bluuebunny/crossref_metadata_2025 huggingface dataset:
Nucleophosmin expression in ovarian cancer.
Authors: Khabele Dineo , Wilson Andrew J , Liu Annie Y , Roland Joseph , Fletcher Sarah , Slaughter James , Crispens Marta A. , Gold Michael , Jones Howard , James Samuel , Fadare Oluwole
Published: March 2020

e15582

Background: The nucleolar protein, nucleophosmin (NPM1) is implicated multiple cellular processes, including proliferation, duplication of centrosomes, ARF-HDM2-p53 signaling. NPM1 is associated with sites of double strand DNA breaks, with persistence of its expression indicative of impaired DNA repair. Data from the TCGA data have emphasized that genomic instability through impaired DNA repair processes is a characteristic feature of many ovarian cancers. Our aim was to determine the expression of NPM1 in ovarian cancers and to determine the relationship between NPM1 expression and clinical outcomes including overall survival (OS), progression-free survival (PFS) and chemotherapy response. Methods: Tissue microarrays were created from 209 patients treated for ovarian cancer at a single institution from 1994-2004. Expression levels of NPM1 were examined by immunohistochemical staining. Slides were scored using the an automated image capture and analysis system. Positive nuclear staining was used to stratify tumors into high (>50%) and low (<50%) groups, and the results were related to overall survival (OS) and progression-free survival (PFS) via Kaplan-Meier analysis. The relationship between ki67, a proliferation marker and pH2AX, a mark of double strand DNA breaks was measured with Spearman rank correlation coefficient analyses. Results: The majority of tumors, 140/209 (69%) were of serous histology, advanced stage 146/209 (70%) and high grade 158/209 (76%). There was >50% NPM1 expression in 83/209 (40%) and <50% in 126/209 (60%) of the cases. Expression of NPM1 was higher in high grade tumors, and its expression alone was a significant predictor of PFS (p=0.022) but not OS (p=0.053). When adjusting for other predictors, NPM1 expression was predictive of PFS (p=0.047), but not OS (p=0.054). No relationship between NPM1 expression and response to platinum chemotherapy was observed. However, NPM1 expression correlated with Ki67 (r=0.43, p<0.0001) and pH2AX (r=0.22, p=0.0014). Conclusions: NPM1 expression is a mark of poor prognosis in ovarian cancer. Whether these observations reflect increased proliferation and/or genomic instability in ovarian cancer cells will be the focus of future investigation.
Nutlin-3: A novel potential therapeutic in p53 wild-type ovarian carcinomas.
Authors: King Erin Rebecca , Mullany Lisa K , Richards JoAnne S , Gershenson David Marc , Wong Kwong-Kwok
Published: March 2020

e15583

Background: Epithelial ovarian cancer (OC) is a molecularly and clinically heterogeneous disease, yet treatment is the same for all subtypes. Type I carcinomas, including low grade serous, mucinous, clear cell, and endometrioid OCs, are relatively chemoresistant. In contrast, Type II or high grade serous OCs are more aggressive yet responsive to chemotherapy. Molecularly, 96% of high grade serous OCs harbor p53 mutations, whereas Type I carcinomas are more frequently p53 wild-type. Nutlin-3 is a novel therapeutic which inhibits MDM2, activates wild-type p53, and induces apoptosis. We therefore sought to validate nutlin-3 as a therapeutic compound for p53 wild-type OCs. Methods: Two low grade serous, 2 clear cell, 2 endometrioid, 3 mucinous, and 4 high grade serous OC cell lines were treated with varying concentrations of nutlin-3, and proliferation assays were performed. A p53-null cell line was used as a negative control. The cells were then treated with nutlin-3 at their IC50s, and qRT-PCR and Western blot (WB) quantified MDM2, p53, and p21 expression at 24, 48, and 72 hours after treatment. The cell lines were sequenced for p53 mutations in exons 5-8. Results: Responses to nutlin-3 were variable and dependent on p53 mutation status. Low grade and clear cell lines were most sensitive to nutlin-3, endometrioid type were intermediately sensitive, and mucinous were resistant. Two of the four high grade cell lines were sensitive to nutlin-3, both of which were p53 wild-type. Endometrioid and low grade serous cell lines possessing heterozygous p53 mutations were still more sensitive than the p53-null cell line. On qRT-PCR and WB, levels of p53 were decreased after nutlin-3 treatment and were absent in the p53-null cell line. MDM2 and p21 were initially upregulated in sensitive cell lines, but returned to near-baseline levels after 72 hours. In the more resistant cell lines, p21 induction was reduced or absent. Conclusions: Nutlin-3 is a novel potential therapeutic agent for p53 wild-type ovarian carcinoma, and is dependent on an intact p53 pathway with p21 upregulation. Even OC cell lines with heterozygous p53 mutation responded modestly to nutlin-3 treatment. Further investigation of nutlin-3 treatment in ovarian cancer is warranted.
Comparison of clinical outcomes between concurrent chemoradiotherapy followed by adjuvant chemotherapy and concurrent chemoradiotherapy alone for patients associated with locally advanced nasopharyngeal carcinoma: A retrospective analysis of single center experience.
Authors: Maeng Chi Hoon , Park Silvia , Jung Hyun Ae , Ahn Hee Kyung , Hwang Deok Won , Park Keunchil , Ahn Myung-Ju , Ji Jun Ho , Park Lee Chun , Cho Su-Hee , Lee Ji Yean
Published: March 2020

