme across all patient interviews was a deep spiritual connection with a supreme being. Praying for healing, intercessory prayer, and seeking guidance through faith with respect to best treatment options were common. The patients verbalized faith in physicians and were willing to seek more experimental treatments largely due to their spirituality. In general, the survivors were highly resilient as measured by the resilience scale and had a high sense of coherence as measured by the sense of coherence scale. They were also unlikely to conceptualize the diagnosis as a ‘catastrophe’ as measured by the new cancer catastrophizing scale. Conclusions: This study provides preliminary evidence of a relationship between spirituality and exceptional survivorship. Findings suggest exceptional survivors may be more willing to participate in clinical trials than other populations of cancer patients. Future studies should prospectively follow cancer patients to ascertain the temporal nature of the association between spirituality and exceptional survivorship.

No significant financial relationships to disclose.
A model to optimize health care assistance for women with breast cancer: The Núcleo Mama Porto Alegre Project
Authors: Caleffi M. , Viegas-Butzke J. P. , Baldisserotto F. D. , Bedin-Junior A. , Weber B. , Duarte-Filho D. , Skonieski G. P. , Graudenz M. , Ribeiro R. A.
Published: August 2020

e17526

Background: The promptness of breast cancer (BC) diagnosis and treatment is cornerstone in reducing the disease's mortality. In Brazil, the main problem to achieve this is lack of access to the insufficient referral centers, which in turn are not used to perform early diagnosis and treatment. To address this problem in our city, we created the Núcleo Mama Porto Alegre (NMPOA) model, through a partnership among the private, public and third sectors. The cohort is composed by 9,218 women, of which 4,500 are in the 40–69 age group and have annual clinical examination and mammography (MMG) at NMPOA, and the remainder (<40 and >=70) have clinical follow-up at primary care facilities. All clinical visits, exams and treatment are conducted in the NMPOA center. Our aim is to demonstrate the effectiveness of a model for underserved population to shorten the time between 1st medical appointment and the start of BC treatment. Methods: We analyzed all BC cases diagnosed up to now. We evaluated 3 time periods of the patient's care: median time (MT) between the medical appointment and MMG, MT between MMG and biopsy, and MT between biopsy and the first treatment as indicated: definitive surgery, neoadjuvant chemo- or hormone therapy. Results: 48 cases were evaluated. Clinical staging were the following: stage 0: 16.6%; I: 37.5%; IIA: 18.8%; IIB: 12.5%; IIIA: 10.4%; and IV: 4.1%. MT between the first visit and MMG was 0 days; between MMG and biopsy, 3 days; and between biopsy and first treatment, 23 days. Conclusions: Our model shows much faster results than the usual delay time in Brazil (4–6 months between first visit and treatment). A nationwide BC screening program in Brazil must be implemented with efficient infrastructure and well trained personnel in order to rapid investigate breast lesions, assuring quick access to treatment and therefore diminishing BC mortality.

No significant financial relationships to disclose.
Toward incident reporting (IR) systems: A safety culture survey within the oncology network of a northern Italian region
Authors: Aita M. , Zanier L. , Rijavec E. , Merlo V. , Menis J. , Della Mea V. , Deroma L. , Donato R. , Puglisi F. , Fasola G.
Published: August 2020