e16003

Background: Up to date, the mainstay of treatment is concurrent chemoradiotherapy (CCRT) with or without adjuvant chemotherapy for locally advanced nasopharyngeal carcinoma. However, the exact role of adjuvant chemotherapy has not been established yet. Methods: Medical record review and data collection were performed for 148 patients who were diagnosed of locally advanced nasopharyngeal carcinoma from October 1996 to September 2009. We analyzed clinical outcomes between the patients who received CCRT followed by adjuvant chemotherapy with cisplatin and 5-FU, and CCRT alone. Results: The estimated 5 year survival rates were 78.3% for the CCRT group and 69.1% for the CCRT followed by adjuvant chemotherapy, respectively (p=0.223). For patients of TNM stage IVA or IVB, the progression-free survival (PFS) and overall survival (OS) had no significant differences between the two groups (p=0.062 and 0.538, respectively). For the patients with stage I, II or III at diagnosis, the PFS and OS were not statistically significant either (p=0.112 and 0.266, respectively). Conclusions: For all stages of nasopharyngeal carcinoma, adjuvant chemotherapy after CCRT did not affect the survival or recurrent rate. A randomized prospective study with long-term follow-up is necessary.
Association of acute phase protein-haptoglobin, and epithelial-mesenchymal transition in buccal cancer.
Authors: Su Yu-Chieh , Lee Ching-Chih , Hung Shih-Kai , Yu Chih-Chia , Li Szu-Chin
Published: March 2020

e16008

Background: The aim of this study was to determine the influence of inflammation on acute phase protein and epithelial-mesenchymal transition (EMT) in buccal cancer. Methods: Western blotting was carried out to investigate the expression of haptoglobin and epithelial-mesenchymal transition in oral cancer cell lines with or without IL-6 stimulation. We studies patients with buccal cancer patients without distant metastasis at diagnosis. Correlation between cellular haptoglobin, EMT, and clinical characteristics of buccal cancer was analyzed to assess the prognostic value of cellular haptoglobin level and EMT. The relationship of haptoglobin, and EMT expression with survival was assessed using Cox proportional hazard models. Results: Western blotting analysis showed that increased haptoglobin protein was associated with overexpression of vimentin. Under IL-6 stimulation, overexpression of haptoglobin, EMT-associated motile phenotype was noted in OC2 cell lines. Overexpression of haptoglobin was also associated with an increased risk for locoregional recurrence (hazard ratio [HR] 1.04; P=0.011) after adjusting for age, gender, disease site, stage, and treatment modality. Conclusions: Increased cellular expression of haptoglobin is associated with EMT in oral cancer cell lines and this phenomenon could be exaggerated with IL-6. Cellular expression of haptoglobin is related to locoregional recurrence rate in buccal cancer patients.
Induction chemotherapy for organ preservation versus surgery for advanced oral cavity squamous cell carcinoma (OCSCC).
Authors: Chinn Steven Bennett , Spector Mathew E , Light Emily , Lin Tasha Lotus , Teknos Theodoros Nicholas , Prince Mark E , Bradford Carol Rossier , Urba Susan , Carey Thomas E , Wolf Gregory T. , Eisbruch Avraham , Worden Francis P. , Chepeha Douglas Brian
Published: March 2020

e16014

Background: The objective of the study is to evaluate the outcomes of an induction selection (IS) concurrent chemotherapy protocol versus primary surgical extirpation in advanced OCSCC. Methods: Retrospective quasi-experimental comparison of patients treated by IS versus surgery. The cohorts were matched based on pretreatment characteristics and compared in an intent-to-treat model.19 patients were accrued with resectable stage III/IV OCSCC without bone involvement between 2000-2002 into a phase II IS trial using 1 cycle of IS to select patients for definitive chemoradiation (CRT). Tumor response was evaluated 3-weeks post-infusion. Patients with >50% response underwent concurrent CRT (70Gy; 35 fractions with concurrent cisplatin 100mg/m2 or carboplatin (AUC 6) every 3-weeks for 3 cycles). Those with <50% underwent surgical treatment and radiation therapy. A comparison cohort of patients with primary surgical extirpation was selected from an OCSCC database from 1998-2009. The surgical cohort of 53 patients was identified based on comparable pretreatment variables to the IS cohort. There was no difference in age, gender, pre-treatment AJCC stage, T-class, N-class, smoking status, alcohol status, or subsite between the two cohorts. Results: Kaplan-Meier estimates demonstrated overall survival (OS) at 5-years was 32% in the IS group and 64% in the surgical cohort. Disease-specific survival (DSS) at 5-years was 46% in the IS group and 76% in the surgical cohort. Local-regional control (LRC) at 5-years was 26% in the IS cohort and 72% in the surgical cohort. Multivariable analysis demonstrated significantly better OS, DSS and LRC (p=0.03, p=0.001 and p=0.0002 respectively) in the surgical cohort compared to the IS cohort. Conclusions: Primary surgical treatment showed significantly better OS, DSS and LRC compared to IS in this quasi-experimental designed comparison. These findings support surgery as the principal treatment for OCSCC.
The PARP inhibitor olaparib (AZD2281) as potent radiosensitizer of head and neck cancer cells.
Authors: Tinhofer Inge , Boyko-Fabian Mariya , Niehr Franziska , Keilholz Ulrich , Budach Volker
Published: March 2020

e16018

Background: Current combined radiotherapy regimens for squamous cell carcinoma of the head and neck (SCCHN) are frequently not curative, necessitating novel therapeutic strategies. Inhibitors of poly(ADP-ribose) polymerases (PARPi), either alone or in combination with chemo- and radiotherapy have been shown to be highly active in tumor cells with intrinsic defects in DNA repair. Despite the frequent occurrence of genomic alterations in SCCHN cells also affecting their capacity of DNA repair the radiosensitizing potential of PARPi has not been addressed in detail so far. In this study, the efficacy of PARPi as radiosensitizer in SCCHN and possible mechanisms of cross-resistance between PARPi and cisplatin were evaluated. Methods: Usingthe clonogenic survival assay and a panel of 10 SCCHN cell lines the sensitivity of SCCHN cells to olaparib alone (0 to 500 nM) or in combination with irradiation (0 to 4 Gy) was determined. Survival fractions for given treatments were calculated on the basis of survival of untreated cells. In addition, the activity of cisplatin to inhibit clonogenic growth and its radiosensitizing potential was determined. From the dose-effect curves the IC50 values and the combinatory indices were calculated using the CalcuSyn Software. Results: In 9 of 10 cell lines, olaparib monotherapy showed significant inhibitory activity on clonogenic survival. Synergistic activity of olaparib in combination with irradiation was observed in all cell lines. No correlation between sensitivity of cells to olaparib and cisplatin (IC50 cisplatin vs IC50 olaparib: r2=0.042, p=.57; IC50 cisplatin vs CI [IR+olaparib]: r2=0.005, p=.95) was observed. Furthermore, the activity of olaparib was not dependent on the p53 genotype. Conclusions: The combination of PARPi with radiotherapy represents an active therapeutic regimen in SCCHN. The observed high activity of this combination even in cells with reduced sensitivity to cisplatin and p53 dysfunction suggests its clinical usefulness also in the group of patients with more aggressive disease and the second-line setting. Currently, detailed molecular characterization for identification of potential biomarker for tumor susceptibility to PARP inhibition is ongoing.
Methotrexate and cetuximab for metastatic advanced head and neck squamous cell carcinoma: A retrospective study.
Authors: Atassi Bassel , Alsibai Khaled , Yoo George H. , Lin Ho-Sheng , Dyson Gregory , Kim Harold , Jacobs John Robert , Kucuk Omer , Sukari Ammar
Published: March 2020

e16019

Background: After the failure of first line palliative chemotherapy in recurrent non-resectable or metastatic head and neck squamous-cell carcinoma (HNSCC), there is no standard of care treatment that improves survival or quality of life. Both, methotrexate and cetuximab have single agent activity in metastatic HNSCC. We are presenting our institutional experience in using unique combination chemotherapy with methotrexate plus cetuximab (MC). Methods: Retrospectively, single institution’s charts were reviewed from 2004-2010, all patients have documented recurrent non-resectable or metastatic HNSCC. Patients received weekly IV methotrexate 25 mg/m2 plus IV cetuximab 250 mg/m2. Each cycle is 4 weeks treatments. Patients who completed at least 2 cycles were included. Patients can receive MC as first line if they have poor performance status. Treatment was continued until progression. Results: Total of 39 patients were included, 27 male and 12 female. Median patients’ age was 57 years old. 35 patients received methotrexate plus cetuximab (MC) after failure of prior line of palliative chemotherapy. 17, 10 and 8 patients received MC as second, third and fourth line therapy, respectively. 4 patients received MC as 1st line because they were not candidate for more aggressive therapy. The average received number of weekly treatments was 31 (8-95) and average number of cycles was 7 (2-23). Prior chemotherapy regimens include taxanes, platinum, 5-flurouracil, and gemcitabin. 13 patients received prior cetuximab as single agent or in combination. Median progression free survival was 7.1 months and overall survival was 9.8 months. Considering the line of therapy, the median survival was 6.9, 10.1, 13.5 and 9.9 months for patients received MC as 1st, 2nd , 3rd and 4th line of therapy respectively (P= 0.356). Grade 1 and 2 skin rash and hypomagnesimia were observed in 47% and 36% of patients. Conclusions: Methotrexate plus cetuximab is a well tolerated regimen with a significant survival benefit. Prospective well designed studies are warranted in order to evaluate this regimen as a second line palliative therapy for patients with advanced non-curable head and neck squamous cell carcinoma.
Association of tissue factor expression in squamous cell head and neck carcinomas with well-differentiated tumors.
Authors: Jacobs Benjamin , Zhang Xinmin , Gaughan John P. , Bromberg Michael
Published: March 2020

e16022

Background: Tissue factor (TF) is a glycoprotein that initiates coagulation when complexed with factor VIIa. High levels of TF expression have been found in many cancers and correlated with tumor aggressiveness. TF has been shown to be expressed in head and neck squamous cell carcinomas (HNSCC) but the role of TF on cell function and prognosis are not known. The epidermal growth factor receptor (EGFR) is overexpressed in many HNSCC and EGFR and TF expression are highly correlated in some tumor types. Our goal was to correlate the expression of TF and EGFR in HNSCC with tumor cell differentiation and prognosis. Methods: Twenty biopsy specimens of squamous cell head and neck carcinomas were studied. Immunohistochemistry for TF, EGFR, and p16 was performed. Cases were scored based upon the staining intensity of tumor cells using a semiquantitative scale as negative, weakly (+), moderately (++) or strongly (+++) positive. Results: The tumor stages ranged from T1N0 to T4N3. Of the 20 specimens, 5 were well differentiated, 12 were of moderate differentiation, and 3 were poorly differentiated. Median survival was 23 months, median follow-up 73 months. TF was expressed in 75% (15/20) of tumors at varying levels. Moderate TF expression was found in 6 specimens, and 9 showed weak expression. None of the poorly differentiated tumors expressed TF, and there was a definite negative correlation between TF expression and tumor differentiation (Pearson r=--0.747, p=0.0002). There was no association between TF expression and survival (Log-Rank 0.3115, p=0.8558). All of the tumors analyzed expressed EGFR and there was no correlation between TF expression and EGFR expression. Overall, 25% (5/20) of tumors expressed p16, suggesting human papilloma virus infection. Conclusions: Results from this retrospective study indicate that well differentiated HNSCC express higher levels of TF than poorly differentiated tumors and that TF and EGFR expression are not tightly linked. Moreover, unlike other cancer sites, HNSCC TF expression did not appear to worsen overall patient survival, and was actually associated with more well-differentiated tumors.
A phase I dose-escalation trial of SRS boost treatment of human papilloma virus (HPV)-unassociated oropharyngeal squamous cell carcinoma (OPSCC).
Authors: Schwartz David L. , Parise Sara , Denitz Jordan , Nguyen Vinh , Fantasia John , Mehrotra Bhoomi , Saltman Benjamin , Frank Douglas
Published: March 2020