e17527

Background: Physicians are reluctant partners in error reporting. Insufficient evidence exists on what may affect IR in a specific cultural and organizational context. The primary endpoint of our study was to offer a critical perspective on the dominant attitudes toward IR systems among health operators of Friuli-Venezia Giulia cancer network. The survey was part of a Health Department patient safety project. Methods: A preliminary PubMed and ASCO database search was performed (keywords: incident/error reporting, attitudes, barriers, blame/safety culture, cancer, oncology, chemotherapy). Two web-based questionnaires were administered to health personnel of Oncology Units (OU) with developing and existing IR systems, respectively. Data were collected in a MySQL database and managed by PhpMyAdmin. SAS 9.1 was used for the analysis of frequency distributions. Results: Target population: 14 OU; 2 University Hospitals, 1 Scientific Institute for Research, Hospitalization, and Health Care (SIRHHC) (2 OU), 10 Hospital Centers; 262 operators (83 physicians, 172 nurses, 2 pharmacists, 5 technicians). Overall response rate: 44.6%; physician/nurse 59/36%; University Hospital (n = 99)/SIRHHC (n = 55)/Hospital Center (n = 101) 73%/9%/38%. Knowledge of risk management issues: 86% (90% of untrained operators from IR-free centers). Eighty-six percent of all operators showed a favourable attitude toward voluntary IR systems. Main reasons: patient safety improvement (65%); organizational growth (38%); professional duty (20.5%). A 78.5% preference for computerized forms was recorded. On a five-point scale, IR features rating 5 in >50% of the answers were: simplicity (85%); getting a feed-back (76%); exhaustivity (66%); adoption of organization more than individual recommendations (59%). Specific training, feedback guarantee and plainness of reporting forms were suggested by 90, 64, and 51% of all operators as essential measures for system acceptance and user satisfaction. Conclusions: Logistic and organizational factors (i.e., time constraints, work overload, resource allocation to incident reporting more than investigation and learning back) should be taken in account by county health directors aiming for successful reporting systems.

No significant financial relationships to disclose.
300% increase rate in juvenile cancer cases unrelated to AIDS: Is it real?
Authors: Gercovich F. G. , Gil Deza E. , Martin Reina G. , Garcia Gerardi C. , Abal M. , Santillan D. , Tognelli F. , Calarame J. , Rivarola E. , Morgenfeld E.
Published: August 2020

e17535

Background: Juvenile Cancer (JC) involves patients between 18 and 29 years old (adult pt less than 30 yo) and can be or not associated to AIDS. The non-AIDS JC pt challenge the clinical oncologist in many ways: there are few preventive measures, avoiding delayed toxicities is mandatory (fertility, cognitive impairment) and there is a lack of evidence-based treatments for uncommon tumors. The aim of this paper is to evaluate the incidence and clinical outcome of JC non AIDS related at the IOHM. Methods: A JC search in the patient database of the IOHM was made. The inclusion criteria was: new cancer pt diagnosed between 18 and 29 yo. The following variables were analyzed: age, gender, date, absolute and relative annual incidence and diagnosis. The tumors were classified as expected (germinal, hematological, sarcoma, melanoma, CNS, thyroid, cervix, trophoblastic disease) or unexpected (breast, colon, ovarian, gastric, pancreatic, head and neck). The Mean Annual New Case (MANC) incidence for pt older than 30 yo (non-JC) and JC in two different four year periods (“A”: 2001–2004, “B”: 2005–2008) were calculated in order to analyze the relative risk between both populations for these periods. Results: A total of 12.828 new pt were managed at the IOHM between January 2001 and January 2008, with 336 of them (2.6%) being JC. Mean age (range) = 23.3 years (18–29). Gender: male = 180 (53%) and female = 156 (47%). Diagnosis: Expected tumors 269 pt (80%) (testicular tumors = 89 pt; lymphoma = 75 pt; sarcoma = 35 pt; melanoma = 17 pt; others = 53), Unexpected tumors 67 pt (20%) (gastrointestinal = 23 pt; breast cancer = 17 pt; ovarian = 13 pt; head and neck = 7 pt; others = 7 pt). MANC for Non JC in A=1458.25 pt/y; MANC for Non JC in B = 1748.75 pt/y (RR Non JC B/A = 1.2). MANC JC in A = 18.5 pt/y; MANC JC in B = 52.75 pt/y (RR JC B/A = 2.85). Conclusions: 1) In our database, 336 cases of JC out of 12.828 new cancer patients between were found 2001 and 2008; 2) Expected tumors represent 80% of the cases; 3) An unexplained trend of new cases of JC is seen in this 8-year period. The comparison of the first 4 years and the second 4 years shows a relative risk increase of 300% of cases in this population. If other investigators confirm this data, a severe public health problem may be unrecognized.