e16026

Background: HPV-negative status and/or significant smoking history predict for poor radiation response in patients with OPSCC. To improve disease control outcomes in this population, we are conducting a phase I dose-escalation trial of stereotactic radiotherapy boost delivery to primary disease. Methods: Thirteen consecutive patients with newly diagnosed HPV-unassociated OPSCC were enrolled onto this IRB-approved clinical trial between 5/2010 and 10/2011. Eligible patients had HPV-negative disease and/or tobacco exposure history of >10 pack-years. The cohort consisted of 12 males/1 female with a median age of 58.5 yrs (range: 46-64). There were 9 tonsil/2 tongue base/1 soft palate/1 GP sulcus cases, with 5 T2/5 T3/3 T4 primaries and 2 AJCC stage III/11 stage IV disease. Primary disease received 60 Gy, gross nodal disease 66 Gy, and prophylactic nodal target volumes 54-60 Gy with routine IMRT technique in 30 daily fractions. All patients received concurrent chemotherapy (12 cisplatinum-based, 1 cetuximab). Within one week of IMRT completion, SRS boost treatment was delivered to the primary disease target volume. Initial SRS dose level was set at 8 Gy, and has been delivered to 11 enrolled patients, with 1 patient pending and 1 patient self-removed from protocol. Median follow up for completed patients is 11 (range: 5-17) months. Results: Twelve cases are evaluable. Post-SRS boost adverse events have remained limited mostly to Gr 2-3 xerostomia, pain, and dysphagia. Five patients have required PEG placement. No acute or chronic Gr 4-5 toxicity has been observed. One patient with bulky T4 disease died of persistent disease. One patient with residual adenopathy had consolidative neck dissection and remains free of disease, as do the remaining 10 patients who responded completely. Conclusions: 8 Gy SRS boost treatment to high-risk primary OPSCC disease is feasible and safe, and step-wise dose escalation is ongoing.
The impact of medical comorbidities on the quality of care for patients with head and neck cancer.
Authors: Ernst Brenda , Busowski Mary T , Weber Randal S. , Shellenberger Thomas D.
Published: March 2020

e16030

Background: Objectively assessing the treatment of patients with cancer offers a basis for raising the standard of care. Quality indicators provide criteria by which the safety of care can be measured and compared to defined benchmarks. However, variables influencing the metrics in quality can limit generalizability and applicability. Medical comorbidities pose significant threats to the care of patients with head and neck cancer. We sought to investigate the impact of medical comorbidities on quality indicators for patients undergoing management by the multidisciplinary team. Methods: Comorbidities were assessed in relation to quality indicators in 49 patients treated for squamous cell carcinoma of the head and neck over a 16-month period. Treatment with surgery, radiation, and chemotherapy was classified by the number and type of modalities delivered. Surgical procedures were stratified by high and low acuity as defined by extent. By univariate and multivariate analysis, medical comorbidities were correlated with length of hospital stay, readmission within 30 days, return to the operating room within 7 days, 30-day mortality, use of blood products, and surgical site infection. Results: Cardiovascular disease was present in 49% of patients, diabetes mellitus in 12%, liver disease in 8%, previous congestive heart failure in 4%, and chronic obstructive pulmonary disease in 17%. The presence of any single comorbidity was correlated with each of the negative indicators (p<0.05), and with multiple negative indicators (p<0.05). Comorbidities occurred more frequently in patients undergoing high acuity surgery (p<0.05) and combined modality therapy (p<0.05). Decreasing performance status and major clinical predictors were the factors most strongly associated with negative quality indicators. Conclusions: Approaches to adjust for comorbid status are critical to accurate assessment of quality indicators. Risk stratification of patients at initial evaluation can offer valuable criteria for selecting treatment. Evaluation and management of comorbidities by evidence-based guidelines may improve care.
Nonstandard first-line therapy and survival in patients (pts) with recurrent/metastatic head and neck cancer (RMHNSCC): Experience of 194 pts in a single institution.
Authors: Fayette Jerome , Polivka Valentine , Chabaud Sylvie , Favier Bertrand , Racadot Severine , Pommier Pascal , Montbarbon Xavier , Neidhardt Eve Marie , Girodet Didier , Zrounba Philippe
Published: March 2020

e16036

Background: With the standard first line association platinum 5FU and cetuximab, median overall survival (OS) for RMHNSCC was 10.1 months (95% CI [8.6 – 11.2]) (N Engl J Med. 359:1116). Due to the toxicity of this treatment we often offer alternative therapy to our pts. This work aimed to evaluate impact of different 1st line treatment on OS. Methods: With the standard first line association platinum 5FU and cetuximab, median overall survival (OS) for RMHNSCC was 10.1 months (95% CI [8.6 – 11.2]) (N Engl J Med. 359:1116). Due to the toxicity of this treatment we often offer alternative therapy to our pts. This work aimed to evaluate impact of different 1st line treatment on OS. Results: At initiation of palliative chemotherapy, median age was 62 [29-87]; PS was 0, 1, 2, 3 in 13%, 59%, 16% and 11% of pts, respectively. First line chemotherapy consists in combination cisplatin+taxanes (CIST) 24%, caboplatin+taxanes (CART) 33%, cisplatin or carboplatin without taxanes (NOT) 15% or others (OTH) 28%. Median OS was estimated to 9.6 months CI95%=[8.1-11.4], with 39% of pts; CI95%=[32-47] still alive at 1-year. Second line of treatment has been initiated in 61% of pts. Some of them have even been able to have up to 3, 4 or more than 4 lines of treatment in 19%, 11% and 4% of pts, respectively. In the subgroup analysis, which represents a population similar to those included in [ref1], first line chemotherapy was CIST, CART, NOT or OTH in 30%, 30%, 18% and 22%, respectively. Median OS was 13.0 months, CI95%=[11.2-17.7] reaching up to 15.3 months for CIST subgroup. Second line of treatment was initiated in 73% of pts, with 20%, 15% and 5% of pts having a third, a fourth, and a fifth line, respectively. Conclusions: We can reach for unselected pts the best OS published in phase III studies. The use in first line of combination of platinum and taxanes, followed by monotherapies with cetuximab, capecitabine and methotrexate allows reaching OS of 13 months.
Overall survival (OS) and risk of distant failure among malignant salivary gland tumors (MSGTs) in a large single-institution registry cohort.
Authors: Rodriguez Cristina P. , Mason Teresa , Mongoue-Tchokote Solange , Stott Will , Andersen Peter , Holland John M , Gross Neil D.
Published: March 2020

e16045

Background: MSGTs are rare, biologically diverse cancers. Registry data and large series suggest 5-year OS exceeding 50%, superior to historical data and attributed to postoperative radiation (pXRT). Hypothesizing OS has remained poor despite modern therapy, we reviewed our cancer registry (OHSUCR), which began collecting data on MSGTs in 1995. Methods: We interrogated the OHSUCR for pts with MSGTs (WHO classification) and obtained data on age, sex, race, AJCC stage, histology, primary site, surgery, pXRT. OS was estimated using the Kaplan Meier (KM) method. The log rank test was used to compare OS among pts treated with and without pXRT, and those diagnosed between 1995-2000, 2001-2005, and 2005-present. Results: 110 pts with MSGTs were entered into the OHSUCR from 5/1996 to 5/2011. The median age was 60 (range 10-90), 65 (59%) were male, and 106 (96%) were white. The primary site was: 101 (92%) parotid, 3 (3%) unspecified major salivary gland, 4 (3%) submandibular gland, and 2 (2%) minor salivary gland. MSGT histologies were: 41 (37%) mucoepidermoid carcinoma, 24 (22%) adenoid cystic carcinoma, 21 (19%) adenocarcinoma, 12 (11%) acinar cell carcinoma, 5 (4%) carcinoma ex pleomorphic adenoma, 3 (3%) epithelial-myoepithelial carcinoma, 1 (1%) undifferentiated carcinoma, 1 (1%) small cell carcinoma, 1(1%) salivary duct carcinoma, 1 (1%) carcinosarcoma. AJCC Stage was: I in 29, (26%) II in 20 (18%), III in 16 (15%), IV in 45 (41%). 102 (96%) underwent surgical resection, 73 (66%) pXRT. 89 (81%) pts were rendered disease free, although 23 (21%) eventually recurred, 20 in distant sites. At the time of analysis 57 (52%) pts were alive and disease free. With a median follow up of 30 months (range 1 to 165), the 5 year KM OS for the entire cohort is 46%. Median survival was not influenced by pXRT (p=0.93) or period of diagnosis (1995-2000, 2001-2005, or 2005-present; p=0.83). Conclusions: In this large single institution series, pts with MSGT remain at high risk for mortality despite routine administration of pXRT. Distant metastasis is the most common pattern of failure indicating a clear unmet need for improved systemic therapy for MSGTs.
Outcome after different treatments for patients with HPV+ tonsillar cancer.
Authors: Attner Per
Published: March 2020

e16048

Background: In the last few years, oncological treatment for tonsillar cancer has intensified with accelerated radiotherapy and chemotherapy, which has resulted in more side effects. Patients with HPV-positive tonsillar cancer have better prognosis than those with HPV-negative tumors, and it is possible that patients with HPV-positive tonsillar cancer may benefit from a reduced, less-toxic treatment without compromising survival. Methods: To evaluate the possible difference in survival after different oncological treatments of patients with HPV-positive tonsillar cancer, we evaluated all 211 patients diagnosed with tonsillar cancer between 2000-2007, in Stockholm, Sweden. Included patients were those with available pretreatment biopsies, and treated with intent to cure. A total of 172 patients had HPV-positive tumors and of those, 98 were treated with conventional radiotherapy, 44 were treated with accelerated radiotherapy and 30 were treated with chemoradiotherapy. Results: No significant differences in overall and disease-free survival were seen between the three treatment groups, but there was a trend, where chemoradiotherapy was better than radiotherapy; and accelerated radiotherapy was better than conventional radiotherapy. This trend needs to be followed further. Conclusions: In this study, patients with HPV-positive tonsillar cancer treated with conventional radiotherapy, accelerated radiotherapy or chemoradiotherapy had similar survival rates. However, there is a trend for better survival and less metastasis after intensified treatment underlining the need for prospective studies, where less intense treatment is compared to more intense treatment.
Physical symptoms and psychological distress in head and neck cancer patients.
Authors: Trevino Lara Anne , Roscoe Joseph , Gewandter Jennifer S. , Morrow Gary R.
Published: March 2020