No significant financial relationships to disclose.
Sunitinib, sorafenib, temsirolimus, or bevacizumab in the treatment of metastatic renal cell carcinoma (RCC): A review of health economic evaluations
Authors: Norum J. , Nieder C. , Kondo M.
Published: August 2020

e17539

Background: Renal cell carcinoma (RCC) is the most prevalent kidney cancer and the 5-year overall survival figure in metastatic disease (mRCC) is about 10%. New targeted drugs (sunitinib, sorafenib, bevacizumab, temsirolimus) have shown activity in the treatment of mRCC, but they are all associated with a significant burden of cost. Methods: To support decision makers in their allocation of resources, cost-effectiveness models are constructed to compare the costs and outcomes of anticancer therapy. The PubMed, ASCO abstracts, Google, and the Igaku Chuo Zasshi databases were searched in November 2008 with key terms: kidney, renal, cancer, cost, sunitinib, sorafenib, temsirolimus, and bevacizumab. Seven studies reporting data on cost-effectiveness were revealed. Three of them were published in full text versions. The countries of application were United Kingdom, Canada, United States, Finland, and Japan. An analytical checklist was applied to the seven economic evaluations. Results: The review reveals figures of cost per LYG or QALY in the range €22,648 to €203,692, depending on line setting and drug focused. The results were limited by short follow up periods and the consequently fact that premature data had to be implemented in the Markov models. When compared, sunitinib has the lowest cost-effectiveness figure. Second-line therapy dose not seem to offer valid incremental cost-effectiveness ratios (ICERs) below accepted cost-effectiveness thresholds. As long as cross-over to the experimental arm is allowed (based on improvement in progression free survival) overall survival data are difficult to interpret and the cost difference between the treatment and the control arm minimised. Conclusions: The review revealed ICERs with a wide range. Sunitinib has the lowest cost-effectiveness figure. Second-line therapy does not look cost-effective.

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An assessment of breast cancer survivorship awareness and educational needs among health care professionals
Authors: De Fusco P. , Chlebowski R.
Published: August 2020

e17542

Background: Tremendous advances in detection and treatment have improved breast cancer survival rates. However, with nearly 22.4 million people worldwide living with cancer, optimal survivorship care has become a major focus of health care professionals (HCPs) and patient advocates. The Breast Cancer Survivorship Alliance (BCSA) is a group of HCPs and patient advocates dedicated to enhancing patient survivorship care and encouraging HCPs to look beyond the diagnosis and treatment of breast cancer. Methods: To identify educational needs in breast cancer survivorship, a 25-question survey was fielded at the 2007 San Antonio Breast Cancer Symposium. Electronic and print surveys were available at the Y-Me National Breast Cancer Organization and AstraZeneca booths. Results: Of the 516 respondents, 29% were from the United States, 63% were from the rest of the world, and 8% did not specify a location. A total of 73% were physicians, 7% were oncology nurses, nurse practitioners, or physician assistants, and 20% represented other aspects of breast cancer care (e.g., advocates and patients). The survey revealed a lack of consensus on the definition of cancer survivor, with only 26% of respondents selecting the definition established by the National Coalition for Cancer Survivorship (ie, from the moment of cancer diagnosis and for the balance of life). More than half (i.e., 51%) defined cancer survivor as a patient who has been disease-free for 5 years. Overall wellness promotion, adherence, and management of treatment-related side effects were ranked as the 3 most essential aspects of survivorship care. While most practices engage in posttreatment survivorship counseling, only 16% provide patients with an end-of-treatment summary or survivorship care plan. Most respondents indicated that their institution has a survivorship program in place (39%) or in development (30%). Conclusions: Although progress has been made in understanding and implementing survivorship care, additional education is needed to optimize care of breast cancer survivors.