e16056

Background: Little is known about the relationship between psychological distress and physical symptoms in head and neck cancer (HNC) patients undergoing radiation therapy (RT), and how these relationships may change over the course of treatment. We conducted exploratory analyses, on a previously published descriptive study examining the occurrence and severity of physical symptoms during RT. The purpose of this secondary analysis was to determine the relationship over time between psychological distress and physical symptoms in HNC patients. Methods: Ninety HNC patients receiving RT completed a Symptom Inventory (SI) weekly for five weeks, beginning with the week prior to the start of treatment. The SI assesses the presence and severity of 12 symptoms, including, pain, fatigue, nausea, disturbed sleep, feeling distressed, shortness of breath, memory, lack of appetite, drowsiness, vomiting, skin problems, and urination difficulty. Change scores in symptom severity between baseline and weeks 2, 3 and 4 were calculated, and Pearson’s correlations were used to determine the associations between psychological distress and physical symptoms. Results: Changes in psychological distress between baseline and week 2 of treatment were significantly correlated with changes in fatigue (r = 0.35, n=52, p = 0.01) and skin problems (r = 0.40, n=36, p = 0.02). Changes in psychological distress between baseline and week 3 of treatment were significantly correlated with changes in fatigue (r = 0.42, n=42, p = 0.006), shortness of breath (r = 0.48, n=42, p = 0.001), memory (r=0.36, n=42, p = 0.02), and lack of appetite (r = 0.53, n=42, p = 0.001). Changes in psychological distress between baseline and week 4 of treatment were correlated with changes in fatigue (r = 0.57, n=40, p=0.001), memory (r=0.48, n=39, p=0.002), and lack of appetite (r=0.49, n=40, p=0.001). Conclusions: Fatigue, memory, shortness of breath, and lack of appetite are significantly related to psychological distress in HNC patients undergoing RT. Additional research is needed to determine how psychological distress affects physical symptoms and if improvements in psychological distress may attenuate physical symptoms in HNC patients receiving RT.
Health care utilization (HCU) by breast cancer (BC) and non-Hodgkin lymphoma (NHL) patients (pts) with chemotherapy (CT) induced febrile neutropenia (FN) in the Netherlands.
Authors: Gelderblom Hans , Lugtenburg Pieternella , Nortier J. W. R. , van Herk-Sukel Myrthe , Issa Djamila , Jager A. , De La Orden Margarita , van der Werf-Langenberg Mirte , Houweling Leanne , De Jong Floris Aart
Published: March 2020

e16526

Background: CT-induced FN can result in reduced CT delivery, unplanned hospitalizations, and increased mortality risk. Changes in clinical practice warrant investigation of current resource use and economic cost of FN; therefore we studied FN-related HCU among BC and NHL pts. Methods: Data from incident adult cancer pts with a primary hospital discharge diagnosis for BC or NHL from 1998–2007 were obtained from the PHARMO Record Linkage System, including pharmacy, hospital and clinical lab data. Eligible pts had ≥12 months medical history available and received CT ≤6 months after cancer diagnosis. Pts developing FN ≤6 months after first CT (“FN pts”) were matched 1:2 on gender, birth year, and CT regimen to pts without FN (“non FN pts”). HCU data (hospitalizations, medical procedures, drug use [number dispensed]) was tallied from entry date (date of FN or matched date for non FN pts) for up to 3 months. Statistics are descriptive with crude odds ratios (OR). Results: 80/1,033 BC pts (8%) developed FN (all were matched). 95/486 NHL pts (20%) developed FN (89 were matched). More FN than non FN pts were hospitalized in the 1st month after the entry date: BC 73% vs 14% (OR=23.0 [95%CI 8.3-63.7]); NHL 78% vs 33% (OR=7.6 [3.9-15.1]). These differences were mainly due to FN-related hospitalizations (BC 55% vs 1%, NHL 47% vs 4%). FN pts also had a longer mean length of stay per all-cause hospitalization: BC 4.6 vs 1.9 days; NHL 10.1 vs 3.0 days. In the 1st month after entry date, the mean number of total drugs dispensed per patient was higher in FN pts than non FN pts (BC 5.8 vs 3.1, NHL 8.5 vs 3.6); use of anti-infectious agents was higher (BC 99% vs 11%, NHL 96% vs 20%), as was number of other non-CT drugs (including corticosteroids, drugs for acid related disorders, laxatives, psycholeptics, analgesics, antithrombotics, and diuretics). More FN than non FN pts had medical procedures (BC 14% vs 3%, NHL 13% vs 8%). HCU differences between FN and non FN pts were maintained after 3 months. Conclusions: This study confirms the high resource utilization currently associated with FN, based on BC and NHL pt data from the Netherlands. Reduction of FN may improve quality of life and save resources.
Impact of an oncology pharmacist attendance at a multidisciplinary lung clinic.
Authors: Kirsa Sue , Walter Clare , Rice Carol , Mellor Dan , Mileshkin Linda R. , Duffy Mary , Ball David
Published: March 2020

e16538

Background: Medication misadventure contributes to unplanned hospital admissions in patients with cancer. Often, numerous medications are added to existing ones and general practitioners (GP) may lack experience in managing problems involving cancer related medication. A survey exploring the unmet needs of our lung cancer outpatients highlighted the need for more medication information. Inpatient clinical pharmacy services are known to impact on patient care and morbidity. This project aimed to evaluate the effects of extending this service to outpatients. Methods: An oncology pharmacist joined the lung cancer clinic team for 6 months. Consented patients completed assessments of medication adherence (using Morisky tool) and satisfaction with medicines information at baseline and within 30 days of review. Post pharmacist review, a medication list and plan (detailing recommendations/interventions) were provided to patients and community and hospital healthcare providers. Uptake of recommendations was evaluated 7 days after review. Assessment results (pre and post review) were analyzed using the matched pairs Wilcoxon test. Interventions were categorized and graded according to risk avoided. Unplanned admissions and clinic attendance rates were compared to the previous year and analyzed using the Rate Ratio Test assuming Poisson counts.GPs opinion of the service was evaluated via survey. Ethics approval was obtained from HREC. The project was supported by an educational grant from Roche Pharmaceuticals. Results: 48 patients were recruited. Medication adherence (p=0.007) and patient satisfaction (p<0.001) were significantly improved. 154 pharmacist interventions were made: 4.5% extreme risk and 43.5% high risk. Ratios of unplanned admissions and clinic attendances decreased; 0.3 to 0.26 (p= 0.265) and 3.32 to 2.98 (p=0.004) respectively. 31 of 48 general practitioners (GPs) completed the survey, 74% found the service useful. Conclusions: Adding a pharmacist to the outpatient lung team led to significant improvements in patient medication adherence. Both patients and GPs were highly satisfied with the service. Medication misadventure, unplanned admissions and clinic attendances were reduced.
The impact of a novel reimbursement (reimb) model on physician (phys) revenue.
Authors: Feinberg Bruce A. , Olson Tim , Wong Winston , Cooper Joseph , Scott Jeffrey A.
Published: March 2020

e16540

Background: CareFirst BlueCross BlueShield (CFBCBS) partnered with Cardinal Health Specialty Solutions (CHSS) to launch the first cancer care clinical pathway in the US in Aug 2008. CFBCBS, CHSS, and members of the provider network sought to create a unique mechanism of reimb for network phys as part of the pathways 2nd-generation program. Fee schedules for IV medications (meds) were reduced, and fee schedules for evaluation and management (EM) codes were increased, so that on an aggregate, weighted basis there was no expected change in overall phys reimb. This would allow phys focus on optimal treatment course without the financial incentive to prescribe chemotherapy (CT). We analyzed the impact of this novel reimb model on phys revenue after 1 year (yr). Methods: Thirty-one CFBCBS network medical oncologists comprising 14 practices volunteered to participate in the pilot program. Using the 2009 benchmark yr, all IV CT J codes, administration (admin) codes, and EM codes were analyzed. Phys were then being paid above Medicare allowable for IV meds. The design of the pilot program was to shift payment for IV meds to Medicare allowable and move the extra dollars to enhance EM codes. This process was prorated more heavily weighted towards the new pt codes. Phys were also offered the option of having meds white bagged through a specialty pharmacy. The same codes from 6 mo of 2011, the yr the plan was instituted, were collected and extrapolated to reflect 12 mo of program experience and compared to pre-program data from 2009. Results: In 2009, phys generated 25,282 J codes, 24,950 EM codes, and 19,340 admin codes. In 2011, they generated 22,288 J codes, 23,040 EM codes, and 15,634 admin codes. The net impact on phys revenue in 2011 was -1.5% (range +2% to -4%) compared to 2009. None of the practices selected the white bag specialty option. Conclusions: This data demonstrates that a reimb model that shifts the focus of reimb from drug sales to cognitive services is possible and can be created by a collaborative effort between payers and providers with minimal impact to overall phys revenue. Despite the parity that can be achieved, phys continue to prefer the “buy and bill” model. Evaluation of changes in phys patterns of care due to this reimb methodology is ongoing.
Clinical trials decision-making in African American patients with cancer: The role of cancer-coping religious beliefs.
Authors: Banda Deliya , Howard Margaret , Tefera Eshetu , Holt Cheryl L , Swain Sandra M.
Published: March 2020

e16543

Background: Religious beliefs have been shown to play a significant role for African American patients coping with a cancer diagnosis. Less established is how these beliefs may relate to specific treatment decisions. The purpose of this study was to explore how patients used religious beliefs for coping and examine the relationship with specific attitudes towards and intention to enroll in a clinical trial (CT). Methods: Participants were 108 active treatment patients at a large urban cancer institute. The primary study outcome was self-reported likelihood to participate in a cancer therapeutic trial. Participant attitudes towards CTs were assessed using the Attitudes and Intention to Enroll in Therapeutic Clinical Trials instrument. The God as Healer construct was used to assess the perception of God as a healer, either directly or through the intervention of physicians and medicine. Kruskal-Wallis and Wilcoxon Mann-Whitney tests were used to examine the relationship between the sum scores of religious beliefs, attitude items and likelihood of patients to participate in CT. Results: The results of these analyses provided limited support for a direct relationship of belief in God as a healer and intention to enroll in a CT. Spearman’s correlation analysis revealed a statistically significant relationship between a belief in God as direct healer with ‘Distrust of doctors’ (rs= 0.26, p < .01 ); and God as direct healer with ‘Fear of losing one’s rights after signing a CT consent form’ (rs= 0.24, p < .05). While not statistically significant in this sample, those with a higher belief in ‘God as a healer through medicine and doctors’ had more negative attitudes of ‘fear of being treated unfairly on a CT due to being poor or a minority’, and of ‘losing their rights after signing a CT consent form’. Conclusions: These findings suggest providers should be aware of the culturally specific roles that religious/spiritual beliefs play in African American patients’ attitudes towards CTs and how they may align with CT decision-making.
Academic and community PCPs underestimate benefits of systemic therapy for lung and breast cancer.
Authors: Abdolmohammadi Alireza , Rai Shesh , Pan Jianmin , Alexander Joseph , Kloecker Goetz H.
Published: March 2020