[Table: see text]
Current trend of breast cancer therapeutics from the U.S. clinical trial database
Authors: Kwok S. S. , Tsang J.
Published: August 2020

e17546

Background: The standard of breast cancer care has been based on clinical trial results. With the International Committee of Medical Journal Editors (ICMJE) requiring all clinical trials registered in a public trial registry as a condition of publication, the US trials registry “ClinicalTrials.gov” has become a global registry of currently available clinical trials. We aim to explore the current clinical trials to study the trend of breast cancer therapeutics development based on analysis of a comprehensive breast cancer trial database. Methods: We performed a systematic review of all breast cancer therapeutic clinical trials. All data were captured from ClinicalTrials.gov for all “industry-sponsored” phase I-IV trials in October, 2007 including trials that were first registered between October 2005 and September 2007. Essential data was extracted by a tailor-made Statistical Analysis System Program developed by Professor JP Karlberg at the University of Hong Kong. The data included register identity, study phase, study compounds and recruitment status etc. Results: Altogether 443 clinical therapeutic interventional trials were identified and classified into 10 modes of action. The latest five mostly studied compounds accounted for 32.73% of all the therapeutic trials (n = 145). Lapatinib, a dual kinase inhibitor is studied most in 31 trials (9 monotherapy). Docetaxel, a mitotic inhibitor is studied in 27 trials (10 monotherapy) while letrozole, an aromatase inhibitor, currently used in adjuvant setting is tested in 18 out of a total 22 trials as monotherapy. Antimetabolites such as gemcitabine being involved in 24 trials (2 monotherapy) with capecitabine studied in 21 trials (11 monotherapy), were followed by bevacizumab, a VEGF monoclonal antibody which is currently studied in 20 trials, and tested as combinations in 75% of the related trials. Conclusions: According to the US trial registry, current most commonly tested compounds for breast cancer include lapatinib, followed by docetaxel, gemcitabine, letrozole, and capecitabine. There is increasing new therapeutics with combination strategy. This supports the trend of personalized medicine in the management of breast cancer which is a heterogeneous disease.

No significant financial relationships to disclose.
Assessment of barriers to patient participation in clinical trials among oncology outpatients at a community teaching hospital in Toronto
Authors: Shamrakov L. , Sampson H. , Nyhof-Young J. , Rahim Y.
Published: August 2020

e17547

Background: This study investigated barriers to patient participation in clinical trials (CTs). In particular, the effect of educational attainment on the understanding of, interest about, and past participation in CTs among cancer patients at a Toronto community teaching hospital was assessed. Methods: A survey was administered to cancer outpatients, containing Yes/No answers, and likert scales. Responses were analyzed quantitatively (SPSS). Results: 101 questionnaires were completed out of 112 administered (90% response rate). 76% of patients self-reported as knowledgeable about clinical trials. Patients education level correlated to their perceived knowledge of clinical trials: 37.5% of patients with a less than grade 9, 59.4% with a high school, and 90.2% with a university background identified themselves as knowing what CTs are. All patients scored poorly on details and held common misconceptions of CTs (e.g. knowing little about placebos and experimental drug testing). Overall, 27% of patients had been previously enrolled in CTs. Of the 34% of patients who had been previously approached, 79% had agreed to participate. The majority were willing to participate or unsure of participating in CTs. A minority stated they will never participate in a trial. Patients also identified concern about lack of hospital resources about CTs and a desire to have a doctor present when learning about CTs. Patients with less education identified a greater desire for a doctor's presence than those with more education. Conclusions: This study revealed lack of staff recruitment, low patient awareness, and lack of availability of trial facilities as potential barriers to participation. Targeted information to patients with different education levels may be appropriate, given variable knowledge about CTs. Education and counseling regarding placebos and experimental drugs should be targeted towards all patients to reduce barriers to patient participation, diminish myths, and increase understanding and interest. In response, this institution will design a brochure for all patients describing clinical trials, providing a glossary of terms, and offering a list of key resources in order to improve awareness and trial recruitment.

No significant financial relationships to disclose.