e16545

Background: In previous studies primary care physicians (PCP) under-appreciated systemic therapy for breast cancer (BC) and even more for lung cancer (LC). Lack of knowledge and a possible bias against lung cancer patients were suggested as potential causes. This study evaluates if the unawareness about beneficial systemic therapy persists in the era of targeted therapy, and if academic PCPs have a different perception than community PCPs. Methods: 3444 surveys were sent out, (printed 2,497, electronic 947) to 1,993 Family Medicine (57%) and 1,451 Internal Medicine MDs (43%), in academic (13%) and non-academic centers (87%). Case scenarios asked if respondents believed in the potential curative and palliative role of chemotherapy in the early and advanced stage of either lung cancer (LC) or breast cancer (BC). The study was testing a 20% difference in response rate between academic and non-academic MDs with a power of 80% and alpha of 5%. Results: 316 physicians (9.1%) responded, 89 academic MDs (28%), 227 non-academic MDs (72%). The rate of returned surveys was equal by specialty. PCPs believed less in curative systemic therapy for LC than BC (42% vs. 72.6%, (p<0.001). PCPs believed less in systemic therapy to improve DFS for LC than BC (58.2% vs. 75.5%, p<0.001). PCPs believed palliative chemotherapy can prevent symptoms and prolong life in advanced asymptomatic disease, 79.5% in LC and 84.6% in BC (ns). Half of the PCPs refer patients with symptomatic advanced disease to palliative care before seeing medical oncology, 50.8% in LC and 53.1% in BC (ns). Academic and community MDs responded in the same pattern for all scenarios (p>0.5). Conclusions: Academic and community PCPs are very often not aware of the curative and palliative benefits of systemic therapy. This persistent lack of awareness by PCPs requires more educational effort by medical oncologists and academic institutions.
A review of clinical endpoints and use of quality of life outcomes in phase III metastatic breast cancer clinical trials.
Authors: Tatla Raman , Landaverde Denis , Victor Charles , Miles David , Verma Sunil
Published: March 2020

e16547

Background: The management of metastatic breast cancer (MBC) is often considered to be palliative, with therapy used to relieve disease symptoms, minimize treatment effects and prolong survival. The impact of disease and treatment on patients has led to an emphasis of quality of life (QoL) measures in clinical trials. This study’s primary objective is to evaluate phase III clinical trials in MBC, and assess the inclusion of QoL as an endpoint. Methods: A PubMed search was conducted to identify phase III clinical trials published from Jan 1990 to Aug 2011, which evaluated systemic therapy in MBC patients. Data pertaining to treatment regimens, study endpoints and clinical findings were collected, with a focus on progression-based (PB), overall survival (OS), and QoL endpoints. The instrument(s) used to evaluate QoL were also noted (if applicable). Results: Of 520 publications identified, 122 phase III MBC clinical trials met the inclusion criteria. Of these studies, 98.4% and 95.9% included PB and OS respectively, as clinical endpoints, while QoL was assessed in only 46 (37.7%) studies. 14 instruments were identified as QoL tools among the studies, with EORTC QLQ-C30 and FACT-B accounting for 54.7% of the instruments used. While the inclusion of QoL was not related to the significance of PB results, there was an association between the inclusion of QoL and OS results, with 59% of significant OS studies and 32% of non-significant OS studies including QoL as an endpoint (p=0.016). Stratification by treatment arm found that studies favouring standard therapy were more likely to include QoL (75%, p=0.045), compared to those favouring the intervention (56%), and those without significant differences (32%). Conclusions: Although the importance of QoL is often emphasized in MBC management, only one-third of identified phase III clinical trials included its assessment. Half of these trials showed no statistically significant differences in QoL endpoint; of note, instruments of varying validity were utilized. There needs to be greater emphasis on the evaluation of QoL, with the use of standard and validated QoL tools in MBC clinical trials, especially as we increasingly focus on progression-based endpoints.
Nature and extent of financial conflicts of interest among National Comprehensive Cancer Network (NCCN) clinical practice guidelines panel members.
Authors: Madadi Anusha Reddy , Go Ronald S.
Published: March 2020

e16555

Background: NCCN Clinical Practice Guidelines are the most widely recognized and comprehensive clinical policies used in oncology written by multidisciplinary panels of expert physicians from NCCN member institutions. However, the recommendations are largely developed from lower levels of evidence or expert opinions, and therefore, potentially vulnerable to influence by financial conflicts of interest (FCOIs) (Poonacha T, et al. J Clin Oncol 2011;29:186-191). Objective: We performed this study to describe the nature and extent of self-reported FCOIs of NCCN panel members among the 10 most common cancers in the US. Methods: We obtained the disclosures from the NCCN website (accessed December 1, 2011). FCOIs are reported under 4 categories: clinical research support (research), advisory board/speaker bureau/expert witness/consultant (honoraria), patent/equity/royalty (equity), and other remunerations. Results: There are 330 panel members with a mean of 33 per panel. Most (94%), but not all, disclosures are up to date as of 2011. 141 (43%) panel members reported FCOIs. The extent of FCOIs among panel members according to disease sites are as follows: non-Hodgkin lymphoma (60%), breast (52%), kidney (49%), colorectal (48%), lung (47%), prostate (41%), bladder (40%), melanoma (29%), thyroid (28%), and uterine (25%) cancers. 74% (n=23) of writing committee members and 83% of panel chairs have FCOIs. Among the panel members with FCOIs, 51%, 48 %, 1%, and 1% of the FCOIs are related to research, honoraria, equity, and other remunerations, respectively. Of those with non-research FCOIs (n=109), 38%, 29%, and 33%, reported 1, 2-3, and >4 disclosures, respectively Conclusions: ASubstantial proportions of NCCN panel members as well as the majority of panel chairs and writing committee members have FCOIs. Nearly half of the FCOIs are unrelated to research support. While the actual impact of FCOIs on the NCCN recommendations cannot be determined from our study, the potential for such influence can be considerable.